The Pervasive Problem With Placebos in Psychology: Why Active Control Groups Are Not Sufficient to Rule Out Placebo Effects.

PubMed

Boot, Walter R; Simons, Daniel J; Stothart, Cary; Stutts, Cassie

2013-07-01

To draw causal conclusions about the efficacy of a psychological intervention, researchers must compare the treatment condition with a control group that accounts for improvements caused by factors other than the treatment. Using an active control helps to control for the possibility that improvement by the experimental group resulted from a placebo effect. Although active control groups are superior to "no-contact" controls, only when the active control group has the same expectation of improvement as the experimental group can we attribute differential improvements to the potency of the treatment. Despite the need to match expectations between treatment and control groups, almost no psychological interventions do so. This failure to control for expectations is not a minor omission-it is a fundamental design flaw that potentially undermines any causal inference. We illustrate these principles with a detailed example from the video-game-training literature showing how the use of an active control group does not eliminate expectation differences. The problem permeates other interventions as well, including those targeting mental health, cognition, and educational achievement. Fortunately, measuring expectations and adopting alternative experimental designs makes it possible to control for placebo effects, thereby increasing confidence in the causal efficacy of psychological interventions. © The Author(s) 2013.

Effects of plyometric training and creatine supplementation on maximal-intensity exercise and endurance in female soccer players.

PubMed

Ramírez-Campillo, Rodrigo; González-Jurado, José Antonio; Martínez, Cristian; Nakamura, Fábio Yuzo; Peñailillo, Luis; Meylan, Cesar M P; Caniuqueo, Alexis; Cañas-Jamet, Rodrigo; Moran, Jason; Alonso-Martínez, Alicia M; Izquierdo, Mikel

2016-08-01

To investigate the effects of a six-week plyometric training and creatine supplementation intervention on maximal-intensity and endurance performance in female soccer players during in-season training. Randomized, double-blind, placebo-controlled trial. Young (age 22.9±2.5y) female players with similar training load and competitive background were assigned to a plyometric training group receiving placebo (PLACEBO, n=10), a plyometric training group receiving creatine supplementation (CREATINE, n=10) or a control group receiving placebo without following a plyometric program (CONTROL, n=10). Athletes were evaluated for jumping, maximal and repeated sprinting, endurance and change-of-direction speed performance before and after six weeks of training. After intervention the CONTROL group did not change, whereas both plyometric training groups improved jumps (ES=0.25-0.49), sprint (ES=0.35-0.41), repeated sprinting (ES=0.48-0.55), endurance (ES=0.32-0.34) and change-of-direction speed performance (ES=0.46-0.55). However, the CREATINE group improved more in the jumps and repeated sprinting performance tests than the CONTROL and the PLACEBO groups. Adaptations to plyometric training may be enhanced with creatine supplementation. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Correction of Abdominal Distention by Biofeedback-Guided Control of Abdominothoracic Muscular Activity in a Randomized, Placebo-Controlled Trial.

PubMed

Barba, Elizabeth; Accarino, Anna; Azpiroz, Fernando

2017-12-01

Abdominal distention is produced by abnormal somatic postural tone. We developed an original biofeedback technique based on electromyography-guided control of abdominothoracic muscular activity. We performed a randomized, placebo-controlled study to demonstrate the superiority of biofeedback to placebo for the treatment of abdominal distention. At a referral center in Spain, we enrolled consecutive patients with visible abdominal distention who fulfilled the Rome III criteria for functional intestinal disorders (47 women, 1 man; 21-74 years old); 2 patients assigned to the placebo group withdrew and 2 patients assigned to biofeedback were not valid for analysis. Abdominothoracic muscle activity was recorded by electromyography. The patients in the biofeedback group were shown the signal and instructed to control muscle activity, whereas patients in the placebo received no instructions and were given oral simethicone. Each patient underwent 3 sessions over a 10-day period. The primary outcomes were subjective sensation of abdominal distention, measured by graphic rating scales for 10 consecutive days before and after the intervention. Patients in the biofeedback group effectively learned to reduce intercostal activity (by a mean 45% ± 3%), but not patients in the placebo group (reduced by a mean 5% ± 2%; P < .001). Patients in the biofeedback group learned to increase anterior wall muscle activity (by a mean 101% ± 10%), but not in the placebo group (decreased by a mean 4% ± 2%; P < .001). Biofeedback resulted in a 56% ± 1% reduction of abdominal distention (from a mean score of 4.6 ± 0.2 to 2.0 ± 0.2), whereas patients in the placebo group had a reduction of only 13% ± 8% (from a mean score of 4.7 ± 0.1 to 4.1 ± 0.4) (P < .001). In a randomized trial of patients with a functional intestinal disorder, we found that abdominal distention can be effectively corrected by biofeedback-guided control of abdominothoracic muscular activity, compared with placebo. ClincialTrials.gov no: NCT01205100. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

PubMed

Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

2013-08-01

Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P < 0.0001, chi-squared test). For proctitis, the endoscopic remission rates after 4 weeks were 83.8% and 36.1% in the mesalazine and placebo suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (P < 0.0001, Fisher's exact test). The percentage of patients without bleeding was significantly higher in the mesalazine group than the placebo group from Day 3 of treatment (P = 0.0001, Fisher's exact test). The effectiveness of mesalazine suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

Celecoxib Versus Placebo in Tonsillectomy: A Prospective, Randomized, Double-Blind Placebo-Controlled Trial.

PubMed

Van Daele, Douglas J; Bodeker, Kellie L; Trask, Douglas K

2016-10-01

Celecoxib is a cyclooxygenase-2-specific inhibitor indicated to treat acute pain and pain secondary to osteoarthritis and rheumatoid arthritis. Surgical models of acute pain have demonstrated superior pain relief to placebo. The objective of this study was to test the safety and efficacy of celecoxib for pain relief after tonsillectomy compared to placebo. Adult subjects were randomized to 200 mg celecoxib versus placebo with a loading dose the night before surgery then twice daily for 10 days. Subjects were instructed to supplement the study drug with hydrocodone/acetaminophen liquid or acetaminophen for pain as needed. Subjects completed a daily diary regarding their pain, nausea, vomiting, diet, and activity. Seventeen subjects enrolled. Intraoperative blood loss was similar between groups, and no subject had postoperative bleeding. Three patients returned to the emergency department for treatment, and 2 patients could not complete the diaries, all in the placebo group. Subjects in the placebo group required statistically significant (P < .05) higher doses of narcotic and acetaminophen to control pain. Pain and diet rating scores were slightly better in the celecoxib group compared to placebo. In this small cohort, celecoxib reduced postoperative narcotic and acetaminophen requirements compared to placebo without complications. © The Author(s) 2016.

The treatment of severe premenstrual syndrome with goserelin with and without 'add-back' estrogen therapy: a placebo-controlled study.

PubMed

Leather, A T; Studd, J W; Watson, N R; Holland, E F

1999-02-01

The study aimed to determine if the addition of daily low-dose oral estrogen with a cyclical progestogen given to young women using a depot gonadotropin-releasing hormone (GnRH) analog implant for the treatment of their premenstrual syndrome (PMS) would affect the clinical outcome. In a double-blind placebo-controlled study in a specialist premenstrual syndrome clinic setting, 60 women aged between 20 and 45 years were randomized to one of three treatment groups: Group A (placebo implant four weekly + placebo tablets daily), Group B (goserelin 3.6 mg implant four weekly + estradiol valerate 2 mg daily with norethisterone 5 mg from days 21-28 of a 28-day cycle) or Group C (goserelin 3.6 mg implant four weekly + placebo tablets daily). Differences between PMS scores at 2, 4 and 6 months were compared with pretreatment values. There was a significant improvement in PMS scores in Group C (Zoladex + placebo) after 2, 4 and 6 months of treatment when compared to pretreatment values and Group A (placebo + placebo). The addition of a low-dose oral estrogen with a cyclical progestogen to GnRH analog treatment (Group B) resulted in a less dramatic response when compared to pretreatment values and no significant improvement when compared to Group A (placebo + placebo) at 2, 4 and 6 months of treatment. The addition of a low-dose oral estrogen with a cyclical progestogen to depot GnRH analog therapy in the treatment of PMS reduces the clinical response.

Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial.

PubMed

Maiden, Matthew J; Chapman, Marianne J; Torpy, David J; Kuchel, Timothy R; Clarke, Iain J; Nash, Coralie H; Fraser, Jonathan D; Ludbrook, Guy L

2016-06-01

Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. Randomized blinded placebo-controlled trial. Preclinical research laboratory. Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

[Effect of Xinling Wan in treatment of stable angina pectoris: a randomized, double-blinded, placebo parallel-controlled, multicenter trial].

PubMed

Gao, Jian-Wei; Gao, Xue-Min; Zou, Ting; Zhao, Tian-Meng; Wang, Dong-Hua; Wu, Zong-Gui; Ren, Chang-Jie; Wang, Xing; Geng, Nai-Zhi; Zhao, Ming-Jun; Liang, Qiu-Ming; Feng, Xing; Yang, Bai-Song; Shi, Jun-Ling; Hua, Qi

2018-03-01

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group. Copyright© by the Chinese Pharmaceutical Association.

Placebo group improvement in trials of pharmacotherapies for alcohol use disorders: a multivariate meta-analysis examining change over time.

PubMed

Del Re, A C; Maisel, Natalya; Blodgett, Janet C; Wilbourne, Paula; Finney, John W

2013-10-01

Placebo group improvement in pharmacotherapy trials has been increasing over time across several pharmacological treatment areas. However, it is unknown to what degree increasing improvement has occurred in pharmacotherapy trials for alcohol use disorders or what factors may account for placebo group improvement. This meta-analysis of 47 alcohol pharmacotherapy trials evaluated (1) the magnitude of placebo group improvement, (2) the extent to which placebo group improvement has been increasing over time, and (3) several potential moderators that might account for variation in placebo group improvement. Random-effects univariate and multivariate analyses were conducted that examined the magnitude of placebo group improvement in the 47 studies and several potential moderators of improvement: (a) publication year, (b) country in which the study was conducted, (c) outcome data source/type, (d) number of placebo administrations, (e) overall severity of study participants, and (f) additional psychosocial treatment. Substantial placebo group improvement was found overall and improvement was larger in more recent studies. Greater improvement was found on moderately subjective outcomes, with more frequent administrations of the placebo, and in studies with greater participant severity of illness. However, even after controlling for these moderators, placebo group improvement remained significant, as did placebo group improvement over time. Similar to previous pharmacotherapy placebo research, substantial pretest to posttest placebo group improvement has occurred in alcohol pharmacotherapy trials, an effect that has been increasing over time. However, several plausible moderator variables were not able to explain why placebo group improvement has been increasing over time.

Effects of once-daily teneligliptin on 24-h blood glucose control and safety in Japanese patients with type 2 diabetes mellitus: a 4-week, randomized, double-blind, placebo-controlled trial.

PubMed

Eto, T; Inoue, S; Kadowaki, T

2012-11-01

To assess blood glucose control over 24 h and the safety of teneligliptin 10 and 20 mg, a novel dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. Ninety-nine patients were administered teneligliptin 10 or 20 mg or placebo before breakfast for 4 weeks in a randomized, double-blind, placebo-controlled, parallel-group study. Both teneligliptin-treated groups showed significantly smaller 2-h postprandial glucose (2-h PPG), 24-h mean glucose and fasting plasma glucose values than the placebo group. The differences between the teneligliptin 10 mg and placebo groups in changes in 2-h PPG after each meal were -50.7 ± 7.8, -34.8 ± 9.2 and -37.5 ± 7.5 mg/dl at breakfast, lunch and dinner, respectively [least-squares (LS) means ± standard error (s.e.), all, p < 0.001]. The corresponding LS means ± s.e. for teneligliptin 20 mg versus placebo were -38.1 ± 7.8, -28.6 ± 9.2 and -36.1 ± 7.5 mg/dl, respectively (p < 0.001, p < 0.01, p < 0.001, respectively). Both doses of teneligliptin increased postprandial plasma active glucagon-like peptide-1 concentrations compared with placebo. The incidence of adverse events and drug-related adverse events was similar among groups. There were no hypoglycaemic symptoms or serious adverse events. Once-daily teneligliptin improved blood glucose levels over 24 h without hypoglycaemia. © 2012 Blackwell Publishing Ltd.

A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment.

PubMed

Morimoto, Bruce H; Schmechel, Don; Hirman, Joe; Blackwell, Andrew; Keith, Julian; Gold, Michael

2013-01-01

AL-108-211 was a placebo-controlled, ascending-dose study that explored the safety, tolerability and efficacy of 12 weeks of treatment with AL-108 in subjects with amnestic mild cognitive impairment. A total of 144 subjects were randomized in a 2:1 drug:placebo ratio. Subjects were enrolled into the low-dose group or placebo and then to the high-dose group or placebo. Pooling of the placebo groups yielded 3 groups (approx. 48/group) whose baseline demographics and disease characteristics were well matched. AL-108 was generally safe and well tolerated. Analyses of efficacy data failed to detect a statistically significant difference between the treatment groups on the composite cognitive memory score. Analyses of the individual cognitive tasks identified signals of potential efficacy in 2 tests of memory and attention. These data suggest that AL-108 was generally safe, well tolerated and merits additional investigation as a treatment for Alzheimer's disease. Copyright © 2013 S. Karger AG, Basel.

Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.

PubMed

Puska, P; Korpelainen, V; Høie, L H; Skovlund, E; Lahti, T; Smerud, K T

2002-04-01

To study whether Abacor, a product based on isolated soy protein with high and standardised levels of isoflavones and cotyledon soy fibres, was more effective in lowering total and LDL cholesterol than placebo. Randomised, placebo-controlled, double-blind, parallel group, single centre study. Primary care in Joensuu, North Karelia, Finland. Subjects were screened from the patient database of the health centre; 30 were randomised to the Abacor group and 30 subjects to placebo. Eight subjects were withdrawn, six from the active group, two from the placebo group. The preparations were given as two daily liquid supplements in addition to the subjects' regular diets for 6 weeks. Abacor showed a statistically significant lipid-lowering effect as compared to placebo, although an unexpected reduction was seen in the placebo group. The estimated difference between active treatment and placebo was 0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL-cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a reduction of 13.2% in the active treatment group, and 8.0% in the placebo group. Abacor showed a rapid onset of effect, as compared with placebo. During a wash-out period of 4 weeks after treatment, the subjects returned to pre-treatment cholesterol levels. Added to a regular diet, Abacor significantly reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred within 6 weeks of treatment.

Therapeutic effects of nandrolone and testosterone in adult male HIV patients with AIDS wasting syndrome (AWS): a randomized, double-blind, placebo-controlled trial.

PubMed

Sardar, Partha; Jha, Ayan; Roy, Deeptarka; Majumdar, Uddalak; Guha, Pradipta; Roy, Sabyasachi; Banerjee, Ramtanu; Banerjee, Amit Kumar; Bandyopadhyay, Dipanjan

2010-01-01

We aimed to compare therapeutic effects of intramuscular (IM) nandrolone decanoate and IM testosterone enanthate in male HIV patients with AIDS wasting syndrome (AWS) with placebo control. In this randomized, double-blind, placebo-controlled, 12-week trial, 104 patients with AWS who satisfied our inclusion criteria were randomly allotted in a 2:2:1 ratio to the 3 intervention groups: nandrolone, testosterone, and placebo. We administered 150 mg nandrolone and 250 mg testosterone (both IM, biweekly). The primary outcome measure was a comparison of absolute change in weight at 12 weeks between the nandrolone decanoate, testosterone, and placebo groups. Intent-to-treat analysis was done. The nandrolone group recorded maximum mean increase in weight (3.20 kg; post hoc P < .01 compared to placebo). Body mass index (BMI) of subjects in the nandrolone group had a significantly greater increase (mean = 1.28) compared to both testosterone (post hoc P < .05) and placebo (post hoc P < .01). Waist circumference and triceps skinfold thickness of patients on nandrolone showed similar results. Nandrolone also ensured a better quality of life. Patients with low testosterone level (<3 ng/mL) benefited immensely from nandrolone therapy, which increased their weight and BMI significantly compared to placebo (P < .05). Our trial demonstrates the superior therapeutic effects of nandrolone in male AWS patients, including the androgen deficient.

Should we reconsider the routine use of placebo controls in clinical research?

PubMed

Avins, Andrew L; Cherkin, Daniel C; Sherman, Karen J; Goldberg, Harley; Pressman, Alice

2012-04-27

Modern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice. We examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups. We find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition. Intentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.

The effect of the homeopathic remedies Arnica montana and Bellis perennis on mild postpartum bleeding--a randomized, double-blind, placebo-controlled study--preliminary results.

PubMed

Oberbaum, Menachem; Galoyan, Narine; Lerner-Geva, Liat; Singer, Shepherd Roee; Grisaru, Sorina; Shashar, David; Samueloff, Arnon

2005-06-01

To evaluate the effect of Arnica Montana and Bellis perennis on postpartum blood loss. Double blind, placebo-controlled, randomized, clinical trial. Department of Gynecology, Shaare Zedek Medical Center, Jerusalem. Forty parturients were randomized to one of three groups: Arnica montana C6 and Bellis perennis C6 (n=14), Arnica montana C30 and Bellis perennis C30 (n=14), or double placebo (n=12). After 48 h the Arnica/placebo was halted, and patients continued the Bellis/placebo until cessation of lochia. Hemoglobin levels (Hb) at 48 and 72 h postpartum. At 72 h postpartum, mean Hb levels remained similar after treatment with homeopathic remedies (12.7 versus 12.4) as compared to a significant decrease in Hb levels in the placebo group (12.7 versus 11.6; p<0.05), in spite of less favorable initial characteristics of the treatment group. The mean difference in Hb levels at 72 h postpartum was -0.29 (95% CI -1.09; 0.52) in the treatment group and -1.18 (95% CI -1.82; -0.54) in the placebo group (p<0.05). Treatment with homeopathic Arnica montana and Bellis perennis may reduce postpartum blood loss, as compared with placebo.

Ethics of placebo-controlled clinical trials in multiple sclerosis: a reassessment.

PubMed

Polman, C H; Reingold, S C; Barkhof, F; Calabresi, P A; Clanet, M; Cohen, J A; Cutter, G R; Freedman, M S; Kappos, L; Lublin, F D; McFarland, H F; Metz, L M; Miller, A E; Montalban, X; O'Connor, P W; Panitch, H; Richert, J R; Petkau, J; Schwid, S R; Sormani, M P; Thompson, A J; Weinshenker, B G; Wolinsky, J S

2008-03-25

The increasing number of established effective therapies for relapsing multiple sclerosis (MS) and emerging consensus for early treatment raise practical concerns and ethical dilemmas for placebo-controlled clinical trials in this disease. An international group of clinicians, ethicists, statisticians, regulators, and representatives from the pharmaceutical industry convened to reconsider prior recommendations regarding the ethics of placebo-controlled trials in MS. The group concluded that placebo-controlled trials can still be done ethically, with restrictions. For patients with relapsing MS for which established effective therapies exist, placebo-controlled trials should only be offered with rigorous informed consent if the subjects refuse to use these treatments, have not responded to them, or if these treatments are not available to them for other reasons (e.g., economics). Suggestions are provided to protect subject autonomy and improve informed consent procedures. Recommendations are tighter than previously suggested for placebo-controlled trials in "resource-restricted" environments where established therapies may not be available. Guidance is also provided on the ethics of alternative trial designs and the balance between study subject burden and risk, scientific rationale and interpretability of trial outcomes.

Effects of p-Synephrine alone and in Combination with Selected Bioflavonoids on Resting Metabolism, Blood Pressure, Heart Rate and Self-Reported Mood Changes

PubMed Central

Stohs, Sidney J.; Preuss, Harry G; Keith, Samuel C.; Keith, Patti L.; Miller, Howard; Kaats, Gilbert R.

2011-01-01

Bitter orange (Citrus aurantium) extract is widely used in dietary supplements for weight management and sports performance. Its primary protoalkaloid is p-synephrine. Most studies involving bitter orange extract and p-synephrine have used products with multiple ingredients. The current study assessed the thermogenic effects of p-synephrine alone and in conjunction with the flavonoids naringin and hesperidin in a double-blinded, randomized, placebo-controlled protocol with 10 subjects per treatment group. Resting metabolic rates (RMR), blood pressure, heart rates and a self-reported rating scale were determined at baseline and 75 min after oral ingestion of the test products in V-8 juice. A decrease of 30 kcal occurred in the placebo control relative to baseline. The group receiving p-synephrine (50 mg) alone exhibited a 65 kcal increase in RMR as compared to the placebo group. The consumption of 600 mg naringin with 50 mg p-synephrine resulted in a 129 kcal increase in RMR relative to the placebo group. In the group receiving 100 mg hesperidin in addition to the 50 mg p-synephrine plus 600 mg naringin, the RMR increased by 183 kcal, an increase that was statistically significant with respect to the placebo control (p<0.02). However, consuming 1000 mg hesperidin with 50 mg p-synephrine plus 600 mg naringin resulted in a RMR that was only 79 kcal greater than the placebo group. None of the treatment groups exhibited changes in heart rate or blood pressure relative to the control group, nor there were no differences in self-reported ratings of 10 symptoms between the treatment groups and the control group. This unusual finding of a thermogenic combination of ingredients that elevated metabolic rates without corresponding elevations in blood pressure and heart-rates warrants longer term studies to assess its value as a weight control agent. PMID:21537493

Adjunctive clindamycin therapy for preterm labor: results of a double-blind, placebo-controlled trial.

PubMed

McGregor, J A; French, J I; Seo, K

1991-10-01

A double-blind, placebo-controlled, randomized trial was conducted to evaluate the efficacy, safety, and tolerance of a course of clindamycin (administered for 3 days intravenously and 4 days orally) among hospitalized women with preterm labor at less than or equal to 34 weeks' gestation who were treated with tocolytics. One hundred three woman-perinate pairs were analyzed. Univariate analysis demonstrated that pregnancies were continued longer in women treated with clindamycin than in women who received placebo (clindamycin-treated group, 35 days; placebo-treated group, 25 days; p = 0.02). Survival analysis showed that pregnancy continued at least 35.5 days in 50% of clindamycin-treated women versus 20 days for control women (p = 0.03). Obstetric and microbiologic parameters associated with treatment outcomes were also sought. Women with bacterial vaginosis more often delivered preterm (p = 0.03; relative risk, 1.4; 95% confidence interval, 1.04 to 2.0). Among women with bacterial vaginosis, trends for increased duration of pregnancy (clindamycin-treated group, 36 days; placebo-treated group, 19 days), increased birth weight (clindamycin-treated group, 2634 gm; placebo-treated group, 2256 gm), and increased mean gestational age at delivery (clindamycin-treated group, 35 weeks; placebo-treated group, 34 weeks) were associated with clindamycin treatment. Women with either group B streptococcus, Chlamydia trachomatis, Trichomonas vaginalis, or Staphylococcus aureus were more likely to have preterm premature rupture of membranes (p = 0.01). Clindamycin treatment of these women reduced the incidence of preterm premature rupture of membranes to that of uninfected subjects. Stratification by gestational age at enrollment showed clindamycin treatment to be associated with an increased interval to delivery only among mothers enrolled before 33 weeks' gestation (clindamycin-treated group, 40 days; placebo-treated group, 28 days; p less than 0.05). Treatment with clindamycin appeared safe and well tolerated, with benefits limited to women who were less than or equal to 32 weeks' gestation.

Efficacy of Febuxostat for Slowing the GFR Decline in Patients With CKD and Asymptomatic Hyperuricemia: A 6-Month, Double-Blind, Randomized, Placebo-Controlled Trial.

PubMed

Sircar, Dipankar; Chatterjee, Soumya; Waikhom, Rajesh; Golay, Vishal; Raychaudhury, Arpita; Chatterjee, Suparna; Pandey, Rajendra

2015-12-01

Hyperuricemia is a putative risk factor for the progression of chronic kidney disease (CKD). We hypothesized that control of asymptomatic hyperuricemia may slow disease progression in CKD. This was a single-center, double-blind, randomized, parallel-group, placebo-controlled study. Eligible participants were adults from Eastern India aged 18 to 65 years with CKD stages 3 and 4, with asymptomatic hyperuricemia. The intervention group received febuxostat, 40mg, once daily for 6 months, while the placebo group received placebo; both groups were followed up for 6 months. The primary outcome was the proportion of patients showing a >10% decline in estimated glomerular filtration rate (eGFR) from baseline in the febuxostat and placebo groups. Secondary outcomes included changes in eGFRs in the 2 groups from baseline and at the end of the study period. 45 patients in the febuxostat group and 48 in the placebo group were analyzed. Mean eGFR in the febuxostat group showed a nonsignificant increase from 31.5±13.6 (SD) to 34.7±18.1mL/min/1.73m(2) at 6 months. With placebo, mean eGFR decreased from a baseline of 32.6±11.6 to 28.2±11.5mL/min/1.73m(2) (P=0.003). The difference between groups was 6.5 (95% CI, 0.08-12.81) mL/min/1.73m(2) at 6 months (P=0.05). 17 of 45 (38%) participants in the febuxostat group had a >10% decline in eGFR over baseline compared with 26 of 48 (54%) from the placebo group (P<0.004). Limitations of this study included small numbers of patients and short follow-up, and ∼10% of the randomly assigned population dropped out prior to completion. Febuxostat slowed the decline in eGFR in CKD stages 3 and 4 compared to placebo. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Lubiprostone plus PEG electrolytes versus placebo plus PEG electrolytes for outpatient colonoscopy preparation: a randomized, double-blind placebo-controlled trial.

PubMed

Sofi, Aijaz A; Nawras, Ali T; Pai, Chetan; Samuels, Qiana; Silverman, Ann L

2015-01-01

Bowel preparation using large volume of polyethylene glycol (PEG) solutions is often poorly tolerated. Therefore, there are ongoing efforts to develop an alternative bowel cleansing regimen that should be equally effective and better tolerated. The aim of this study was to assess the efficacy of lubiprostone (versus placebo) plus PEG as a bowel cleansing preparation for colonoscopy. Our study was a randomized, double-blind placebo-controlled design. Patients scheduled for screening colonoscopy were randomized 1:1 to lubiprostone (group 1) or placebo (group 2) plus 1 gallon of PEG. The primary endpoints were patient's tolerability and endoscopist's evaluation of the preparation quality. The secondary endpoint was to determine any reduction in the amount of PEG consumed in the lubiprostone group compared with the placebo group. One hundred twenty-three patients completed the study and were included in the analysis. There was no difference in overall cleanliness. The volume of PEG was similar in both the groups. The volume of PEG approached significance as a predictor of improved score for both the groups (P = 0.054). Lubiprostone plus PEG was similar to placebo plus PEG in colon cleansing and volume of PEG consumed. The volume of PEG consumed showed a trend toward improving the quality of the colon cleansing.

Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China.

PubMed

He, Zhong; Chen, Rong; Zhou, Yingfang; Geng, Li; Zhang, Zhenyu; Chen, Shuling; Yao, Yanjun; Lu, Junli; Lin, Shouqing

2009-05-20

To investigate the efficacy and safety of VAC BNO 1095 extract in Chinese women suffering from moderate to severe premenstrual syndrome (PMS). Prospective, double-blind, placebo controlled, parallel-group, multi-center clinical trial design was employed. After screening and preparation phase lasting three cycles, Eligible patients were randomly assigned into treatment or placebo groups and had treatment with VAC extract or placebo for up to three cycles. Efficacy was assessed using the Chinese version PMS-diary (PMSD) and PMTS. Two hundred and seventeen women were eligible to enter the treatment phase (TP) and were randomly assigned into the treatment group (108) or the placebo group (109), 208 provided the efficacy data (treatment 104, placebo 104), and 202 completed the treatment phase (treatment 101, placebo 101). The mean total PMSD score decreased from 29.23 at baseline (0 cycle) to 6.41 at the termination (3rd cycle) for the treatment group and from 28.14 at baseline (0 cycle) to 12.64 at the termination (3rd cycle) for the placebo group. The total PMSD score of 3rd cycle was significantly lower than the baseline in both groups (p<0.0001). The difference in the mean scores from the baseline to the 3rd cycle in the treatment group (22.71+/-10.33) was significantly lower than the difference in the placebo group (15.50+/-12.94, p<0.0001). Results of PMTS were similar, the total scores for PMTS were significantly lower between the two groups (p<0.01) and within each group (p<0.01). The score was decreased from 26.17+/-4.79 to 9.92+/-9.01 for the treatment group, and from 27.10+/-4.76 to 14.59+/-10.69 for the placebo group. A placebo effect of 50% was found in the present study. No serious adverse event (SAE) occurred in both groups. Vitex agnus castus (VAC BNO 1095 corresponding to 40mg herbal drug) is a safe, well tolerated and effective drug of the treatment for Chinese women with the moderate to severe PMS.

Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

PubMed Central

2009-01-01

Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS) scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis of predictors of the placebo versus treatment response. Whilst this study does not explore neurobiological mechanisms, these observations are consistent with the hypotheses that 'drug' effects and placebo effects are not necessarily additive, and that mutually exclusive mechanisms may be operating in the two arms. The need for more research in the area of mechanisms and mediators of placebo versus active responses is supported. Trial Registration International Clinical Trials Registry ISRCTN98972974. PMID:19549306

[Extracorporeal shockwave therapy (ESWT) as therapeutic option in supraspinatus tendon syndrome? One year results of a placebo controlled study].

PubMed

Schmitt, J; Tosch, A; Hünerkopf, M; Haake, M

2002-07-01

Extracorporeal shock wave therapy (ESWT) is seen as a therapeutic option in the treatment of chronic supraspinatus tendinitis by some authors. To test whether ESWT comprising 3 x 2000 pulses with the positive energy flux density ED+ of 0.33 mJ/mm2 is clinically superior to a sham ESWT treatment, a prospective, randomized, single-blinded, placebo-controlled study with an independent observer was performed. Forty patients were treated either by verum ESWT or sham ESWT under local anesthesia. Target criteria were the age-corrected Constant score, pain at rest and during activity on a visual analogue scale, and subjective improvement. Patients who reported no subjective improvement after 12 weeks were deblinded and received verum ESWT if they had belonged to the placebo group (partial crossover). The results of the verum group lie within the range of results for ESWT published by other authors. Patients in the placebo group with local anesthetic showed equally good results. At 12 weeks, and 1 year after intervention, no difference could be found between the verum and placebo groups regarding Constant score, pain, shoulder function, or subjective improvement. The nonresponders to the placebo ESWT continued to show no improvement after receiving verum ESWT. This contradicts a specific ESWT effect. Based on the results of this placebo-controlled study, ESWT appears to have no clinically relevant effect on supraspinatus tendinitis. The study underlines the importance of a control group in evaluating new treatment methods for diseases with unknown natural history.

A randomized, placebo-controlled trial of 1% topical minoxidil solution in the treatment of androgenetic alopecia in Japanese women.

PubMed

Tsuboi, Ryoji; Tanaka, Takao; Nishikawa, Tooru; Ueki, Rie; Yamada, Hidekazu; Katsuoka, Kensei; Ogawa, Hideoki; Takeda, Katsuyuki

2007-01-01

Minoxidil is effective in inducing hair growth in patients with androgenetic alopecia by stimulating hair follicles to undergo transition from early to late anagen phase. However, there have been no controlled studies of topical minoxidil in Asian women. The objective of this trial was to investigate the efficacy of 1% topical minoxidil for androgenetic alopecia in Japanese female patients using a double-blind controlled method. This trial included 280 Japanese female patients aged 20 years or older with androgenetic alopecia who were administered either 1% topical minoxidil (n = 140) or placebo (n = 140) for 24 weeks. The primary efficacy variable was mean change from baseline in non-vellus hair count/cm(2). The mean change was 8.15 in the 1% topical minoxidil group and 2.03 in the placebo group, with a significant difference between groups (p < 0.001) [difference: 6.12 (two-sided 95% confidence interval (CI): 3.29-8.96)]. Secondary variables included investigators' assessments and patients' self-assessments. As assessed by investigators, 29.2% (40/137) of the patients had moderate or better improvement in the 1% topical minoxidil group compared to 11.8% (16/136) in the placebo group (p < 0.001 versus placebo). The effect on hair growth was assessed as improved or better by 36.5% (50/137) of the patients themselves in the 1% topical minoxidil group compared to 23.5% (32/136) in the placebo group (p = 0.019 versus placebo). The patients tolerated treatment with 1% topical minoxidil well without significant adverse effects.

Long-term efficacy and safety of ertugliflozin monotherapy in patients with inadequately controlled T2DM despite diet and exercise: VERTIS MONO extension study.

PubMed

Aronson, Ronnie; Frias, Juan; Goldman, Allison; Darekar, Amanda; Lauring, Brett; Terra, Steven G

2018-06-01

This phase III, multicentre, randomized study (ClinicalTrials.gov; NCT01958671) evaluated the efficacy and safety of ertugliflozin monotherapy in adults with inadequately controlled type 2 diabetes (glycated haemoglobin [HbA1c], 7.0% to 10.5% [53-91 mmol/mol]) despite diet and exercise. The 52-week study comprised a 26-week, double-blind, placebo-controlled period (Phase A) during which 461 participants received placebo, ertugliflozin 5 mg/d or ertugliflozin 15 mg/d. This was followed by a 26-week active-controlled period (Phase B) during which participants in the placebo group who had not received glycaemic rescue therapy had blinded metformin added. Results to Week 52 are reported. Because of the use of metformin in Phase B, no statistical comparisons of efficacy were made between the ertugliflozin and placebo/metformin groups at Week 52. The mean (standard error) change from baseline to Week 52 in HbA1c was -0.9% (0.1) and -1.0% (0.1) in the ertugliflozin 5 and 15 mg groups, respectively. The proportions of participants with HbA1c <7.0% at Week 52 were 25.6% and 28.5%, respectively. Ertugliflozin reduced fasting plasma glucose, body weight and systolic blood pressure (SBP). The incidence of genital mycotic infections (GMIs) in females was significantly higher in both ertugliflozin groups (5 mg, 26.9%; 15 mg, 29.0%) vs the placebo/metformin group (9.9%), and in males was significantly higher in the 15 mg group (7.8%) vs the placebo/metformin group (1.2%). Ertugliflozin was not associated with increased incidence of urinary tract infections, symptomatic hypoglycaemia or hypovolaemia adverse events compared with placebo/metformin. Ertugliflozin treatment over 52 weeks improved glycaemic control and reduced body weight and SBP, but increased GMIs. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

A randomized, placebo-controlled trial of an amino acid preparation on timing and quality of sleep.

PubMed

Shell, William; Bullias, Debbie; Charuvastra, Elizabeth; May, Lawrence A; Silver, David S

2010-01-01

This study was an outpatient, randomized, double-blind, placebo-controlled trial of a combination amino acid formula (Gabadone) in patients with sleep disorders. Eighteen patients with sleep disorders were randomized to either placebo or active treatment group. Sleep latency and duration of sleep were measured by daily questionnaires. Sleep quality was measured using a visual analog scale. Autonomic nervous system function was measured by heart rate variability analysis using 24-hour electrocardiographic recordings. In the active group, the baseline time to fall asleep was 32.3 minutes, which was reduced to 19.1 after Gabadone administration (P = 0.01, n = 9). In the placebo group, the baseline latency time was 34.8 minutes compared with 33.1 minutes after placebo (P = nonsignificant, n = 9). The difference was statistically significant (P = 0.02). In the active group, the baseline duration of sleep was 5.0 hours (mean), whereas after Gabadone, the duration of sleep increased to 6.83 (P = 0.01, n = 9). In the placebo group, the baseline sleep duration was 7.17 +/- 7.6 compared with 7.11 +/- 3.67 after placebo (P = nonsignificant, n = 9). The difference between the active and placebo groups was significant (P = 0.01). Ease of falling asleep, awakenings, and am grogginess improved. Objective measurement of parasympathetic function as measured by 24-hour heart rate variability improved in the active group compared with placebo. An amino acid preparation containing both GABA and 5-hydroxytryptophan reduced time to fall asleep, decreased sleep latency, increased the duration of sleep, and improved quality of sleep.

Immediate Effect of Needling at CV-12 (Zhongwan) Acupuncture Point on Blood Glucose Level in Patients with Type 2 Diabetes Mellitus: A Pilot Randomized Placebo-Controlled Trial.

PubMed

Kumar, Ranjan; Mooventhan, A; Manjunath, Nandi Krishnamurthy

2017-08-01

Diabetes mellitus is a major global health problem. Needling at CV-12 has reduced blood glucose level in diabetic rats. The aim of this study was to evaluate the effect of needling at CV-12 (Zhongwan) on blood glucose level in patients with type 2 diabetes mellitus (T2DM). Forty T2DM patients were recruited and randomized into either the acupuncture group or placebo control group. The participants in the acupuncture group were needled at CV-12 (4 cun above the center of the umbilicus), and those in the placebo control group were needled at a placebo point on the right side of the abdomen (1 cun beside the CV-12). For both groups, the needle was retained for 30 minutes. Assessments were performed prior to and after the intervention. Statistical analysis was performed using SPSS version 16. There was a significant reduction in random blood glucose level in the acupuncture group compared to baseline. No such significant change was observed in the placebo control group. The result of this study suggests that 30 minutes of needling at CV-12 might be useful in reducing blood glucose level in patients with T2DM. Copyright © 2017. Published by Elsevier B.V.

Effect of modulated-frequency and modulated-intensity transcutaneous electrical nerve stimulation after abdominal surgery: a randomized controlled trial.

PubMed

Tokuda, Mitsunori; Tabira, Kazuyuki; Masuda, Takashi; Nishiwada, Takashi; Shomoto, Koji

2014-07-01

This study aimed to evaluate the effectiveness of transcutaneous electrical nerve stimulation (TENS) for treatment of postoperative pain and pulmonary functions (vital capacity [VC]; cough peak flow, [CPF]) in patients who underwent abdominal surgery. Forty-eight patients were randomly allocated to receive TENS, placebo TENS, or no TENS (control) 1 hour a day for 3 days postoperatively. A 0-100 visual analog scale was used to assess pain at preintervention, mid-intervention, and postintervention on the third postoperative day. Pulmonary functions (VC, CPF) were evaluated by spirometer at preoperation (baseline) and at preintervention, mid-intervention, and postintervention on the third postoperative day. One-way analysis of variance was used to assess differences between groups at baseline. Mann-Whitney test was used to compare the control group with the placebo-TENS and TENS group, at each assessment timepoint. Two-way analysis of variance and Bonferroni post hoc test assessed the difference between the 2 (placebo-TENS×TENS) groups. A value of P<0.01 was considered statistically significant. The baselines were not significantly different between any groups. The TENS group had significant reductions in postoperative pain compared with the placebo group (P<0.01) and control group (P<0.01). There was also improvement in pulmonary functions (VC, CPF) at mid-TENS and post-TENS, but not in the placebo-TENS (P<0.01) or control groups (P<0.01). TENS is a valuable treatment to alleviate postoperative pain and improve pulmonary functions (ie, VC, CPF) in patients following abdominal surgery.

Bromelain and cardiovascular risk factors in diabetes: An exploratory randomized, placebo controlled, double blind clinical trial.

PubMed

Ley, Chit Moy; Ni, Qing; Liao, Xing; Gao, Huai-Lin; Robinson, Nicola

2016-10-01

To assess whether the dietary supplement (bromelain) has the potential to reduce plasma fibrinogen and other cardiovascular disease (CVD) risk factors in patients with diabetes. This randomized placebo controlled, double blind, parallel design, efficacy study was carried out in China and investigated the effect of 12 weeks of bromelain (1,050 mg/day) on plasma fibrinogen. This randomized controlled trial (RCT) recruited 68 Chinese diabetic patients [32 males and 36 females; Han origin, mean age of 61.26 years (standard deviation (SD), 12.62 years)] with at least one CVD risk factor. Patients were randomized into either bromelain or placebo group. While bromelain group received bromelain capsule, the placebo group received placebo capsule which consisted inert ingredient and has no treatment effect. Subjects were required to take 1,050 mg (3×350 mg) of either bromelain or starch-filled placebo capsules, two to be taken (2×350 mg) after breakfast and another (350 mg) after dinner, daily for 12 weeks. Plasma fibrinogen, CVD risk factors and anthropometric indicators were determined at baseline and at 12 weeks. The change in the fibrinogen level in the bromelain group at the end of the study showed a mean reduction of 0.13 g/L (standard deviation (SD) 0.86g/L) compared with the mean reduction of 0.36 g/L (SD 0.96 g/L) for the placebo group. However, there was no significant difference in the mean change in fibrinogen between the placebo and bromelain groups (mean difference=0.23g/L (SD 0.22 g/L), =0.291). Similarly, the difference in mean change in other CVD risk factors (blood lipids, blood pressure), blood glucose, C-reactive protein and anthropometric measures between the bromelain and placebo groups was also not statistically significant. Statistical differences in fibrinogen between bromelain and placebo groups before the trial despite randomization may have influenced the results of this study. This RCT failed to show a beneficial effect in reducing fibrinogen or influencing other selected CVD risk factors but suggests other avenues for subsequent research on bromelain.

An evaluation of the hypolipidemic effect of an extract of Hibiscus Sabdariffa leaves in hyperlipidemic Indians: a double blind, placebo controlled trial.

PubMed

Kuriyan, Rebecca; Kumar, Divya R; R, Rajendran; Kurpad, Anura V

2010-06-17

Hibiscus sabdariffa is used regularly in folk medicine to treat various conditions. The study was a double blind, placebo controlled, randomized trial. Sixty subjects with serum LDL values in the range of 130-190 mg/dl and with no history of coronary heart disease were randomized into experimental and placebo groups. The experimental group received 1 gm of the extract for 90 days while the placebo received a similar amount of maltodextrin in addition to dietary and physical activity advice for the control of their blood lipids. Anthropometry, blood biochemistry, dietary and physical activity were assessed at baseline, day 45 and day 90. While body weight, serum LDL cholesterol and triglyceride levels decreased in both groups, there were no significant differences between the experimental and placebo group. It is likely that the observed effects were as a result of the patients following the standard dietary and physical activity advice. At a dose of 1 gm/day, hibiscus sabdariffa leaf extract did not appear to have a blood lipid lowering effect. REFCTRI2009000472.

A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial of Aminophylline to Prevent Acute Kidney Injury in Children following Congenital Heart Surgery with Cardiopulmonary Bypass

PubMed Central

Axelrod, David M.; Sutherland, Scott M.; Anglemyer, Andrew; Grimm, Paul C.; Roth, Stephen J.

2015-01-01

Objective Acute kidney injury (AKI) occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass (CPB) and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of AKI in certain populations. This study sought to determine if post-operative administration of aminophylline attenuates AKI in children undergoing congenital cardiac surgery with CPB. Design Single-center, double-blinded, placebo-controlled, randomized clinical trial (RCT). Setting Tertiary center, pediatric cardiovascular intensive care unit. Patients 144 children after congenital heart surgery with CPB. Interventions Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every six hours for 72 hours. Measurements and Main Results The primary outcome variable was development of any AKI, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes (KDIGO) criteria. Secondary outcomes included the development of severe AKI, time between CVICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase-associated lipocalin (NGAL). The unadjusted rate and severity of AKI were not different between groups; 43/72 (60%) of the treatment group and 36/72 (50%) of the placebo group developed AKI (p=0.32). Stage 2/3 AKI occurred in 23/72 (32%) of the treatment group and 15/72 (21%) of the placebo group (p=0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group versus 18% in the placebo group, p =0.30). Conclusions In this placebo-controlled RCT, we found no effect of aminophylline to prevent AKI in children recovering from cardiac surgery performed with CPB. Future study of pre-operative aminophylline administration to prevent AKI may be warranted. PMID:26669642

Early interventional treatment with intranasal corticosteroids compared with postonset treatment in pollinosis.

PubMed

Higaki, Takaya; Okano, Mitsuhiro; Makihara, Seiichiro; Fujiwara, Tazuko; Haruna, Takenori; Noda, Yohei; Kariya, Shin; Nishizaki, Kazunori

2012-12-01

The usefulness of early interventional treatment (EIT) with intranasal corticosteroids (INSs) compared with postonset treatment (POT) has not been clarified. To study the efficacy and safety of EIT with INSs compared with POT and placebo in Japanese cedar/cypress pollinosis. We designed a 3-armed, double-blinded, randomized, placebo-controlled trial. Patients received mometasone furoate nasal spray (EIT group: n = 25), placebo (n = 25), or 4 weeks of placebo followed by 8 weeks of mometasone (POT group: n = 25) for a 12-week period starting on February 1, 2011. The primary end point was the comparison of the total nasal symptom score (TNSS) among the 3 groups. Total ocular symptom score (TOSS), total naso-ocular symptom score (TSS), Allergic Rhinitis and Its Impact (ARIA) on Asthma classification, and safety were the main secondary end points. The placebo and POT groups, but not the EIT group, had a significant exacerbation of TNSS and TOSS soon after the start of pollen counts being high on consecutive days. The 12-week mean TSS in the EIT group (score, 2.3) was significantly lower than in the placebo (5.0; P < .01) and POT (3.9; P = .03) groups. All patients in the placebo and POT groups were classified as having persistent rhinitis, whereas 80% of the EIT group met the ARIA classification criteria (P = .03). The quality-of-life score and nasal eosinophil cationic protein levels were lower in the EIT and POT groups compared with the placebo group. Daytime sleepiness, smell disturbance, and the mean dose of loratadine taken as the rescue medication were similar. Treatment with mometasone was well tolerated. EIT with INSs is superior to POT in controlling pollinosis. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A diet containing whey protein, glutamine, and TGFbeta modulates gut protein metabolism during chemotherapy-induced mucositis in rats.

PubMed

Boukhettala, Nabile; Ibrahim, Ayman; Claeyssens, Sophie; Faure, Magali; Le Pessot, Florence; Vuichoud, Jacques; Lavoinne, Alain; Breuillé, Denis; Déchelotte, Pierre; Coëffier, Moïse

2010-08-01

Mucositis, a common side effect of chemotherapy, is characterized by compromised digestive function, barrier integrity and immune competence. Our aim was to evaluate the impact of a specifically designed diet Clinutren Protect (CP), which contains whey proteins, TGFbeta-rich casein, and free glutamine, on mucositis in rats. Mucositis was induced by three consecutive injections (day 0, day 1, day 2) of methotrexate (2.5 mg/kg). Rats had free access to CP or placebo diets from days -7 to 9. In the placebo diet, whey proteins and TGFbeta-rich casein were replaced by TGFbeta-free casein and glutamine by alanine. Intestinal parameters were assessed at day 3 and 9. Values, expressed as mean +/- SEM, were compared using two-way ANOVA. At day 3, villus height was markedly decreased in the placebo (296 +/- 11 microm) and CP groups (360 +/- 10 microm) compared with controls (464 +/- 27 microm), but more markedly in the placebo as compared to CP group. The intestinal damage score was also reduced in the CP compared with the placebo group. Glutathione content increased in the CP compared with the placebo group (2.2 +/- 0.2 vs. 1.7 +/- 0.2 micromol/g tissue). Gut protein metabolism was more affected in the placebo than in the CP group. The fractional synthesis rate was decreased in the placebo group (93.8 +/- 4.9%/day) compared with controls (121.5 +/- 12.1, P < 0.05), but not in the CP group (106.0 +/- 13.1). In addition, at day 9, rats exhibited improved body weight and food intake recovery in the CP compared to the placebo group. Clinutren Protect feeding reduces intestinal injury in the acute phase of methotrexate-induced mucositis in rats and improves recovery.

Exploring the Effect of Lactium™ and Zizyphus Complex on Sleep Quality: A Double-Blind, Randomized Placebo-Controlled Trial

PubMed Central

Scholey, Andrew; Benson, Sarah; Gibbs, Amy; Perry, Naomi; Sarris, Jerome; Murray, Greg

2017-01-01

Acute, non-clinical insomnia is not uncommon. Sufferers commonly turn to short-term use of herbal supplements to alleviate the symptoms. This placebo-controlled, double-blind study investigated the efficacy of LZComplex3 (lactium™, Zizyphus, Humulus lupulus, magnesium and vitamin B6), in otherwise healthy adults with mild insomnia. After a 7-day single-blind placebo run-in, eligible volunteers (n = 171) were randomized (1:1) to receive daily treatment for 2 weeks with LZComplex3 or placebo. Results revealed that sleep quality measured by change in Pittsburgh Sleep Quality Index (PSQI) score improved in both the LZComplex3 and placebo groups. There were no significant between group differences between baseline and endpoint on the primary outcome. The majority of secondary outcomes, which included daytime functioning and physical fatigue, mood and anxiety, cognitive performance, and stress reactivity, showed similar improvements in the LZComplex3 and placebo groups. A similar proportion of participants reported adverse events (AEs) in both groups, with two of four treatment-related AEs in the LZComplex3 group resulting in permanent discontinuation. It currently cannot be concluded that administration of LZComplex3 for 2 weeks improves sleep quality, however, a marked placebo response (despite placebo run-in) and/or short duration of treatment may have masked a potential beneficial effect on sleep quality. PMID:28218661

A randomised controlled trial of oral zinc sulphate for primary dysmenorrhoea in adolescent females.

PubMed

Zekavat, Omid R; Karimi, Mohammad Y; Amanat, Aida; Alipour, Farzaneh

2015-08-01

Primary dysmenorrhoea, the most common gynaecologic problem of adolescent females, is commonly treated with nonsteroidal anti-inflammatory drugs or oral contraceptive pills. To compare the effect of zinc sulphate with that of placebo on the control of pain severity and duration in adolescent girls with primary dysmenorrhoea. In a three-month randomised double-blind placebo-controlled clinical trial, 120 adolescent females with primary dysmenorrhoea were randomly divided into two groups of sixty: an intervention group (zinc) and a control group (placebo). Zinc was administered in the form of a capsule containing 50 mg/day zinc sulphate beginning on the first day of menses and continuing until three days prior to the end of menses. Each month, the duration and severity of primary dysmenorrhoea were determined. Severity scoring was performed by using a 0-10 scaling system. In the first month, the duration of pain was significantly lower in the zinc group compared with the placebo group (P-value = 0.044), while there was no significant difference in pain severity between the groups (P-value = 0.497). In the second and third month, pain severity and duration in the zinc group were significantly lower than the placebo group (P-value <0.001). Both pain duration and pain severity were decreased by taking oral zinc. The results of our interventional study suggests that zinc may be used to treat primary dysmenorrhoea in adolescents. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Comparison of Effect of Lavandula officinalis and Venlafaxine in Treating Depression: A Double Blind Clinical Trial

PubMed Central

Nikfarjam, Masoud; Rakhshan, Reza

2017-01-01

Introduction Major depressive disorder is a chronic disease which may be associated with other mental illnesses. Lavandula officinalis and venlafaxine, herbal and chemical drugs respectively, are used to treat depression. Despite pharmacotherapy, major depressive disorder has a complicated pattern of resistance and recurrence. Aim The aim of this study was to determine the effect of L. officinalis and venlafaxine in treating depression. Materials and Methods For this study, 120 patients referred to the psychiatry clinic of the Shahrekord University of Medical Sciences, Shahrekord, Iran, were randomly selected. The participants were randomly assigned to three groups: venlafaxine (Control Group), venlafaxine + L. officinalis (L. officinalis Group), and venlafaxine + placebo (Placebo Group). All the patients underwent treatment for six weeks. Depression test was administered to the three groups at different time intervals before the treatment, four weeks after the treatment and at completion of the treatment. The data were analysed by SPSS version17.0. Results Depression scores of all the groups decreased over time (p=0.001). The depression scores were significantly different between the control and L. officinalis groups (p=0.004), and the control and placebo groups (p=0.002), but were not significantly different between the L. officinalis and placebo groups (p=0.95). Conclusion Adding L. officinalis or a placebo is equally effective in decreasing mean depression score and venlafaxine obviously decreased this score. PMID:28892932

Developing a placebo-controlled trial in surgery: issues of design, acceptability and feasibility.

PubMed

Campbell, M K; Entwistle, V A; Cuthbertson, B H; Skea, Z C; Sutherland, A G; McDonald, A M; Norrie, J D; Carlson, R V; Bridgman, S

2011-02-21

Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot.Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007.

Developing a placebo-controlled trial in surgery: Issues of design, acceptability and feasibility

PubMed Central

2011-01-01

Background Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Methods Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). Results There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot. Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Conclusions Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. Trial registration number The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007. PMID:21338481

A double-blind, placebo-controlled, multicenter study with alprazolam and extended-release alprazolam in the treatment of panic disorder.

PubMed

Pecknold, J; Luthe, L; Munjack, D; Alexander, P

1994-10-01

This is a double-blind, placebo-controlled, flexible-dose, multicenter, 6-week study comparing regular alprazolam (compressed tablet, CT), given four times per day, and extended release alprazolam (XR), given once in the morning. The aim of the XR preparation is to offer less frequent dosing and to reduce interdose anxiety. Of the intent-to-treat group of 209 patients, 184 completed 3 weeks of medication and were evaluated according to protocol. There was a completer rate for the 6 weeks of 94% (CT), 97% (XR), and 87% (placebo). On global measures, Hamilton Rating Scale for Anxiety, phobia rating, and work disability measures, both active treatment groups were equally effective and significantly more efficacious than the placebo cell on endpoint MANOVA analysis. On analysis of the panic factor with endpoint data, both active treatment groups were equally effective throughout the 6-week trial and significantly more efficacious than the placebo group. Drowsiness occurred more frequently with CT alprazolam (86% of patients) than with the XR preparation (79%) or placebo (49%).

Memantine as an Adjuvant Treatment for Obsessive Compulsive Symptoms in Manic Phase of Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

PubMed

Sahraian, Ali; Jahromi, Leila Razeghian; Ghanizadeh, Ahmad; Mowla, Arash

2017-04-01

The aim of this study is to examine the effects of memantine as an adjuvant treatment for obsessive compulsive (OC) symptoms in patients with bipolar disorder (BD) type I, manic phase. In this 16-week double-blind placebo-controlled randomized clinical trial, 58 patients in the manic phase of BD who had OC symptoms were randomly allocated to receive memantine or placebo plus their routine medications (lithium + olanzapine + clonazepam). The Yale Brown Obsessive Compulsive Behavior Scale was used to assess the outcomes. Adverse effects were also recorded. Thirty-eight patients (19 in the memantine group and 19 in the placebo group) completed the trial. Throughout the trial, the mean score decreased from 20.26 ± 5.91 to 9.73 ± 5.44 in the memantine group (P < 0.000) and from 22.89 ± 5.70 to 16.63 ± 4.00 in the placebo group (P < 0.000). At the end of the study, 15 (78.94%) patients in the memantine group and 7 (36.84%) patients in the placebo group demonstrated more than 34% decline in the Yale Brown Obsessive Compulsive Behavior Scale score (P < 0.01). No serious adverse effects were reported. Our double-blind controlled clinical trial showed that memantine is an effective adjuvant agent for reducing OC symptoms in patients with BD. However, it needs to be noted that our study is preliminary, and larger double-blind controlled studies are needed to confirm the results.

The effect of calcium and vitamin D supplementation on obesity in postmenopausal women: secondary analysis for a large-scale, placebo controlled, double-blind, 4-year longitudinal clinical trial.

PubMed

Zhou, Jiapeng; Zhao, Lan-Juan; Watson, Patrice; Zhang, Qin; Lappe, Joan M

2010-07-23

It is undetermined whether calcium supplementation has an effect on obesity or body composition in postmenopausal women. The purpose of the study is to detect the effect of calcium supplementation on indices of obesity and body composition. This is a secondary analysis of data from a population-based, double-blind, placebo-controlled, randomized trial designed to determine the effects of calcium and vitamin D on osteoporotic fractures. The cohort included 1179 postmenopausal women who were randomly assigned into one of three groups: 1) supplemental calcium (1400 mg/d or 1500 mg/d) plus vitamin D placebo (Ca-only group); 2) supplemental calcium (1400 mg/d or 1500 mg/d) plus supplemental vitamin D3 (1100 IU/d) (Ca + D group); or, 3) two placebos (placebo group). After applying the exclusion criteria for this analysis, 870 subjects were included in this study. The primary outcomes for the present study were changes in body mass index, trunk fat, trunk lean, and percentage of trunk fat after calcium supplementation. Changes in trunk fat, trunk lean, and percentage of trunk fat were significantly different between the calcium intervention groups (Ca-only group or Ca + D group) and the placebo group during the trial (P < 0.05). The calcium intervention groups gained less trunk fat and maintained more trunk lean when compared to the placebo group. No significant difference was observed for body mass index between groups. Calcium supplementation over four years has a beneficial effect on body composition in postmenopausal women.

Randomized Controlled Double-blind Trial Comparing Haloperidol Combined With Conventional Therapy to Conventional Therapy Alone in Patients With Symptomatic Gastroparesis.

PubMed

Roldan, Carlos J; Chambers, Kimberly A; Paniagua, Linda; Patel, Sonali; Cardenas-Turanzas, Marylou; Chathampally, Yashwant

2017-11-01

Gastroparesis is a debilitating condition that causes nausea, vomiting, and abdominal pain. Management includes analgesics and antiemetics, but symptoms are often refractory. Haloperidol has been utilized in the palliative care setting for similar symptoms. The study objective was to determine whether haloperidol as an adjunct to conventional therapy would improve symptoms in gastroparesis patients presenting to the emergency department (ED). This was a randomized, double-blind, placebo-controlled trial of adult ED patients with acute exacerbation of previously diagnosed gastroparesis. The treatment group received 5 mg of haloperidol plus conventional therapy (determined by the treating physician). The control group received a placebo plus conventional therapy. The severity of each subject's abdominal pain and nausea were assessed before intervention and every 15 minutes thereafter for 1 hour using a 10-point scale for pain and a 5-point scale for nausea. Primary outcomes were decreased pain and nausea 1 hour after treatment. Of the 33 study patients, 15 were randomized to receive haloperidol. Before treatment, the mean intensity of pain was 8.5 in the haloperidol group and 8.28 in the placebo group; mean pretreatment nausea scores were 4.53 and 4.11, respectively. One hour after therapy, the mean pain and nausea scores in the haloperidol group were 3.13 and 1.83 compared to 7.17 and 3.39 in the placebo group. The reduction in mean pain intensity therapy was 5.37 in the haloperidol group (p ≤ 0.001) compared to 1.11 in the placebo group (p = 0.11). The reduction in mean nausea score was 2.70 in the haloperidol group (p ≤ 0.001) and 0.72 in the placebo group (p = 0.05). Therefore, the reductions in symptom scores were statistically significant in the haloperidol group but not in the placebo group. No adverse events were reported. Haloperidol as an adjunctive therapy is superior to placebo for acute gastroparesis symptoms. © 2017 by the Society for Academic Emergency Medicine.

Rofecoxib versus ibuprofen for acute treatment of migraine: a randomised placebo controlled trial

PubMed Central

Misra, U; Jose, M; Kalita, J

2004-01-01

Background: Rofecoxib is a potent cyclo-oxygenase-2 inhibitor with a long duration of action. Its role in migraine has not been systematically evaluated. Aim: To study the efficacy of rofecoxib in migraine. Method: In a randomised placebo controlled trial rofecoxib 25 mg, ibuprofen 400 mg, and placebo were compared regarding their efficacy in relieving acute migraine attack. Migraine patients with 2–6 attacks per month were recruited. Headache severity, functional disability, and severity of associated symptoms were graded on a 0–3 scale. The primary endpoint was pain relief at two hours. Relief of associated symptoms and sustained pain relief for 24 hours were also noted. Result: One hundred and twenty four patients were randomised into rofecoxib (42), ibuprofen (40), and placebo (42) groups. One hundred and one patients were followed up: 33 on rofecoxib, 35 ibuprofen, and 33 placebo. Patients' ages ranged from 16–62 (mean 31.4) years, and 83 were females. Pain relief at two hours was noted in 45.5% on rofecoxib, 55.6% on ibuprofen, and 9.1% in the placebo group. The associated symptoms at two hours were reduced in 39.4% on rofecoxib, 50% on ibuprofen, and 9.1% in the placebo group. Sustained 24 hour pain relief was noted in 36.4% on rofecoxib, 41% on ibuprofen, and 6.1% in the placebo group. In the ibuprofen group, five patients had abdominal pain but there were no side effects in those on rofecoxib or in the control group. Both rofecoxib and ibuprofen were significantly effective in relieving pain, associated symptoms at two hours, and in sustained pain relief. There was no significant difference between rofecoxib and ibuprofen in aborting acute migraine attacks. Conclusions: Both ibuprofen and rofecoxib were superior to placebo in aborting an acute migraine attack, and there was no significant difference in their efficacy in an acute migraine attack. PMID:15579612

Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome.

PubMed

Pasquali, R; Gambineri, A; Biscotti, D; Vicennati, V; Gagliardi, L; Colitta, D; Fiorini, S; Cognigni, G E; Filicori, M; Morselli-Labate, A M

2000-08-01

Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was well tolerated. In the PCOS group, metformin therapy improved hirsutism and menstrual cycles significantly more than placebo. Baseline anthropometric and CT parameters were similar in all groups. Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups, without any significant effect on CT scan parameters. In both PCOS and control women, however, metformin treatment reduced body weight and BMI significantly more than placebo. Changes in the waist-to-hip ratio values were similar in PCOS women and controls, regardless of pharmacological treatment. Metformin treatment significantly decreased SAT values in both PCOS and control groups, although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment. On the contrary, visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups, but only in the former was the effect of metformin treatment significantly higher than that of placebo. Fasting insulin significantly decreased in both PCOS women and controls, regardless of treatment, whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin. Neither metformin or placebo significantly modified the levels of LH, FSH, dehydroepiandrosterone sulphate, and progesterone in any group, whereas testosterone concentrations decreased only in PCOS women treated with metformin. SHBG concentrations remained unchanged in all PCOS women; whereas in the control group, they significantly increased after both metformin and placebo. Leptin levels decreased only during metformin treatment in both PCOS and control groups. (ABSTRACT TRUNCATED)

Homeopathic arnica for prevention of pain and bruising: randomized placebo-controlled trial in hand surgery

PubMed Central

Stevinson, C; Devaraj, V S; Fountain-Barber, A; Hawkins, S; Ernst, E

2003-01-01

Homeopathic arnica is widely believed to control bruising, reduce swelling and promote recovery after local trauma; many patients therefore take it perioperatively. To determine whether this treatment has any effect, we conducted a double-blind, placebo-controlled, randomized trial with three parallel arms. 64 adults undergoing elective surgery for carpal tunnel syndrome were randomized to take three tablets daily of homeopathic arnica 30C or 6C or placebo for seven days before surgery and fourteen days after surgery. Primary outcome measures were pain (short form McGill Pain Questionnaire) and bruising (colour separation analysis) at four days after surgery. Secondary outcome measures were swelling (wrist circumference) and use of analgesic medication (patient diary). 62 patients could be included in the intention-to-treat analysis. There were no group differences on the primary outcome measures of pain (P=0.79) and bruising (P=0.45) at day four. Swelling and use of analgesic medication also did not differ between arnica and placebo groups. Adverse events were reported by 2 patients in the arnica 6C group, 3 in the placebo group and 4 in the arnica 30C group. The results of this trial do not suggest that homeopathic arnica has an advantage over placebo in reducing postoperative pain, bruising and swelling in patients undergoing elective hand surgery. PMID:12562974

Homeopathic arnica for prevention of pain and bruising: randomized placebo-controlled trial in hand surgery.

PubMed

Stevinson, C; Devaraj, V S; Fountain-Barber, A; Hawkins, S; Ernst, E

2003-02-01

Homeopathic arnica is widely believed to control bruising, reduce swelling and promote recovery after local trauma; many patients therefore take it perioperatively. To determine whether this treatment has any effect, we conducted a double-blind, placebo-controlled, randomized trial with three parallel arms. 64 adults undergoing elective surgery for carpal tunnel syndrome were randomized to take three tablets daily of homeopathic arnica 30C or 6C or placebo for seven days before surgery and fourteen days after surgery. Primary outcome measures were pain (short form McGill Pain Questionnaire) and bruising (colour separation analysis) at four days after surgery. Secondary outcome measures were swelling (wrist circumference) and use of analgesic medication (patient diary). 62 patients could be included in the intention-to-treat analysis. There were no group differences on the primary outcome measures of pain (P=0.79) and bruising (P=0.45) at day four. Swelling and use of analgesic medication also did not differ between arnica and placebo groups. Adverse events were reported by 2 patients in the arnica 6C group, 3 in the placebo group and 4 in the arnica 30C group. The results of this trial do not suggest that homeopathic arnica has an advantage over placebo in reducing postoperative pain, bruising and swelling in patients undergoing elective hand surgery.

On-demand tramadol hydrochloride use in premature ejaculation treatment.

PubMed

Kaynar, Mehmet; Kilic, Ozcan; Yurdakul, Talat

2012-01-01

To determine the efficacy of tramadol in premature ejaculation (PE) treatment compared with placebo. A single-blind, placebo-controlled, crossover study was conducted with 60 lifelong (primary) patients with PE. The patients were randomized into 2 groups, each consisting of 30 patients, who took tramadol or placebo on demand. PE was defined as an intravaginal ejaculation latency time of ≤60 seconds in 90% of intercourse episodes. The efficacy of the drugs was assessed using the intravaginal ejaculation latency time, ability of ejaculation control, and sexual satisfaction scores after an 8-week treatment period. All participants completed the study voluntarily. Two groups were similar in terms of the patient demographics. Increases in the intravaginal ejaculation latency time, ability of ejaculation control, and sexual satisfaction score between the placebo and tramadol groups were compared with the baseline values in both groups. At the end of study period, the tramadol group had significantly (P<.001) greater values for all 3 parameters compared with those in the placebo group. On-demand use of low-dose tramadol is effective for lifelong PE. Currently, selective seratonin reuptake inhibitors such as dapoxetine, are a more popular treatment option for PE. However, tramadol might be considered an alternative agent for primary PE treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study.

PubMed

Krymchantowski, A V; Barbosa, J S; Cheim, C; Alves, L A

2001-03-01

Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, were studied prospectively. Patients received LC or placebo once the headache reached moderate or severe intensity for 6 consecutive attacks. With regard to the moderate attacks, LC was superior than placebo after 1, 2 and 4 hours. The consumption of other rescue medications after 4 hours was significantly higher in the placebo group. With regard to the severe attacks, there was no difference between the active drug group and the placebo group concerning headache intensity and consumption of other rescue medications. We conclude that the NSAID lysine clonixinate is effective in treating moderately severe migraine attacks. It is not superior than placebo in treating severe migraine attacks.

Challenges and Recommendations for Placebo Controls in Randomized Trials in Physical and Rehabilitation Medicine

PubMed Central

Fregni, Felipe; Imamura, Marta; Chien, Hsin Fen; Lew, Henry L.; Boggio, Paulo; Kaptchuk, Ted J; Riberto, Marcelo; Hsing, Wu Tu; Battistella, Linamara Rizzo; Furlan, Andrea

2010-01-01

Compared to other specialties, the field of Physical and Rehabilitation Medicine (PRM) has not received the deserved recognition from clinicians and researchers in the scientific community. One of the reasons is the lack of sound evidence to support the traditional PRM treatments. The best way to change this disadvantage is through well-conducted clinical research, such as the standard placebo or sham-controlled randomized clinical trials. Therefore, having placebo groups in clinical trials is essential to improve the level of evidence-based practice in PRM that ultimately translates in a better clinical care. To address the challenges for the use of placebo in PRM randomized clinical trials, and to create useful recommendations, we convened a working group during the inaugural International Symposium in Placebo (February 2009, in Sao Paulo, Brazil) in which the following topics were discussed: (1) current status of randomized clinical trials in PRM, (2) challenges for the use of placebo in PRM, (3) bioethical issues, (4) use of placebo in acupuncture trials and for the treatment of low-back pain, (5) mechanisms of placebo, and (6) insights from other specialties. The current article represents the consensus report from the working group. PMID:20090428

A randomized clinical trial of the safety and efficacy of sitagliptin in patients with type 2 diabetes mellitus inadequately controlled by acarbose alone.

PubMed

Wang, Weiqing; Ning, Guang; Ma, Jianhua; Liu, Xiaomin; Zheng, Shaoxiong; Wu, Fan; Xu, Lei; O'Neill, Edward A; Fujita, Kenji P; Engel, Samuel S; Kaufman, Keith D; Shankar, R Ravi

2017-04-01

To evaluate the safety and efficacy of sitagliptin when added to the treatment of patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on acarbose monotherapy. This was a multicenter, randomized, placebo-controlled, double-blind clinical trial. Patients (N = 381) with T2DM and inadequate glycemic control (glycated hemoglobin [HbA1c] ≥ 7.0% and ≤10.0%) on acarbose monotherapy (at least 50 mg three times daily) were randomized in a 1:1 ratio to receive the addition of sitagliptin 100 mg or matching placebo once daily for 24 weeks. Changes from baseline in HbA1c and fasting plasma glucose (FPG) at Week 24. The mean baseline HbA1c in randomized patients was 8.1%. At Week 24, the placebo-controlled, least squares mean changes from baseline (95% confidence interval) in HbA1c and FPG in the sitagliptin group were -0.62% and -0.8 mmol/L (p < .001), respectively. At Week 24, 37.8% of patients in the sitagliptin group were at HbA1c goal of <7% compared with 17.2% in the placebo group (p < .001). Sitagliptin was generally well tolerated, and there were no significant between-group differences in prespecified safety parameters (symptomatic hypoglycemia, diarrhea, abdominal pain, nausea, vomiting). A higher incidence of serious adverse events was observed in the sitagliptin group (5.2%) relative to placebo (0.5%); all but one, in the sitagliptin group, were not considered related to drug. Sitagliptin was generally well tolerated and provided statistically superior and clinically meaningful improvements in glycemic control after 24 weeks of treatment compared to placebo when added to treatment of patients with inadequate glycemic control on acarbose monotherapy. Clinicaltrials.gov: NCT01177384.

Amiodarone prophylaxis for tachycardias after coronary artery surgery: a randomised, double blind, placebo controlled trial.

PubMed Central

Butler, J; Harriss, D R; Sinclair, M; Westaby, S

1993-01-01

BACKGROUND--Arrhythmias are a common cause of morbidity after cardiac surgery. This study assessed the efficacy of prophylactic amiodarone in reducing the incidence of atrial fibrillation or flutter and ventricular arrhythmias after coronary artery surgery. METHODS--A double blind, randomised, placebo controlled trial. 60 patients received a 24 hour intravenous infusion of amiodarone (15 mg/kg started after removal of the aortic cross clamp) followed by 200 mg orally three times daily for 5 days, and 60 patients received placebo. RESULTS--6 patients (10%) in the amiodarone group and 14 (23%) in the placebo group needed treatment for arrhythmias (95% confidence interval (95% CI) for the difference between groups was 0 to 26%, p = 0.05). The incidence of supraventricular tachycardia detected clinically and requiring treatment was lower in the amiodarone group (8% amiodarone v 20% placebo, 95% CI 0 to 24%, p = 0.07). The incidence detected by 24 hour Holter monitoring was similar (17% amiodarone v 20% placebo). Untreated arrhythmias in the amiodarone group were either clinically benign and undetected (n = 3) or the ventricular response rate was slow (n = 2). Age > 60 years was a positive risk factor for the development of supraventricular tachycardia in the amiodarone group but not in the placebo group. Fewer patients had episodes of ventricular tachycardia or fibrillation recorded on Holter monitoring in the amiodarone group (15% amiodarone v 33% placebo, 95% CI 3 to 33%, p = 0.02). Bradycardia (78% amiodarone v 48% placebo, 95% CI 14% to 46%, p < 0.005) and pauses (7% amiodarone v 0% placebo) occurred in more amiodarone treated patients. Bradycardia warranted discontinuation of treatment in one patient treated with amiodarone. CONCLUSIONS--The incidence of clinically significant tachycardia was reduced by amiodarone. The ventricular response rate was slowed in supraventricular tachycardia, but the induction of bradycardia may preclude the routine use of amiodarone for prophylaxis. PMID:8038000

Metformin does not affect postabsorptive hepatic free fatty acid uptake, oxidation or resecretion in humans: A 3-month placebo-controlled clinical trial in patients with type 2 diabetes and healthy controls.

PubMed

Gormsen, Lars C; Søndergaard, Esben; Christensen, Nana L; Jakobsen, Steen; Nielsen, Erik H T; Munk, Ole L; Tolbod, Lars P; Jessen, Niels; Nielsen, Søren

2018-06-01

To explore whether the pre-clinical findings that metformin improves lipid metabolism, possibly through modulation of intrahepatic partitioning of fatty acids towards oxidation and away from re-esterification and resecretion as triglycerides (TGs), can be translated to a human setting. We performed a 3-month randomized, placebo-controlled, parallel-group clinical trial in patients with type 2 diabetes (T2D; n = 24) and healthy controls (n = 12). Patients with T2D received either placebo (placebo group) or 1000 mg metformin twice daily (metformin group), while healthy subjects were all treated with metformin (control group). Hepatic fatty acid metabolism was measured by [ 11 C]palmitate positron-emission tomography, hepatic TG secretion and peripheral oxidation by ex vivo labelled [1- 14 C]VLDL-TG and VLDL particle size by TG/apolipoprotein B ratio. Body composition was assessed by dual-energy X-ray and whole-body lipid oxidation by indirect calorimetry. Metformin treatment for 3 months produced the anticipated decrease in fasting plasma glucose (FPG) in the metformin group (FPG 7.9 ± 1.8 mM [study day 1] vs 6.4 ± 1.1 mM [study day 2]), whereas patients in the placebo group and healthy controls had similar FPG levels before and after the trial (mixed model group vs time interaction; P = .003); however, contrary to our hypothesis, metformin treatment did not affect hepatic lipid metabolism or peripheral oxidation. The observed beneficial effects on lipid metabolism during metformin treatment in humans appear to be secondary to long-term alterations in body composition or glucose homeostasis. © 2018 John Wiley & Sons Ltd.

Antioxidative Activity of Onion Peel Extract in Obese Women: A Randomized, Double-blind, Placebo Controlled Study.

PubMed

Kim, Kyung-Ah; Yim, Jung-Eun

2015-09-01

Quercetin, found abundantly in onion peel, has been known to have anticholesterol, antithrombotic and insulin-sensitizing properties. Here, we investigated the effect of quercetin-rich onion peel extract (OPE) on reactive oxygen species (ROS) production and antioxidative defense in obese woman. This study was randomized, double-blind, placebo controlled study. Thirty-seven healthy obese participants were randomly assigned that eighteen subjects received red soft capsuled OPE (100 mg/d, 50 mg bis in die), while the other nineteen subjects received same capsuled placebo for 12 weeks. ROS production and superoxide dismutase (SOD) activity in plasma were determined by using ROS and SOD assay kits, respectively. Baseline characteristics of anthropometric indicators and blood metabolic profiles were not significantly different between the two groups. Compared with baseline values, OPE consumption significantly reduced waist and hip circumference. Plasma ROS level and SOD activity were decreased in both placebo and OPE groups compared with baseline values. However, plasma ROS level in OPE group was significantly lower than in placebo group while plasma SOD activity in OPE group was significantly higher than in placebo group after 12 weeks of consumption. These findings indicate that OPE consumption may exert antioxidative effect by preventing the decrease of SOD activity as well as the production of ROS in obese women.

Addition of atropine to submaximal exercise stress testing in patients evaluated for suspected ischaemia with SPECT imaging: a randomized, placebo-controlled trial.

PubMed

Manganelli, Fiore; Spadafora, Marco; Varrella, Paola; Peluso, Giuseppina; Sauro, Rosario; Di Lorenzo, Emilio; Rosato, Giuseppe; Daniele, Stefania; Cuocolo, Alberto

2011-02-01

To evaluate the effects of the addition of atropine to exercise testing in patients who failed to achieve their target heart rate (HR) during stress myocardial perfusion imaging with single-photon emission computed tomography (SPECT). The study was a prospective, randomized, placebo-controlled design. Patients with suspected or known coronary artery disease who failed to achieve a target HR (≥85% of maximal predicted HR) during exercise SPECT imaging were randomized to receive intravenous atropine (n=100) or placebo (n=101). The two groups of patients did not differ with respect to demographic or clinical characteristics. A higher proportion of patients in the atropine group achieved the target HR compared to the placebo group (60% versus 3%, p<0.0001). SPECT imaging was abnormal in a higher proportion of patients in the atropine group as compared to the placebo group (57% versus 42%, p<0.05). Stress-induced myocardial ischaemia was present in more patients in the atropine group as compared to placebo (47% versus 29%, p<0.01). In both groups of patients, no major side effects occurred. The addition of atropine at the end of exercise testing is more effective than placebo in raising HR to adequate levels, without additional risks of complications. The use of atropine in patients who initially failed to achieve their maximal predicted HR is associated with a higher probability of achieving a diagnostic myocardial perfusion study.

A randomized, double blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis.

PubMed

Rastegarpanah, Mansoor; Malekzadeh, Reza; Vahedi, Homayoun; Mohammadi, Maryam; Elahi, Elham; Chaharmahali, Meghedi; Safarnavadeh, Tahereh; Abdollahi, Mohammad

2015-12-01

To evaluate the clinical efficacy of silymarin in ulcerative colitis (UC) patients. A randomized double blinded placebo-controlled clinical trial was conducted in 80 UC patients whose disease had been documented and were in remission state between September 2009 and October 2010. Patients were assigned to silymarin group (42 cases) and placebo group (38 cases) using a random number table. Either silymarin (140 mg) or placebo (lactose mono-hydrate, corn starch magnesium stearate) tablets were given once daily for 6 months along with their standard therapy. The efficacies were assessed by disease activity index (DAI), frequency difference of the disease flare-up, and paraclinical data. Ten patients (4 in the silymarin group due to nausea and 6 in the placebo group due to disease flare-up and abdominal pain) discontinued the study. An improvement in hemoglobin level (11.8±1.6 g/dL vs. 13.4±1.2 g/dL,P<0.05) and erythrocyte sedimentation rate (23.7±11.5 mm/h vs.10.8±3.2 mm/h,P<0.05) was observed in the silymarin group but not in the placebo group. DAI significantly decreased in the silymarin group and reached from 11.3±3.5 to 10.7±2.8 (P<0.05). Thirty-five out of 38 patients in the silymarin group were in complete remission with no flare-up after 6 months as compared to 21 out of 32 patients in the placebo group (P=0.5000). Silymarin as a natural supplement may be used in UC patients to maintain remission.

Knowledge, attitude and practice among Chinese acupuncturists receiving sham and/or placebo acupuncture: a cross-sectional survey.

PubMed

Jin, Chunlan; Zhou, Xinyao; Pang, Ran

2015-06-01

Placebo and sham acupuncture are common control strategies in acupuncture studies. However, the perception and practice of these approaches in acupuncturists are poorly documented. To investigate knowledge of, attitude towards and practice of sham and/or placebo acupuncture among Chinese acupuncturists. A cross-sectional survey conducted in six different tertiary care hospitals of traditional Chinese medicine in Beijing, China. A total of 92 licensed acupuncturists were asked to complete a predesigned and structured questionnaire on-site. A response rate of 92.4% (n=85) was achieved. Almost all participants (99%, n=84) had moderate knowledge about sham and/or placebo acupuncture, but only a minority (27%, n=23) reported an excellent understanding. The general attitude towards sham and/or placebo acupuncture was positive. Most respondents (99%, n=84) thought such controls were necessary and the majority (81%, n=69) believed they were feasible in acupuncture research. More than two-thirds of participants (71%, n=60) had applied sham and/or placebo acupuncture, but only a few (8%, 5/60) used it as the most common control strategy in clinical trials. The result of our survey suggests that Chinese acupuncturists have a moderate knowledge of, and a positive attitude towards, sham and/or placebo acupuncture. Research into sham and/or placebo acupuncture is limited in comparison with other control strategies. Therefore, an in-service education programme for acupuncturists and standardisation of sham and/or placebo acupuncture need to be developed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Efficacy and Safety of Paliperidone Extended Release 1.5 mg/day-A Double-blind, Placebo- and Active-Controlled, Study in the Treatment of Patients with Schizophrenia.

PubMed

Coppola, Danielle; Melkote, Rama; Lannie, Caroline; Singh, Jaskaran; Nuamah, Isaac; Gopal, Srihari; Hough, David; Palumbo, Joseph

2011-05-15

Paliperidone extended-release (paliperidone ER) is an approved oral antipsychotic medication (dosing range 3-12 mg/day) for treatment of schizophrenia and schizoaffective disorder in adults. In this 3-arm, double-blind, placebo- and active-controlled, parallel-group study, paliperidone ER 1.5 mg was assessed to determine the lowest efficacious dose in patients (N = 201) with acute schizophrenia. Paliperidone ER 6 mg was included for assay sensitivity. Patients (intent-to-treat analysis set) had a mean age of 39.4 years; 74% were men, 43% Asian, and 40% black. The baseline mean (SD) Positive and Negative Syndrome Scale (PANSS) total score was 92.6 (13.02) and the mean (SD) change from baseline to endpoint was: placebo group, -11.4 (20.81); paliperidone ER 1.5 mg group, -8.9 (23.31); and paliperidone ER 6 mg group, -15.7 (26.25). Differences between paliperidone groups versus placebo were not significant (paliperidone ER 1.5 mg [p = 0.582], paliperidone ER 6 mg, [p = 0.308]). Safety results of paliperidone ER 1.5 mg and placebo were comparable. The most frequently reported treatment emergent adverse events (≥10%) were: placebo group-headache (15.6%) and psychotic disorder (14.1%); paliperidone ER 1.5 mg group-insomnia (13.6%); and paliperidone ER 6 mg group-headache (11.4%), insomnia (10%), and tremor (10%). In this study, paliperidone ER 1.5 mg did not demonstrate efficacy in patients with acute schizophrenia. A markedly high placebo response was noted. Assay sensitivity with the 6 mg dose was not established. Paliperidone ER 1.5 mg was generally tolerable with a safety profile comparable to placebo.

An evaluation of the hypolipidemic effect of an extract of Hibiscus Sabdariffa leaves in hyperlipidemic Indians: a double blind, placebo controlled trial

PubMed Central

2010-01-01

Background Hibiscus sabdariffa is used regularly in folk medicine to treat various conditions. Methods The study was a double blind, placebo controlled, randomized trial. Sixty subjects with serum LDL values in the range of 130-190 mg/dl and with no history of coronary heart disease were randomized into experimental and placebo groups. The experimental group received 1 gm of the extract for 90 days while the placebo received a similar amount of maltodextrin in addition to dietary and physical activity advice for the control of their blood lipids. Anthropometry, blood biochemistry, dietary and physical activity were assessed at baseline, day 45 and day 90. Results While body weight, serum LDL cholesterol and triglyceride levels decreased in both groups, there were no significant differences between the experimental and placebo group. Conclusions It is likely that the observed effects were as a result of the patients following the standard dietary and physical activity advice. At a dose of 1 gm/day, hibiscus sabdariffa leaf extract did not appear to have a blood lipid lowering effect. Trial Registration REFCTRI2009000472 PMID:20553629

The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial

PubMed Central

2010-01-01

Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole) pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo) per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p < .05) greater pain reduction. Fifty six of sixty subjects (93.3%) receiving Neuragen PN® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0%) subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601 PMID:20487567

Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with Type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: a 24-week randomized, double-blind study

PubMed Central

Bajaj, M; Gilman, R; Patel, S; Kempthorne-Rawson, J; Lewis-D'Agostino, D; Woerle, H-J

2014-01-01

Aims To investigate the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with Type 2 diabetes mellitus inadequately controlled by a combination of metformin and pioglitazone. Methods This was a multi-centre, phase 3, randomized, double-blind, placebo-controlled study comparing linagliptin 5 mg once daily (n = 183) and placebo (n = 89) as add-on to metformin and pioglitazone. The primary endpoint was the change from baseline in glycated haemoglobin (HbA1c) after 24 weeks. Results The placebo-corrected adjusted mean (se) change in HbA1c from baseline to 24 weeks was –6 (1) mmol/mol [–0.57 (0.13)%] (P < 0.0001). In patients with baseline HbA1c ≥ 53 mmol/mol (7.0%), 32.4% of patients in the linagliptin group and 13.8% in the placebo group achieved HbA1c < 53 mmol/mol (7.0%) (odds ratio 2.94; P = 0.0033). The placebo-corrected adjusted mean (se) change from baseline in fasting plasma glucose at week 24 was –0.57 (0.26) mmol/l [–10.4 (4.7) mg/dl] (P = 0.0280). The incidence of serious adverse events was 2.2% with linagliptin and 3.4% with placebo. Investigator-defined hypoglycaemia occurred in 5.5% of the linagliptin group and 5.6% of the placebo group. No meaningful changes in mean body weight were noted for either group. Conclusions Linagliptin as add-on therapy to metformin and pioglitazone produced significant and clinically meaningful improvements in glycaemic control, without an additional risk of hypoglycaemia or weight gain (Clinical Trials Registry No: NCT 00996658). PMID:24824197

Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

PubMed

Hong, S; Park, C-Y; Han, K A; Chung, C H; Ku, B J; Jang, H C; Ahn, C W; Lee, M-K; Moon, M K; Son, H S; Lee, C B; Cho, Y-W; Park, S-W

2016-05-01

We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Effect of Acarbose on Glycemic Variability in Patients with Poorly Controlled Type 2 Diabetes Mellitus Receiving Stable Background Therapy: A Placebo-Controlled Trial.

PubMed

Derosa, Giuseppe; Franzetti, Ivano; Querci, Fabrizio; D'Angelo, Angela; Maffioli, Pamela

2015-11-01

To evaluate the effect of acarbose on glycemic control and glycemic variability, using a continuous glucose-monitoring system, in patients with type 2 diabetes mellitus who were not well controlled on metformin and vildagliptin therapy. Multicenter, randomized, double-blind, placebo-controlled study. Clinical research units at three hospitals in Italy. Fifty-three patients with type 2 diabetes who were taking stable dosages of metformin 850 mg 3 times/day and vildagliptin 50 mg twice/day for at least 3 months and who were not adequately controlled with these therapies. Patients were randomized to either placebo or acarbose 100 mg 3 times/day to be added to their metformin-vildagliptin regimen. Glycemic excursions were assessed by using a continuous glucose-monitoring system for 1 week. Glycemic control was estimated as the mean blood glucose (MBG) level, the area under the glucose concentration-time curve for a glucose level above 70 mg/dl (AUC above 70) or 180 mg/dl (AUC above 180), and the percentage of time that the glucose level was above 70 mg/dl (T above 70) or 180 mg/dl (T above 180). Intraday glycemic variability was assessed by the standard deviation of the blood glucose level, the mean amplitude of glycemic excursions (MAGE), the M value, and continuous overlapping net glycemic action. Day-to-day glycemic variability was assessed as the mean of daily difference (MODD). The MBG level was ~20 mg/dl lower in the acarbose group than in the placebo group (p<0.05), particularly during the postprandial period. The AUC above 70 did not significantly differ between the two groups, whereas the AUC above 180 was ~40% lower in the acarbose group than in the placebo group during the daytime (p<0.01). The T above 180 was significantly higher in the placebo group than in the acarbose group (31% vs 8%, p<0.01. Moreover, the standard deviation and MAGE values were significantly lower in the acarbose group. The MODD value was not significantly changed in either group, and no significant differences were recorded between groups. All adverse events were mild in both groups, with only a significantly greater frequency of flatulence noted in the acarbose group (5% with acarbose vs 0.5% with placebo, p<0.05). The addition of acarbose to metformin and vildagliptin background therapy in patients with inadequately controlled type 2 diabetes decreased intraday glycemic variability, especially postprandial variability, but it was not associated with a significant change in interday glycemic variability. © 2015 Pharmacotherapy Publications, Inc.

Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

PubMed Central

Wahner-Roedler, Dietlind L.; Thompson, Jeffrey M.; Luedtke, Connie A.; King, Susan M.; Cha, Stephen S.; Elkin, Peter L.; Bruce, Barbara K.; Townsend, Cynthia O.; Bergeson, Jody R.; Eickhoff, Andrea L.; Loehrer, Laura L.; Sood, Amit; Bauer, Brent A.

2011-01-01

Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P < .001). The difference in change in scores between the groups was not significant (P = .16). With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004) and in the placebo group by 15% (P = .05). The change in scores was similar in the groups (P = .83). Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated. PMID:18990724

Exploration of the validity of weak magnets as a suitable placebo in trials of magnetic therapy.

PubMed

Greaves, C J; Harlow, T N

2008-06-01

To investigate whether 50 mT magnetic bracelets would be suitable as a placebo control condition for studying the pain relieving effects of higher strength magnetic bracelets in arthritis. Randomised controlled comparison between groups given either a weak 50 mT or a higher strength 180 mT magnetic bracelets to test. Four arthritis support groups in Devon, UK. One hundred sixteen people with osteoarthritis and rheumatoid arthritis. Beliefs about group allocation and expectation of benefit. There was no significant difference between groups in beliefs about allocation to the 'active magnet' group. Participants were however more likely to have an expectation of benefit (pain relief) with the higher strength magnetic bracelets. Asking about perceived group allocation is not sufficient to rule out placebo effects in trials of magnetic bracelets which use weak magnets as a control condition. There are differences in expectation of benefit between different magnet strengths.

Randomized, double-blind, placebo-controlled trial of saw palmetto in men with lower urinary tract symptoms.

PubMed

Gerber, G S; Kuznetsov, D; Johnson, B C; Burstein, J D

2001-12-01

To assess the effects of saw palmetto on urinary symptoms, sexual function, and urinary flow rate in men with lower urinary tract symptoms using a double-blind, randomized, placebo-controlled trial. The eligible patients were 45 years of age or older and had an International Prostate Symptom Score of 8 or greater. After a 1-month placebo run-in period, 85 men were randomized to receive saw palmetto or placebo for 6 months. Patients were evaluated using the International Prostate Symptom Score, a sexual function questionnaire, and by measurement of the urinary flow rate. The mean symptom score decreased from 16.7 to 12.3 in the saw palmetto group compared with 15.8 to 13.6 in the placebo group (P = 0.038). The quality-of-life score improved to a greater degree in the saw palmetto group, but this difference was not statistically significant. No change occurred in the sexual function questionnaire results in either group. The peak flow rate increased by 1.0 mL/s and 1.4 mL/s in the saw palmetto and placebo groups, respectively (P = 0.73). Saw palmetto led to a statistically significant improvement in urinary symptoms in men with lower urinary tract symptoms compared with placebo. Saw palmetto had no measurable effect on the urinary flow rates. The mechanism by which saw palmetto improves urinary symptoms remains unknown.

Short-term tibolone does not interfere with endothelial function: a double-blinded, randomized, controlled trial.

PubMed

Celani, M F S; Hurtado, R; Brandão, A H F; Maciel da Fonseca, A M R; Geber, S

2016-06-01

Objective To evaluate the effect of short-term hormone replacement therapy with tibolone 2.5 mg daily on endothelial function of healthy postmenopausal women, using flow-mediated dilation (FMD) of the brachial artery. Methods We performed a randomized, double-blinded, placebo-controlled study. A total of 100 healthy postmenopausal women were randomly allocated to receive tibolone (n = 50) or placebo (n = 50) for 28 days. Measurement of the FMD of the brachial artery was performed before and after the use of tibolone and placebo. Results A total of 31 women completed the study in the tibolone group, and 32 women completed the study in the control group. The results of the FMD measurements obtained from the women in the two groups before treatment were similar (0.018 and 0.091, for tibolone and placebo, p = 0.57). The values of the FMD in women who used tibolone and placebo, before and after the treatment, were similar in both groups. The numbers of women who presented an increase in the values of the FMD in both groups were also similar. Conclusion Our results demonstrate that the administration of 2.5 mg tibolone to healthy postmenopausal women for 28 days does not promote endothelial-dependent vasodilation, measured by FMD of the brachial artery.

The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial

PubMed Central

Lian, Fengmei; Tian, Jiaxing; Chen, Xinyan; Li, Zhibin; Piao, Chunli; Guo, Junjie; Ma, Licheng; Zhao, Lijuan; Xia, Chengdong; Wang, Chong-Zhi; Yuan, Chun-Su; Tong, Xiaolin

2015-01-01

Background Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone. Methods A total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA- β) were also evaluated. Results At week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69 - 1.14 for the Jinlida group vs. 0.34 - 0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p < 0.01). Both FG and 2h PG levels of the Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2h PG level reductions between the two groups after 12 weeks (both p < 0.01). The Jinlida group also showed improved β-cell function with a HOMA-β increase (p < 0.05). No statistical significance was observed in the body weight and BMI changes. No serious adverse events were reported. Conclusion Jinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy. Trial Registration Chinese Clinical Trial Register ChiCTR-TRC-13003159 PMID:26098833

The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial.

PubMed

Lian, Fengmei; Tian, Jiaxing; Chen, Xinyan; Li, Zhibin; Piao, Chunli; Guo, Junjie; Ma, Licheng; Zhao, Lijuan; Xia, Chengdong; Wang, Chong-Zhi; Yuan, Chun-Su; Tong, Xiaolin

2015-01-01

Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone. A total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2 h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were also evaluated. At week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69-1.14 for the Jinlida group vs. 0.34-0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p < 0.01). Both FG and 2 h PG levels of the Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2 h PG level reductions between the two groups after 12 weeks (both p < 0.01). The Jinlida group also showed improved β-cell function with a HOMA-β increase (p < 0.05). No statistical significance was observed in the body weight and BMI changes. No serious adverse events were reported. Jinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy. Chinese Clinical Trial Register ChiCTR-TRC-13003159.

Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study.

PubMed

Tazaki, Y; Sakai, F; Otomo, E; Kutsuzawa, T; Kameyama, M; Omae, T; Fujishima, M; Sakuma, A

1988-02-01

A multicenter double-blind placebo-controlled study of cytidine 5'-diphosphocholine (CDP-choline) was conducted to evaluate possible clinical benefits of the drug in patients with acute, moderate to severe cerebral infarction. The patients included also suffered from moderate to mild disturbances of consciousness, and all were admitted within 14 days of the ictus. Patients were allocated randomly to treatment with either CDP-choline (1,000 mg/day i.v. once daily for 14 days) or with placebo (physiological saline). One hundred thirty-three patients received CDP-choline treatment, and 139 received placebo. The group treated with CDP-choline showed significant improvements in level of consciousness compared with the placebo-treated group, and CDP-choline was an entirely safe treatment.

Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial.

PubMed

Calabrese, Carlo; Gregory, William L; Leo, Michael; Kraemer, Dale; Bone, Kerry; Oken, Barry

2008-07-01

Study aims were to evaluate effects of Bacopa monnieri whole plant standardized dry extract on cognitive function and affect and its safety and tolerability in healthy elderly study participants. The study was a randomized, double-blind, placebo-controlled clinical trial with a placebo run-in of 6 weeks and a treatment period of 12 weeks. Volunteers were recruited from the community to a clinic in Portland, Oregon by public notification. Fifty-four (54) participants, 65 or older (mean 73.5 years), without clinical signs of dementia, were recruited and randomized to Bacopa or placebo. Forty-eight (48) completed the study with 24 in each group. Standardized B. monnieri extract 300 mg/day or a similar placebo tablet orally for 12 weeks. The primary outcome variable was the delayed recall score from the Rey Auditory Verbal Learning Test (AVLT). Other cognitive measures were the Stroop Task assessing the ability to ignore irrelevant information, the Divided Attention Task (DAT), and the Wechsler Adult Intelligence Scale (WAIS) letter-digit test of immediate working memory. Affective measures were the State-Trait Anxiety Inventory, Center for Epidemiologic Studies Depression scale (CESD)-10 depression scale, and the Profile of Mood States. Vital signs were also monitored. Controlling for baseline cognitive deficit using the Blessed Orientation-Memory-Concentration test, Bacopa participants had enhanced AVLT delayed word recall memory scores relative to placebo. Stroop results were similarly significant, with the Bacopa group improving and the placebo group unchanged. CESD-10 depression scores, combined state plus trait anxiety scores, and heart rate decreased over time for the Bacopa group but increased for the placebo group. No effects were found on the DAT, WAIS digit task, mood, or blood pressure. The dose was well tolerated with few adverse events (Bacopa n = 9, placebo n = 10), primarily stomach upset. This study provides further evidence that B. monnieri has potential for safely enhancing cognitive performance in the aging.

Placebo can enhance creativity.

PubMed

Rozenkrantz, Liron; Mayo, Avraham E; Ilan, Tomer; Hart, Yuval; Noy, Lior; Alon, Uri

2017-01-01

The placebo effect is usually studied in clinical settings for decreasing negative symptoms such as pain, depression and anxiety. There is interest in exploring the placebo effect also outside the clinic, for enhancing positive aspects of performance or cognition. Several studies indicate that placebo can enhance cognitive abilities including memory, implicit learning and general knowledge. Here, we ask whether placebo can enhance creativity, an important aspect of human cognition. Subjects were randomly assigned to a control group who smelled and rated an odorant (n = 45), and a placebo group who were treated identically but were also told that the odorant increases creativity and reduces inhibitions (n = 45). Subjects completed a recently developed automated test for creativity, the creative foraging game (CFG), and a randomly chosen subset (n = 57) also completed two manual standardized creativity tests, the alternate uses test (AUT) and the Torrance test (TTCT). In all three tests, participants were asked to create as many original solutions and were scored for originality, flexibility and fluency. The placebo group showed higher originality than the control group both in the CFG (p<0.04, effect size = 0.5) and in the AUT (p<0.05, effect size = 0.4), but not in the Torrance test. The placebo group also found more shapes outside of the standard categories found by a set of 100 CFG players in a previous study, a feature termed out-of-the-boxness (p<0.01, effect size = 0.6). The findings indicate that placebo can enhance the originality aspect of creativity. This strengthens the view that placebo can be used not only to reduce negative clinical symptoms, but also to enhance positive aspects of cognition. Furthermore, we find that the impact of placebo on creativity can be tested by CFG, which can quantify multiple aspects of creative search without need for manual coding. This approach opens the way to explore the behavioral and neural mechanisms by which placebo might amplify creativity.

Placebo can enhance creativity

PubMed Central

Rozenkrantz, Liron; Mayo, Avraham E.; Ilan, Tomer; Hart, Yuval

2017-01-01

Background The placebo effect is usually studied in clinical settings for decreasing negative symptoms such as pain, depression and anxiety. There is interest in exploring the placebo effect also outside the clinic, for enhancing positive aspects of performance or cognition. Several studies indicate that placebo can enhance cognitive abilities including memory, implicit learning and general knowledge. Here, we ask whether placebo can enhance creativity, an important aspect of human cognition. Methods Subjects were randomly assigned to a control group who smelled and rated an odorant (n = 45), and a placebo group who were treated identically but were also told that the odorant increases creativity and reduces inhibitions (n = 45). Subjects completed a recently developed automated test for creativity, the creative foraging game (CFG), and a randomly chosen subset (n = 57) also completed two manual standardized creativity tests, the alternate uses test (AUT) and the Torrance test (TTCT). In all three tests, participants were asked to create as many original solutions and were scored for originality, flexibility and fluency. Results The placebo group showed higher originality than the control group both in the CFG (p<0.04, effect size = 0.5) and in the AUT (p<0.05, effect size = 0.4), but not in the Torrance test. The placebo group also found more shapes outside of the standard categories found by a set of 100 CFG players in a previous study, a feature termed out-of-the-boxness (p<0.01, effect size = 0.6). Conclusions The findings indicate that placebo can enhance the originality aspect of creativity. This strengthens the view that placebo can be used not only to reduce negative clinical symptoms, but also to enhance positive aspects of cognition. Furthermore, we find that the impact of placebo on creativity can be tested by CFG, which can quantify multiple aspects of creative search without need for manual coding. This approach opens the way to explore the behavioral and neural mechanisms by which placebo might amplify creativity. PMID:28892513

Effect of BCAA supplement timing on exercise-induced muscle soreness and damage: a pilot placebo-controlled double-blind study.

PubMed

Ra, Song-Gyu; Miyazaki, Teruo; Kojima, Ryo; Komine, Shoichi; Ishikura, Keisuke; Kawanaka, Kentaro; Honda, Akira; Matsuzaki, Yasushi; Ohmori, Hajime

2017-09-22

The aim of present study was to compare the effects of branched-chain amino acid (BCAA) supplementation taken before or after exercise on delayed onset muscle soreness (DOMS) and exercise-induced muscle damage (EIMD). Fifteen young men (aged 21.5 ± 0.4 years) were given either BCAA (9.6 g·day-1) or placebo before and after exercise (and for 3 days prior to and following the exercise day) in three independent groups: the Control group (placebo before and after exercise), the PRE group (BCAA before exercise and placebo after exercise), and the POST group (placebo before exercise and BCAA after exercise). Participants performed 30 repetitions of eccentric exercise with the non-dominant arm. DOMS, upper arm circumference (CIR), elbow range of motion (ROM), serum creatine kinase (CK), lactate dehydrogenase (LDH), and aldolase, BCAA, and Beta-hydroxy-Beta-methylbutyrate (3HMB) were measured immediately before and after the exercise and on the following 4 days. Serum BCAA and 3HMB concentrations increased significantly in the PRE group immediately after the exercise, recovering to baseline over the following days. In the days following the exercise day, DOMS, CIR, and ROM were significantly improved in the PRE group compared to the Control group, with weaker effects in the POST group. Serum activities of CK, LDH, and aldolase in the days following the exercise day were significantly suppressed in the PRE group compared to Control group. Present study confirmed that repeated BCAA supplementation before exercise had a more beneficial effect in attenuating DOMS and EIMD induced by eccentric exercise than repeated supplementation after exercise.

Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

DTIC Science & Technology

2010-09-30

a novel hypocretiniorexin antagonist, almorexant (ALM), to a standard hypnotic , zolpidem (ZOL), and placebo (PBO) on neurocognitive performance at...Placebo-Controlled, Randomized, Parallel- Group Study Comparing the Effect of a Novel HypocretiniOrexin Antagonist (Almorexant) Versus a Standard Hypnotic ...Group Study Comparing the Effect of a Novel HypocretiniOrexin Antagonist (Almorexant) Versus a Standard Hypnotic (Zolpidem) and Placebo on

A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial of Aminophylline to Prevent Acute Kidney Injury in Children Following Congenital Heart Surgery With Cardiopulmonary Bypass.

PubMed

Axelrod, David M; Sutherland, Scott M; Anglemyer, Andrew; Grimm, Paul C; Roth, Stephen J

2016-02-01

Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass. Single-center, double-blinded, placebo-controlled, randomized clinical trial. Tertiary center, pediatric cardiovascular ICU. A total of 144 children after congenital heart surgery with cardiopulmonary bypass. Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours. The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase-associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30). In this placebo-controlled randomized clinical trial, we found no effect of aminophylline to prevent acute kidney injury in children recovering from cardiac surgery performed with cardiopulmonary bypass. Future study of preoperative aminophylline administration to prevent acute kidney injury may be warranted.

Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: a randomized, double-blind, placebo-controlled trial.

PubMed

Kim, Ji Young; Park, Ju Yeon; Kang, Hee Jung; Kim, Oh Yoen; Lee, Jong Ho

2012-07-17

The reported health benefits of Korean red ginseng (KRG) include antioxidant, antitumor, antimutagenic, and immunomodulatory activities; however, the effects on oxidative stress have not yet been evaluated. Therefore, we assessed the effect of KRG on antioxidant enzymes and oxidative stress markers in humans. We conducted a randomized, double-blind, placebo-controlled study with three groups, including placebo, low-dose (3 g/day), and high-dose (6 g/day), which were randomly assigned to healthy subjects aged 20-65 years. Lymphocyte DNA damage, antioxidative enzyme activity, and lipid peroxidation were assessed before and after the 8-week supplementation. Fifty-seven subjects completed the protocol. Plasma superoxide dismutase (SOD) activity after the 8-week KRG supplementation was significantly higher in the low-and high-dose groups compared to baseline. Plasma glutathione peroxidase (GPx) and catalase activities were also increased after the high-dose supplementation. Furthermore, the DNA tail length and tail moment were significantly reduced after the supplementation (low-dose and high-dose), and plasma oxidized low-density lipoprotein (LDL) levels were reduced in low-dose and high-dose groups, but increased in the placebo group. The net changes in oxidized LDL after the supplementation differed significantly between both KRG supplementation groups and the placebo group. Net changes in GPx, SOD and catalase activities, and DNA tail length and tail moment were significantly different between the high-dose group and the placebo group. Additionally, the net changes in urinary 8-epi-PGF(2α) were significantly different between the KRG supplementation groups and the placebo group. KRG supplementation may attenuate lymphocyte DNA damage and LDL oxidation by upregulating antioxidant enzyme activity.

Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: a randomized, double-blind, placebo-controlled trial

PubMed Central

2012-01-01

Background The reported health benefits of Korean red ginseng (KRG) include antioxidant, antitumor, antimutagenic, and immunomodulatory activities; however, the effects on oxidative stress have not yet been evaluated. Therefore, we assessed the effect of KRG on antioxidant enzymes and oxidative stress markers in humans. Methods We conducted a randomized, double-blind, placebo-controlled study with three groups, including placebo, low-dose (3 g/day), and high-dose (6 g/day), which were randomly assigned to healthy subjects aged 20–65 years. Lymphocyte DNA damage, antioxidative enzyme activity, and lipid peroxidation were assessed before and after the 8-week supplementation. Results Fifty-seven subjects completed the protocol. Plasma superoxide dismutase (SOD) activity after the 8-week KRG supplementation was significantly higher in the low-and high-dose groups compared to baseline. Plasma glutathione peroxidase (GPx) and catalase activities were also increased after the high-dose supplementation. Furthermore, the DNA tail length and tail moment were significantly reduced after the supplementation (low-dose and high-dose), and plasma oxidized low-density lipoprotein (LDL) levels were reduced in low-dose and high-dose groups, but increased in the placebo group. The net changes in oxidized LDL after the supplementation differed significantly between both KRG supplementation groups and the placebo group. Net changes in GPx, SOD and catalase activities, and DNA tail length and tail moment were significantly different between the high-dose group and the placebo group. Additionally, the net changes in urinary 8-epi-PGF2α were significantly different between the KRG supplementation groups and the placebo group. Conclusions KRG supplementation may attenuate lymphocyte DNA damage and LDL oxidation by upregulating antioxidant enzyme activity. PMID:22805313

Synbiotic supplementation in lean patients with non-alcoholic fatty liver disease: a pilot, randomised, double-blind, placebo-controlled, clinical trial.

PubMed

Mofidi, Fatemeh; Poustchi, Hossein; Yari, Zahra; Nourinayyer, Babak; Merat, Shahin; Sharafkhah, Maryam; Malekzadeh, Reza; Hekmatdoost, Azita

2017-03-01

Although non-alcoholic fatty liver disease (NAFLD) is the leading aetiology of liver disorders in the world, there is no proven treatment for NAFLD patients with normal or low BMI. The aim of this study was to evaluate the efficacy of synbiotics supplementation in NAFLD patients with normal or low BMI. In this randomised, double-blind, placebo-controlled, clinical trial, fifty patients with NAFLD were assigned to take either a synbiotic supplement or a placebo capsule for 28 weeks. Both groups were advised to follow a healthy lifestyle. At the end of the study, hepatic steatosis and fibrosis reduced in both groups; however, the mean reduction was significantly greater in the synbiotic group rather than in the placebo group (P<0·001). Furthermore, serum levels of fasting blood sugar, TAG and most of the inflammatory mediators reduced in the synbiotic group significantly compared with the placebo group (P<0·05). Our results provide evidence that synbiotic supplementation improves the main features of NAFLD in patients with normal and low BMI, at least partially through reduction in inflammatory indices. Further studies are needed to address the exact mechanism of action of these effects.

Another face of placebo: The lessebo effect in Parkinson disease

PubMed Central

Mestre, Tiago A.; Shah, Prakesh; Marras, Connie; Tomlinson, George

2014-01-01

Objective: To study the impact of negative expectation related to receiving a placebo (the “lessebo effect”) on efficacy outcome measures of symptomatic treatments in Parkinson disease (PD). Methods: We conducted meta-analyses of double-blind randomized controlled trials (RCTs) of dopamine agonists in PD and compared the pooled mean score change of the motor section of the Unified Parkinson's Disease Rating Scale (mUPDRS) across active treatment arms according to the presence of a placebo arm or the probability of placebo assignment (0%, <50%, and 50%) of the original RCT. A mixed-effects model was used. Heterogeneity was assessed by subgroup analyses and meta-regression modeling. Results: A total of 28 study arms were extracted from active-controlled trials (3,277 patients) and 42 from placebo-controlled trials (4,554 patients). The overall difference between groups in the pooled mean score change in the mUPDRS was 1.6 units (95% confidence interval [CI] 0.2, 3.0; p = 0.023), in favor of the active-controlled group. In subgroup analyses, this difference was of higher magnitude in the early PD group without motor fluctuations (3.3 mUPDRS units, 95% CI 1.1, 5.4; p = 0.003) and for study duration ≤12 weeks (4.1 mUPDRS units, 95% CI 1.0, 7.2; p = 0.009). There was no between-group difference using probability of placebo assignment as criterion. Conclusions: This study shows that the use of a placebo can be associated with a clinically significant reduction in the magnitude of change of the mUPDRS after an active treatment in RCTs for PD. These new findings have potential implications in the development of new treatments and appraisal of current treatment options for PD and possibly for other neurologic disorders. PMID:24658930

Effect of Pumpkin Seed Oil on Hair Growth in Men with Androgenetic Alopecia: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Jeong, Dong Wook; Choi, Eun Jung; Kim, Yun Jin; Lee, Jeong Gyu; Yi, Yu Hyeon; Cha, Hyeong Soo

2014-01-01

Pumpkin seed oil (PSO) has been shown to block the action of 5-alpha reductase and to have antiandrogenic effects on rats. This randomized, placebo-controlled, double-blind study was designed to investigate the efficacy and tolerability of PSO for treatment of hair growth in male patients with mild to moderate androgenetic alopecia (AGA). 76 male patients with AGA received 400 mg of PSO per day or a placebo for 24 weeks. Change over time in scalp hair growth was evaluated by four outcomes: assessment of standardized clinical photographs by a blinded investigator; patient self-assessment scores; scalp hair thickness; and scalp hair counts. Reports of adverse events were collected throughout the study. After 24 weeks of treatment, self-rated improvement score and self-rated satisfaction scores in the PSO-treated group were higher than in the placebo group (P = 0.013, 0.003). The PSO-treated group had more hair after treatment than at baseline, compared to the placebo group (P < 0.001). Mean hair count increases of 40% were observed in PSO-treated men at 24 weeks, whereas increases of 10% were observed in placebo-treated men (P < 0.001). Adverse effects were not different in the two groups. PMID:24864154

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial.

PubMed

Moll, Etelka; Bossuyt, Patrick M M; Korevaar, Johanna C; Lambalk, Cornelis B; van der Veen, Fulco

2006-06-24

To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. Randomised clinical trial. Multicentre trial in 20 Dutch hospitals. 228 women with polycystic ovary syndrome. Clomifene citrate plus metformin or clomifene citrate plus placebo. The primary outcome measure was ovulation. Secondary outcome measures were ongoing pregnancy, spontaneous abortion, and clomifene resistance. 111 women were allocated to clomifene citrate plus metformin (metformin group) and 114 women were allocated to clomifene citrate plus placebo (placebo group). The ovulation rate in the metformin group was 64% compared with 72% in the placebo group, a non-significant difference (risk difference - 8%, 95% confidence interval - 20% to 4%). There were no significant differences in either rate of ongoing pregnancy (40% v 46%; - 6%, - 20% to 7%) or rate of spontaneous abortion (12% v 11%; 1%, - 7% to 10%). A significantly larger proportion of women in the metformin group discontinued treatment because of side effects (16% v 5%; 11%, 5% to 16%). Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome. Current Controlled Trials ISRCTN55906981 [controlled-trials.com].

Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis.

PubMed

Mease, Philip; Hall, Stephen; FitzGerald, Oliver; van der Heijde, Désirée; Merola, Joseph F; Avila-Zapata, Francisco; Cieślak, Dorota; Graham, Daniela; Wang, Cunshan; Menon, Sujatha; Hendrikx, Thijs; Kanik, Keith S

2017-10-19

Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs). In this 12-month, double-blind, active-controlled and placebo-controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to receive one of the following regimens: tofacitinib at a 5-mg dose taken orally twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily (104), adalimumab at a 40-mg dose administered subcutaneously once every 2 weeks (106), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months (52), or placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months (53). Placebo groups were pooled for analyses up to month 3. Primary end points were the proportion of patients who had an American College of Rheumatology 20 (ACR20) response (≥20% improvement from baseline in the number of tender and swollen joints and at least three of five other important domains) at month 3 and the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score (scores range from 0 to 3, with higher scores indicating greater disability) at month 3. ACR20 response rates at month 3 were 50% in the 5-mg tofacitinib group and 61% in the 10-mg tofacitinib group, as compared with 33% in the placebo group (P=0.01 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the rate was 52% in the adalimumab group. The mean change in the HAQ-DI score was -0.35 in the 5-mg tofacitinib group and -0.40 in the 10-mg tofacitinib group, as compared with -0.18 in the placebo group (P=0.006 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the score change was -0.38 in the adalimumab group. The rate of adverse events through month 12 was 66% in the 5-mg tofacitinib group, 71% in the 10-mg tofacitinib group, 72% in the adalimumab group, 69% in the placebo group that switched to the 5-mg tofacitinib dose, and 64% in the placebo group that switched to the 10-mg tofacitinib dose. There were four cases of cancer, three serious infections, and four cases of herpes zoster in patients who received tofacitinib during the trial. The efficacy of tofacitinib was superior to that of placebo at month 3 in patients with psoriatic arthritis who had previously had an inadequate response to conventional synthetic DMARDs. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Broaden ClinicalTrials.gov number, NCT01877668 .).

The Effects of Doming of the Diaphragm in Subjects With Short-Hamstring Syndrome: A Randomized Controlled Trial.

PubMed

Valenza, Marie Carmen; Cabrera-Martos, Irene; Torres-Sánchez, Irene; Garcés-García, Aurelio; Mateos-Toset, Sara; Valenza-Demet, Gerald

2015-11-01

Taking into account the complex structure of the diaphragm and its important role in the postural chain, the authors were prompted to check the effects of a diaphragm technique on hamstring flexibility. To evaluate the effects of the doming-of-the-diaphragm (DD) technique on hamstrings flexibility and spine mobility. Randomized placebo-controlled trial. University laboratory. Sixty young adults with short-hamstring syndrome were included in this randomized clinical trial using a between-groups design. The sample was randomly allocated to a placebo group (n = 30) or an intervention group (n = 30). Duration, position, and therapist were the same for both treatments. Hamstring flexibility was assessed using the forward-flexion-distance (FFD) and popliteal-angle test (PAT). Spinal motion was evaluated using the modified Schober test and cervical range of movement. Two-way ANOVA afforded pre- to postintervention statistically significant differences (P < .001) in the intervention group compared with the placebo group for hamstring flexibility measured by the FFD (mean change 4.59 ± 5.66 intervention group vs 0.71 ± 2.41 placebo group) and the PAT (mean change intervention group 6.81 ± 8.52 vs placebo group 0.57 ± 4.41). Significant differences (P < .05) were also found in the modified Schober test (mean change intervention group -1.34 ± 3.95 vs placebo group 1.02 ± 3.05) and cervical range of movement. Significant between-groups differences (P < .05) were also found in all the variables measured. The DD technique provides sustained improvement in hamstring flexibility and spine mobility.

The placebo effect and its determinants in fibromyalgia: meta-analysis of randomised controlled trials.

PubMed

Chen, Xi; Zou, Kun; Abdullah, Natasya; Whiteside, Nicola; Sarmanova, Aliya; Doherty, Michael; Zhang, Weiya

2017-07-01

The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition.

The effects of transdermal testosterone and oestrogen therapy on dry eye in postmenopausal women: a randomised, placebo-controlled, pilot study.

PubMed

Golebiowski, Blanka; Badarudin, Noor; Eden, John; Gerrand, Leanne; Robinson, Jennifer; Liu, Jinzhu; Hampel, Ulrike; You, Jingjing; Stapleton, Fiona

2017-07-01

Sex hormones could provide a future treatment avenue for dry eye post menopause. However, there are few well-controlled studies. This study investigates the impact of testosterone and oestrogen on dry eye symptoms and signs in postmenopausal women. A randomised double-blind placebo-controlled pilot study was conducted involving 40 women with dry eye (age 63.9±5.1 years, 13.2±6.3 years post menopause). Ten women were assigned to each of four treatment groups: transdermal testosterone, oestradiol, testosterone/oestradiol combination and placebo. Assessment at baseline and after 8 weeks: ocular symptoms, tear osmolarity, tear stability, tear secretion, meibomian gland assessment, corneal and conjunctival sensitivity, serum concentrations of 17β-oestradiol, 3-α-androstanediol-glucuronide and dehydroepiandrosterone sulfate. Differences from placebo were examined using one-way analysis of variance and Dunnett's t-test. Within-group analyses included paired t-tests and Spearman correlation. Dryness intensity after 8 weeks was significantly worse in the oestrogen group compared with placebo (p=0.04). No significant changes in other symptoms, tear function, meibomian gland function, lid morphology, corneal or conjunctival sensitivity were observed in any of the groups when compared with the change in placebo after 8 weeks. Within-group analyses showed increased tear secretion in the testosterone/oestradiol combination group (p=0.03) and a strong association between increased serum androgen and improved tear stability in the testosterone group (ρ=0.83,p=0.01). Oestrogen supplementation may worsen ocular symptoms in postmenopausal women with dry eye, whereas no impact of testosterone therapy on symptoms was apparent. The positive effects of oestrogen and testosterone on tear function require confirmation in a larger study, with sample size calculated from the data generated herein. Placebo control is essential in studies of dry eye therapies. ACTRN12612000281897. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effects and Safety of Gyejibongnyeong-Hwan on Dysmenorrhea Caused by Blood Stagnation: A Randomized Controlled Trial

PubMed Central

Park, Jeong-Su; Park, Sunju; Cheon, Chun-Hoo; Jo, Seong-Cheon; Cho, Han Baek; Lim, Eun-Mee; Lim, Hyung Ho; Shin, Yong-Cheol; Ko, Seong-Gyu

2013-01-01

Objective. This study was a multicenter, randomized, double-blind, and controlled trial with two parallel arms: the GJBNH group and the placebo group. This trial recruited 100 women aging 18 to 35 years with primary dysmenorrhea caused by blood stagnation. The investigational drugs, GJBNH or placebo, were administered for two menstrual periods (8 weeks) to the participants three times per day. The participants were followed up for two menstrual cycles after the administration. Results. The results were analyzed by the intention-to-treat (ITT) dataset and the per-protocol (PP) dataset. In the ITT dataset, the change of the average menstrual pain VAS score in the GJBNH group was statistically significantly lower than that in the control group. Significant difference was not observed in the SF-MPQ score change between the GJBNH group and the placebo group. No significant difference was observed in the PP analyses. In the follow-up phase, the VAS scores of the average menstrual pain and the maximum menstrual pain continually decreased in the placebo group, but they increased in the GJBNH group. Conclusion. GJBNH treatment for eight weeks improved the pain of the dysmenorrhea caused by blood stagnation, but it should be successively administered for more than two menstrual cycles. Trial Registration. This trial is registered with Current Controlled Trials no. ISRCTN30426947. PMID:24191165

Safety and Efficacy of ABT-089 in Pediatric Attention-Deficit/Hyperactivity Disorder: Results from Two Randomized Placebo-Controlled Clinical Trials

ERIC Educational Resources Information Center

Wilens, Timothy E.; Gault, Laura M.; Childress, Ann; Kratochvil, Christopher J.; Bensman, Lindsey; Hall, Coleen M.; Olson, Evelyn; Robieson, Weining Z.; Garimella, Tushar S.; Abi-Saab, Walid M.; Apostol, George; Saltarelli, Mario D.

2011-01-01

Objective: To assess the safety and efficacy of ABT-089, a novel alpha[subscript 4]beta[subscript 2] neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD). Method: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years…

Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study.

PubMed

Vanky, Eszter; Stridsklev, Solhild; Heimstad, Runa; Romundstad, Pål; Skogøy, Kristin; Kleggetveit, Odrun; Hjelle, Sissel; von Brandis, Philip; Eikeland, Torunn; Flo, Karin; Berg, Kristin Flaten; Bunford, Gabor; Lund, Agnethe; Bjerke, Cecilie; Almås, Ingunn; Berg, Ann Hilde; Danielson, Anna; Lahmami, Gulim; Carlsen, Sven Magnus

2010-12-01

Metformin is widely prescribed to pregnant women with polycystic ovary syndrome (PCOS) in an attempt to reduce pregnancy complications. Metformin is not approved for this indication, and evidence for this practice is lacking. Our objective was to test the hypothesis that metformin, from first trimester to delivery, reduces pregnancy complications in women with PCOS. We conducted a randomized, placebo-controlled, double-blind, multicenter study at 11 secondary care centers. The participants were 257 women with PCOS, in the first trimester of pregnancy, aged 18-42 yr. We randomly assigned 274 singleton pregnancies (in 257 women) to receive metformin or placebo, from first trimester to delivery. The prevalence of preeclampsia, gestational diabetes mellitus, preterm delivery, and a composite of these three outcomes is reported. Preeclampsia prevalence was 7.4% in the metformin group and 3.7% in the placebo group (3.7%; 95% CI, -1.7-9.2) (P=0.18). Preterm delivery prevalence was 3.7% in the metformin group and 8.2% in the placebo group (-4.4%; 95%, CI, -10.1-1.2) (P=0.12). Gestational diabetes mellitus prevalence was 17.6% in the metformin group and 16.9% in the placebo group (0.8%; 95% CI, -8.6-10.2) (P=0.87). The composite primary endpoint prevalence was 25.9 and 24.4%, respectively (1.5%; 95% CI, -8.9-11.3) (P=0.78). Women in the metformin group gained less weight during pregnancy compared with those in the placebo group. There was no difference in fetal birth weight between the groups. Metformin treatment from first trimester to delivery did not reduce pregnancy complications in PCOS.

Effects of Topical Tamoxifen on Wound Healing of Burned Skin in Rats

PubMed Central

Mehrvarz, Shaban; Ebrahimi, Ali; Sahraei, Hedayat; Bagheri, Mohammad Hasan; Fazili, Sima; Manoochehry, Shahram; Rasouli, Hamid Reza

2017-01-01

Background This study aimed to assess the effects of the topical application of tamoxifen on wound healing of burned skin in Wistar rats by evaluating 3 healing characteristics: fibrotic tissue thickness (FTT), scar surface area (SSA), and angiogenesis in the healed scar tissue. Methods Eighteen male Wistar rats were used in this study. A third-degree burn wound was made on the shaved animals’ back, measuring 2×2×2 cm. In the first group, a 2% tamoxifen ointment was applied to the wound twice daily for 8 weeks. The second group received a placebo ointment during the same period. The third group did not receive any treatment and served as the control group. Results The median (interquartile range=[Q1, Q3]) FTT was 1.35 (1.15, 1.62) mm, 1.00 (0.95, 1.02) mm, and 1.25 (0.8, 1.5) mm in the control, tamoxifen, and placebo groups, respectively (P=0.069). However, the FTT in the tamoxifen group was less than in the placebo and control groups. The median angiogenesis was 3.5 (3.00, 6.25), 8.00 (6.75, 9.25), and 7.00 (5.50, 8.25) vessels per high-power field for the control, tamoxifen, and placebo groups, respectively (P=0.067). However, the median angiogenesis was higher in the tamoxifen group than in the control group. No significant difference was observed in the mean SSA between the tamoxifen group and the control group (P=0.990). Conclusions Local application of tamoxifen increased angiogenesis and decreased the FTT, with no change in the SSA in burned skin areas. These effects are expected to expedite the wound healing process, reducing contracture and preventing hypertrophic scar and keloid formation. PMID:28946718

Symptomatic treatment of the common cold with a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine: a randomized, placebo-controlled trial.

PubMed

Picon, Paulo Dornelles; Costa, Marisa Boff; da Veiga Picon, Rafael; Fendt, Lucia Costa Cabral; Suksteris, Maurício Leichter; Saccilotto, Indara Carmanim; Dornelles, Alicia Dorneles; Schmidt, Luis Felipe Carissimi

2013-11-22

The common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults. This study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured. Mean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups. A fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults. NCT01389518.

Symptomatic treatment of the common cold with a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine: a randomized, placebo-controlled trial

PubMed Central

2013-01-01

Background The common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults. Methods This study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured. Results Mean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups. Conclusion A fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults. Trial registration NCT01389518 PMID:24261438

Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study.

PubMed

Safarinejad, Mohammad Reza

2005-01-01

To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen (PSA), testosterone levels, and prostate size. At the end of 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months. 558 patients (90%) completed the study (287/305, 91% in the Urtica dioica group, and 271/315, 86% in the placebo group). By intention- to-treat analysis, at the end of 6-month trial, 232 (81%) of 287 patients in the Urtica dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the placebo group (P < 0.001). Both IPSS and Qmax showed greater improvement with drug than with placebo. The IPSS went from 19.8 down to 11.8 with Urtica dioica and from 19.2 to 17.7 with placebo (P = 0.002). Peak flow rates improved by 3.4 mL/s for placebo recipients and by 8.2 mL/s for treated patients (P < 0.05). In Urtica dioica group, PVR decreased from an initial value of 73 to 36 mL (P < 0.05). No appreciable change was seen in the placebo group. Serum PSA and testosterone levels were unchanged in both groups. A modest decrease in prostate size as measured by transrectal ultrasonography (TRUS) was seen in Urtica dioica group (from 40.1 cc initially to 36.3 cc; P < 0.001). There was no change in the prostate volume at the end of study with placebo. At 18-month follow-up, only patients who continued therapy, had a favorable treatment variables value. No side effects were identified in either group. In the present study, Urtica dioica have beneficial effects in the treatment of symptomatic BPH. Further clinical trials should be conducted to confirm these results before concluding that Urtica dioica is effective.

Effects of Functional Fascial Taping on pain and function in patients with non-specific low back pain: a pilot randomized controlled trial.

PubMed

Chen, Shu-Mei; Alexander, Ron; Lo, Sing Kai; Cook, Jill

2012-10-01

To compare the short-term and medium-term effect of Functional Fascial Taping to placebo taping on pain and function in people with non-specific low back pain. A pilot randomized controlled trial with a 2-week intervention, and 2-, 6- and 12-week follow-up. Individuals with non-specific low back pain recruited from local communities. Forty-three participants with non-specific low back pain for more than 6 weeks were randomized into either Functional Fascial Taping group (n = 21) or placebo group (n = 22). The intervention group was treated with Functional Fascial Taping while the control group was treated with placebo taping. Both groups received four treatments over 2 weeks. Worst and average pain and function were assessed at baseline, after the 2-week intervention, and at 6 and 12 weeks follow-up. The Functional Fascial Taping group demonstrated significantly greater reduction in worst pain compared to placebo group after the 2-week intervention (P = 0.02, effect size = 0.74; 95% confidence interval 0.11-1.34). A higher proportion of participants in Functional Fascial Taping group attained the minimal clinically important difference in worst pain (P = 0.007) and function (P = 0.007) than those in placebo group after the 2-week intervention. There were no significant differences in either group's disability rating or clinically important difference in average pain at any time. Functional Fascial Taping reduced worst pain in patients with non-acute non-specific low back pain during the treatment phase. No medium-term differences in pain or function were observed.

The effect of tranexamic acid for treatment irregular uterine bleeding secondary to DMPA use.

PubMed

Senthong, A-Jaree; Taneepanichskul, Surasak

2009-04-01

Evaluate the efficacy of tranexamic acid and placebo for controlling irregular uterine bleeding in depot-medroxyprogesterone acetate (DMPA) users. A double-blind, placebo-controlled study was conducted on 100 DMPA users attending the Family Planning Clinic King Chulalongkorn Memorial Hospital. All users had abnormal bleeding. They were randomly divided in two groups; a group of 50 received tranexamic acid, 250 mg four times a day for 5 days and another group of 49 received placebo in the same manner. One subject dropped out from the study. Total day of bleeding/spotting and percentage of women in whom bleeding was stopped were analyzed at the end of weeks 1 and 4. The percentage of subjects in whom bleeding was stopped during the first week after initial treatment was significantly higher in the tranexamic acid group than the placebo group (88% vs. 8.2%, p < 0.001). During the follow-up period (4 weeks after initial treatment), a bleeding-free interval of > 20 days was found in 68% of subjects treated with tranexamic acid and 0% treated with placebo(p < 0.001). The mean number of bleeding/spotting days were also significantly different between the groups (5.7 +/- 2.5 vs. 17.5 +/- 7.2 days, p < 0.05). Tranexamic acid was more effective than placebo in short-term treatment of irregular uterine bleeding/spotting associated with DMPA use.

Effects of Quercetin on Adiponectin-Mediated Insulin Sensitivity in Polycystic Ovary Syndrome: A Randomized Placebo-Controlled Double-Blind Clinical Trial.

PubMed

Rezvan, N; Moini, A; Janani, L; Mohammad, K; Saedisomeolia, A; Nourbakhsh, M; Gorgani-Firuzjaee, S; Mazaherioun, M; Hosseinzadeh-Attar, M J

2017-02-01

Polycystic ovary syndrome (PCOS) is a heterogeneous, multi-causal, and genetically complex disorder, which is related to the failure in endocrine glands. Adiponectin has been reported to be low in PCOS, even in the absence of adiposity. Quercetin reduces serum glucose, insulin, triglycerides, and cholesterol levels and increases the expression and secretion of adiponectin. The aim of this study was to determine the effect of quercetin on the adiponectin-mediated insulin sensitivity in PCOS patients. Eighty-four women with PCOS were selected and randomly assigned to 2 groups of treatment and control. The treatment group received 1 g quercetin (two 500 mg capsules) daily for 12 weeks, and the control group received placebo. In addition to anthropometric assessments, fasting serum levels of total adiponectin, high-molecular-weight (HMW) adiponectin, glucose, insulin, testosterone, LH, and SHBG were also measured at the baseline and at the end of the trial. Quercetin could slightly increase the level of adiponectin by 5.56% as compared to placebo (adjusted p-value=0.001) and HMW adiponectin by 3.9% as compared to placebo (adjusted p-value=0.017), while it reduced the level of testosterone (0.71 ng/dl in quercetin vs. 0.77 ng/dl in placebo; p<0.001) and LH (8.42 IU/l in quercetin vs. 8.68 IU/l in placebo; p=0.009). HOMA-IR levels were also significantly (p<0.001) lower in quercetin (1.84) group compared to placebo group (2.21). Oral quercetin supplementation was effective in improving the adiponectin-mediated insulin resistance and hormonal profile of women with PCOS. © Georg Thieme Verlag KG Stuttgart · New York.

Validation of Placebo in a Manual Therapy Randomized Controlled Trial

PubMed Central

Chaibi, Aleksander; Šaltytė Benth, Jūratė; Bjørn Russell, Michael

2015-01-01

At present, no consensus exists among clinical and academic experts regarding an appropriate placebo for randomized controlled trials (RCTs) of spinal manipulative therapy (SMT). Therefore, we investigated whether it was possible to conduct a chiropractic manual-therapy RCT with placebo. Seventy migraineurs were randomized to a single-blinded placebo-controlled clinical trial that consisted of 12 treatment sessions over 3 months. The participants were randomized to chiropractic SMT or placebo (sham manipulation). After each session, the participants were surveyed on whether they thought they had undergone active treatment (“yes” or “no”) and how strongly they believed that active treatment was received (numeric rating scale 0–10). The outcome measures included the rate of successful blinding and the certitude of the participants’ beliefs in both treatment groups. At each treatment session, more than 80% of the participants believed that they had undergone active treatment, regardless of group allocation. The odds ratio for believing that active treatment was received was >10 for all treatment sessions in both groups (all p < 0.001). The blinding was maintained throughout the RCT. Our results strongly demonstrate that it is possible to conduct a single-blinded manual-therapy RCT with placebo and to maintain the blinding throughout 12 treatment sessions given over 3 months. PMID:26145718

To compare the effect of dextromethorphan, promethazine and placebo on nocturnal cough in children aged 1-12 y with upper respiratory infections: a randomized controlled trial.

PubMed

Bhattacharya, Malobika; Joshi, Neha; Yadav, Sangita

2013-11-01

To evaluate whether promethazine and dextromethorphan reduce nocturnal cough and improve sleep quality in children aged 1-12 y with upper respiratory tract infection (URI). This randomised double-blinded placebo-controlled trial was conducted in Pediatric outpatient department of Lok Nayak Hospital, Delhi. After randomization into promethazine, dextromethorphan and placebo groups, parental assessment of 120 children with URI for nocturnal cough severity (child), post-tussive vomiting (child) and sleep quality (child and parent) on the night before enrolment and after 3 d of assigned medication was measured using an internally validated indigenously prepared ordinal scale. Entire cohort improved in all the study parameters after 3 d. However, no superior benefit was noted when individual parameters were compared in the promethazine and dextromethorphan groups with the placebo group. Adverse effects were more frequent in the dextromethorphan and promethazine groups although the difference was not statistically significant. Nocturnal cough in URI is self-resolving and dextromethorphan and promethazine prescribed for the same are not superior to placebo.

Efficacy of topical chamomile oil for mild and moderate carpal tunnel syndrome: A randomized double-blind placebo-controlled clinical trial.

PubMed

Hashempur, Mohammad Hashem; Ghasemi, Mohammad Sadegh; Daneshfard, Babak; Ghoreishi, Parissa Sadat; Lari, Zeinab Nasiri; Homayouni, Kaynoosh; Zargaran, Arman

2017-02-01

To evaluate the efficacy of topical chamomile oil in patients with mild and moderate carpal tunnel syndrome (CTS). Eighty six patients with electrodiagnostic criteria of mild and moderate CTS were enrolled in this randomized double-blind placebo-controlled clinical trial and received wrist splint plus topical chamomile oil or placebo for 4 weeks. They were evaluated at the baseline and end of the study regarding functional and symptomatic scores, dynamometry, and electrodiagnostic indexes. Dynamometry, functionality, and symptom severity scores of the patients were significantly improved in the chamomile oil group compared with the placebo group (P = 0.040, P = 0.0001, P = 0.017, respectively). Additionally, compound latency of the median nerve in the chamomile oil group significantly decreased (P = 0.035) compared to the placebo group. Other electerodiagnostic measurements did not change significantly. Complementary treatment with topical chamomile oil may have some benefits for patients with mild and moderate CTS, both subjectively and objectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

A preliminary investigation on the efficacy of N-acetyl cysteine for mania or hypomania.

PubMed

Magalhães, Pedro Vieira da Silva; Dean, Olivia M; Bush, Ashley I; Copolov, David L; Malhi, Gin S; Kohlmann, Kristy; Jeavons, Susan; Schapkaitz, Ian; Anderson-Hunt, Murray; Berk, Michael

2013-06-01

Oxidative imbalance has emerged as a treatment target in bipolar disorder. As very limited data are available on the clinical use of antioxidants for mania, we report here results from a post hoc and exploratory subgroup analysis of a randomized, placebo-controlled trial of N-acetyl cysteine (NAC). This was a placebo-controlled, randomized, clinical trial assessing the effect of NAC over 24 weeks in mania or hypomania. Symptomatic and functional outcomes were collected over the study period. Fifteen participants were available for this report; two participants in each group failed to complete all assessments. Within-group analyses pointed to an improvement in the NAC group on manic symptoms and worsening in the placebo group on depressive symptoms at endpoint. Although the sample size was small, these results indicated within-group efficacy for this glutathione precursor as compared to placebo. Future trials specifically designed to demonstrate the efficacy of NAC in mania are needed.

21 CFR 343.80 - Professional labeling.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., randomized, multi-center, placebo-controlled trials of predominantly male post-MI subjects and one randomized... group on the aspirin molecule. This acetyl group is responsible for the inactivation of cyclo-oxygenase... event rate was reduced to 5 percent from the 10 percent rate in the placebo group. Chronic Stable Angina...

21 CFR 343.80 - Professional labeling.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., randomized, multi-center, placebo-controlled trials of predominantly male post-MI subjects and one randomized... group on the aspirin molecule. This acetyl group is responsible for the inactivation of cyclo-oxygenase... event rate was reduced to 5 percent from the 10 percent rate in the placebo group. Chronic Stable Angina...

21 CFR 343.80 - Professional labeling.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., randomized, multi-center, placebo-controlled trials of predominantly male post-MI subjects and one randomized... group on the aspirin molecule. This acetyl group is responsible for the inactivation of cyclo-oxygenase... event rate was reduced to 5 percent from the 10 percent rate in the placebo group. Chronic Stable Angina...

21 CFR 343.80 - Professional labeling.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., randomized, multi-center, placebo-controlled trials of predominantly male post-MI subjects and one randomized... group on the aspirin molecule. This acetyl group is responsible for the inactivation of cyclo-oxygenase... event rate was reduced to 5 percent from the 10 percent rate in the placebo group. Chronic Stable Angina...

21 CFR 343.80 - Professional labeling.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., randomized, multi-center, placebo-controlled trials of predominantly male post-MI subjects and one randomized... group on the aspirin molecule. This acetyl group is responsible for the inactivation of cyclo-oxygenase... event rate was reduced to 5 percent from the 10 percent rate in the placebo group. Chronic Stable Angina...

Effect of Arnica D30 in marathon runners. Pooled results from two double-blind placebo controlled studies.

PubMed

Tveiten, D; Bruset, S

2003-10-01

To examine whether the homeopathic medicine Arnica D30 has an effect on muscle soreness and cell damage after marathon running. The subjects were 82 marathon runners from two separate randomised double-blind placebo controlled trials participating in the Oslo Marathon in 1990 and 1995. Five pills of Arnica D30 or placebo were given morning and evening. Treatment started on the evening before the marathon and continued on day of the race and the three following days. The runners assessed muscular soreness on a visual analogue scale. Muscle enzymes, electrolytes and creatinine were measured before and after the marathon. Muscle soreness immediately after the marathon run was lower in the Arnica group than in the placebo group (P = 0.04). Cell damage measured by enzymes was similar in the Arnica and the placebo group. These pooled results suggest that Arnica D30 has a positive effect on muscle soreness after marathon running, but not on cell damage measured by enzymes.

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series.

PubMed

Taylor, M A; Reilly, D; Llewellyn-Jones, R H; McSharry, C; Aitchison, T C

To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Randomised, double blind, placebo controlled, parallel group, multicentre study. Four general practices and a hospital ear, nose, and throat outpatient department. 51 patients with perennial allergic rhinitis. Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo.

The Efficacy and Safety of On-demand Tramadol and Paroxetine Use in Treatment of Life Long Premature Ejaculation: A Randomized Double-blind Placebo-controlled Clinical Trial

PubMed Central

Hamidi-Madani, Ali; Motiee, Reza; Mokhtari, Gholamreza; Nasseh, Hamidreza; Esmaeili, Samaneh; Kazemnezhad, Ehsan

2018-01-01

Background: Several medical therapies have been proposed for the treatment of premature ejaculation (PE). Paroxetine and tramadol were both reported to be effective in treatment of PE. In this study, the therapeutic effects of tramadol, paroxetine and placebo were compared in treatment of primary PE. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 150 patients were divided into 3 groups. One group was treated with tramadol 50 mg ondemand, the other group took paroxetine 20 mg on-demand and the third group was treated with placebo. Before starting treatment and after 12 weeks, patients were asked to measure their average intravaginal ejaculation latency time (IELT) and fill the PEP (Premature Ejaculation Profile) questionnaire. Results: At the end of the 12th week, the mean IELT and average of PEP scores improved in all 3 groups. The increase in tramadol group was significantly higher than the paroxetine and placebo groups (p<0.0001). There were no significant differences in terms of side effects between the 3 groups. Conclusion: The results showed that despite an increase in mean IELT and PEP scores in all 3 groups, the rate of improvement in tramadol group was significantly more than the others. Thus, tramadol may be considered as an appropriate alternative therapeutic option for lifelong PE. PMID:29850442

The Efficacy and Safety of On-demand Tramadol and Paroxetine Use in Treatment of Life Long Premature Ejaculation: A Randomized Double-blind Placebo-controlled Clinical Trial.

PubMed

Hamidi-Madani, Ali; Motiee, Reza; Mokhtari, Gholamreza; Nasseh, Hamidreza; Esmaeili, Samaneh; Kazemnezhad, Ehsan

2018-01-01

Several medical therapies have been proposed for the treatment of premature ejaculation (PE). Paroxetine and tramadol were both reported to be effective in treatment of PE. In this study, the therapeutic effects of tramadol, paroxetine and placebo were compared in treatment of primary PE. In this randomized, double-blind, placebo-controlled clinical trial, 150 patients were divided into 3 groups. One group was treated with tramadol 50 mg ondemand, the other group took paroxetine 20 mg on-demand and the third group was treated with placebo. Before starting treatment and after 12 weeks, patients were asked to measure their average intravaginal ejaculation latency time (IELT) and fill the PEP (Premature Ejaculation Profile) questionnaire. At the end of the 12th week, the mean IELT and average of PEP scores improved in all 3 groups. The increase in tramadol group was significantly higher than the paroxetine and placebo groups (p<0.0001). There were no significant differences in terms of side effects between the 3 groups. The results showed that despite an increase in mean IELT and PEP scores in all 3 groups, the rate of improvement in tramadol group was significantly more than the others. Thus, tramadol may be considered as an appropriate alternative therapeutic option for lifelong PE.

Tribulus terrestris versus placebo in the treatment of erectile dysfunction: A prospective, randomized, double blind study.

PubMed

Santos, C A; Reis, L O; Destro-Saade, R; Luiza-Reis, A; Fregonesi, A

2014-05-01

To evaluate the possible effects of Tribulus terrestris herbal medicine in the erectile dysfunction treatment and to quantify its potential impact on serum testosterone levels. Prospective, randomized, double-blind and placebo-controlled study including thirty healthy men selected from 100 patients who presented themselves spontaneously complaining of erectile dysfunction, ≥ 40 years of age, nonsmokers, not undergoing treatment for prostate cancer or erectile dysfunction, no dyslipidemia, no phosphodiesterase inhibitor use, no hormonal manipulation and, if present hypertension and/or diabetes mellitus should be controlled. International Index of Erectile Function (IIEF-5) and serum testosterone were obtained before randomization and after 30 days of study. Patients were randomized into two groups of fifteen subjects each. The study group received 800 mg of Tribulus terrestris, divided into two doses per day for thirty days and the control group received placebo administered in the same way. The groups were statistically equivalent in all aspects evaluated. The mean (SD) age was 60 (9.4) and 62.9 (7.9), P = .36 for intervention and placebo groups, respectively. Before treatment, the intervention group showed mean IIEF-5 of 13.2 (5-21) and mean total testosterone 417.1 ng/dl (270.7-548.4 ng/dl); the placebo group showed mean IIEF-5 of 11.6 (6-21) and mean total testosterone 442.7 ng/dl (301-609.1 ng/dl). After treatment, the intervention group showed mean IIEF-5 of 15.3 (5-21) and mean total testosterone 409.3 ng/dl (216.9-760.8 ng/dl); the placebo group showed mean IIEF-5 of 13.7 (6-21) and mean total testosterone 466.3 ng/dl (264.3-934.3 ng/dl). The time factor caused statistically significant changes in both groups for IIEF-5 only (P = .0004), however, there was no difference between the two groups (P = .7914). At the dose and interval studied, Tribulus terrestris was not more effective than placebo on improving symptoms of erectile dysfunction or serum total testosterone. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.

PubMed

Sunay, Didem; Sunay, Melih; Aydoğmuş, Yasin; Bağbancı, Sahin; Arslan, Hüseyin; Karabulut, Ayhan; Emir, Levent

2011-05-01

Acupuncture therapy has been used by many researchers in both male and female sexual dysfunction studies. To determine whether acupuncture is effective as a premature ejaculation (PE) treatment compared with paroxetine and placebo. The study was conducted with methodologic rigor based on Consolidated Standards of Reporting Trials (CONSORT) criteria. Ninety patients referred to the urology clinic at a tertiary training and research hospital with PE were included in this randomized controlled trial and randomly assigned into paroxetine, acupuncture, and placebo groups. Heterosexual, sexually active men aged between 28 and 50 yr were included. Men with other sexual disorders, including erectile dysfunction; with chronic psychiatric or systemic diseases; with alcohol or substance abuse; or who used any medications were excluded. The medicated group received paroxetine 20 mg/d; the acupuncture or sham-acupuncture (placebo) groups were treated twice a week for 4 wk. Intravaginal ejaculation latency times (IELTs) and the Premature Ejaculation Diagnostic Tool (PEDT) were used to assess PE. IELTs were calculated by using a partner-held stopwatch. Data were analyzed statistically. Median PEDT scores of paroxetine, acupuncture, and placebo groups were 17.0, 16.0, and 15.5 before treatment, and 10.5, 11.0, and 16.0 after treatment, respectively (p=0.001, p=0.001, and p=0.314, respectively). Subscores after treatment were significantly lower than subscores before treatment in the paroxetine and acupuncture groups but remained the same in the placebo group. Significant differences were found between mean-rank IELTs of the paroxetine and placebo groups (p=0.001) and the acupuncture and placebo groups (p=0.001) after treatment. Increases of IELTs with paroxetine, acupuncture, and placebo acupuncture were 82.7, 65.7, and 33.1 s, respectively. Extent of ejaculation delay induced by paroxetine was significantly higher than that of acupuncture (p=0.001). The most important limitation of the study was the lack of follow-up. Although less effective than daily paroxetine, acupuncture had a significant stronger ejaculation-delaying effect than placebo. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Efficacy and safety of once-yearly zoledronic acid in Japanese patients with primary osteoporosis: two-year results from a randomized placebo-controlled double-blind study (ZOledroNate treatment in Efficacy to osteoporosis; ZONE study).

PubMed

Nakamura, T; Fukunaga, M; Nakano, T; Kishimoto, H; Ito, M; Hagino, H; Sone, T; Taguchi, A; Tanaka, S; Ohashi, M; Ota, Y; Shiraki, M

2017-01-01

In a 2-year randomized, placebo-controlled study of 665 Japanese patients with primary osteoporosis, once-yearly administration of zoledronic acid (5 mg) reduced the risk of new morphometric vertebral fractures. The purpose of this study was to determine the efficacy and safety of once-yearly intravenous infusion of ZOL in Japanese patients with primary osteoporosis. This was a two-year multicenter, randomized, placebo-controlled, double-blind, parallel-group comparative study (ZONE Study). Subjects were 665 Japanese patients between the ages of 65 and 89 years who had prevalent vertebral fracture. Subjects were randomly assigned to receive once-yearly intravenous infusion of 5 mg of ZOL or placebo at baseline and 12 months. The 2-year incidence of new morphometric vertebral fracture was 3.0 % (10/330 subjects) in the ZOL group and 8.9 % (29/327) in the placebo group (p = 0.0016). The 24-month cumulative incidence of new morphometric vertebral fracture was 3.3 % in the ZOL group versus 9.7 % in the placebo group (log-rank test: p = 0.0029; hazard ratio: 0.35; 95 % confidence interval: 0.17-0.72). The cumulative incidence of any clinical fracture, clinical vertebral fracture, and non-vertebral fracture was significantly reduced in the ZOL group by 54, 70, and 45 %, respectively, compared to the placebo group. At 24 months, ZOL administration increased bone mineral density in the lumbar spine, femoral neck, and total hip (t test: p < 0.0001). No new adverse events or osteonecrosis of the jaw were observed in this study. Once-yearly administration of ZOL 5 mg to Japanese patients with primary osteoporosis reduced the risk of new morphometric vertebral fractures and was found to be safe.

Effects of auriculotherapy on labour pain: a randomized clinical trial.

PubMed

Mafetoni, Reginaldo Roque; Shimo, Antonieta Keiko Kakuda

2016-01-01

Assessing the effects of auriculotherapy in pain control and its outcomes on the duration of labour. This is a randomized, controlled, double-blind trial with preliminary data. Thirty pregnant women with gestational age ≥ 37 weeks, cervical dilatation ≥ 4 cm and two or more contractions in 10 minutes were selected and randomly divided into three groups: auriculotherapy, placebo and control. Auriculotherapy was applied using crystal beads on four strategic points. No statistical significance was found between the groups with regard to pain; however, the women from the auriculotherapy group had lower intensity and less perception of pain at 30, 60 and 120 minutes of treatment. The average duration of labour was shorter in the auriculotherapy group (248.7 versus placebo 414.8 versus control 296.3 minutes); caesarean section rates were higher in the placebo group (50%) and the same in the other groups (10%). Mothers who received auriculotherapy presented a tendency for greater pain control and shorter labour duration; however, caesarean section rates in this group were similar to the control group. This trial precedes a larger study in progress. Registration of Brazilian Clinical Trials: RBR-47hhbj. Avaliar os efeitos da auriculoterapia no controle da dor e seus desfechos na duração do trabalho de parto. Trata-se de um ensaio controlado, randomizado e duplo-cego, com dados preliminares. Foram selecionadas 30 parturientes com idade gestacional ≥ 37 semanas, dilatação cervical ≥ 4 cm e duas ou mais contrações em 10 minutos, divididas aleatoriamente em três grupos: auriculoterapia, placebo ou controle. A auriculoterapia foi aplicada com microesferas de cristais em quatro pontos estratégicos. Não houve significância estatística entre os grupos com relação à dor; no entanto, as mulheres do grupo de auriculoterapia, apresentaram menor intensidade e menor percepção da dor aos 30, 60 e 120 minutos do tratamento. A média de duração do trabalho de parto foi menor no grupo de auriculoterapia (248,7 versus placebo 414,8 versus controle 296,3 minutos); a taxa de cesárea foi maior no grupo placebo (50%) e igual nos outros (10%). As parturientes que receberam auriculoterapia apresentaram tendência a um maior controle da dor e menor duração do trabalho de parto, porém a taxa de cesárea neste grupo foi semelhante à do grupo controle. Este ensaio precede um estudo maior, em andamento. Registro Brasileiro de Ensaio Clínico: RBR-47hhbj.

Creatine Supplementation Associated or Not with Strength Training upon Emotional and Cognitive Measures in Older Women: A Randomized Double-Blind Study

PubMed Central

Alves, Christiano Robles Rodrigues; Merege Filho, Carlos Alberto Abujabra; Benatti, Fabiana Braga; Brucki, Sonia; Pereira, Rosa Maria R.; de Sá Pinto, Ana Lucia; Lima, Fernanda Rodrigues; Roschel, Hamilton; Gualano, Bruno

2013-01-01

Purpose To assess the effects of creatine supplementation, associated or not with strength training, upon emotional and cognitive measures in older woman. Methods This is a 24-week, parallel-group, double-blind, randomized, placebo-controlled trial. The individuals were randomly allocated into one of the following groups (n=14 each): 1) placebo, 2) creatine supplementation, 3) placebo associated with strength training or 4) creatine supplementation associated with strength training. According to their allocation, the participants were given creatine (4 x 5 g/d for 5 days followed by 5 g/d) or placebo (dextrose at the same dosage) and were strength trained or not. Cognitive function, assessed by a comprehensive battery of tests involving memory, selective attention, and inhibitory control, and emotional measures, assessed by the Geriatric Depression Scale, were evaluated at baseline, after 12 and 24 weeks of the intervention. Muscle strength and food intake were evaluated at baseline and after 24 weeks. Results After the 24-week intervention, both training groups (ingesting creatine supplementation and placebo) had significant reductions on the Geriatric Depression Scale scores when compared with the non-trained placebo group (p = 0.001 and p = 0.01, respectively) and the non-trained creatine group (p < 0.001 for both comparison). However, no significant differences were observed between the non-trained placebo and creatine (p = 0.60) groups, or between the trained placebo and creatine groups (p = 0.83). Both trained groups, irrespective of creatine supplementation, had better muscle strength performance than the non-trained groups. Neither strength training nor creatine supplementation altered any parameter of cognitive performance. Food intake remained unchanged. Conclusion Creatine supplementation did not promote any significant change in cognitive function and emotional parameters in apparently healthy older individuals. In addition, strength training per se improved emotional state and muscle strength, but not cognition, with no additive effects of creatine supplementation. Trial Registration Clinicaltrials.gov NCT01164020 PMID:24098469

[Pharmacotherapy of attention deficit hyperactivity disorder in children: the results of a multicenter double-blind placebo-controlled study of hopantenic acid].

PubMed

Zavadenko, N N; Suvorinova, N Yu; Vakula, I N; Malinina, E V; Kuzenkova, L M

To assess the efficacy and safety of hopantenic acid (pantogam) compared to placebo in the treatment of attention deficit hyperactivity disorder (ADHD) in children, aged from 6 to 12 years, during 4 month in the prospective multicenter comparative double-blind placebo-controlled study in parallel groups. One hundred patients enrolled in the safety assessment population were stratified into two equal pantogam and placebo groups. Eighty-nine patients who completed the study in according to the protocol were included in the efficacy assessment group: 45 in the pantogam group and 44 in the placebo group. Pantogam was administered in tablets (250 mg) in the therapeutic dose 30 mg/kg of body mass, divided into 2 doses, during 4 month. Patient's state was assessed by the total score on ADHD-DSM-IV, CGI-S WFIRS-P and results of the Toulouse-Piéron test for sustained attention. There was a trend towards an increase in the percentage of patients with positive changes (a decrease in the total ADHD-DSM-IV by ≥25%) in the end of the 3rd and 4th month in the pantogam group (treatment response was 66.7 and 68.9%, respectively) compared to the placebo group (treatment response was 52.3 and 61.4%, respectively). A significant decrease in disease severity assessed by the CGI-S was noted in the pantogam group compared to the placebo group. After 4 month of treatment with pantogam, the severity of functional disturbances was reduced by 4 out of 6 WFIRS-P domains: Family, School and learning, Child's self-concept and Risky activities. Pantogam improved the measures of sustained attention (accuracy and speed) in the Toulouse-Piéron test. The drug used in mean daily dose 30 mg/kg during 4 month had a favorable safety profile which did not differ from that of placebo.

Oral scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled study.

PubMed

Khajavi, Danial; Farokhnia, Mehdi; Modabbernia, Amirhossein; Ashrafi, Mandana; Abbasi, Seyed-Hesammedin; Tabrizi, Mina; Akhondzadeh, Shahin

2012-11-01

To evaluate the antidepressant effect of oral scopolamine as an adjunct to citalopram. In this randomized double-blind placebo-controlled study, patients were assessed in the outpatient clinics of 2 large hospitals from November 2011 to January 2012. Forty patients (18-55 years) with major depressive disorder (DSM-IV-TR criteria) and 17-Item Hamilton Depression Rating Scale (HDRS) score ≥ 22 were randomly assigned to scopolamine hydrobromide (1 mg/d) (n = 20) or placebo (n = 20) in addition to citalopram for 6 weeks. HDRS score was measured at baseline and days 4, 7, 14, 28, and 42. The primary outcome measure was HDRS score change from baseline to week 6 in the scopolamine group versus the placebo group. Response was defined as ≥ 50% decrease in HDRS score; remission, as HDRS score ≤ 7. Augmentation with scopolamine was significantly more effective than placebo (F(1,38) = 5.831, P = .021). Patients receiving scopolamine showed higher rates of response (65%, 13/20 at week 4) and remission (65%, 13/20 at week 6) than the placebo group (30%, 6/20 and 20%, 4/20, respectively; P = .027, P = .004, respectively). Patients in the scopolamine group showed higher rates of dry mouth, blurred vision, and dizziness than the placebo group. Oral scopolamine is a safe and effective adjunct for treatment of patients with moderate to severe major depressive disorder. Iranian Registry of Clinical Trials identifier: IRCT201201181556N31. © Copyright 2012 Physicians Postgraduate Press, Inc.

Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso-occlusive crises in patients with sickle cell disease: a phase III randomized, placebo-controlled, double-blind study of the Gardos channel blocker senicapoc (ICA-17043).

PubMed

Ataga, Kenneth I; Reid, Marvin; Ballas, Samir K; Yasin, Zahida; Bigelow, Carolyn; James, Luther St; Smith, Wally R; Galacteros, Frederic; Kutlar, Abdullah; Hull, James H; Stocker, Jonathan W

2011-04-01

Red blood cell (RBC) hydration is regulated in part by the Ca(2+) -activated K(+) efflux (Gardos) channel. Senicapoc selectively blocks potassium efflux through the Gardos channel, reducing RBC dehydration and haemolysis, and increasing haemoglobin levels in sickle cell disease (SCD). This randomized, placebo-controlled trial was designed to determine the safety and clinical efficacy of senicapoc in SCD patients. One hundred and forty-five patients were randomized to receive senicapoc and 144 patients to receive placebo for 52 weeks. Consistent with a previous study, patients in the senicapoc group had significantly increased haematocrit, haemoglobin, and decreased numbers of both dense erythrocytes and reticulocytes when compared to the placebo group. The unblinded Data Monitoring Committee terminated this study early due to a lack of efficacy when it determined that, despite improvements in anaemia and haemolysis, no significant improvement in the rate of sickle cell painful crises was observed in patients treated with senicapoc compared to those on placebo (0·38 vs. 0·31, respectively). Comparisons of the times to first, second and third crises between the senicapoc and placebo groups were not statistically significant. Nausea and urinary tract infections occurred more frequently in the senicapoc group than placebo. Serious adverse events were similar in the two groups. © 2011 Blackwell Publishing Ltd.

Protective effects of fermented honeybush (Cyclopia intermedia) extract (HU-018) against skin aging: a randomized, double-blinded, placebo-controlled study.

PubMed

Choi, Sun Young; Hong, Ji Yeon; Ko, Eun Jung; Kim, Beom Joon; Hong, Sung-Woon; Lim, Mi Hyoung; Yeon, Sung Hum; Son, Rak Ho

2018-02-01

Oxidative stress and photodamage resulting from ultraviolet radiation exposure play key roles in skin aging. Fermented Cyclopia intermedia, which is used to brew honeybush tea, exerts antioxidant and anti-wrinkle effects by inhibiting reactive oxygen species production and downregulating matrix metalloproteinase activity. This randomized, double-blinded, placebo-controlled study aimed to evaluate the efficacy and safety of fermented honeybush (Cyclopia intermedia) extract (HU-018) for skin rejuvenation. 120 Korean subjects with crow's feet wrinkles were randomized to receive either low-dose extract (400 mg/day), high-dose extract (800 mg/day), or placebo (negative control, only dextran) for 12 weeks. Wrinkles were evaluated using JANUS ® and PRIMO pico ® . Skin elasticity, hydration and transepidermal water loss were measured. Global skin wrinkle grade was significantly improved in both low-dose and high-dose groups compared to placebo group, as well as for skin hydration and elasticity. Both the low- and high-dose groups showed significantly decreased TEWL compared to the placebo group. There were no adverse effects during the entire study period. Our data indicate that HU-018 is effective for improving skin wrinkles, elasticity, and hydration. Therefore, daily supplementation with fermented honeybush could be helpful for protecting against skin aging.

Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial.

PubMed

Amaro, Cynthia M; Bello, Jose A; Jain, Deepak; Ramnath, Alexandra; D'Ugard, Carmen; Vanbuskirk, Silvia; Bancalari, Eduardo; Claure, Nelson

2018-05-01

To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P = .7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P = .22). Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. ClinicalTrials.gov: NCT01751724. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of Cue-Controlled Desensitization, Rational Restructuring, and a Credible Placebo in the Treatment of Speech Anxiety.

ERIC Educational Resources Information Center

Lent, Robert W.; And Others

1981-01-01

The efficacy of cue-controlled desensitization and systematic rational restructuring was compared with a placebo method and a waiting-list control in reducing public speaking and nontargeted anxieties. Cue-controlled desensitization was generally more effective than the other groups in reducing subjective speech anxiety. (Author)

Effects of Plyometric Training and Beta-Alanine Supplementation on Maximal-Intensity Exercise and Endurance in Female Soccer Players

PubMed Central

Rosas, Fabián; Ramírez-Campillo, Rodrigo; Martínez, Cristian; Cañas-Jamet, Rodrigo; McCrudden, Emma; Meylan, Cesar; Moran, Jason; Nakamura, Fábio Y.; Pereira, Lucas A.; Loturco, Irineu; Diaz, Daniela; Izquierdo, Mikel

2017-01-01

Abstract Plyometric training and beta-alanine supplementation are common among soccer players, although its combined use had never been tested. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to compare the effects of a plyometric training program, with or without beta-alanine supplementation, on maximal-intensity and endurance performance in female soccer players during an in-season training period. Athletes (23.7 ± 2.4 years) were assigned to either a plyometric training group receiving a placebo (PLACEBO, n = 8), a plyometric training group receiving beta-alanine supplementation (BA, n = 8), or a control group receiving placebo without following a plyometric training program (CONTROL, n = 9). Athletes were evaluated for single and repeated jumps and sprints, endurance, and change-of-direction speed performance before and after the intervention. Both plyometric training groups improved in explosive jumping (ES = 0.27 to 1.0), sprinting (ES = 0.31 to 0.78), repeated sprinting (ES = 0.39 to 0.91), 60 s repeated jumping (ES = 0.32 to 0.45), endurance (ES = 0.35 to 0.37), and change-of-direction speed performance (ES = 0.36 to 0.58), whereas no significant changes were observed for the CONTROL group. Nevertheless, compared to the CONTROL group, only the BA group showed greater improvements in endurance, repeated sprinting and repeated jumping performances. It was concluded that beta-alanine supplementation during plyometric training may add further adaptive changes related to endurance, repeated sprinting and jumping ability. PMID:28828081

Effects of Plyometric Training and Beta-Alanine Supplementation on Maximal-Intensity Exercise and Endurance in Female Soccer Players.

PubMed

Rosas, Fabián; Ramírez-Campillo, Rodrigo; Martínez, Cristian; Caniuqueo, Alexis; Cañas-Jamet, Rodrigo; McCrudden, Emma; Meylan, Cesar; Moran, Jason; Nakamura, Fábio Y; Pereira, Lucas A; Loturco, Irineu; Diaz, Daniela; Izquierdo, Mikel

2017-09-01

Plyometric training and beta-alanine supplementation are common among soccer players, although its combined use had never been tested. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to compare the effects of a plyometric training program, with or without beta-alanine supplementation, on maximal-intensity and endurance performance in female soccer players during an in-season training period. Athletes (23.7 ± 2.4 years) were assigned to either a plyometric training group receiving a placebo (PLACEBO, n = 8), a plyometric training group receiving beta-alanine supplementation (BA, n = 8), or a control group receiving placebo without following a plyometric training program (CONTROL, n = 9). Athletes were evaluated for single and repeated jumps and sprints, endurance, and change-of-direction speed performance before and after the intervention. Both plyometric training groups improved in explosive jumping (ES = 0.27 to 1.0), sprinting (ES = 0.31 to 0.78), repeated sprinting (ES = 0.39 to 0.91), 60 s repeated jumping (ES = 0.32 to 0.45), endurance (ES = 0.35 to 0.37), and change-of-direction speed performance (ES = 0.36 to 0.58), whereas no significant changes were observed for the CONTROL group. Nevertheless, compared to the CONTROL group, only the BA group showed greater improvements in endurance, repeated sprinting and repeated jumping performances. It was concluded that beta-alanine supplementation during plyometric training may add further adaptive changes related to endurance, repeated sprinting and jumping ability.

Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.

PubMed

Pozzoni, Pietro; Riva, Alessia; Bellatorre, Alessandro Giacco; Amigoni, Maria; Redaelli, Elena; Ronchetti, Anna; Stefani, Mariangela; Tironi, Rosangela; Molteni, Edoardo Ennio; Conte, Dario; Casazza, Giovanni; Colli, Agostino

2012-06-01

Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients. A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for <48 h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of probiotics, lack of informed consent, inability to ingest capsules, and severe pancreatitis. Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment. Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60). In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.

Implant decontamination during surgical peri-implantitis treatment: a randomized, double-blind, placebo-controlled trial.

PubMed

de Waal, Yvonne C M; Raghoebar, Gerry M; Huddleston Slater, James J R; Meijer, Henny J A; Winkel, Edwin G; van Winkelhoff, Arie Jan

2013-02-01

The objective of this randomized, double-blind, placebo-controlled trial was to study the effect of implant surface decontamination with chlorhexidine (CHX)/cetylpyridinium chloride (CPC) on microbiological and clinical parameters. Thirty patients (79 implants) with peri-implantitis were treated with resective surgical treatment consisting of apically re-positioned flap, bone re-contouring and surface debridement and decontamination. Patients were randomly allocated to decontamination with 0.12% CHX + 0.05% CPC (test-group) or a placebo-solution (without CHX/CPC, placebo-group). Microbiological parameters were recorded during surgery; clinical and radiographical parameters were recorded before (pre-) treatment (baseline), and at 3, 6 and 12 months after treatment. Nine implants in two patients in the placebo-group were lost due to severe persisting peri-implantitis. Both decontamination procedures resulted in significant reductions of bacterial load on the implant surface, but the test-group showed a significantly greater reduction than the placebo-group (log 4.21 ± 1.89 versus log 2.77 ± 2.12, p = 0.006). Multilevel analysis showed no differences between both groups in the effect of the intervention on bleeding, suppuration, probing pocket depth and radiographical bone loss over time. Implant surface decontamination with 0.12% CHX + 0.05% CPC in resective surgical treatment of peri-implantitis leads to a greater immediate suppression of anaerobic bacteria on the implant surface than a placebo-solution, but does not lead to superior clinical results. The long-term microbiological effect remains unknown. © 2012 John Wiley & Sons A/S.

Randomized, double-blind, placebo-controlled trial of orlistat for weight loss in adolescents.

PubMed

Maahs, David; de Serna, Daniela Gonzalez; Kolotkin, Ronette L; Ralston, Shawn; Sandate, Jeffrey; Qualls, Clifford; Schade, David S

2006-01-01

To evaluate the efficacy of orlistat to enhance weight loss in obese adolescents. The study was a 6-month randomized, double-blind, placebo-controlled trial to compare the effects of orlistat (120 mg orally 3 times a day) and placebo on reduction of body mass index (BMI). Forty adolescents between 14 and 18 years of age with a mean BMI of 40 kg/m2 entered the protocol between December 2002 and February 2003. Study subjects stayed overnight in the General Clinical Research Center, during which dietary records were reviewed and lifestyle recommendations were given. The study participants received either orlistat (120 mg orally 3 times a day) or placebo and were assessed monthly for 6 months. At 0, 3, and 6 months, fasting laboratory tests were performed. The primary end point was the change in BMI from baseline to 6 months. Secondary outcomes included changes in weight, lean body mass, and results of blood chemistry studies. No statistically significant difference was noted between the 2 study groups for decrease in BMI from baseline to 6 months (P = 0.39). The decrease in BMI within the orlistat group (-1.3 +/- 1.6 kg/m2; P = 0.04) and within the placebo group (-0.8 +/- 3.0 kg/m2; P = 0.02), however, was statistically significant. Laboratory measurements did not differ between the 2 groups. In comparison with the placebo group, the orlistat group had increased adverse events, primarily gastrointestinal symptoms and findings. In this study of obese adolescents, orlistat did not significantly reduce BMI in comparison with placebo at 6 months.

Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial.

PubMed

Havens, Peter L; Stephensen, Charles B; Hazra, Rohan; Flynn, Patricia M; Wilson, Craig M; Rutledge, Brandy; Bethel, James; Pan, Cynthia G; Woodhouse, Leslie R; Van Loan, Marta D; Liu, Nancy; Lujan-Zilbermann, Jorge; Baker, Alyne; Kapogiannis, Bill G; Mulligan, Kathleen

2012-04-01

The study goal was to determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C-telopeptide (CTX) in youth infected with human immunodeficiency virus (HIV) receiving and not receiving combination antiretroviral therapy (cART) containing tenofovir disoproxil fumarate (TDF). This randomized, double-blind, placebo-controlled multicenter trial enrolled HIV-infected youth 18-25 years based on stable treatment with cART containing TDF (n = 118) or no TDF (noTDF; n = 85), and randomized within those groups to vitamin D3, 50 000 IU (n = 102) or placebo (n = 101), administered at 0, 4, and 8 weeks. Outcomes included change in TRP, PTH, BAP, and CTX from baseline to week 12 by TDF/noTDF; and VITD/placebo. At baseline, VITD and placebo groups were similar except those on TDF had lower TRP and higher PTH and CTX. At week 12, 95% in the VITD group had sufficient serum 25-hydroxy vitamin D (25-OHD; ≥20 ng/mL), increased from 48% at baseline, without change in placebo (P < .001). PTH decreased in the TDF group receiving VITD (P = .031) but not in the noTDF group receiving VITD, or either placebo group. The decrease in PTH with VITD in those on TDF occurred with insufficient and sufficient baseline 25-OHD (mean PTH change, -7.9 and -6.2 pg/mL; P = .031 and .053, respectively). In youth on TDF, vitamin D3 supplementation decreased PTH, regardless of baseline 25-OHD concentration. NCT00490412.

Orthostatic responses to nitric oxide synthase inhibition in persons with tetraplegia.

PubMed

Wecht, Jill M; Radulovic, Miroslav; Lafountaine, Michael F; Rosado-Rivera, Dwindally; Zhang, Run-Lin; Bauman, William A

2009-08-01

To determine the effects of 1.0 mg/kg nitro-L-arginine methyl ester (L-NAME) on orthostatic mean arterial pressure (MAP), serum aldosterone, and plasma renin concentrations in persons with chronic tetraplegia compared with nonspinal cord-injured controls. Prospective placebo-controlled intervention study. James J. Peters Veterans Affairs Medical Center. Patients (n=5) with tetraplegia and controls (n=7) participated. The groups were matched for age, height, and weight; the average duration of injury in the tetraplegia group was 22+/-14 years. Subjects with tetraplegia visited the laboratory twice, receiving placebo on day 1 and L-NAME (1.0 mg/kg) on day 2. The agents were infused via an intravenous catheter over 60 minutes with the patient in the supine position. Data were collected during the infusion and then during head-up tilt to 45 degrees for 30 minutes. Control subjects visited the laboratory once for placebo infusion and the head-up tilt maneuver. Orthostatic MAP. Orthostatic MAP was reduced after placebo infusion in subjects with tetraplegia compared with controls (69+/-11 vs 89+/-9 mmHg, respectively; P<.01) and compared with L-NAME infusion (90+/-16 mmHg; P<.01). Orthostatic MAP did not differ when comparing the tetraplegia group with controls after L-NAME infusion. Orthostatic aldosterone levels were increased after placebo compared with L-NAME infusion in persons with tetraplegia; plasma renin levels did not differ among the groups. These data suggest that nitric oxide synthase inhibition may have clinical potential for treatment of orthostatic hypotension in persons with chronic tetraplegia.

Is TENS purely a placebo effect? A controlled study on chronic low back pain.

PubMed

Marchand, S; Charest, J; Li, J; Chenard, J R; Lavignolle, B; Laurencelle, L

1993-07-01

Although high-frequency low-intensity transcutaneous electric nerve stimulation (TENS) has been extensively used to relieve low back pain, experimental studies of its effectiveness have yielded contradictory findings mainly due to methodological problems in pain evaluation and placebo control. In the present study, separate visual analog scales (VAS) were used to measure the sensory-discriminative and motivational-affective components of low back pain. Forty-two subjects were randomly assigned to 1 of 3 groups: TENS, placebo-TENS, and no treatment (control). In order to measure the short-term effect of TENS, VAS pain ratings were taken before and after each treatment session. Also, to measure long-term effects, patients rated their pain at home every 2 h throughout a 3-day period before and 1 week, 3 months and 6 months after the treatment sessions. In comparing the pain evaluations made immediately before and after each treatment session, TENS and placebo-TENS significantly reduced both the intensity and unpleasantness of chronic low back pain. TENS was significantly more efficient than placebo-TENS in reducing pain intensity but not pain unpleasantness. TENS also produced a significant additive effect over repetitive treatment sessions for pain intensity and relative pain unpleasantness. This additive effect was not found for placebo-TENS. When evaluated at home, pain intensity was significantly reduced more by TENS than placebo-TENS 1 week after the end of treatment, but not 3 months and 6 months later. At home evaluation of pain unpleasantness in the TENS group was never different from the placebo-TENS group.(ABSTRACT TRUNCATED AT 250 WORDS)

Women's experiences as members of attention control and experimental intervention groups in a randomized controlled trial.

PubMed

Beal, Claudia C; Stuifbergen, Alexa; Volker, Deborah; Becker, Heather

2009-12-01

Attention control groups are often used in research testing the efficacy of psychosocial and behavioural interventions in order to control for placebo effects. The authors conducted a descriptive qualitative study to investigate how participants viewed their experiences in attention control and experimental intervention groups following a randomized controlled trial for women with fibromyalgia syndrome. Moderately structured interviews were conducted with 18 women (12 from the experimental intervention group and 6 from the attention control group). Members of the control group reported some benefits but few behavioural changes as a result of participating in the RCT, and some participants expressed disappointment at not receiving the intervention. Perceptions of changes in attitudes towards fibromyalgia syndrome and behaviours reported by the intervention group appear to be consistent with the theory underlying the intervention. Possible placebo effects identified in both groups include negative and positive social interactions with other participants.

Effects of the Preoperative Administration of Dexketoprofen Trometamol on Pain and Swelling After Implant Surgery: A Randomized, Double-Blind Controlled Trial.

PubMed

Sánchez-Pérez, Arturo; Muñoz-Peñalver, Jesús; Moya-Villaescusa, María José; Sánchez-Matás, Carmen

2018-04-01

The fear of postoperative pain is often mentioned by patients as one of the factors that is most frequently associated with dental implants. To reduce this factor, a single oral dose of 25 mg dexketoprofen trometamol (DKT) or placebo was administered 15 minutes before implant surgery. One hundred patients who required single-implant treatments were randomly assigned to 1 of 2 blinded groups. The patients in the test group were given 25 mg DKT (DKT group), and those in the control group were given 500 mg vitamin C as a placebo (PLACEBO group). A subjective visual analogue scale of 100 mm in length was used to evaluate pain. Inflammation and complications were assessed using a 5-point Likert scale. An analysis of variance, t-tests, and a Mann-Whitney U test were performed. Among the 100 patients, 83 completed the study (there were 8 dropouts in the PLACEBO group and 9 in the DKT group). The patients who received DKT reported a lower pain intensity during the immediate postoperative period. The inflammatory response was weaker in the DKT group than the control group at 48 hours, but bleeding was greater. There were no other complications in either of the groups. In conclusion, the preemptive use of 25 mg soluble DKT administered orally 15 minutes before implant surgery can reduce the severity of immediate postoperative pain.

Electric field-navigated transcranial magnetic stimulation for chronic tinnitus: a randomized, placebo-controlled study.

PubMed

Sahlsten, Hanna; Virtanen, Juuso; Joutsa, Juho; Niinivirta-Joutsa, Katri; Löyttyniemi, Eliisa; Johansson, Reijo; Paavola, Janika; Taiminen, Tero; Sjösten, Noora; Salonen, Jaakko; Holm, Anu; Rauhala, Esa; Jääskeläinen, Satu K

2017-09-01

Repetitive transcranial magnetic stimulation (rTMS) may alleviate tinnitus. We evaluated effects of electric field (E-field) navigated rTMS targeted according to tinnitus pitch. No controlled studies have investigated anatomically accurate E-field-rTMS for tinnitus. Effects of E-field-rTMS were evaluated in a prospective randomised placebo-controlled 6-month follow-up study on parallel groups. Patients received 10 sessions of 1 Hz rTMS or placebo targeted to the left auditory cortex corresponding to tonotopic representation of tinnitus pitch. Effects were evaluated immediately after treatment and at 1, 3 and 6 months. Primary outcome measures were visual analogue scores (VAS 0-100) for tinnitus intensity, annoyance and distress, and the Tinnitus Handicap Inventory (THI). Thirty-nine patients (mean age 50.3 years). The mean tinnitus intensity (F 3  = 15.7, p < 0.0001), annoyance (F 3  = 8.8, p = 0.0002), distress (F 3  = 9.1, p = 0.0002) and THI scores (F 4  = 13.8, p < 0.0001) decreased in both groups over time with non-significant differences between the groups. After active rTMS, 42% and 37% of the patients showed excellent response at 1 and 3 months against 15% and 10% in the placebo group (p = 0.082 and p = 0.065). Despite the significant effects of rTMS on tinnitus, differences between active and placebo groups remained non-significant, due to large placebo-effect and wide inter-individual variation.

Steroid injection for osteoarthritis of the hip: a randomized, double-blind, placebo-controlled trial.

PubMed

Lambert, Robert G W; Hutchings, Edna J; Grace, Michael G A; Jhangri, Gian S; Conner-Spady, Barbara; Maksymowych, Walter P

2007-07-01

To determine the efficacy of fluoroscopically guided corticosteroid injection for hip osteoarthritis (OA) in a randomized, double-blind, placebo-controlled trial. Fifty-two patients with symptomatic hip OA were randomly allocated to receive placebo (10 mg bipuvicaine, 2 ml saline) (n = 21) or corticosteroid treatment (10 mg bipuvicaine, 40 mg triamcinolone hexacetonide) (n = 31). Patients were followed up for 1, 2, 3, and 6 months. The primary outcome measure was the pain improvement response, defined as a 20% decrease in the Western Ontario and McMaster Universities OA Index (WOMAC) pain score (on 5 100-mm visual analog scales [VAS]) (WOMAC20) from baseline to 2 months postinjection. Secondary outcomes were a 50% decrease in the WOMAC pain score (WOMAC50), changes in other WOMAC subscale scores, patient's global assessment of health (on a 100-mm VAS), and Short Form 36 (SF-36) quality of life indices. Analyses were based on the intent-to-treat principle. The mean WOMAC pain score fell 49.2% (decreasing from 310.1 mm to 157.4 mm) at 2 months postinjection in patients receiving corticosteroid, compared with a decrease of 2.5% (from 314.3 mm to 306.5 mm) in the placebo group (P < 0.0001). The proportion of WOMAC20 responders at 2 months' followup was significantly higher in the corticosteroid group (67.7%) compared with the placebo group (23.8%) (P = 0.004); similar proportions of WOMAC50 responders were observed between groups (61.3% in the corticosteroid group versus 14.3% in the placebo group; P = 0.001). Response differences were maintained at 3 months' followup (58.1% responders in the corticosteroid group versus 9.5% responders in the placebo group; P = 0.004). Significant differences in the WOMAC stiffness and physical function scores (P < 0.0001), patient's global health scores (P = 0.005), and SF-36 physical component scores (P = 0.04) were observed, with patients in the corticosteroid group showing greater improvements. There were no differences in the frequency of adverse events between groups. This placebo-controlled trial confirms that corticosteroid injection can be an effective treatment of pain in hip OA, with benefits lasting up to 3 months in many cases. Future studies should address questions related to the benefits of repeated steroid injection and the effects of this treatment on disease modification.

Effects of placebos without deception compared with no treatment: protocol for a systematic review and meta-analysis.

PubMed

Petkovic, Grace; Charlesworth, James E G; Kelley, John; Miller, Franklin; Roberts, Nia; Howick, Jeremy

2015-11-26

Placebos have long provided a robust control for evaluating active pharmacological preparations, but frequently demonstrate a variable therapeutic effect when delivered in double-blinded placebo-controlled trials. Delivery of placebos as treatment alone has been considered unethical, as it has been thought that deception is essential for their effect. However, recent evidence suggests that clinical benefit can be derived from placebos delivered without deception (unblinded/open-label) manner. Here, we present a protocol for the first systematic review and meta-analysis of studies of the effects of non-deceptive placebos compared with no treatment. This protocol will compare the effect of placebos delivered non-deceptively to no treatment. It will also assess the methods of delivery used for non-deceptive placebos. Studies will be sought through relevant database searches and will include those within disease settings and those among healthy controls. To be included, trials must include both non-deceptive (open-label) placebo and no treatment groups. All data extraction and analysis will be conducted by two independent reviewers. The analysis will evaluate any differences in outcome measures between the non-deceptive placebo and no treatment groups. Outcome measures will be the clinically-relevant outcomes detailed in the primary papers. The delivery methods, such as verbal instructions, which may provide positive expectations and outcomes, of non-deceptive placebos will also be assessed. Each study will be comprehensively assessed for bias. Subgroup analyses will identify any discrepancies among heterogeneous data. This review does not require ethical approval. The completed review will be widely disseminated by publication and social media where appropriate. This protocol has been registered on PROSPERO (2015:CRD42015023347). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Treatment of canine parvoviral enteritis with interferon-omega in a placebo-controlled field trial.

PubMed

de Mari, K; Maynard, L; Eun, H M; Lebreux, B

2003-01-25

The clinical efficacy of a recombinant feline interferon (IFN) (type omega) was evaluated under field conditions for the treatment of dogs with parvoviral enteritis. In this multicentric, double-blind, placebo-controlled trial, 94 dogs from one to 28 months old were randomly assigned to two groups which were treated intravenously either with IFN (2.5 million units/kg) or placebo once a day for three consecutive days, and monitored for clinical signs and mortality for 10 days. Each dog received individual supportive treatment The data from 92 interpretable cases (43 IFN-treated and 49 placebo) showed that the clinical signs of the IFN-treated animals improved significantly in comparison with the control animals, and that there were only three deaths in the IFN group compared with 14 deaths in the placebo group (P = 0.0096) corresponding to a 4.4-fold reduction. Alternative analyses of the data taking into account the prior vaccination status of the dogs against canine parvovirus suggested that the IFN therapy resulted in a 6.4-fold reduction in mortality (P = 0.044) in the unvaccinated cohort, a significant reduction when compared with the vaccinated cohort.

Is ginger effective for the treatment of irritable bowel syndrome? A double blind randomized controlled pilot trial.

PubMed

van Tilburg, Miranda A L; Palsson, Olafur S; Ringel, Yehuda; Whitehead, William E

2014-02-01

Ginger is one of the most commonly used herbal medicines for irritable bowel syndrome (IBS) but no data exists about its effectiveness. Double blind randomized controlled trial. University of North Carolina, Chapel Hill, North Carolina, USA. Forty-five IBS patients were randomly assigned to three groups: placebo, 1g of ginger, and 2g of ginger daily for 28 days. The IBS severity scale (IBS-SS) was administered, as well as adequate relief of symptoms scale. A responder was defined as having at least 25% reduction in IBS-SS post-treatment. There were 57.1% responders to placebo, 46.7% to 1g and 33.3% to 2g of ginger. Adequate relief was reported by 53.3% on placebo and 53.3% in both ginger groups combined. Side effects were mild and reported by 35.7% in the placebo and 16.7% in the ginger groups. This double blind randomized controlled pilot study suggests ginger is well tolerated but did not perform better than placebo. Larger trials are needed before any definitive conclusions can be drawn. Copyright © 2014 Elsevier Ltd. All rights reserved.

A pilot randomized placebo-controlled trial of adjunctive aripiprazole for chronic PTSD in US military Veterans resistant to antidepressant treatment.

PubMed

Naylor, Jennifer C; Kilts, Jason D; Bradford, Daniel W; Strauss, Jennifer L; Capehart, Bruce P; Szabo, Steven T; Smith, Karen D; Dunn, Charlotte E; Conner, Kathryn M; Davidson, Jonathan R T; Wagner, Henry Ryan; Hamer, Robert M; Marx, Christine E

2015-05-01

Many individuals with post-traumatic stress disorder (PTSD) experience persistent symptoms despite pharmacological treatment with antidepressants. Several open-label monotherapy and adjunctive studies have suggested that aripiprazole (a second-generation antipsychotic) may have clinical utility in PTSD. However, there have been no randomized placebo-controlled trials of aripiprazole use for PTSD. We thus conducted a pilot randomized controlled trial of adjunctive aripiprazole versus placebo among Veterans with chronic PTSD serving in the US military since 11 September 2001 to assess the feasibility, safety, tolerability, and therapeutic potential of aripiprazole. Sixteen Veterans were randomized, and 14 completed at least 4 weeks of the study; 12 completed the entire 8-week trial. Outcome measures included the Clinician-Administered PTSD Scale (CAPS), PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores. Aripiprazole was well-tolerated in this cohort, and improvements in CAPS, PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores were as hypothesized. Although CAPS change scores did not reach statistical significance, aripiprazole outperformed placebo by 9 points on the CAPS in the last observation carried forward analysis compared with the placebo group (n = 7 per group), and by 20 points in the group randomized to aripiprazole that completed the entire study (n = 5) compared with the placebo group (n = 7). Results suggest promise for aripiprazole as an adjunctive strategy for the treatment of PTSD.

Effect of blue-blocking glasses in major depressive disorder with sleep onset insomnia: A randomized, double-blind, placebo-controlled study.

PubMed

Esaki, Yuichi; Kitajima, Tsuyoshi; Takeuchi, Ippei; Tsuboi, Soji; Furukawa, Osamu; Moriwaki, Masatsugu; Fujita, Kiyoshi; Iwata, Nakao

2017-01-01

Blue wavelengths form the portion of the visible electromagnetic spectrum that most potently regulates circadian rhythm. We hypothesized that wearing blue-blocking (BB) glasses in the evening may influence circadian rhythm disturbances in patients with major depressive disorder (MDD), resulting in improved sleep and mood. We used a randomized placebo-controlled double-blinded design. Patients with MDD with sleep onset insomnia were randomly assigned to wearing either BB glasses or clear glasses (placebo). Patients were instructed to wear the glasses from 20:00 hours until bedtime for 2 weeks. We assessed sleep state (sleep quality on a visual analog scale, the Morningness-Eveningness Questionnaire [MEQ], and a sleep diary) and depressive symptoms at baseline and after 2 weeks. Data were analyzed with a full analysis set. In total, 20 patients were randomly assigned to the BB and placebo groups (BB group, n = 10; placebo group, n = 10). There were three dropouts (BB group, n = 1; placebo group, n = 2). At baseline, sleep quality, sleep latency (assessed via a sleep diary), and antipsychotics use differed between the groups. To take account of these differences, the baseline sleep state or depressive symptoms and antipsychotics use were used as covariates in the later analysis. The change scores for sleep quality did not show a significant improvement in the BB group compared with the placebo group (mean [standard deviation, SD] scores for BB versus placebo: 36.1 [31.7] versus 16.2 [15.1], p = 0.43), although half of the BB group showed a clear improvement in sleep quality. The change in MEQ scores did not significantly differ between the groups (p = 0.14), although there was a trend of a shift to morning type in the BB group (3.10 [4.95] points) and to evening type in the placebo group (0.50 [3.89] points). There were no statistically significant changes in depressive symptoms in either group. Across both groups, 40% of the participants reported pain or discomfort from wearing the glasses, which were available in only one size. Thus, the failure to find significant differences may have resulted from the glasses used in this study. Glasses fitted to individual patients may improve efficacy and safety. Replication of the study with a larger sample size and size-adjustable glasses is needed.

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2012-11-01

randomized placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer...and that this risk differed between men who took finasteride versus those who took the placebo. The strongest association was seen for a cluster of 9...SNPs in NPAS2, which was associated with total prostate cancer risk in the finasteride group but not in the placebo group. The most significant NPAS2

Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial.

PubMed

Kumar, Ashok; Begum, Nargis; Prasad, Sudha; Aggarwal, Sarita; Sharma, Shashi

2014-11-01

To study the impact of administration of dydrogesterone in early pregnancy on pregnancy outcome and its correlation with Th1 and Th2 cytokine levels. Double-blind, randomized, placebo-controlled study. A medical college and its associated hospital. Women with either: [1] a history of idiopathic recurrent pregnancy loss (RPL), in either a dydrogesterone group or a placebo group, or [2] no history of miscarriage. Dydrogesterone 20 mg/day from confirmation of pregnancy to 20 weeks of gestation. Occurrence of another pregnancy loss and concentrations of T-helper (Th)1 (interferon-γ and tumor necrosis factor-α) and Th2 (interleukin (IL)-4 and IL-10) cytokines in serum at recruitment (4-8 weeks of gestation) and at abortion or 20 weeks of gestation, using commercially available ELISA kits. Occurrence of another abortion after 3 consecutive abortions was significantly higher (29 of 173; 16.76%) in women with RPL compared with healthy pregnant controls (6 of 174; 3.45%). Risk of occurrence of miscarriage after 3 abortions was 2.4 times higher in the placebo group vs. the treatment group (risk ratio=2.4, 95% CI=1.3-5.9). Mean gestational age at delivery (excluding those aborted before 20 weeks of gestation) increased significantly in the dydrogesterone group (38.01±1.96 weeks) compared with the placebo group (37.23±2.41 weeks). Baby weight was significantly lower in the placebo group (2421.4±321.6 g) compared with the healthy pregnant controls (2545.3±554.3 g). At recruitment, serum IL-4 and tumor necrosis factor-α levels were significantly lower in the RPL group compared with the healthy pregnant controls. However, serum interferon-γ level was significantly higher in the RPL group (8.87±0.72 pg/mL) compared with the healthy pregnant controls (8.08±1.27 pg/mL). The present study supports the use of dydrogesterone in women with recurrent abortions to improve pregnancy outcome, such as a reduction in abortions and improved gestational age and baby weight at delivery. However, these outcomes were not modulated by Th1 and Th2 cytokine production. CTRI/2010/091/000373. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Double-blind trial of recombinant gamma-interferon versus placebo in the treatment of rheumatoid arthritis. 1989.

PubMed

Cannon, Grant W; Pincus, Seth H; Emkey, Ronald D; Denes, Alex; Cohen, Selwyn A; Wolfe, Frederick; Saway, P Anthony; Jaffer, Adrian M; Weaver, Arthur L; Cogen, Lewis; Schindler, John D

2008-02-01

One hundred five patients were enrolled in a 12-week, randomized, prospective, double-blind, placebo-controlled trial of recombinant human gamma-interferon (rHu gamma-IFN) for the treatment of rheumatoid arthritis. Fifty-four patients received rHu gamma-IFN and 51 received placebo. Forty-two patients in each group completed the 12-week trial. Some clinical improvement occurred in both groups of patients. Although the improvement with rHu gamma-IFN was greater than that with placebo, the differences were generally not statistically significant.

Efficacy of Celecoxib for Early Postoperative Pain Management in Hip Arthroscopy: A Prospective Randomized Placebo-Controlled Study.

PubMed

Kahlenberg, Cynthia A; Patel, Ronak M; Knesek, Michael; Tjong, Vehniah K; Sonn, Kevin; Terry, Michael A

2017-06-01

To determine whether 400 mg of celecoxib administered 1 hour before hip arthroscopy surgery would reduce pain, provide reduction in overall narcotic consumption, and lead to more rapid discharge from recovery rooms. Ninety-eight patients were randomized to either the celecoxib group (n = 50) or the placebo group (n = 48). An a priori power analysis was done set to detect a difference of 0.50 on the visual analog scale (VAS), based on the senior author's preference. The number of patients planned for recruitment was rounded up to 100 to allow for flexibility in the study. Inclusion criteria were any patient at least 18 years old who underwent hip arthroscopy surgery performed by the senior author. All patients had less than Tönnis grade 2 arthritis. Exclusion criteria were allergy to sulfa-based drugs, prior adverse reaction to celecoxib, or patients who were on chronic narcotics for whom alternative pain management regimens were arranged before surgery. Randomization was performed on a 1:1 basis in blocks of 10 using sealed envelopes stating celecoxib or placebo. One hour before surgery, all patients received either 400 mg celecoxib or placebo. Patients were evaluated using a VAS preoperatively, immediately postoperatively, and at 1 and 2 hours postoperatively. Time from the operating room to "ready for discharge" and number of morphine equivalents of narcotic medication required in the postanesthesia care unit were recorded. Age and preoperative VAS were similar between the celecoxib and placebo control group, with average ages of 34.2 ± 11.9 and 35.8 ± 11.6 (P = .27) and preoperative VAS of 2.1 ± 2.06 and 2.3 ± 1.98 (P = .29), respectively. The celecoxib group had 26 females and 24 males, whereas the placebo group had 29 females and 19 males (P = .42). The most common surgical procedures were labral repair (31 patients in the celecoxib group and 29 patients in the placebo group), and labral repair with acetabular osteoplasty (13 patients in the celecoxib group and 11 patients in the placebo group). There were no significant differences in procedures performed between the 2 groups (P > .05). At 1 hour postoperatively, patients who received celecoxib had a lower pain score that was statistically significant compared with the placebo group (4.6 vs 5.4, P = .03). There was a significant difference in discharge time between patients who received celecoxib and the control group (152.9 minutes vs 172.9 minutes, P = .04). There was no significant difference found in morphine equivalents consumed in the postanesthesia care unit between the 2 groups (15.3 vs 15.4, P = .48). A preoperative dose of 400 mg of celecoxib led to statistically significantly reduced patient-reported pain on the VAS in the acute postoperative period after hip arthroscopy surgery, though the difference is not likely clinically significant. There was a significantly shorter time to discharge in patients who received celecoxib versus placebo. Level I, randomized controlled trial. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Metformin extended release treatment of adolescent obesity: a 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up.

PubMed

Wilson, Darrell M; Abrams, Stephanie H; Aye, Tandy; Lee, Phillip D K; Lenders, Carine; Lustig, Robert H; Osganian, Stavroula V; Feldman, Henry A

2010-02-01

Metformin has been proffered as a therapy for adolescent obesity, although long-term controlled studies have not been reported. To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release (XR) therapy will reduce body mass index (BMI) in obese adolescents, as compared with placebo. Multicenter, randomized, double-blind, placebo-controlled clinical trial. The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007. Obese (BMI > or = 95th percentile) adolescents (aged 13-18 years) were randomly assigned to the intervention (n = 39) or placebo groups. Intervention Following a 1-month run-in period, subjects following a lifestyle intervention program were randomized 1:1 to 48 weeks' treatment with metformin hydrochloride XR, 2000 mg once daily, or an identical placebo. Subjects were monitored for an additional 48 weeks. Main Outcome Measure Change in BMI, adjusted for site, sex, race, ethnicity, and age and metformin vs placebo. After 48 weeks, mean (SE) adjusted BMI increased 0.2 (0.5) in the placebo group and decreased 0.9 (0.5) in the metformin XR group (P = .03). This difference persisted for 12 to 24 weeks after cessation of treatment. No significant effects of metformin on body composition, abdominal fat, or insulin indices were observed. Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program. clinicaltrials.gov Identifiers: NCT00209482 and NCT00120146.

Effect of preoperative medications on the efficacy of inferior alveolar nerve block in patients with irreversible pulpitis: A placebo-controlled clinical study

PubMed Central

Jena, Amit; Shashirekha, Govind

2013-01-01

Background: The purpose of this prospective, randomized, double-blind, placebo-controlled study was to compare the effect of the administration of preoperative ibuprofen, ketorolac, combination of etodolac with paracetamol and combination of aceclofenac with paracetamol versus placebo for the potential increased effectiveness of the inferior alveolar nerve block [IANB] anesthesia. Materials and Methods: A total of 100 endodontic emergency patients in moderate to severe pain diagnosed with irreversible pulpitis of a mandibular posterior tooth randomly received, in a double-blind manner, either a drug or placebo 30 minutes before the administration of a conventional IANB. Cold testing was done before administration of anesthesia to determine level of pain using Heft-Parker Visual Analogue Scale (VAS) score. Success was defined as no pain or pain (VAS) on access or initial instrumentation. Results: Overall success was 54% for all the groups. Success was highest (70%) for the ketorolac group, 55% for both ibuprofen group and combination of aceclofenac with paracetamol group, 50% for combination of etodolac with paracetamol group, and 40% for the placebo group. Conclusions: Under the conditions of this study, the use of preoperative medication did improve the anesthetic efficacy of IANB for the treatment of teeth diagnosed with irreversible pulpitis but not significantly. PMID:23716973

Effect of preoperative medications on the efficacy of inferior alveolar nerve block in patients with irreversible pulpitis: A placebo-controlled clinical study.

PubMed

Jena, Amit; Shashirekha, Govind

2013-03-01

The purpose of this prospective, randomized, double-blind, placebo-controlled study was to compare the effect of the administration of preoperative ibuprofen, ketorolac, combination of etodolac with paracetamol and combination of aceclofenac with paracetamol versus placebo for the potential increased effectiveness of the inferior alveolar nerve block [IANB] anesthesia. A total of 100 endodontic emergency patients in moderate to severe pain diagnosed with irreversible pulpitis of a mandibular posterior tooth randomly received, in a double-blind manner, either a drug or placebo 30 minutes before the administration of a conventional IANB. Cold testing was done before administration of anesthesia to determine level of pain using Heft-Parker Visual Analogue Scale (VAS) score. Success was defined as no pain or pain (VAS) on access or initial instrumentation. Overall success was 54% for all the groups. Success was highest (70%) for the ketorolac group, 55% for both ibuprofen group and combination of aceclofenac with paracetamol group, 50% for combination of etodolac with paracetamol group, and 40% for the placebo group. Under the conditions of this study, the use of preoperative medication did improve the anesthetic efficacy of IANB for the treatment of teeth diagnosed with irreversible pulpitis but not significantly.

Ingestion of hyaluronans (molecular weights 800 k and 300 k) improves dry skin conditions: a randomized, double blind, controlled study.

PubMed

Kawada, Chinatsu; Yoshida, Takushi; Yoshida, Hideto; Sakamoto, Wakako; Odanaka, Wataru; Sato, Toshihide; Yamasaki, Takeshi; Kanemitsu, Tomoyuki; Masuda, Yasunobu; Urushibata, Osamu

2015-01-01

Hyaluronan (HA) has been increasingly used as a dietary supplement to improve the skin. However, the effect of ingested HA may depend on its molecular weight (MW) because its physiological activities in the body vary with its MW. In this study, we examined the effects of ingested HA with varying MW on the skin. In this randomized, double blind, placebo controlled study, 61 subjects with dry skin received oral HA (120 mg/day), of MWs 800 k and 300 k or placebo, for 6 weeks. The skin moisture contents of the first two groups increased more than those of the placebo group during the ingestion period. In addition, group HA 300 k exhibited significant improvements in skin moisture content 2 weeks after ingestion ended compared with the placebo group. A questionnaire survey about subjective facial aging symptoms showed that the HA treated groups exhibited significantly improved the skin condition compared with the placebo treated group. Furthermore, dermatologists objectively evaluated the clinical symptoms of the facial and whole body skin, showing that no adverse events were related to daily ingestion of HA. This study shows that both of ingesting HAs (MWs 800 k and 300 k) improved the skin condition by increasing the moisture content.

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial

PubMed Central

Moll, Etelka; Bossuyt, Patrick M M; Korevaar, Johanna C; Lambalk, Cornelis B; van der Veen, Fulco

2006-01-01

Objective To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. Design Randomised clinical trial. Setting Multicentre trial in 20 Dutch hospitals. Participants 228 women with polycystic ovary syndrome. Interventions Clomifene citrate plus metformin or clomifene citrate plus placebo. Main outcome measure The primary outcome measure was ovulation. Secondary outcome measures were ongoing pregnancy, spontaneous abortion, and clomifene resistance. Results 111 women were allocated to clomifene citrate plus metformin (metformin group) and 114 women were allocated to clomifene citrate plus placebo (placebo group). The ovulation rate in the metformin group was 64% compared with 72% in the placebo group, a non-significant difference (risk difference - 8%, 95% confidence interval - 20% to 4%). There were no significant differences in either rate of ongoing pregnancy (40% v 46%; - 6%, - 20% to 7%) or rate of spontaneous abortion (12% v 11%; 1%, - 7% to 10%). A significantly larger proportion of women in the metformin group discontinued treatment because of side effects (16% v 5%; 11%, 5% to 16%). Conclusion Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome. Trial registration Current Controlled Trials ISRCTN55906981 [controlled-trials.com]. PMID:16769748

Treatment discontinuation and tolerability as a function of dose and titration of duloxetine in the treatment of major depressive disorder.

PubMed

Harada, Eiji; Shirakawa, Osamu; Satoi, Yoichi; Marangell, Lauren B; Escobar, Rodrigo

2016-01-01

We sought to better understand how dose and titration with duloxetine treatment may impact tolerability and treatment discontinuation in patients with major depressive disorder. We investigated Phase III duloxetine trials. Group 1 was a single placebo-controlled study with a 20 mg initial dose and a slow titration to 40 and 60 mg. Group 2 was a single study with a 40 mg initial dose and final "active" doses of 40 and 60 mg (5 mg control group), with 1-week titration. Group 3 consisted of eight placebo-controlled studies with starting doses of 40, 60, and 80 mg/day with minimal titration (final dose 40-120 mg/day). Tolerability was measured by rate of discontinuation due to adverse events (DCAE). The DCAE in Group 1 were 3.6% in the 60 mg group, 3.3% in the 40 mg group, and 3.2% in the placebo group. In Group 2, the DCAE were 15.0% in the 60 mg group, 8.1% in the 40 mg group, and 4.9% in the 5 mg group. In Group 3, the DCAE were 9.7% and 4.2% in the duloxetine and placebo groups, respectively. This study suggests that starting dose and titration may have impacted tolerability and treatment discontinuation. A lower starting dose of duloxetine and slower titration may contribute to improving treatment tolerability for patients with major depressive disorder.

Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study.

PubMed

Hotta, N; Toyota, T; Matsuoka, K; Shigeta, Y; Kikkawa, R; Kaneko, T; Takahashi, A; Sugimura, K; Koike, Y; Ishii, J; Sakamoto, N

2001-10-01

The purpose of this study was to evaluate the efficacy of fidarestat, a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy. A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity, F-wave minimum latency, F-wave conduction velocity (FCV), and median sensory nerve conduction velocity (forearm and distal), as well as an assessment of subjective symptoms. Over the course of the study, five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group, whereas no measure showed significant deterioration. In contrast, in the placebo group, no electrophysiological measure was improved, and one measure significantly deteriorated (i.e., median nerve FCV). At the study conclusion, the fidarestat-treated group was significantly improved compared with the placebo group in two electrophysiological measures (i.e., median nerve FCV and minimal latency). Subjective symptoms (including numbness, spontaneous pain, sensation of rigidity, paresthesia in the sole upon walking, heaviness in the foot, and hypesthesia) benefited from fidarestat treatment, and all were significantly improved in the treated versus placebo group at the study conclusion. At the dose used, fidarestat was well tolerated, with an adverse event profile that did not significantly differ from that seen in the placebo group. The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy.

Influence of loxoprofen use on recovery from naturally acquired upper respiratory tract infections: a randomized controlled trial.

PubMed

Goto, Masashi; Kawamura, Takashi; Shimbo, Takuro; Takahashi, Osamu; Ando, Masahiko; Miyaki, Koichi; Nohara, Takahiko; Watanabe, Hidetsuna; Suzuki, Isamu; Aono, Mitsuru

2007-01-01

To investigate whether loxoprofen, one of the nonsteroidal anti-inflammatory drugs, prolongs the recovery process of naturally acquired upper respiratory tract infections (URTIs) in the clinical setting. A double-blind, randomized, placebo-controlled trial was conducted in 23 outpatient facilities in Japan. Patients aged 18 through 65 years suffering from URTIs were randomly assigned to receive loxoprofen or its placebo. The primary outcome was duration of illness in days. A total of 174 patients were available for the analyses. Duration of illness was 8.94 +/- 3.20 days in the loxoprofen group compared to 8.39 +/- 3.39 days in the placebo group (P=.19). The number of days with limited daily activities was fewer in the loxoprofen group than in the placebo group (2.12 +/- 2.05 days vs. 2.68 +/- 2.54 days, P=.17). Although severe symptoms were less frequent on days 1, 2, and 3 in the loxoprofen group (27%, 33%, and 29%, respectively) than in the placebo group (32%, 39%, and 37%, respectively), symptoms were more frequent on days 6 through 12 in the loxoprofen group (difference, 5-13%). Adverse events were more common in the loxoprofen group (9.5% vs. 1.1%, P=.051). Loxoprofen did not significantly modify the recovery process of URTIs except for a slight tendency to delay.

Cyclosporin treatment for rheumatoid arthritis: a placebo controlled, double blind, multicentre study.

PubMed Central

van Rijthoven, A W; Dijkmans, B A; Goei The, H S; Hermans, J; Montnor-Beckers, Z L; Jacobs, P C; Cats, A

1986-01-01

The efficacy and safety of cyclosporin for patients with rheumatoid arthritis (RA) were assessed in a six month double blind, placebo controlled, multicentre study. The initial dosage of the drug was 10 mg/kg daily for two months. There were many discontinuations in both the cyclosporin group (eight out of 17) and the placebo group (six out of 19). Of the patients who completed the six months of therapy, those who had received cyclosporin showed a significant improvement in the number of swollen joints, the Ritchie articular index, and pain at active movement and at rest, compared not only with their condition at the start of the study, but also with the end results of the placebo group. Major adverse reactions to the drug were gastrointestinal disturbances and nephrotoxicity, which were probably due to the relatively high dosages of cyclosporin given in combination with non-steroidal anti-inflammatory drugs. PMID:3532966

A double-blind, placebo-controlled trial of sibutramine for clozapine-associated weight gain.

PubMed

Henderson, D C; Fan, X; Copeland, P M; Borba, C P; Daley, T B; Nguyen, D D; Zhang, H; Hayden, D; Freudenreich, O; Cather, C; Evins, A E; Goff, D C

2007-02-01

This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine-associated weight gain. This was a 12-week double-blind, placebo controlled, randomized trial of sibutramine for weight loss in obese clozapine-treated schizophrenia or schizoaffective disorder subjects. Ten patients were enrolled into the placebo group and 11 patients into the sibutramine group. There were no significant baseline differences between the two groups on age, gender, education, ethnicity, diagnosis, weight, body mass index (BMI), and blood pressure. At week 12, there were no significant differences in changes in weight, BMI, abdominal and waist circumferences, Hba1c, fasting glucose, or cholesterol levels. Sibutramine treatment did not show significant weight loss compared with placebo in clozapine-treated patients with schizophrenia or schizoaffective disorder. Further research with a larger sample size and longer follow-up duration is warranted.

The use of Lactobacillus GG in irritable bowel syndrome in children: a double-blind randomized control trial.

PubMed

Bauserman, Melissa; Bausserman, Melissa; Michail, Sonia

2005-08-01

To determine whether oral administration of the probiotic Lactobacillus GG under randomized, double-blinded, placebo-controlled conditions would improve symptoms of irritable bowel syndrome (IBS) in children. Fifty children fulfilling the Rome II criteria for IBS were given Lactobacillus GG or placebo for 6 weeks. Response to therapy was recorded and collected on a weekly basis using the Gastrointestinal Symptom Rating Scale (GSRS). Lactobacillus GG was not superior to placebo in relieving abdominal pain (40.0% response rate in the placebo group vs 44.0% in the Lactobacillus GG group; P=.774). There was no difference in the other gastrointestinal symptoms, except for a lower incidence of perceived abdominal distention (P=.02 favoring Lactobacillus GG). Lactobacillus GG was not superior to placebo in the treatment of abdominal pain in children with IBS but may help relieve such symptoms as perceived abdominal distention.

Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU).

PubMed

Jull, Andrew; Wadham, Angela; Bullen, Chris; Parag, Varsha; Kerse, Ngaire; Waters, Jill

2017-11-24

Objective  To determine the effect of low dose aspirin on ulcer healing in patients with venous leg ulcers. Design  Pragmatic, community based, parallel group, double blind, randomised controlled trial. Setting  Five community nursing centres in New Zealand. Participants  251 adults with venous leg ulcers who could safely be treated with aspirin or placebo: 125 were randomised to aspirin and 126 to placebo. Interventions  150 mg oral aspirin daily or matching placebo for up to 24 weeks treatment, with compression therapy as standard background treatment. Main outcome measures  The primary outcome was time to complete healing of the reference ulcer (largest ulcer if more than one ulcer was present). Secondary outcomes included proportion of participants healed, change in ulcer area, change in health related quality of life, and adverse events. Analysis was by intention to treat. Results  The median number of days to healing of the reference ulcer was 77 in the aspirin group and 69 in the placebo group (hazard ratio 0.85, 95% confidence interval 0.64 to 1.13, P=0.25). The number of participants healed at the endpoint was 88 (70%) in the aspirin group and 101 (80%) in the placebo group (risk difference -9.8%, 95% confidence interval -20.4% to 0.9%, P=0.07). Estimated change in ulcer area was 4.1 cm 2 in the aspirin group and 4.8 cm 2 in the placebo group (mean difference -0.7 cm 2 , 95% confidence interval -1.9 to 0.5 cm 2 , P=0.25). 40 adverse events occurred among 29 participants in the aspirin group and 37 adverse events among 27 participants in the placebo group (incidence rate ratio 1.1, 95% confidence interval 0.7 to 1.7, P=0.71). Conclusion  Our findings do not support the use of low dose aspirin as adjuvant treatment for venous leg ulcers. Trial registration  ClinicalTrials.gov NCT02158806. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Safety and immunogenicity of a killed Leishmania (L.) amazonensis vaccine against cutaneous leishmaniasis in Colombia: a randomized controlled trial.

PubMed

Vélez, I D; del Pilar Agudelo, S; Arbelaez, M P; Gilchrist, K; Robledo, S M; Puerta, J A; Zicker, F; Berman, J; Modabber, F

2000-01-01

The safety and immunogenicity of an intramuscular (i.m.) and intradermal (ID) formulation of autoclaved Leishmania (Leishmania) amazonensis vaccine was evaluated in 296 volunteers in a randomized, placebo-controlled, double-blind trial in Colombia. There were 4 vaccination groups: i.m. vaccine, i.m. placebo, ID vaccine, and ID placebo. The ID formulations were mixed with BCG as adjuvant at the time of injection. For each group, 3 vaccinations were given with a 20-day interval between injections, and adverse events were monitored at 20 min, and at 2, 7 and 21 days after each injection. BCG-induced adverse reactions resulted in cancellation of the third vaccine administration in the ID groups. Antibody titres did not differ significantly between the groups. Montenegro skin-test conversion was achieved by 86.4% and 90% of the i.m. vaccine group and by 25% and 5% of the i.m. placebo group 80 days and 1 year after vaccination, respectively. A significant increase in mean Leishmania-antigen lymphocyte proliferation indexes was observed after i.m. vaccine immunization, but not after i.m. placebo immunization, 80 days and 1 year after vaccination. Significant levels of IFN gamma but not IL-10 were observed 1 year after vaccination in the i.m. vaccine group compared to the i.m. placebo group. The good safety profile and evidence of Th1 immune reactions due to i.m. vaccination in this phase-I/II study suggest that a population-based phase-III efficacy trial of the i.m. vaccine should be initiated.

Aacap 2002 Research Forum: Placebo and Alternatives to Placebo in Randomized Controlled Trials in Pediatric Psychopharmacology

ERIC Educational Resources Information Center

March, John; Kratochvil, Christopher; Clarke, Gregory; Beardslee, William; Derivan, Albert; Emslie, Graham; Green, Evelyn P.; Heiligenstein, John; Hinshaw, Stephen; Hoagwood, Kimberly; Jensen, Peter; Lavori, Philip; Leonard, Henrietta; McNulty, James; Michaels, M. Alex; Mossholder, Andrew; Osher, Trina; Petti, Theodore; Prentice, Ernest; Vitiello, Benedetto; Wells, Karen

2004-01-01

Objective: The use of placebo in the pediatric age group has come under increasing scrutiny. At the 2002 Annual Meeting of the American Academy of Child and Adolescent Psychiatry, the Academy's Workgroup on Research conducted a research forum. The purpose was to identify challenges and their solutions regarding the use of placebo in randomized…

Utility of intranasal Ketamine and Midazolam to perform gastric aspirates in children: a double-blind, placebo controlled, randomized study

PubMed Central

2014-01-01

Background We performed a prospective, randomized, placebo-controlled study aimed to evaluate the efficacy and safety of a sedation protocol based on intranasal Ketamine and Midazolam (INKM) administered by a mucosal atomizer device in uncooperative children undergoing gastric aspirates for suspected tuberculosis. Primary outcome: evaluation of Modified Objective Pain Score (MOPS) reduction in children undergoing INKM compared to the placebo group. Secondary outcomes: evaluation of safety of INKM protocol, start time sedation effect, duration of sedation and evaluation of parents and doctors’ satisfaction about the procedure. Methods In the sedation group, 19 children, mean age 41.5 months, received intranasal Midazolam (0.5 mg/kg) and Ketamine (2 mg/kg). In the placebo group, 17 children received normal saline solution twice in each nostril. The child’s degree of sedation was scored using the MOPS. A questionnaire was designed to evaluate the parents’ and doctors’ opinions on the procedures of both groups. Results Fifty-seven gastric washings were performed in the sedation-group, while in the placebo-group we performed 51 gastric aspirates. The degree of sedation achieved by INMK enabled all procedures to be completed without additional drugs. The mean duration of sedation was 71.5 min. Mean MOPS was 3.5 (range 1-8) in the sedation-group, 7.2 (range 4-9) in the placebo-group (p <0.0001). The questionnaire revealed high levels of satisfaction by both doctors and parents in the sedation-group compared to the placebo-group. The only side effect registered was post-sedation agitation in 6 procedures in the sedation group (10.5%). Conclusions Our experience suggests that atomized INKM makes gastric aspirates more acceptable and easy to perform in children. Trial registration Unique trial Number: UMIN000010623; Receipt Number: R000012422. PMID:24598046

Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department: A Randomized Controlled Trial.

PubMed

Bowers, Karen J; McAllister, Kelly B; Ray, Meredith; Heitz, Corey

2017-06-01

This study had five objectives: 1) to measure and compare total opioid use and number of opioid doses in patients treated with opioids versus ketamine in conjunction with opioids; 2) to measure pain scores up to 2 hours after presentation in the ED patient with pain, comparing standard opioid pain control to ketamine in conjunction with opioids; 3) to compare patient satisfaction with pain control using opioids alone versus ketamine in conjunction with opioids; 4) to monitor and compare side effects in patients treated with opioids versus ketamine in conjunction with opioids; and 5) to identify effect variation between different subgroups of patients, with the purpose of focusing future research. We hypothesized that low-dose ketamine, compared to placebo, as an adjunctive treatment to opioids would result in better pain control over 2 hours and greater patient satisfaction with pain control; further, this protocol will result in a lower opioid dosage over 2 hours. This was a randomized, double-blinded, placebo-controlled trial at a single academic emergency department evaluating the use of ketamine versus placebo in conjunction with opioids for moderate to severe pain. Subjects with a continued high level of pain after an initial dose of opioid analgesia were randomized to receive either 0.1 mg/kg ketamine or placebo prior to protocol-based dosing of additional opioid analgesia, if required. Over 120 minutes, subjects were assessed for pain level (0-10), satisfaction with pain control (0-4), side effects, sedation level, and need for additional pain medication. Total opioid dose, including the initial dose, was compared between groups. Sixty-three subjects were randomized to the placebo group and 53 to the ketamine group. No significant differences were found in demographics between the groups. Patients receiving ketamine reported lower pain scores over 120 minutes than patients receiving placebo (p = 0.015). Total opioid dose was lower in the ketamine group (mean ± SD = 9.95 ± 4.83 mg) compared to placebo (mean ± SD = 12.81 ± 6.81 mg; p = 0.02). Satisfaction did not differ between groups. Fewer patients in the ketamine group required additional opioid doses. More patients reported light-headedness and dizziness in the ketamine group. Ketamine, as an adjunct to opioid therapy, was more effective at reducing pain over 120 minutes and resulted in a lower total opioid dose as well as fewer repeat doses of analgesia. More side effects were reported in the ketamine group (51% vs. 19%), but the side effect profile appears tolerable. © 2017 by the Society for Academic Emergency Medicine.

A pilot randomized double-blind placebo-controlled trial on topical chamomile (Matricaria chamomilla L.) oil for severe carpal tunnel syndrome.

PubMed

Hashempur, Mohammad Hashem; Lari, Zeinab Nasiri; Ghoreishi, Parissa Sadat; Daneshfard, Babak; Ghasemi, Mohammad Sadegh; Homayouni, Kaynoosh; Zargaran, Arman

2015-11-01

To assess the effectiveness of standardized topical Chamomile (Matricaria chamomilla L.) oil in patients with severe carpal tunnel syndrome, as a complementary treatment. A pilot randomized double-blind placebo-controlled trial was conducted. Twenty six patients with documented severe carpal tunnel syndrome were treated in two parallel groups with a night splint plus topical chamomile oil or placebo. They were instructed to use their prescribed oil for 4 weeks, twice daily. Symptomatic and functional status of the patients and their electrodiagnostic parameters were evaluated when enrolled and after the trial period, as our outcome measures. A significant improvement of symptomatic and functional status of patients in the chamomile oil group was observed (p = 0.019 and 0.016, respectively) compared with those in the placebo group. However, electrodiagnostic parameters showed no significant changes between the two groups. Chamomile oil improved symptomatic and functional status of patients with severe carpal tunnel syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy and safety of oral robenacoxib (tablet) for the treatment of pain associated with soft tissue surgery in client-owned dogs.

PubMed

Friton, Gabriele; Thompson, Caryn Marie; Karadzovska, Daniela; King, Stephen; King, Jonathan N

2017-06-26

Non-steroidal anti-inflammatory drugs (NSAIDs) have been proven to be effective in controlling peri-operative pain in dogs. Robenacoxib is an NSAID with high selectivity for the cyclooxygenase (COX)-2 isoform. The objective of this study was to assess the efficacy and safety of an oral tablet formulation of robenacoxib in client-owned dogs undergoing soft tissue surgery. The study was a prospective, multi-center, randomized, masked, placebo-controlled, parallel-group clinical trial. A total of 239 dogs were included and randomly allocated in a 1:1 ratio to receive either robenacoxib or placebo. Each dog received an oral tablet administration of either robenacoxib, at a target dose of 2 mg/kg, or placebo once prior to surgery and for two additional days post-operatively. All dogs also received a pre-anesthetic dose of 0.2 mg/kg butorphanol (intravenous or intramuscular). Pain assessments were performed using the short form of the Glasgow Composite Measure Pain Scale. Robenacoxib was compared to the placebo group on a success/failure basis. Treatment failure was defined as the need for rescue therapy to control post-operative pain. Significantly (P = 0.019) more dogs administered robenacoxib were considered treatment successes (89 of 116, 76.72%) compared to dogs given placebo (74 of 115, 64.35%). The percentage of treatment failure was therefore 23.28% in the robenacoxib and 35.65% in the placebo group. The least squares mean total pain scores were significantly different between groups and in favor of robenacoxib at 3 and 5 hours (P < 0.05) and 8 hours post-extubation (P < 0.01). Pain at the surgery sites (response to touch) was also significantly improved at 3, 5 and 8 hours post-extubation in dogs receiving robenacoxib versus placebo (P < 0.01). In addition, a significant overall improvement in posture/activity was revealed with robenacoxib having lower scores versus placebo (P < 0.01). No significant differences between the robenacoxib and placebo groups in the frequency of reported adverse events were observed. Robenacoxib by oral (tablet) administration was effective and well tolerated in the control of peri-operative pain and inflammation associated with soft tissue surgery in dogs.

Effects of a Standardized Bacopa monnieri Extract on Cognitive Performance, Anxiety, and Depression in the Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Gregory, William L.; Leo, Michael; Kraemer, Dale; Bone, Kerry; Oken, Barry

2008-01-01

Abstract Objectives Study aims were to evaluate effects of Bacopa monnieri whole plant standardized dry extract on cognitive function and affect and its safety and tolerability in healthy elderly study participants. Design The study was a randomized, double-blind, placebo-controlled clinical trial with a placebo run-in of 6 weeks and a treatment period of 12 weeks. Setting/location Volunteers were recruited from the community to a clinic in Portland, Oregon by public notification. Subjects Fifty-four (54) participants, 65 or older (mean 73.5 years), without clinical signs of dementia, were recruited and randomized to Bacopa or placebo. Forty-eight (48) completed the study with 24 in each group. Interventions Standardized B. monnieri extract 300 mg/day or a similar placebo tablet orally for 12 weeks. Outcome measures The primary outcome variable was the delayed recall score from the Rey Auditory Verbal Learning Test (AVLT). Other cognitive measures were the Stroop Task assessing the ability to ignore irrelevant information, the Divided Attention Task (DAT), and the Wechsler Adult Intelligence Scale (WAIS) letter-digit test of immediate working memory. Affective measures were the State-Trait Anxiety Inventory, Center for Epidemiologic Studies Depression scale (CESD)-10 depression scale, and the Profile of Mood States. Vital signs were also monitored. Results Controlling for baseline cognitive deficit using the Blessed Orientation–Memory–Concentration test, Bacopa participants had enhanced AVLT delayed word recall memory scores relative to placebo. Stroop results were similarly significant, with the Bacopa group improving and the placebo group unchanged. CESD-10 depression scores, combined state plus trait anxiety scores, and heart rate decreased over time for the Bacopa group but increased for the placebo group. No effects were found on the DAT, WAIS digit task, mood, or blood pressure. The dose was well tolerated with few adverse events (Bacopa n = 9, placebo n = 10), primarily stomach upset. Conclusions This study provides further evidence that B. monnieri has potential for safely enhancing cognitive performance in the aging. PMID:18611150

Training attention improves decision making in individuals with elevated self-reported depressive symptoms.

PubMed

Cooper, Jessica A; Gorlick, Marissa A; Denny, Taylor; Worthy, Darrell A; Beevers, Christopher G; Maddox, W Todd

2014-06-01

Depression is often characterized by attentional biases toward negative items and away from positive items, which likely affects reward and punishment processing. Recent work has reported that training attention away from negative stimuli reduced this bias and reduced depressive symptoms. However, the effect of attention training on subsequent learning has yet to be explored. In the present study, participants were required to learn to maximize reward during decision making. Undergraduates with elevated self-reported depressive symptoms received attention training toward positive stimuli prior to performing the decision-making task (n = 20; active training). The active-training group was compared to two other groups: undergraduates with elevated self-reported depressive symptoms who received placebo training (n = 22; placebo training) and a control group with low levels of depressive symptoms (n = 33; nondepressive control). The placebo-training depressive group performed worse and switched between options more than did the nondepressive controls on the reward maximization task. However, depressives that received active training performed as well as the nondepressive controls. Computational modeling indicated that the placebo-trained group learned more from negative than from positive prediction errors, leading to more frequent switching. The nondepressive control and active-training depressive groups showed similar learning from positive and negative prediction errors, leading to less-frequent switching and better performance. Our results indicate that individuals with elevated depressive symptoms are impaired at reward maximization, but that the deficit can be improved with attention training toward positive stimuli.

Efficacy and Safety of Paliperidone Extended Release 1.5 mg/day—A Double-blind, Placebo- and Active-Controlled, Study in the Treatment of Patients with Schizophrenia

PubMed Central

Coppola, Danielle; Melkote, Rama; Lannie, Caroline; Singh, Jaskaran; Nuamah, Isaac; Gopal, Srihari; Hough, David; Palumbo, Joseph

2011-01-01

Background Paliperidone extended-release (paliperidone ER) is an approved oral antipsychotic medication (dosing range 3–12 mg/day) for treatment of schizophrenia and schizoaffective disorder in adults. Methods In this 3-arm, double-blind, placebo- and active-controlled, parallel-group study, paliperidone ER 1.5 mg was assessed to determine the lowest efficacious dose in patients (N = 201) with acute schizophrenia. Paliperidone ER 6 mg was included for assay sensitivity. Results Patients (intent-to-treat analysis set) had a mean age of 39.4 years; 74% were men, 43% Asian, and 40% black. The baseline mean (SD) Positive and Negative Syndrome Scale (PANSS) total score was 92.6 (13.02) and the mean (SD) change from baseline to endpoint was: placebo group, –11.4 (20.81); paliperidone ER 1.5 mg group, –8.9 (23.31); and paliperidone ER 6 mg group, –15.7 (26.25). Differences between paliperidone groups versus placebo were not significant (paliperidone ER 1.5 mg [p = 0.582], paliperidone ER 6 mg, [p = 0.308]). Safety results of paliperidone ER 1.5 mg and placebo were comparable. The most frequently reported treatment emergent adverse events (≥10%) were: placebo group—headache (15.6%) and psychotic disorder (14.1%); paliperidone ER 1.5 mg group—insomnia (13.6%); and paliperidone ER 6 mg group—headache (11.4%), insomnia (10%), and tremor (10%). Conclusions In this study, paliperidone ER 1.5 mg did not demonstrate efficacy in patients with acute schizophrenia. A markedly high placebo response was noted. Assay sensitivity with the 6 mg dose was not established. Paliperidone ER 1.5 mg was generally tolerable with a safety profile comparable to placebo. PMID:27738355

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series

PubMed Central

Taylor, Morag A; Reilly, David; Llewellyn-Jones, Robert H; McSharry, Charles; Aitchison, Tom C

2000-01-01

Objective To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Design Randomised, double blind, placebo controlled, parallel group, multicentre study. Setting Four general practices and a hospital ear, nose, and throat outpatient department. Participants 51 patients with perennial allergic rhinitis. Intervention Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Main outcome measures Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Results Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). Conclusion The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo. PMID:10948025

Transdermal rotigotine in advanced Parkinson's disease: a randomized, double-blind, placebo-controlled trial.

PubMed

Nomoto, Masahiro; Mizuno, Yoshikuni; Kondo, Tomoyoshi; Hasegawa, Kazuko; Murata, Miho; Takeuchi, Masahiro; Ikeda, Junji; Tomida, Takayuki; Hattori, Nobutaka

2014-10-01

Rotigotine, a non-ergot dopamine receptor agonist, offers potential for continuous dopaminergic stimulation that could avoid the fluctuations observed with traditional treatments. We conducted a randomized, double-blind, placebo-controlled trial in Japanese patients with advanced Parkinson's disease (PD) to investigate the efficacy and safety of rotigotine. Inclusion criteria included the presence of motor complications, such as wearing off, on-off, delayed-on/no-on, any circumstances that could interfere with levodopa dose escalation because of side effects, or declining levodopa efficacy. The enrolled patients received once-daily applications of rotigotine transdermal patches or matched placebo patches. A total of 174 patients were randomly assigned to rotigotine (87 patients) or placebo (87 patients). The full analysis set included 172 patients (86 for the rotigotine group and 86 for the placebo group). The maximum maintenance dose of rotigotine was set at 16 mg/24 h. The changes in unified PD rating scale Part III scores from baseline to the end of the trial were -10.1 ± 9.0 (mean ± standard deviation) in the rotigotine group and -4.4 ± 7.4 in the placebo group (p < 0.001). There was a significantly greater reduction in the off-time (p = 0.014) in the rotigotine group. Rotigotine was well tolerated, with serious adverse events being reported in only three patients in each group. Rotigotine at doses of up to 16 mg/24 h is efficacious and safe in Japanese patients with advanced PD.

Effects of oral iron(III) hydroxide polymaltose complex supplementation on hemoglobin increase, cognitive function, affective behavior and scholastic performance of adolescents with varying iron status: a single centre prospective placebo controlled study.

PubMed

Devaki, Pallaki Baby; Chandra, Ranjit K; Geisser, Peter

2009-01-01

To assess the effects of iron supplementation on iron status, cognitive function, affective behavior and scholastic performance in adolescents with varying iron status. Adolescents of both sexes with varying iron status were allocated to four treatment groups by using inclusion criteria. Three of the four groups (iron deficient anemic, iron deficient and control supplement) received iron(III) hydroxide polymaltose complex (IPC, Maltofer) containing 100 mg of elemental iron 6 days a week for 8 months, while the fourth group (control placebo) was given a placebo. Hematological parameters, cognitive function, affective behavior and scholastic performance were assessed at baseline, 4 months and 8 months of supplementation. Cognitive and scholastic performance test scores for the three supplemented groups increased from baseline to 4 months and from 4 months to 8 months (with concomitant increases in hematological parameters), whereas no increase was observed in the placebo group. No increase was seen in affective behavior scores for any of the groups during or after supplementation. IPC supplementation for eight months yielded significant improvements in cognitive function and scholastic performance in Indian adolescents with and without iron deficiency and anemia.

The effects of sequential use of oxytocin and sublingual nitroglycerin in the cases of retained placenta.

PubMed

Kashanian, Maryam; Hasankhani, Samira; Sheikhansari, Narges; Bahasadri, Shohreh; Homam, Homa

2016-10-01

To evaluate the effects of adding sublingual nitroglycerin to oxytocin, for delivery of retained placenta after vaginal delivery. The study was performed as a placebo controlled clinical trial on women who did not finish delivering placenta after 30 min of active management of the third stage of labor. In case group, 1 mg nitroglycerin and in the control group, placebo was prescribed sublingually. In total, 80 women finished the study. The number of manual removal of placenta did not show significant difference between the two groups [25 women (62.5%) in the case and 30 women (75%) in the control group, p = 0.335]. There was no significant difference between the two groups according to duration of the third stage of labor, hemoglobin index, decline in HB index >30% and maternal vital signs after treatment. There was no significant difference between the two groups according to adverse effects [eight women (20%) in the case group and four (10%) in the control group (p = 0.348)]. The sequential use of oxytocin and sublingual nitroglycerin could not lead to delivery of more placentas and did not reduce the necessity of manual removal of placenta in comparison with placebo.

Gongronema latifolium delays gastric emptying of semi-solid meals in diabetic dogs.

PubMed

Ogbu, Sylvester Osita; Agwu, Kenneth Kalu; Asuzu, Isaac Uzoma

2013-01-01

The aim of the study was to investigate sonographically the effect of Gongronema latifolium on gastric emptying of semi-solid meals in diabetic dogs. Twenty-five alloxan-induced diabetic dogs were randomly allotted into five groups of five dogs each in a randomised placebo-controlled study. These are placebo, prokinetic dose, low dose, moderate dose and high dose groups. The placebo group served as the control. The low, moderate and high dose groups ingested methanolic leaf extract of G. latifolium at 100 mg/kg, 250 mg/kg, 500 mg/kg respectively, while the prokinetic group ingested 0.5 mg/kg of metoclopramide. After a 12-hour fast, each group ingested its treatment capsules 30 minutes before the administration of test meal. Measurements of gastric emptying and blood glucose levels were obtained from each dog 30 minutes before and immediately after the ingestion of a test meal, every 15 minutes for another 4 hours and then every 30 minutes for further 2 hours. Gastric emptying of the moderate and high dose groups were 227.8 ± 9.9 min and 261.3 ± 19.3 min respectively and significantly (p < 0.0001) slower than the placebo control group of 143.0 ± 17.8 min. The gastric emptying of the low dose group (169.8 ± 3.8) and control group did not differ significantly (p > 0.05). A strong inverse relationship between gastric emptying and the incremental blood glucose levels was noted in the diabetic dogs after the ingestion of Gongronema latifolium (r = -0.90; p < 0.0001). Gonogronema latifolium delayed gastric emptying in diabetic dogs.

A compound herbal preparation (CHP) in the treatment of children with ADHD: a randomized controlled trial.

PubMed

Katz, M; Levine, A Adar; Kol-Degani, H; Kav-Venaki, L

2010-11-01

Evaluation of the efficacy of a patented, compound herbal preparation (CHP) in improving attention, cognition, and impulse control in children with ADHD. A randomized, double-blind, placebo-controlled trial. University-affiliated tertiary medical center. 120 children newly diagnosed with ADHD, meeting DSM-IV criteria. Random assignment to the herbal treatment group (n = 80) or control group (placebo; n = 40); 73 patients in the treatment group (91%) and 19 in the control group (48%) completed the 4-month trial. Test of Variables of Attention (TOVA) administered before and after the treatment period; overall score and 4 subscales. The treatment group showed substantial, statistically significant improvement in the 4 subscales and overall TOVA scores, compared with no improvement in the control group, which persisted in an intention-to-treat analysis. The well-tolerated CHP demonstrated improved attention, cognition, and impulse control in the intervention group, indicating promise for ADHD treatment in children.

Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain.

PubMed

Johnson, Jeremy R; Burnell-Nugent, Mary; Lossignol, Dominique; Ganae-Motan, Elena Doina; Potts, Richard; Fallon, Marie T

2010-02-01

This study compared the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer. In total, 177 patients with cancer pain, who experienced inadequate analgesia despite chronic opioid dosing, entered a two-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. Patients were randomized to THC:CBD extract (n = 60), THC extract (n = 58), or placebo (n = 59). The primary analysis of change from baseline in mean pain Numerical Rating Scale (NRS) score was statistically significantly in favor of THC:CBD compared with placebo (improvement of -1.37 vs. -0.69), whereas the THC group showed a nonsignificant change (-1.01 vs. -0.69). Twice as many patients taking THC:CBD showed a reduction of more than 30% from baseline pain NRS score when compared with placebo (23 [43%] vs. 12 [21%]). The associated odds ratio was statistically significant, whereas the number of THC group responders was similar to placebo (12 [23%] vs. 12 [21%]) and did not reach statistical significance. There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups. No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment. However, the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Questionnaire showed a worsening in nausea and vomiting with THC:CBD compared with placebo (P = 0.02), whereas THC had no difference (P = 1.0). Most drug-related adverse events were mild/moderate in severity. This study shows that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids. Copyright 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial

PubMed Central

McGarvey, Lorcan; Pavord, Ian D.; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S.

2017-01-01

Background To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. Methods This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. Results At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (−12.2±23.28 in BC1036 group and −11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. Conclusions This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. Clinical trial registration ClinicalTrials.gov: NCT01656668. PMID:28839984

A randomized, double-blind, placebo-controlled trial on the role of preemptive analgesia with acetaminophen [paracetamol] in reducing headache following electroconvulsive therapy [ECT].

PubMed

Isuru, Amila; Rodrigo, Asiri; Wijesinghe, Chamara; Ediriweera, Dileepa; Premadasa, Shan; Wijesekara, Carmel; Kuruppuarachchi, Lalith

2017-07-28

Electroconvulsive therapy (ECT) is a safe and efficient treatment for several severe psychiatric disorders, but its use is limited by side effects. Post-ECT headache is one of the commonest side effects. Preemptive analgesia is effective in post-surgical pain management. The most commonly used analgesic is acetaminophen (paracetamol). However, acetaminophen as a preemptive analgesic for post-ECT headache has not been studied adequately. This study was conducted to compare the incidence and severity of post-ECT headache in patients who were administered acetaminophen pre-ECT with a placebo group. This study was a randomised, double-blind, placebo-controlled trial. Sixty-three patients received 1 g acetaminophen and 63 patients received a placebo identical to acetaminophen. The incidence and severity of headache 2 h before and after ECT were compared between placebo and acetaminophen groups. The severity was measured using a visual analog scale. Generalised linear models were used to evaluate variables associated with post ECT headache. Demographic and clinical variables of placebo and acetaminophen groups were comparable except for the energy level used to induce a seizure. Higher proportion of the placebo group (71.4%) experienced post-ECT headache when compared to the acetaminophen group (p < 0.001). The median pain score for headache was 0 (Inter quartile range: 0-2) in acetaminophen group whereas the score was 2 (IQR: 0-4) in placebo group (P < 0.001). Model fitting showed that the administration of acetaminophen is associated with less post-ECT headache (odds ratio = 0.23, 95% CI: 0.11-0.48, P < 0.001). A significant reduction was seen in both the incidence and severity of post-ECT headache with preemptive analgesia with acetaminophen. Ethical approval was granted by an Ethic review committee, University of Kelaniya, Sri Lanka (P/166/10/2015) and the trial was registered in the Sri Lanka Clinical Trials Registry ( SLCTR/2015/27 ).

The impact of intranasal oxytocin on attention to social emotional stimuli in patients with anorexia nervosa: a double blind within-subject cross-over experiment.

PubMed

Kim, Youl-Ri; Kim, Chan-Hyung; Park, Jin Hong; Pyo, Jimin; Treasure, Janet

2014-01-01

Social factors may be of importance causally and act as maintenance factors in patients with anorexia nervosa. Oxytocin is a neuromodulatory hormone involved in social emotional processing associated with attentional processes. This study aimed to examine the impact of oxytocin on attentional processes to social faces representing anger, disgust, and happiness in patients with anorexia nervosa. A double-blind, placebo-controlled within-subject crossover design was used. Intranasal oxytocin or placebo followed by a visual probe detection task with faces depicting anger, disgust, and happiness was administered to 64 female subjects: 31 patients with anorexia nervosa and 33 control students. Attentional bias to the disgust stimuli was observed in both groups under the placebo condition. The attentional bias to disgust was reduced under the oxytocin condition (a moderate effect in the patient group). Avoidance of angry faces was observed in the patient group under the placebo condition and vigilance was observed in the healthy comparison group; both of these information processing responses were moderated by oxytocin producing an increase in vigilance in the patients. Happy/smiling faces did not elicit an attentional response in controls or the patients under either the placebo or oxytocin conditions. Oxytocin attenuated attentional vigilance to disgust in patients with anorexia nervosa and healthy controls. On the other hand, oxytocin changed the response to angry faces from avoidance to vigilance in patients but reduced vigilance to anger in healthy controls. We conclude that patients with anorexia nervosa appear to use different strategies/circuits to emotionally process anger from their healthy counterparts.

Scotopic sensitivity/Irlen syndrome and the use of coloured filters: a long-term placebo-controlled study of reading strategies using analysis of miscue.

PubMed

Robinson, G L; Foreman, P J

1999-02-01

This study investigated the long-term effects of using coloured filters on the frequency and type of errors in oral reading. A double-masked, placebo-controlled crossover experimental design was used, with subjects being assessed over a period of 20 months. There were three experimental groups (Placebo tints, Blue tints, and Diagnosed tints) involving 113 subjects with reading difficulties, ranging in age from 9.2 yr. to 13.1 yr. The 35 controls (ranging in age from 9.4 yr. to 12.9 yr.) had reading difficulties but did not require coloured filters. There was a significant improvement for all groups in the accuracy of miscues over the period, although experimental groups over-all did not improve at a significantly different rate than the control group. The failure to find significantly greater improvement for the experimental groups over the control group for the total period, despite subjects' reports of improved print clarity, may be partly related to the lack of effective letter-sound analysis and synthesis skills and to the use of a word-identification strategy of guessing based on partial visual analysis.

Transdermal rotigotine in early stage Parkinson's disease: a randomized, double-blind, placebo-controlled trial.

PubMed

Mizuno, Yoshikuni; Nomoto, Masahiro; Kondo, Tomoyoshi; Hasegawa, Kazuko; Murata, Miho; Takeuchi, Masahiro; Ikeda, Junji; Tomida, Takayuki; Hattori, Nobutaka

2013-09-01

We conducted a randomized, double-blind, placebo-controlled trial to determine the safety and efficacy of transdermal rotigotine at doses up to 16 mg/24 hours in patients with early stage Parkinson's disease (PD) in Japan. Patients received once-daily rotigotine 2 to 16 mg/24 hours (mean dose, 12.8 mg/24 hours; n = 82) or placebo (n = 90) for 12 weeks. The primary endpoint was the change in Unified Parkinson's Disease Rating Scale (UPDRS) part II (activities of daily living) and part III (motor function) scores from baseline to the end of treatment. The mean (± standard deviation) changes in UPDRS part II and III scores were -8.4 ± 9.7 in the rotigotine group and -4.1 ± 8.2 in the placebo group and were significantly different (P = 0.002). More patients in the rotigotine group than in the placebo group had a ≥ 20% score reduction. No serious drug-related adverse events were reported. Rotigotine at doses up to 16 mg/24 hours was well tolerated and improved function in patients with early stage PD. © 2013 International Parkinson and Movement Disorder Society.

A randomized controlled trial of the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea.

PubMed

Moses, R G; Kalra, S; Brook, D; Sockler, J; Monyak, J; Visvanathan, J; Montanaro, M; Fisher, S A

2014-05-01

To evaluate the efficacy and safety of saxagliptin as add-on therapy in adults with type 2 diabetes with inadequate glycaemic control on metformin plus a sulphonylurea. In this 24-week, multicentre, randomized, parallel-group, double-blind study, outpatients aged ≥18 years with type 2 diabetes, body mass index ≤40 kg/m(2) and inadequate glycaemic control, received saxagliptin 5 mg or placebo once-daily added to background medication consisting of a stable maximum tolerated dose of metformin plus a sulphonylurea. The primary end point was change in glycated haemoglobin (HbA1c) from baseline to week 24. Safety and tolerability assessments included adverse events (AEs), hypoglycaemia and body weight. A total of 257 patients were randomized, treated and included in the safety analysis (saxagliptin, n = 129; placebo, n = 128); 255 were included in the efficacy analysis (saxagliptin, n = 127; placebo, n = 128). HbA1c reduction was greater with saxagliptin versus placebo [between-group difference in adjusted mean change from baseline, -0.66%; 95% confidence interval (CI), -0.86 to -0.47 (7 mmol/mol, -9.4 to -5.1); p < 0.0001]. The proportion of patients with ≥1 AE was 62.8% with saxagliptin and 71.7% with placebo. In the saxagliptin and placebo groups, rates of reported hypoglycaemia were 10.1 and 6.3%, respectively, and rates of confirmed hypoglycaemia (symptoms + glucose < 2.8 mmol/l) were 1.6 and 0%. Mean change in body weight was 0.2 kg for saxagliptin and -0.6 kg for placebo (p = 0.0272). Addition of saxagliptin 5 mg/day in patients inadequately controlled on metformin and sulphonylurea effectively improved glycaemic control and was well tolerated. © 2013 John Wiley & Sons Ltd.

Efficacy of Trimetazidine Dihydrochloride for Relieving Chronic Tinnitus: A Randomized Double-Blind Study

PubMed Central

Kumral, Tolgar Lütfi; Yıldırım, Güven; Berkiten, Güler; Saltürk, Ziya; Ataç, Enes; Atar, Yavuz; Uyar, Yavuz

2016-01-01

Objectives. To evaluate the efficacy of trimetazidine dihydrochloride as a treatment for chronic tinnitus. Methods. A total of 97 chronic tinnitus patients were evaluated in this randomized, prospective, double-blind, placebo-controlled trial. After assessing for eligibility, 82 patients were randomly assigned into placebo or trimetazidine groups according to the medication. The trimetazidine group received 20×3 mg/day per oral trimetazidine dihydrochloride and the placebo group received 20×3 mg/day per oral placebo for 3 months. Tinnitus handicap inventory (THI), visual analogue scale (VAS) questionnaires and audiometric results were used to determine the effectiveness of trimetazidine treatment. Results. The study group comprised 82 tinnitus subjects, 42 (51%) of whom received trimetazidine dihydrochloride and 40 (49%) who received placebo. There was no significant difference between placebo and trimetazidine groups in THI grade and VAS (both pre- and posttreatment scores) (P>0.05) and no significant improvement was observed in subjective loudness score in either group (P>0.05). Additionally there was no significant difference between groups in pre- and posttreatment pure tone hearing thresholds at all measured frequencies (P>0.05). Conclusion. Trimetazidine dihydrochloride therapy was ineffective for relieving chronic tinnitus. PMID:27230273

A take-home placebo treatment can reduce stress, anxiety and symptoms of depression in a non-patient population.

PubMed

Darragh, Margot; Yow, Boris; Kieser, Anel; Booth, Roger J; Kydd, Robert R; Consedine, Nathan S

2016-09-01

With a healthcare system burdened by symptomatic and mental-health related conditions, the placebo effect may represent a useful clinical tool. First, however, there is a need to broaden research attention and investigate placebo effects outside laboratories and beyond experimental pain. This study investigated the effectiveness of a take-home placebo treatment in the short-term alleviation of stress, anxiety and symptoms of depression in a non-patient population. A sample of 77 participants was randomized to either the 'oxytocin' treatment group (n = 22), the 'serotonin' treatment group (n = 22) or the wait-list control group (n = 33). The two treatment groups were given an 'anti-stress treatment spray' (placebo) to self-administer for 3 days, and completed online measures of perceived stress (Perceived Stress Scale-10), anxiety (Cognitive Somatic Anxiety Questionnaire) and symptoms of depression (Centre for Epidemiological Studies - Depression) before and after the 3-day protocol. Both the 'serotonin' and 'oxytocin' treatment sprays were effective in reducing symptoms of depression; however, only those in the 'oxytocin' group reported less stress and anxiety as compared with controls. Overall, the 'oxytocin' was perceived as more effective. Placebo effects can be translated to a real-life setting in the short-term reduction of stress, anxiety and symptoms of depression in a non-patient population. In treating psychological distress, placebos may be useful addition to the treatment repertoire. The information given with treatment may also be an important consideration for practitioners. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Randomized, double-blinded, placebo-controlled trial comparing two multimodal opioid-minimizing pain management regimens following transsphenoidal surgery.

PubMed

Shepherd, Deborah M; Jahnke, Heidi; White, William L; Little, Andrew S

2018-02-01

OBJECTIVE Pain control is an important clinical consideration and quality-of-care metric. No studies have examined postoperative pain control following transsphenoidal surgery for pituitary lesions. The study goals were to 1) report postoperative pain scores following transsphenoidal surgery, 2) determine if multimodal opioid-minimizing pain regimens yielded satisfactory postoperative pain control, and 3) determine if intravenous (IV) ibuprofen improved postoperative pain scores and reduced opioid use compared with placebo. METHODS This study was a single-center, randomized, double-blinded, placebo-controlled intervention trial involving adult patients with planned transsphenoidal surgery for pituitary tumors randomized into 2 groups. Group 1 patients were treated with scheduled IV ibuprofen, scheduled oral acetaminophen, and rescue opioids. Group 2 patients were treated with IV placebo, scheduled oral acetaminophen, and rescue opioids. The primary end point was patient pain scores (visual analog scale [VAS], rated 0-10) for 48 hours after surgery. The secondary end point was opioid use as estimated by oral morphine equivalents (OMEs). RESULTS Of 136 patients screened, 62 were enrolled (28 in Group 1, 34 in Group 2). The study was terminated early because the primary and secondary end points were reached. Baseline characteristics between groups were well matched except for age (Group 1, 59.3 ± 14.4 years; Group 2, 49.8 ± 16.2 years; p = 0.02). Mean VAS pain scores were significantly different, with a 43% reduction in Group 1 (1.7 ± 2.2) compared with Group 2 (3.0 ± 2.8; p < 0.0001). Opioid use was significantly different, with a 58% reduction in Group 1 (26.3 ± 28.7 mg OME) compared with Group 2 (62.5 ± 63.8 mg OME; p < 0.0001). CONCLUSIONS Multimodal opioid-minimizing pain-management protocols resulted in acceptable pain control following transsphenoidal surgery. IV ibuprofen resulted in significantly improved pain scores and significantly decreased opioid use compared with placebo. Postoperative multimodal pain management, including a nonsteroidal antiinflammatory medication, should be considered after surgery to improve patient comfort and to limit opioid use. Clinical trial registration no.: NCT02351700 (clinicaltrials.gov) ■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: randomized, controlled trial; evidence: Class III.

A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial Evaluating the Effectiveness of Daily Vibration After Arthroscopic Rotator Cuff Repair.

PubMed

Lam, Patrick H; Hansen, Kaitlyn; Keighley, Geffrey; Hackett, Lisa; Murrell, George A C

2015-11-01

Rotator cuff repair is a common method to treat rotator cuff tears; however, retear rates remain high. High-frequency, low-magnitude vibration has been demonstrated to promote new bone formation in both animal models and in humans. This type of mechanical stimulation applied postoperatively will enhance tendon-to-bone healing and reduce postoperative retear rates. Randomized controlled trial; Level of evidence, 1. A randomized, double-blinded, placebo-controlled clinical trial was conducted to investigate the effects of 5 minutes of 80-Hz vibration applied daily after arthroscopic rotator cuff repair for 6 months on postoperative rotator cuff healing. The primary outcome was ultrasound-assessed repair integrity at 6 months after repair. Recruited patients were randomized into 2 groups: one group received a vibration device that oscillated at 80 Hz, and the other group received a placebo device. The postoperative retear rates of both groups were similar (9.1% [5/55] in the vibration group, and 9.3% [5/54] in the placebo group) at 6 months as determined by ultrasound imaging. Vibration did provide acute pain relief at 6 weeks after surgery (visual analog scale [VAS] score, 2.24 ± 0.29 cm) compared with placebo (VAS score, 3.67 ± 0.48 cm) (P < .003). Six months after surgery, both groups had significant reductions in pain during overhead activities, at rest, and during sleep and overall shoulder pain compared with before surgery (P < .001). Both the vibration and placebo groups had significant increases in shoulder strength with abduction in the scapular plane, adduction, liftoff, internal rotation, and external rotation 6 months after surgery. Statistical analysis showed that vibration was not a contributing factor at improving these parameters in these periods. High-frequency, low-magnitude vibration did provide acute pain relief on application 6 weeks after arthroscopic rotator cuff repair surgery. However, vibration did not improve tendon-to-bone healing, shoulder range of motion, shoulder strength, or shoulder pain with activities, at rest, and at night when compared with placebo. © 2015 The Author(s).

Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin-Angiotensin System Blockade: A 16-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Jin, Sang-Man; Han, Kyung Ah; Yu, Jae Myung; Sohn, Tae Seo; Choi, Sung Hee; Chung, Choon Hee; Park, Ie Byung; Rhee, Eun Jung; Baik, Sei Hyun; Park, Tae Sun; Lee, In-Kyu; Ko, Seung-Hyun; Hwang, You-Cheol; Cha, Bong Soo; Lee, Hyoung Woo; Nam, Moon-Suk; Lee, Moon-Kyu

2016-10-01

To determine the effect of probucol on urine albumin excretion in type 2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. This was a 16-week, phase II, randomized, placebo-controlled, parallel-group study in type 2 diabetes mellitus patients with a urinary albumin/creatinine ratio of ≥300 mg/g using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, conducted in 17 tertiary referral hospitals. Eligible patients were randomized to probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in a ratio of 1:1:1 after block randomization procedures, keeping the treatment assignment blinded to the investigators, patients, and study assistants. The primary end point was change in the geometric mean of urinary albumin/creatinine ratio from baseline to week 16 (ClinicalTrials.gov identifier NCT01726816). The study was started on November 8, 2012, and completed on March 24, 2014. The least squares mean change±SE from baseline in urinary albumin/creatinine ratio at week 16 was -7.2±639.5 mg/g in the probucol 250 mg/d group (n=43; P=0.2077 versus placebo group), 9.3±587.4 mg/g in the probucol 500 mg/d group (n=40; P=0.1975 versus placebo group), and 259.0±969.1 mg/g in the placebo group (n=41). Although the majority of subjects were on statins, probucol treatment significantly lowered total cholesterol and low-density lipoprotein cholesterol levels. QT prolongation occurred in one and two subjects in control and probucol 250 mg/d groups, respectively. Four months of probucol up to 500 mg/d failed to reduce urinary albumin excretion. © 2016 American Heart Association, Inc.

Is pre-emptive administration of ketamine a significant adjunction to intravenous morphine analgesia for controlling postoperative pain? A randomized, double-blind, placebo-controlled clinical trial.

PubMed

Fiorelli, Alfonso; Mazzella, Antonio; Passavanti, Beatrice; Sansone, Pasquale; Chiodini, Paolo; Iannotti, Mario; Aurilio, Caterina; Santini, Mario; Pace, Maria Caterina

2015-09-01

To evaluate if the pre-emptive administration of ketamine would potentiate the effect of intravenous morphine analgesia in the management of post-thoracotomy pain. This was a unicentre, double-blind, placebo-controlled, parallel-group, prospective study. Patients were randomly assigned to receive 1 mg/kg ketamine (ketamine group) or an equivalent dose of normal saline (placebo group) before thoracotomy in 1:1 ratio. All patients received postoperatively intravenous morphine administration as additional analgesic regimen. Primary end-point was the pain relief measured with Visual Analogue Scale at rest. The secondary end-points were the reduction of inflammatory response expressed by plasma C-reactive protein levels, the morphine consumption and the rate of side effects. The measurements were carried out 6, 12, 24, 36 and 48 hours postoperatively. A total of 75 patients were randomized of whom 38 were allocated to ketamine group and 37 to placebo group. Baseline characteristics were comparable. Ketamine compared with placebo group showed a significant reduction of pain scores (P = 0.01), C-reactive protein (P < 0.001) and morphine consumption (P < 0.001). No acute psychological side effects related to the use of ketamine were registered. The administration of ketamine before surgery may be an effective adjunct to intravenous morphine analgesia in acute post-thoracotomy pain management. In ketamine group, satisfaction of pain relief was significantly higher with a significant reduction of inflammatory response and morphine consumption compared with placebo group. Our results, if confirmed by larger studies, may be of clinical relevance in situations where epidural analgesia or other analgesic procedures different from systemic opioid analgesia are unavailable or contraindicated. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

A randomized, placebo-controlled proof-of-concept trial of adjunctive topiramate for alcohol use disorders in bipolar disorder.

PubMed

Sylvia, Louisa G; Gold, Alexandra K; Stange, Jonathan P; Peckham, Andrew D; Deckersbach, Thilo; Calabrese, Joseph R; Weiss, Roger D; Perlis, Roy H; Nierenberg, Andrew A; Ostacher, Michael J

2016-03-01

Topiramate is effective for alcohol use disorders (AUDs) among non-psychiatric patients. We examined topiramate for treating comorbid AUDs in bipolar disorder (BD). Twelve participants were randomized to topiramate or placebo for 12 weeks. The topiramate group, with two out of five participants (40%) completing treatment, experienced less improvement in drinking patterns than the placebo group, with five out of seven participants (71%) completing treatment. Topiramate did not improve drinking behavior and was not well-tolerated. This study failed to recruit adequately. Problems surrounding high attrition, a small study sample, and missing data preclude interpretation of study findings. This is the first randomized, placebo-controlled trial of topiramate for AUDs in BD. © American Academy of Addiction Psychiatry.

Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia.

PubMed

Kennedy, Stephen B; Bolay, Fatorma; Kieh, Mark; Grandits, Greg; Badio, Moses; Ballou, Ripley; Eckes, Risa; Feinberg, Mark; Follmann, Dean; Grund, Birgit; Gupta, Swati; Hensley, Lisa; Higgs, Elizabeth; Janosko, Krisztina; Johnson, Melvin; Kateh, Francis; Logue, James; Marchand, Jonathan; Monath, Thomas; Nason, Martha; Nyenswah, Tolbert; Roman, François; Stavale, Eric; Wolfson, Julian; Neaton, James D; Lane, H Clifford

2017-10-12

The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSV∆G-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated. A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSV∆G-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (P<0.001 for all comparisons); these differences were not seen at 1 month. Serious adverse events within 12 months after injection were seen in 40 participants (8.0%) in the ChAd3-EBO-Z group, in 47 (9.4%) in the rVSV∆G-ZEBOV-GP group, and in 59 (11.8%) in the placebo group. By 1 month, an antibody response developed in 70.8% of the participants in the ChAd3-EBO-Z group and in 83.7% of those in the rVSV∆G-ZEBOV-GP group, as compared with 2.8% of those in the placebo group (P<0.001 for both comparisons). At 12 months, antibody responses in participants in the ChAd3-EBO-Z group (63.5%) and in those in the rVSV∆G-ZEBOV-GP group (79.5%) remained significantly greater than in those in the placebo group (6.8%, P<0.001 for both comparisons). A randomized, placebo-controlled phase 2 trial of two vaccines that was rapidly initiated and completed in Liberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407 .).

Naproxen or Estradiol for Bleeding and Spotting with the Levonorgestrel Intrauterine System: A Randomized Controlled Trial

PubMed Central

MADDEN, Tessa; PROEHL, Sarah; ALLSWORTH, Jenifer E.; SECURA, Gina M.; PEIPERT, Jeffrey F.

2011-01-01

Objective To evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women initiating the levonorgestrel-releasing intrauterine system (LNG-IUS). Study Design We conducted a randomized controlled trial of naproxen, estradiol, or placebo administered over the first 12 weeks of LNG-IUS use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis. Results There were 129 women randomized to naproxen (n=42), estradiol (n=44), or placebo (n=43). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared to placebo, 42.9% versus 16.3% (p=0.03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (RRadj 0.90, 95%CI 0.84–0.97) compared to placebo. More frequent bleeding and spotting was observed in the estradiol group (RRadj 1.25, 95%CI 1.17–1.34). Conclusions Administration of naproxen resulted in a reduction in bleeding and spotting days compared to placebo. (150 words) PMID:22055339

Symptom-based tendencies of Helicobacter pylori eradication in patients with functional dyspepsia.

PubMed

Lan, Ling; Yu, Jing; Chen, Yu-Long; Zhong, Ya-Li; Zhang, Hao; Jia, Chang-He; Yuan, Yuan; Liu, Bo-Wei

2011-07-21

To investigate whether there were symptom-based tendencies in the Helicobacter pylori (H. pylori) eradication in functional dyspepsia (FD) patients. A randomized, single-blind, placebo-controlled study of H. pylori eradication for FD was conducted. A total of 195 FD patients with H. pylori infection were divided into two groups: 98 patients in the treatment group were treated with rabeprazole 10 mg twice daily for 2 wk, amoxicillin 1.0 g and clarithromycin 0.5 g twice daily for 1 wk; 97 patients in the placebo group were given placebos as control. Symptoms of FD, such as postprandial fullness, early satiety, nausea, belching, epigastric pain and epigastric burning, were assessed 3 mo after H. pylori eradication. By per-protocol analysis in patients with successful H. pylori eradication, higher effective rates of 77.2% and 82% were achieved in the patients with epigastric pain and epigastric burning than those in the placebo group (P < 0.05). The effective rates for postprandial fullness, early satiety, nausea and belching were 46%, 36%, 52.5% and 33.3%, respectively, and there was no significant difference from the placebo group (39.3%, 27.1%, 39.1% and 31.4%) (P > 0.05). In 84 patients who received H. pylori eradication therapy, the effective rates for epigastric pain (73.8%) and epigastric burning (80.7%) were higher than those in the placebo group (P < 0.05). The effective rates for postprandial fullness, early satiety, nausea and belching were 41.4%, 33.3%, 50% and 31.4%, respectively, and did not differ from those in the placebo group (P > 0.05). By intention-to-treat analysis, patients with epigastric pain and epigastric burning in the treatment group achieved higher effective rates of 60.8% and 65.7% than the placebo group (33.3% and 31.8%) (P < 0.05). The effective rates for postprandial fullness, early satiety, nausea and belching were 34.8%, 27.9%, 41.1% and 26.7% respectively in the treatment group, with no significant difference from those in the placebo group (34.8%, 23.9%, 35.3% and 27.1%) (P > 0.05). The efficacy of H. pylori eradication has symptom-based tendencies in FD patients. It may be effective in the subgroup of FD patients with epigastric pain syndrome.

Efficacy and safety of vitamin C vaginal tablets in the treatment of non-specific vaginitis. A randomised, double blind, placebo-controlled study.

PubMed

Petersen, E Eiko; Magnani, Paola

2004-11-10

This was a randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of Vitamin C vaginal tablets (250 mg) given once a day in patients suffering from non-specific vaginitis. The total length of the study was 20 days, including a treatment phase of 6 days. The primary end-point was the presence in the two groups of non-specific vaginitis 1 and 2 weeks after the end of treatment, as assessed by at least 3 out of the 4 characteristic symptoms: discharge, fishy odour, vaginal pH >/= 4.7, and presence of clue cells. Secondary end-points were the individual symptoms and signs, above reported, and pruritus, fever, superinfections, microscopic findings on vaginal smear, and colposcopy. One hundred female patients aged 18 years or older and suffering from non-specific vaginitis were included in the study after giving their informed consent. Fifty were randomised to the active treatment and 50 to placebo. Seven patients, three in the Vitamin C group and four in the placebo group, were lost to follow-up and did not complete the treatment period. Two patients in the active group showed protocol deviations (age under 18 years and HIV-positive, respectively). The two groups resulted comparable for demographics, history and baseline clinical picture. A cluster analysis of the four main symptoms showed a statistically significant difference between the active group and the placebo group; significantly more patients were still affected by non-specific vaginitis after placebo (35.7%) compared to patients treated with Vitamin C tablets (14.0%). The meaningful secondary variable, referring to the microscopic examination of vaginal smear, supported the trend for efficacy in the Vitamin C treated group. The clue cells disappeared in 79% of patients treated with the drug and in 53% of patients on placebo. Similarly, bacteria disappeared in 77 and 54%, respectively, while lactobacilli reappeared in 79.1 and 53.3%, respectively. Vaginal pH values decreased significantly in both groups, but the frequency rate of subjects with pH >/= 4.7, as measured 1 week after the drug discontinuation, was significantly lesser in the Vitamin C group (16.3%) than in the placebo group (38.6%). Adverse events occurred in four patients, two on placebo (pruritus, cystitis) and two on Vitamin C (two candidiasis).

Placebo-controlled trial of atomoxetine for weight reduction in people with schizophrenia treated with clozapine or olanzapine.

PubMed

Ball, M Patricia; Warren, Kimberly R; Feldman, Stephanie; McMahon, Robert P; Kelly, Deanna L; Buchanan, Robert W

2011-04-01

In recent years, several pharmacological and psychosocial interventions have examined ways to prevent or treat weight gain in people receiving second-generation antipsychotics. While there has been some success, in general, results have not been compelling. Atomoxetine is a selective norepinepherine reuptake inhibitor found to be associated with appetite suppression. Therefore, we examined whether atomoxetine may be of benefit for those who have gained weight on either clozapine or olanzapine. The study was a double-blind, placebo-controlled trial. All participants received the same psychosocial platform: a structured support and exercise group. People with schizophrenia or schizoaffective disorder, on olanzapine or clozapine, who had gained at least 7% of their pre-clozapine or pre-olanzapine weight were eligible for a 24-week, randomized, parallel group, double-blind comparison of adjunctive atomoxetine or placebo. Thirty-seven participants (20 atomoxetine, 17 placebo) were randomized and 26 participants (14 atomoxetine, 12 placebo; 70.2%) completed the study. There were no significant group differences in baseline BMI (atomoxetine: 34.5±4.9; placebo: 35.7±7.0) or weight (atomoxetine: 102.2±15.7 kg; placebo: 104.3±17.5 kg). Both treatment groups showed modest, not significant, trends in weight loss, averaging about 2 kg. Gender or baseline antipsychotic treatment did not modify treatment effects on weight. Secondary outcomes included neuropsychological assessments, symptom assessments (BPRS, SANS) and safety assessments. Of these, only the group difference in Gordon distractibility test scores was statistically significant and favored treatment with atomoxetine. Atomoxetine is not effective for weight loss in this population, but both olanzapine and clozapine participants can lose weight with structured group support and exercise.

Comparison of the Effects of pH-Dependent Peppermint Oil and Synbiotic Lactol (Bacillus coagulans + Fructooligosaccharides) on Childhood Functional Abdominal Pain: A Randomized Placebo-Controlled Study.

PubMed

Asgarshirazi, Masoumeh; Shariat, Mamak; Dalili, Hosein

2015-04-01

Still there is no consensus on the best treatment for abdominal pain-related functional Gastrointestinal Disorders (FGIDs). The purpose of this study was to compare the effects of a synbiotic Lactol (Bacillus coagulans + fructooligosaccharide (FOS)), peppermint oil (Colpermin) and placebo (folic acid) on abdominal pain-related FGIDs except for abdominal migraine. This placebo-controlled study was conducted on 120 children aged 4 - 13 years to compare the efficacy of pH-dependent peppermint oil (Colpermin) versus synbiotic Lactol (Bacillus coagulans + fructooligosaccharids (FOS)) in decreasing duration, severity and frequency of functional abdominal pain. The patients were randomly allocated into three equal groups (n = 40 in each group) and each group received Colpermin or Lactol or placebo. Eighty-eight out of 120 enrolled patients completed a one-month protocol and analyses were performed on 88 patients' data. Analyses showed that improvement in pain duration, frequency and severity in the Colpermin group was better than the placebo group (P = 0.0001, P = 0.0001 and P = 0.001, respectively). Moreover, pain duration and frequency were decreased in the Lactol group more than the placebo (P = 0.012 and P = 0.0001, respectively), but changes in pain severity were not significant (P = 0.373). Colpermin was superior to Lactol in decreasing pain duration and severity (P = 0.040 and P = 0.013, respectively). No known side effects or intolerance were seen with Colpermin or Lactol. The pH-dependent peppermint oil capsule and Lactol tablet (Bacillus coagulans+ FOS) as synbiotics seem to be superior to placebo in decreasing the severity, duration and frequency of pain in abdominal pain-related functional GI disorders.

Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial

PubMed Central

Naumann, M; Lowe, N J

2001-01-01

Objectives To evaluate the safety and efficacy of botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis. Design Multicentre, randomised, parallel group, placebo controlled trial. Setting 17 dermatology and neurology clinics in Belgium, Germany, Switzerland, and the United Kingdom. Participants Patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living. 465 were screened, 320 randomised, and 307 completed the study. Interventions Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhidrotic area of each axilla, defined by Minor's iodine starch test. Main outcome measures Percentage of responders (patients with ⩾50% reduction from baseline of spontaneous axillary sweat production) at four weeks, patients' global assessment of treatment satisfaction score, and adverse events. Results At four weeks, 94% (227) of the botulinum toxin type A group had responded compared with 36% (28) of the placebo group. By week 16, response rates were 82% (198) and 21% (16), respectively. The results for all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group. Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group (3.3 v 0.8, P<0.001 at 4 weeks). Adverse events were reported by only 27 patients (11%) in the botulinum toxin group and four (5%) in the placebo group (P>0.05). Conclusion Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction. What is already known on this topicPrimary hyperhidrosis is a chronic disorder that can affect any part of the body, especially the axillas, palms, feet, and faceCurrent treatments are often ineffective, short acting, or poorly toleratedWhat this study addsBotulinum toxin type A was significantly better than placebo on all measures of sweatingPatient satisfaction was high and few adverse events were reportedEffects of treatment remained apparent at 16 weeks PMID:11557704

Effectiveness of a new non-hydrogen peroxide bleaching agent after single use - a double-blind placebo-controlled short-term study.

PubMed

Bizhang, Mozhgan; Domin, Julia; Danesh, Gholamreza; Zimmer, Stefan

2017-01-01

Tooth whitening represents perhaps the most common aesthetic procedure in dentistry worldwide. The efficacy of bleaching depends on three aspects: bleaching agent, bleaching method, and tooth color. This in vivo study aimed to examine whitening effects on frontal teeth of the upper and lower jaws using an over-the-counter (OTC) non-hydrogen peroxide bleaching agent in comparison to a placebo after one single use. Forty subjects (25 female; 15 male) participated in this double-blind randomized placebo-controlled trial. The subjects were randomly allocated to two groups (n=20). The test group received the OTC product (iWhite Instant) and the placebo group received an identically composed product except for the active agents. Each subject was treated with a prefilled tray containing iWhite Instant or the placebo for 20 minutes. The tooth shade of the front teeth (upper and lower jaws) was assessed before (E_0), immediately after (E_1) and 24 h after treatment (E_2), using a shade guide (VITA classical). Statistical testing was accomplished using the Mann-Whitney U test (p<0.001). The dropout rate was 0%. There were no significant differences at E_0 between placebo and test groups regarding the tooth color. Differences in tooth color changes immediately after (ΔE1_0) and 24 h after treatment (ΔE2_0) were calculated for both groups. The mean values (standard deviations) of tooth color changes for ΔE1_0 were 2.26 (0.92) in the test group and 0.01 (0.21) in the placebo group. The color changes for ΔE2_0 showed mean values of 2.15 (1.10) in the test group and 0.07 (0.35) in the placebo group. For ΔE1_0 and ΔE2_0 significant differences were found between the groups. In this short-term study, the results showed that a non-hydrogen peroxide bleaching agent has significant whitening effects immediately and 24 h after a single-use treatment.

Do fatty acids help in overcoming reading difficulties? A double-blind, placebo-controlled study of the effects of eicosapentaenoic acid and carnosine supplementation on children with dyslexia.

PubMed

Kairaluoma, L; Närhi, V; Ahonen, T; Westerholm, J; Aro, M

2009-01-01

There are claims that dietary supplementation of unsaturated fatty acids could help children with dyslexia to overcome their reading problems. However, these claims have not yet been empirically tested. This study was designed to test whether dietary supplementation was superior to placebo in treating reading, spelling or other reading-related skills of children with dyslexia. The experimental group (eicosapentaenoic acid, EPA, n = 30) ate dietary supplements and the control group (placebo, n = 31) placebos during the 90-day treatment period. The supplements contained omega-3 fatty acid (ethyl-EPA, 500 mg/day) and carnosine (400 mg/day). The groups were matched for reading skills, grade, gender, attention problems, intelligence and amount of special education. The literacy-related skills of the two groups were assessed before and after the treatment period. No group differences were observed between EPA and placebo in measures of reading accuracy or speed, spelling, decoding fluency, arithmetical skills, reading-related language skills, attention or behavioural problems. The present findings do not support the hypothesis that omega-3 fatty acid (ethyl-EPA) or carnosine has a role in the treatment of reading and spelling problems in children with dyslexia.

A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hille, Andrea; Schmidberger, Heinz; Hermann, Robert M.

2005-12-01

Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo andmore » the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding.« less

Homeopathic Arnica montana for post-tonsillectomy analgesia: a randomised placebo control trial.

PubMed

Robertson, A; Suryanarayanan, R; Banerjee, A

2007-01-01

To evaluate the efficacy of Homeopathic Arnica in reducing the morbidity following tonsillectomy. Randomised double blind, placebo controlled trial at a tertiary referral centre. 190 patients over the age of 18 undergoing tonsillectomy were randomised into intervention and control groups receiving either Arnica 30c or identical placebo, 2 tablets 6 times in the first post-operative day and then 2 tablets twice a day for the next 7 days. The primary outcome measure was the change in pain scores (visual analogue scale) recorded by the patient on a questionnaire over 14 days post-operatively; Secondary outcome measures were: analgesia consumption, visits to the GP or hospital, antibiotic usage, the day on which their swallowing returned to normal and the day on which they returned to work. 111 (58.4%) completed questionnaires were available for analysis. The Arnica group had a significantly larger drop in pain score from day 1 to day 14 (28.3) compared to the placebo group (23.8) with p < 0.05. The two groups did not differ significantly on analgesic consumption or any of the other secondary outcome measures (number of post-operative visits to GP, use of antibiotics and secondary haemorrhage readmissions). The results of this trial suggest that Arnica montana given after tonsillectomy provides a small, but statistically significant, decrease in pain scores compared to placebo.

Efficacy of bupropion alone and in combination with nicotine gum

PubMed Central

Piper, Megan E.; Federman, E. Belle; McCarthy, Danielle E.; Bolt, Daniel M.; Smith, Stevens S.; Fiore, Michael C.; Baker, Timothy B.

2010-01-01

In this double-blind placebo-controlled smoking cessation treatment study, 608 participants were randomly assigned to receive active bupropion and active 4-mg gum (AA, n = 228), active bupropion and placebo gum (AP, n = 224), or placebo bupropion and placebo gum (PP, n = 156). Relative to the PP group, the AA and AP groups were each significantly more likely to be abstinent at one week, end of treatment and six months, but not twelve months post-quit. After the first week post-quit there were no differences in abstinence rates between the AA and AP groups. There were no significant individual difference variables that moderated outcome beyond one week post-quit. PMID:17763111

The effect of Vaccinium uliginosum extract on tablet computer-induced asthenopia: randomized placebo-controlled study.

PubMed

Park, Choul Yong; Gu, Namyi; Lim, Chi-Yeon; Oh, Jong-Hyun; Chang, Minwook; Kim, Martha; Rhee, Moo-Yong

2016-08-18

To investigate the alleviation effect of Vaccinium uliginosum extract (DA9301) on tablet computer-induced asthenopia. This was a randomized, placebo-controlled, double-blind and parallel study (Trial registration number: 2013-95). A total 60 volunteers were randomized into DA9301 (n = 30) and control (n = 30) groups. The DA9301 group received DA9301 oral pill (1000 mg/day) for 4 weeks and the control group received placebo. Asthenopia was evaluated by administering a questionnaire containing 10 questions (responses were scored on a scales of 0-6; total score: 60) regarding ocular symptoms before (baseline) and 4 weeks after receiving pills (DA9301 or placebo). The participants completed the questionnaire before and after tablet computer (iPad Air, Apple Inc.) watching at each visit. The change in total asthenopia score (TAS) was calculated and compared between the groups TAS increased significantly after tablet computer watching at baseline in DA9301 group. (from 20.35 to 23.88; p = 0.031) However, after receiving DA9301 for 4 weeks, TAS remained stable after tablet computer watching. In the control group, TAS changes induced by tablet computer watching were not significant both at baseline and at 4 weeks after receiving placebo. Further analysis revealed the scores for "tired eyes" (p = 0.001), "sore/aching eyes" (p = 0.038), "irritated eyes" (p = 0.010), "watery eyes" (p = 0.005), "dry eyes" (p = 0.003), "eye strain" (p = 0.006), "blurred vision" (p = 0.034), and "visual discomfort" (p = 0.018) significantly improved in the DA9301 group. We found that oral intake of DA9301 (1000 mg/day for 4 weeks) was effective in alleviating asthenopia symptoms induced by tablet computer watching. The study is registered at www.clinicaltrials.gov (registration number: NCT02641470, date of registration December 30, 2015).

Effect of diacerein on renal function and inflammatory cytokines in participants with type 2 diabetes mellitus and chronic kidney disease: A randomized controlled trial

PubMed Central

Piovesan, Fabiana; Tres, Glaucia S.; Moreira, Leila B.; Andrades, Michael E.; Lisboa, Hugo K.

2017-01-01

Diacerein seems to improve metabolic control and reduce inflammatory marker levels in individuals with type 2 diabetes mellitus (Type 2 DM), but for participants with chronic kidney disease (CKD) its effect is unknown. This study aimed to evaluate the effect of diacerein vs. placebo on urinary albumin/creatinine ratio (ACR), glomerular filtration rate (GFR), and inflammatory cytokines in type 2 DM participants with CKD. Blood pressure (BP) and metabolic control were secondary outcomes. This randomized, placebo-controlled, parallel trial of adjuvant treatment of type 2 DM with diacerein enrolled seventy-two participants with CKD, aged 30–80 years, with glycated hemoglobin levels from 53–97 mmol/mol (7.0–11.0%), receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antidiabetic agents. Participants randomized to diacerein or placebo were followed-up up to 90 days. Both groups had a marked reduction in ACR, but there was no effect on glomerular filtration rate. While the diacerein group had reduced TNF-α levels at the 75th percentile with a borderline significance (P = 0.05), there were no changes in the IL levels at the 75th percentile. Diacerein prevented the increase in blood glucose to the level observed in the placebo group (P = 0.04), improving metabolic control by 74%, reducing 24-hour diastolic BP, nighttime systolic and diastolic BP compared to the placebo group. In conclusion, among patients with type 2 DM and CKD, diacerein does not have an effect on ACR or GFR, but slows metabolic control deterioration and is associated with lower nighttime systolic and diastolic blood pressure. Trial registration: Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clinicos; ReBeC) U1111-1156-0255 PMID:29049415

Effect of diacerein on renal function and inflammatory cytokines in participants with type 2 diabetes mellitus and chronic kidney disease: A randomized controlled trial.

PubMed

Piovesan, Fabiana; Tres, Glaucia S; Moreira, Leila B; Andrades, Michael E; Lisboa, Hugo K; Fuchs, Sandra C

2017-01-01

Diacerein seems to improve metabolic control and reduce inflammatory marker levels in individuals with type 2 diabetes mellitus (Type 2 DM), but for participants with chronic kidney disease (CKD) its effect is unknown. This study aimed to evaluate the effect of diacerein vs. placebo on urinary albumin/creatinine ratio (ACR), glomerular filtration rate (GFR), and inflammatory cytokines in type 2 DM participants with CKD. Blood pressure (BP) and metabolic control were secondary outcomes. This randomized, placebo-controlled, parallel trial of adjuvant treatment of type 2 DM with diacerein enrolled seventy-two participants with CKD, aged 30-80 years, with glycated hemoglobin levels from 53-97 mmol/mol (7.0-11.0%), receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antidiabetic agents. Participants randomized to diacerein or placebo were followed-up up to 90 days. Both groups had a marked reduction in ACR, but there was no effect on glomerular filtration rate. While the diacerein group had reduced TNF-α levels at the 75th percentile with a borderline significance (P = 0.05), there were no changes in the IL levels at the 75th percentile. Diacerein prevented the increase in blood glucose to the level observed in the placebo group (P = 0.04), improving metabolic control by 74%, reducing 24-hour diastolic BP, nighttime systolic and diastolic BP compared to the placebo group. In conclusion, among patients with type 2 DM and CKD, diacerein does not have an effect on ACR or GFR, but slows metabolic control deterioration and is associated with lower nighttime systolic and diastolic blood pressure. Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clinicos; ReBeC) U1111-1156-0255.

Placebo analgesia is not due to compliance or habituation: EEG and behavioural evidence.

PubMed

Watson, Alison; El-Deredy, Wael; Vogt, Brent A; Jones, Anthony K P

2007-05-28

This study was designed to resolve whether experimental placebo responses are due to either increased compliance or habituation. We stimulated both forearms and recorded laser-evoked potentials from 18 healthy volunteers treated on one arm with a sham analgesic cream and an inactive cream on the other (treatment group), and 13 volunteers with an inactive cream on both arms (controls). The treatment group showed a significant reduction in the pain ratings and laser-evoked potentials with both the sham and inactive creams. The control group showed no evidence of habituation to the laser stimulus. The results indicate that the reduction in pain during experimental placebo response is unlikely to be due to sensory habituation or compliance with the experimental instructions.

Efficacy and safety of vardenafil in men with erectile dysfunction caused by spinal cord injury.

PubMed

Giuliano, F; Rubio-Aurioles, E; Kennelly, M; Montorsi, F; Kim, E D; Finkbeiner, A E; Pommerville, P J; Colopy, M W; Wilkins, H J; Wachs, B H

2006-01-24

To assess the efficacy and tolerability of vardenafil in men with erectile dysfunction (ED) due to traumatic spinal cord injury (SCI). In this multicenter, double-blind, placebo-controlled, parallel-group 12-week study, 418 men aged 18 years and older with ED for more than 6 months consequent to SCI were randomized to vardenafil (n = 207) or placebo (n = 211) (10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8). Efficacy assessments included the erectile function (EF) domain score of the International Index of Erectile Function questionnaire and diary questions regarding penetration, maintenance of erection to completion of intercourse, and ejaculation. Baseline patient characteristics were similar in the vardenafil (mean age 40 years) and placebo (mean age 39 years) groups. Mean baseline EF domain scores were 11.6 in the vardenafil group and 12.1 (moderate ED) in the placebo group. EF domain score in the vardenafil group improved to 22.0 (mild ED) at last observation carried forward vs 13.5 in the placebo group (p < 0.001). Over 12 weeks of treatment, mean per-patient penetration (76% vs 41%), maintenance (59% vs 22%), and ejaculation (19% vs 10%) success rates were significantly greater vs placebo (all p < 0.001). The most frequently reported drug-related adverse events were headache (vardenafil 15%, placebo 4%), flushing (vardenafil 6%, placebo 0%), nasal congestion (vardenafil 5%, placebo 0%), and dyspepsia (vardenafil 4%, placebo 0%). Vardenafil significantly improved erectile and ejaculatory function and was generally well tolerated in men with erectile dysfunction due to spinal cord injury.

Effects of Saccharomyces boulardii in children with acute diarrhoea.

PubMed

Kurugöl, Z; Koturoğlu, G

2005-01-01

Certain probiotic agents, e.g. Lactobacillus GG, have shown efficacy in clinical trials for the treatment of acute childhood diarrhoea, but few studies have examined the effect of Saccharomyces boulardii. We evaluated the effect of S. boulardii in children with acute diarrhoea. Two hundred children were randomized to receive S. boulardii in a granulated form in a daily dose of 250 mg (S. boulardii group) or placebo (placebo group) for 5 d. Clinical and demographic characteristics on admission were similar between the study groups. The medians of the average stool frequency after the second day of the treatment were significantly lower in the S. boulardii group than in the placebo group (p = 0.003). The duration of diarrhoea significantly reduced in the S. boulardii group compared with the placebo group (4.7 vs 5.5 d, p = 0.03). The effect of S. boulardii on watery diarrhoea became apparent after the second day of the treatment. The duration of hospital stay was shorter in the S. boulardii group than in the placebo group (2.9 vs 3.9 d, p < 0.001). Four children from the placebo group versus only one child from the S. boulardii group had persisting diarrhoea. The placebo-controlled study suggested that S. boulardii significantly reduced the duration of acute diarrhoea and the duration of hospital stay. S. boulardii seems to be a promising agent for the amelioration of the course of acute diarrhoea in children when used therapeutically.

STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain.

PubMed

Coffey, Frank; Wright, John; Hartshorn, Stuart; Hunt, Paul; Locker, Thomas; Mirza, Kazim; Dissmann, Patrick

2014-08-01

To evaluate the short-term efficacy and safety of methoxyflurane for the treatment of acute pain in patients presenting to an emergency department (ED) with minor trauma. STOP! was a randomised, double-blind, multicentre, placebo-controlled study conducted at six sites in the UK. A total of 300 patients, 90 of whom were adolescent patients (age 12-17 years), were randomised 150:150 to receive either methoxyflurane via a Penthrox inhaler or placebo. The primary end point of the study was the change in pain intensity as measured using the visual analogue scale (VAS) from baseline to 5, 10, 15 and 20 min after the start of study drug inhalation. Patients were supplied with one inhaler containing 3 mL methoxyflurane or 5 mL placebo after enrolment and initial assessments. Age group (adolescent/adult) and baseline VAS score were controlled for in the statistical analyses. A total of 149 patients received methoxyflurane, and 149 patients received placebo. Demographic and baseline characteristics were comparable between the groups. Methoxyflurane reduced pain severity significantly more than placebo (p<0.0001) at all time points tested, with the greatest estimated treatment effect of -18.5 mm (adjusted change from baseline) seen at 15 min after the start of treatment. Methoxyflurane was well tolerated, with the majority of adverse reactions being mild, transient and in line with anticipated pharmacological action. The results of this study suggest that methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and rapidly acting analgesic. NCT01420159. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Therapeutic Effects of Fermented Red Ginseng in Allergic Rhinitis: A Randomized, Double-Blind, Placebo-Controlled Study

PubMed Central

Jung, Jae-Woo; Ji, Geun-Eog; Park, Myeong-Soo; Song, Woo-Jung; Kim, Min-Hye; Kwon, Jae-Woo; Kim, Tae-Whan; Park, Heung-Woo; Cho, Sang-Heon; Min, Kyung-Up

2011-01-01

Purpose Allergic rhinitis is clinically defined as a disorder of the nose induced by IgE mediated inflammation after allergen exposure of the nasal mucosa. Many reports have stated that Panax ginseng and fermented red ginseng have anti-inflammatory effects, especially against Th2-type inflammation. This study was conducted to evaluate the therapeutic effects of fermented red ginseng in allergic rhinitis. Methods In this 4-week, double-blind, placebo-controlled study, 59 patients with persistent perennial allergic rhinitis were randomly divided into two groups: those receiving fermented red ginseng tablets (experimental group) and those receiving placebo (control group). The primary efficacy variable was the total nasal symptom score (TNSS; rhinorrhea, sneezing, itchy nose, and nasal congestion). Secondary efficacy variables were the Rhinitis Quality of Life (RQoL) score and skin reactivity to inhalant allergens, as determined by the skin prick test. Results There was no significant difference in the TNSS score and TNSS duration score between the experimental and placebo groups in weeks 1, 2, 3, or 4. For nasal congestion, fermented red ginseng was significantly effective (P<0.005), while placebo caused no change. The activity and emotion of RQoL improved markedly secondary to treatment with fermented red ginseng (P<0.05), while placebo caused no change. Additionally, fermented red ginseng reduced skin reactivity to sensitized perennial allergens (P<0.05). Fermented red ginseng was well tolerated. Conclusions Fermented red ginseng improved nasal congestion symptoms and RQoL in patients with perennial allergic rhinitis. PMID:21461249

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period.

PubMed

Kadowaki, Takashi; Kondo, Kazuoki; Sasaki, Noriyuki; Miyayama, Kyoko; Yokota, Shoko; Terata, Ryuji; Gouda, Maki

2017-09-01

To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was -0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P < 0.001). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. NCT02081599.

The Anesthetic Efficacy of Articaine and Lidocaine in Equivalent Doses as Buccal and Non-Palatal Infiltration for Maxillary Molar Extraction: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

PubMed

Majid, Omer Waleed; Ahmed, Aws Mahmood

2018-04-01

The purpose of the present study was to evaluate the anesthetic adequacy of 4% articaine 1.8 mL versus 2% lidocaine 3.6 mL without palatal injection compared with the standard technique for the extraction of maxillary molar teeth. This randomized, double-blinded, placebo-controlled clinical trial included patients requiring extraction of 1 maxillary molar under local anesthesia. Patients were randomly distributed into 1 of 3 groups: group A received 4% articaine 1.8 mL as a buccal injection and 0.2 mL as a palatal injection, group B received 4% articaine 1.8 mL plus normal saline 0.2 mL as a palatal injection, and group C received 2% lidocaine 3.6 mL plus normal saline 0.2 mL as a palatal injection. Pain was measured during injection, 8 minutes afterward, and during extraction using a visual analog scale. Initial palatal anesthesia and patients' satisfaction were measured using a 5-score verbal rating scale. Statistical analyses included descriptive statistics, analysis of variance, and Pearson χ 2 test. Differences with a P value less than .05 were considered significant. Eighty-four patients were included in the study. The average pain of injection was comparable among all study groups (P = .933). Pain during extraction in the articaine group was significantly less than that experienced in the placebo groups (P < .001), although the differences between placebo groups were insignificant. Satisfaction scores were significantly higher in the articaine group compared with the placebo groups (P < .001), with comparable results between placebo groups. Although the anesthetic effects of single placebo-controlled buccal injections of 4% articaine and 2% lidocaine were comparable, the level of anesthetic adequacy was statistically less than that achieved by 4% articaine given by the standard technique. These results do not justify the buccal and non-palatal infiltration of articaine or lidocaine as an effective alternative to the standard technique in the extraction of maxillary molar teeth. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

No effect of magnesium supplementation on metabolic control and insulin sensitivity in type 2 diabetic patients with normomagnesemia.

PubMed

Navarrete-Cortes, Adrian; Ble-Castillo, Jorge L; Guerrero-Romero, Fernando; Cordova-Uscanga, Ruben; Juárez-Rojop, Isela E; Aguilar-Mariscal, Hidemi; Tovilla-Zarate, Carlos Alfonso; Lopez-Guevara, Maria Del Rocio

2014-01-01

There are limited and conflicting data from clinical trials concerning the beneficial effects of magnesium supplementation on diabetic patients. We investigated the effects of magnesium supplementation on metabolic control and insulin sensitivity in type 2 diabetic patients with normomagnesemia. A total of 98 normomagnesemic subjects with type 2 diabetes were enrolled in a randomized, crossover, double-blind, placebo-controlled trial. Participants were randomly assigned to receive magnesium lactate (360 mg elemental magnesium) or placebo for three months, followed by a three-month washout period. Treatment assignments were then reversed over an additional three months of follow-up. The primary endpoint was a reduction in fasting glucose and HbA1c. A total of 56 subjects completed the follow-up in the magnesium and placebo supplementation groups. Urinary magnesium excretion was increased following magnesium supplementation in the intervention group compared with the placebo group (p = 0.0002). Fasting glucose, HbA1c, insulin and HOMA-IR, as well as lipid profile, did not change significantly during treatment. We concluded that magnesium supplementation does not improve metabolic control or insulin sensitivity in diabetic subjects with normomagnesemia.

Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study

PubMed Central

Schellenberg, R

2001-01-01

Objectives To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome. Design Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles. Setting General medicine community clinics. Participants 178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days. Interventions Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles. Main outcome measures Main efficacy variable: change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. Secondary efficacy variables: changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms). Results Improvement in the main variable was greater in the active group compared with placebo group (P<0.001). Analysis of the secondary variables showed significant (P<0.001) superiority of active treatment in each of the three global impression items. Responder rates were 52% and 24% for active and placebo, respectively. Seven women reported mild adverse events (four active; three placebo), none of which caused discontinuation of treatment. Conclusions Dry extract of agnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome. PMID:11159568

Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study.

PubMed

Schellenberg, R

2001-01-20

To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome. Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles. General medicine community clinics. 178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days. Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles. Main efficacy variable: change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. Secondary efficacy variables: changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms). Improvement in the main variable was greater in the active group compared with placebo group (P<0.001). Analysis of the secondary variables showed significant (P<0.001) superiority of active treatment in each of the three global impression items. Responder rates were 52% and 24% for active and placebo, respectively. Seven women reported mild adverse events (four active; three placebo), none of which caused discontinuation of treatment. Dry extract of agnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome.

Etoricoxib - preemptive and postoperative analgesia (EPPA) in patients with laparotomy or thoracotomy - design and protocols

PubMed Central

2010-01-01

Background and Objective Our objective was to report on the design and essentials of the Etoricoxib protocol- Preemptive and Postoperative Analgesia (EPPA) Trial, investigating whether preemptive analgesia with cox-2 inhibitors is more efficacious than placebo in patients who receive either laparotomy or thoracotomy. Design and Methods The study is a 2 × 2 factorial armed, double blinded, bicentric, randomised placebo-controlled trial comparing (a) etoricoxib and (b) placebo in a pre- and postoperative setting. The total observation period is 6 months. According to a power analysis, 120 patients scheduled for abdominal or thoracic surgery will randomly be allocated to either the preemptive or the postoperative treatment group. These two groups are each divided into two arms. Preemptive group patients receive etoricoxib prior to surgery and either etoricoxib again or placebo postoperatively. Postoperative group patients receive placebo prior to surgery and either placebo again or etoricoxib after surgery (2 × 2 factorial study design). The Main Outcome Measure is the cumulative use of morphine within the first 48 hours after surgery (measured by patient controlled analgesia PCA). Secondary outcome parameters include a broad range of tests including sensoric perception and genetic polymorphisms. Discussion The results of this study will provide information on the analgesic effectiveness of etoricoxib in preemptive analgesia and will give hints on possible preventive effects of persistent pain. Trial registration NCT00716833 PMID:20504378

Effects of enzyme-treated asparagus extract on heat shock protein 70, stress indices, and sleep in healthy adult men.

PubMed

Ito, Tomohiro; Goto, Kazunori; Takanari, Jun; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Tanaka, Aiko; Nishihira, Jun

2014-01-01

Enzyme-treated asparagus extract (ETAS) has been developed as a novel anti-stress functional food ingredient that is produced from asparagus. Two human intervention trials with ETAS were conducted in healthy adult male volunteers. Study 1 was a randomized, double-blind, placebo-controlled study to assess the effects of ETAS on expression of heat shock protein 70 (HSP70) mRNA in blood and the autonomic nervous system (ANS). The ETAS group showed a tendency to enhance HSP70 mRNA expression level compared to the placebo group. Several ANS condition parameters were significantly improved in the ETAS group when compared to the placebo group. In Study 2, a randomized, double-blind, placebo-controlled, crossover trial investigated the influence on stress-related hormones and sleep. Serum and salivary cortisol levels were significantly elevated compared to baseline during the placebo period, but remained unchanged during the ETAS period. The salivary chromogranin A level was significantly decreased in the ETAS-treated subjects compared to their baseline levels. The actual sleep time was not significantly different between ETAS and placebo. However, when the subjects were divided into two categories based on sleep efficiency or the average of night sleeping time, ETAS intake was effective to modulate the sleep state among those with low sleep efficiency or excess sleep time.

Training Attention Improves Decision Making in Individuals with Elevated Self-Reported Depressive Symptoms

PubMed Central

Cooper, Jessica A.; Gorlick, Marissa A.; Denny, Taylor; Worthy, Darrell A.; Beevers, Christopher G.; Maddox, W. Todd

2013-01-01

Depression is often characterized by attentional biases toward negative items and away from positive items, which likely affects reward and punishment processing. Recent work reported that training attention away from negative stimuli reduced this bias and reduced depressive symptoms. However, the effect of attention training on subsequent learning has yet to be explored. In the current study, participants were required to learn to maximize reward during decision-making. Undergraduates with elevated self-reported depressive symptoms received attention training toward positive stimuli prior to performing the decision-making task (n=20; active training). The active training group was compared to two groups: undergraduates with elevated self-reported depressive symptoms who received placebo training (n=22; placebo training) and control subjects with low levels of depressive symptoms (n=33; non-depressive control). The placebo-training depressive group performed worse and switched between options more than non-depressive controls on the reward maximization task. However, depressives that received active training performed as well as non-depressive controls. Computational modeling indicated that the placebo-trained group learned more from negative than from positive prediction errors, leading to more frequent switching. The non-depressive control and active training depressive groups showed similar learning from positive and negative prediction errors, leading to less frequent switching and better performance. Our results indicate that individuals with elevated depressive symptoms are impaired at reward maximization, but that the deficit can be improved with attention training toward positive stimuli. PMID:24197612

Effect of submucosal dexamethasone injection on postoperative pain, oedema, and trismus following mandibular third molar surgery: a prospective, randomized, double-blind clinical trial.

PubMed

Mojsa, I M; Pokrowiecki, R; Lipczynski, K; Czerwonka, D; Szczeklik, K; Zaleska, M

2017-04-01

The aim of this study was to investigate the effect of the submucosal injection of 1ml dexamethasone (4mg/ml) on pain, swelling, and trismus following the extraction of retained lower third molars. Ninety patients (mean age 23.5 years) were split randomly into three equal study groups (30 patients in each): the 'before' group received dexamethasone 15min before surgery and placebo 15min after surgery; the 'after' group received placebo 15min before surgery and dexamethasone 15min after surgery; the 'placebo' group received placebo 15min before surgery and placebo 15min after surgery. Postoperative pain was recorded by the patients using a visual analogue scale, numerical rating scale, and the McGill Pain Questionnaire at 1, 2, 4, 6, 8, 12, and 24h after surgery. The patients also recorded the total number of analgesic doses consumed during the 24h after the procedure. Swelling (determined using linear measurements of the face) and trismus (determined through measurement of maximum mouth opening) were assessed at 48h, 72h, and 7 days following surgery. Better control of pain, swelling, and trismus was demonstrated for dexamethasone in comparison to placebo. Postoperative dexamethasone provided better pain control than preoperative dexamethasone. There was no difference in total rescue analgesic intake between the preoperative and postoperative dexamethasone groups. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Efficacy of fermented green tea on peripheral skin temperature: a randomized and placebo-controlled clinical study.

PubMed

Lee, Eunyoung; Lee, Bum-Jin; Ha, Jaehyoun; Shin, Hyun-Jung; Chung, Jin-Oh

2016-09-01

This study was aimed at assessing the therapeutic efficacy of green tea on peripheral skin for cold hypersensitive subjects, who had the feeling of cold hands and feet at cold temperatures, one of the most common complaints in Asian women. This randomized and placebo-controlled clinical study included 60 female Korean subjects who had the feeling of cold hands and feet at cold temperatures. The subjects were randomly assigned into two groups to receive fermented green tea or a placebo (hot water). The skin temperature of the hands and feet was measured using digital infrared thermography at the baseline and at 15, 30, 45, and 60 min after the oral administration of the tea or placebo. The skin temperature of the hands and feet of the fermented green tea-administered group was significantly higher than that of the placebo-administered group. The temperature difference between the finger and the dorsum of the hand was significantly lower in the fermented green tea-administered group than that in the placebo group. Fermented green tea is helpful for cold hypersensitivity. This is the first clinical study to evaluate the efficacy of fermented green tea on peripheral skin in subjects having the feeling of cold hands and feet at cold temperatures by infrared thermography. However, further studies are necessary to evaluate the long-term effects of the fermented green tea for cold hypersensitivity and to elucidate the underlying physiological mechanism. © 2015 Wiley Periodicals, Inc.

Treatment of Plantar Fasciitis With Botulinum Toxin.

PubMed

Ahmad, Jamal; Ahmad, Stacy H; Jones, Kennis

2017-01-01

This study examined the effect of botulinum toxin upon plantar fasciitis through a randomized, controlled, and blinded trial. Between 2012 and 2015, 50 patients presented with plantar fasciitis. Twenty-five patients each randomly received an IncobotulinumtoxinA (IBTA) or saline injection of their affected foot. Pre- and postinjection function and pain were graded with the Foot and Ankle Ability Measures (FAAM) and visual analog scale (VAS), respectively. All 50 study patients who randomly received either placebo or IBTA presented at 6 and 12 months after injection. At 6 months, the mean FAAM increased from 35.9 to 40.9 of 100, and the mean pain score decreased from 8.4 to 7.9 of 10 within the placebo group. At 6 months, the mean FAAM increased from 36.3 to 73.8 of 100, and mean pain score decreased from 7.2 to 3.6 of 10 within the IBTA group. These postinjection scores were significantly better than the placebo group ( P = .01). At 12 months after injection, the IBTA group maintained significantly better function and pain than the placebo group ( P < .05). By that time, 0 (0%) and 3 (12%) patients who received IBTA and saline, respectively, underwent surgery for recalcitrant plantar fasciitis ( P < .005). Compared with placebo saline injection, using IBTA to treat plantar fasciitis resulted in significantly better improvement in foot function and pain. IBTA also lessened the need for operative treatment of plantar fasciitis. I, Randomized, double-blinded, placebo-controlled study.

Effect of a plaster containing DHEP and heparin in acute ankle sprains with oedema: a randomized, double-blind, placebo-controlled, clinical study.

PubMed

Coudreuse, J-M; de Vathaire, F

2010-09-01

Ankle sprains are the most frequent injuries in sport and daily life, and are usually treated with anti-inflammatory drugs or compounds that have an effect on microcirculation. The efficacy and tolerability of a novel plaster containing both diclofenac epolamine (DHEP) and heparin in the treatment of acute painful ankle sprains with oedema was investigated in a randomized, double-blind, placebo-controlled study. This study, carried out in 32 French medical centres, enrolled 233 patients (148 male and 86 female, aged 18-65 years) with an ankle sprain that had occurred within the previous 48 hours. Patients were treated once daily with DHEP heparin or placebo plaster for 7 days. Reduction in ankle joint swelling measured by submalleolar circumference was the primary efficacy endpoint; secondary endpoints were pain (at rest, in active mobilization, by passive stretch and by pressure), functional disability and global judgement of efficacy and tolerability. DHEP heparin-treated patients experienced a significantly greater reduction in joint swelling compared with placebo (p = 0.005). The reduction in pain was also in favour of DHEP heparin patients, with significantly lower pain in DHEP heparin-treated than placebo-treated patients within 3 hours of the first application (p < 0.05). Only two patients in the DHEP heparin plaster group and six in the placebo group experienced minor adverse events, all of which resolved spontaneously. By design, the study was limited to a placebo-controlled comparison, and there was no test for possible selection bias (subsequently ruled out by choice of efficacy parameters and measures) that may have resulted in a baseline imbalance between patient groups. Results confirm the efficacy of DHEP heparin plaster compared with placebo for the treatment of painful ankle sprain with oedema. Prompt control of pain and oedema may shorten the time to initiation of a rehabilitation programme, thus reducing the risk of ankle disability recurrence and the development of chronic injury.

Comparative Evaluation of Antiplaque Efficacy of Coconut Oil Pulling and a Placebo, Among Dental College Students: A Randomized Controlled Trial

PubMed Central

Kulkarni, Suhas; Madupu, Padma Reddy; Doshi, Dolar; Bandari, Srikanth Reddy; Srilatha, Adepu

2017-01-01

Introduction Oil pulling, has been extensively used as traditional Indian folk remedy since many years to prevent dental diseases and for strengthening teeth and gums. Aim To compare and evaluate antiplaque efficacy of coconut oil pulling with a placebo among dental students, in Hyderabad city of India. Materials and Methods A randomized controlled study was carried out among 40 dental students. Out of 40, 20 subjects were randomly assigned to study group and other 20 to control group. Subjects in the study group were given the coconut oil and control group a placebo, and advised to rinse for 10 minutes, once daily in the morning for a period of seven days. Plaque levels were assessed on day zero, third and seventh day using Turesky-Gilmore-Glickman Modification of the Quigley-Hein Plaque Index (1970) for both the groups. Results The mean plaque scores showed a significant difference at baseline, third day and seventh day among both study (p<0.001) and control groups (p<0.001). Group wise comparison revealed, though the mean plaque scores were low among study group on third day and seventh day on comparison with the control group, significant difference was noticed only on the seventh day. Furthermore, the mean percentage reduction of plaque scores were also significant only on the seventh day with a high mean plaque reduction among study groups (p<0.001). Conclusion Oil pulling is effective in controlling plaque levels. PMID:29207824

Epigallocatechin gallate enhances treatment efficacy of oral nifedipine against pregnancy-induced severe pre-eclampsia: A double-blind, randomized and placebo-controlled clinical study.

PubMed

Shi, D-D; Guo, J-J; Zhou, L; Wang, N

2018-02-01

Oral nifedipine is commonly used to treat pre-eclampsia, one of the most severe complications during pregnancy, but its clinical efficacy is less than ideal. Epigallocatechin gallate (EGCG), a natural compound from green tea, could benefit cardiovascular health especially hypertension. We investigated the clinical efficacy of EGCG, when complemented with oral nifedipine, in treating pre-eclampsia. A total of 350 pregnant women with severe pre-eclampsia were recruited and randomized to receive oral nifedipine, together with placebo (NIF+placebo) or EGCG (NIF+EGCG). The primary treatment outcome was the time needed to control blood pressure and interval time before a new hypertensive crisis, whereas the secondary treatment outcome was the number of treatment doses to effectively control blood pressure, maternal adverse effects and neonatal complications. Comparing NIF+EGCG group to NIF+placebo group, the time needed to control blood pressure was significantly shorter (NIF+EGCG 31.2±16.7 minutes, NIF+placebo 45.3±21.9 minutes; 95% CI 9.7-18.5 minutes), whereas interval time before a new hypertensive crisis was significantly prolonged (NIF+EGCG 7.2±2.9 hours, NIF+placebo 4.1±3.7 hours; 95% CI 2.3-3.9 hours), and the number of treatment dosages needed to effectively control blood pressure was also lower. Between the two treatment groups, no differences in incidence rates of maternal adverse effects or neonatal complications were observed. EGCG is both safe and effective in enhancing treatment efficacy of oral nifedipine against pregnancy-induced severe pre-eclampsia, but formal validation is required prior to its recommendation for use outside of clinical trials. © 2017 John Wiley & Sons Ltd.

Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes.

PubMed

Albarracin, Cesar A; Fuqua, Burcham C; Evans, Joseph L; Goldfine, Ira D

2008-01-01

Chromium and biotin play essential roles in regulating carbohydrate metabolism. This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of the combination of chromium picolinate and biotin on glycaemic control. Four hundred and forty-seven subjects with poorly controlled type 2 diabetes (HbA(1c) > or = 7.0%) were enrolled and received either chromium picolinate (600 microg Cr(+3)) with biotin (2 mg), or matching placebo, for 90 days in combination with stable oral anti-diabetic agents (OADs). Major endpoints were reductions in HbA(1c), fasting glucose, and lipids. Safety and tolerability were assessed. Change in HbA(1c) was significantly different between treatment groups (p = 0.03). HbA(1c) in the chromium picolinate/biotin group decreased 0.54%. The decrease in HbA(1c) was most pronounced in chromium picolinate/biotin subjects whose baseline HbA(1c) > or = 10%, and highly significant when compared with placebo (-1.76% vs - 0.68%; p = 0.005). Fasting glucose levels were reduced in the entire chromium picolinate/biotin group versus placebo (-9.8 mg/dL vs 0.7 mg/dL; p = 0.02). Reductions in fasting glucose were also most marked in those subjects whose baseline HbA(1c) > or = 10.0%, and significant when compared to placebo (-35.8 mg/dL vs. 16.2 mg/dL; p = 0.01). Treatment was well tolerated with no adverse effects dissimilar from placebo. These results suggest that the chromium picolinate/biotin combination, administered as an adjuvant to current prescription anti-diabetic medication, can improve glycaemic control in overweight to obese individuals with type 2 diabetes; especially those patients with poor glycaemic control on oral therapy. 2007 John Wiley & Sons, Ltd

Placebo-Controlled Study of Pimozide Augmentation of Fluoxetine in Body Dysmorphic Disorder

PubMed Central

Phillips, Katharine A.

2006-01-01

Objective Although body dysmorphic disorder often responds to serotonin reuptake inhibitors (SRIs), most patients do not respond or respond only partially. However, placebo-controlled studies of augmentation of SRIs have not been done. Furthermore, although 40%–50% of patients are delusional, studies of antipsychotic medications have not been done. Method Twenty-eight patients with body dysmorphic disorder or its delusional variant participated in an 8-week, placebo-controlled, double-blind, parallel-group study of pimozide augmentation of fluoxetine. Results Pimozide was not more effective than placebo: two (18.2%) of 11 subjects responded to pimozide and three (17.6%) of 17 subjects responded to placebo. There was no significant effect of baseline delusionality on endpoint severity of body dysmorphic disorder. Delusionality did not decrease significantly more with pimozide than placebo. Conclusions Pimozide augmentation of fluoxetine treatment for body dysmorphic disorder was not more effective than placebo, even in more delusional patients. Further studies of augmentation for SRIs are needed. PMID:15677604

A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression.

PubMed

Keitner, Gabor I; Garlow, Steven J; Ryan, Christine E; Ninan, Philip T; Solomon, David A; Nemeroff, Charles B; Keller, Martin B

2009-01-01

Patients (30-50%) with non-psychotic major depression will not respond despite an adequate trial of antidepressant medication. This study evaluated risperidone as an augmenting agent for patients who failed or only partially responded to an adequate trial of an antidepressant medication. Ninety-seven patients with unipolar non-psychotic major depression who were not responsive to antidepressant monotherapy were randomized to risperidone (0.5-3mg/day) or placebo augmentation in a four-week, double-blind, placebo controlled treatment trial. The primary outcome measure was remission defined by a score of < or =10 on the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes measures were the Hamilton Rating Scale for Depression, the Clinician Global Impression of Severity scale and the overall satisfaction item of the Quality of Life and Enjoyment Questionnaire. Subjects in both treatment groups improved significantly over time. The odds of remitting were significantly better for patients in the risperidone vs. placebo arm (OR=3.33, p=.011). At the end of 4 weeks of treatment 52% of the risperidone augmentation group remitted (MADRS< or =10) compared to 24% of the placebo augmentation group (CMH(1)=6.48, p=.011), but the two groups were converging. Patients in the risperidone group also reported significantly more improvement in quality-of-life than patients in the placebo group. There were no between-group differences in the number of adverse events reported, however, weight gain was significantly higher in the group receiving risperidone. Augmentation of an antidepressant with risperidone for patients with difficult-to-treat depression leads to more rapid response and a higher remission rate and better quality-of-life.

The effects of natural S-equol supplementation on skin aging in postmenopausal women: a pilot randomized placebo-controlled trial.

PubMed

Oyama, Ayuko; Ueno, Tomomi; Uchiyama, Shigeto; Aihara, Tomohiko; Miyake, Akira; Kondo, Sumio; Matsunaga, Kayoko

2012-02-01

The aim of this study was to investigate the effects of the natural S-equol supplement on skin aging in equol-nonproducing Japanese postmenopausal women. A randomized, double-blind, placebo-controlled trial examined the use of the natural S-equol supplement for 12 weeks in 101 postmenopausal Japanese women who were equol nonproducers. They were randomly assigned to one of three groups: placebo (n = 34), 10 mg S-equol/day (EQL10; n = 34), or 30 mg S-equol/day (EQL30; n = 33). Skin parameters of crow's-feet wrinkles (area and depth), hydration, transepidermal water loss, and elasticity were measured at baseline and at monthly intervals during treatment. Vaginal cytology, endometrial thickness, and mammography were performed before and after treatment. Serum hormone concentrations were measured at the same time as skin parameters. The EQL10 and EQL30 groups showed significant reductions in wrinkle area compared with the placebo group (P < 0.05). There was a significant difference in wrinkle depth between the placebo group and the EQL30 group (P < 0.05). Other skin parameters did not show significant differences after the treatment in any group. There were no abnormal results in hormone status or gynecological examinations. Our data suggest that natural S-equol supplementation (EQL10 and EQL30) may have a beneficial effect on crow's-feet wrinkles in postmenopausal women without serious adverse events.

Ingestion of hyaluronans (molecular weights 800 k and 300 k) improves dry skin conditions: a randomized, double blind, controlled study

PubMed Central

Kawada, Chinatsu; Yoshida, Takushi; Yoshida, Hideto; Sakamoto, Wakako; Odanaka, Wataru; Sato, Toshihide; Yamasaki, Takeshi; Kanemitsu, Tomoyuki; Masuda, Yasunobu; Urushibata, Osamu

2015-01-01

Hyaluronan (HA) has been increasingly used as a dietary supplement to improve the skin. However, the effect of ingested HA may depend on its molecular weight (MW) because its physiological activities in the body vary with its MW. In this study, we examined the effects of ingested HA with varying MW on the skin. In this randomized, double blind, placebo controlled study, 61 subjects with dry skin received oral HA (120 mg/day), of MWs 800 k and 300 k or placebo, for 6 weeks. The skin moisture contents of the first two groups increased more than those of the placebo group during the ingestion period. In addition, group HA 300 k exhibited significant improvements in skin moisture content 2 weeks after ingestion ended compared with the placebo group. A questionnaire survey about subjective facial aging symptoms showed that the HA treated groups exhibited significantly improved the skin condition compared with the placebo treated group. Furthermore, dermatologists objectively evaluated the clinical symptoms of the facial and whole body skin, showing that no adverse events were related to daily ingestion of HA. This study shows that both of ingesting HAs (MWs 800 k and 300 k) improved the skin condition by increasing the moisture content. PMID:25834304

Effects of Ginger on Serum Lipids and Lipoproteins in Peritoneal Dialysis Patients: A Randomized Controlled Trial.

PubMed

Tabibi, Hadi; Imani, Hossein; Atabak, Shahnaz; Najafi, Iraj; Hedayati, Mehdi; Rahmani, Leila

2016-01-01

♦ In peritoneal dialysis (PD) patients, one of the major risk factors for cardiovascular disease is lipid abnormalities. This study was designed to investigate the effects of ginger supplementation on serum lipids and lipoproteins in PD patients. ♦ In this randomized, double-blind, placebo-controlled trial, 36 PD patients were randomly assigned to either the ginger or the placebo group. The patients in the ginger group received 1,000 mg ginger daily for 10 weeks, while the placebo group received corresponding placebos. At baseline and at the end of week 10, 7 mL of blood were obtained from each patient after a 12- to 14-hour fast, and serum concentrations of triglyceride, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and lipoprotein (a) [Lp (a)] were measured. ♦ Serum triglyceride concentration decreased significantly up to 15% in the ginger group at the end of week 10 compared with baseline (p < 0.01), and the reduction was significant in comparison with the placebo group (p < 0.05). There were no significant differences between the 2 groups in mean changes of serum total cholesterol, LDL-C, HDL-C, and Lp (a). ♦ This study indicates that daily administration of 1,000 mg ginger reduces serum triglyceride concentration, which is a risk factor for cardiovascular disease, in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

Effect of fat on serum 25-hydroxyvitamin D levels after a single oral dose of vitamin D in young healthy adults: a double-blind randomized placebo-controlled study.

PubMed

Raimundo, Fabiana Viegas; Lang, Maria Augusta Britto; Scopel, Luciano; Marcondes, Natália Aydos; Araújo, Mirna Griselda Anocibar; Faulhaber, Gustavo Adolpho Moreira; Furlanetto, Tania Weber

2015-04-01

This double-blind placebo-controlled trial evaluated serum 25-hydroxyvitamin D [25(OH)D] levels after the oral intake of a single dose of cholecalciferol during one of the three meals, containing different amounts of fat or placebo. Sixty-four healthy medical residents or students of a university hospital in Porto Alegre, latitude 30° S, Brazil, were divided into four groups. Three groups received a single 50,000 IU oral dose of cholecalciferol during a meal containing 0 g (Group 1), 15 g (Group 2) or 30 g (Group 3) of fat, and one group received placebo (Group 4), according to randomization. Serum 25(OH)D, parathyroid hormone, total calcium, albumin, magnesium, and creatinine levels, and urinary calcium, magnesium, and creatinine levels were measured at baseline and after 14 days. Baseline mean serum 25(OH)D levels were low in all groups. Vitamin D given during breakfast increased the mean change of serum 25(OH)D levels, when compared to placebo. Furthermore, the intake of fat with vitamin D increased the mean change of serum 25(OH)D levels. A single oral dose of vitamin D given with food increased mean serum 25(OH)D levels, after 2 weeks, and the mean increase was larger, when the meal had at least 15 g of fat. These findings can have important implications to oral vitamin D supplementation.

Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study.

PubMed

Senin, U; Abate, G; Fieschi, C; Gori, G; Guala, A; Marini, G; Villardita, C; Parnetti, L

1991-12-01

One hundred and nine elderly patients suffering from mild to moderate cognitive impairment fulfilling NINCDS-ADRDA criteria for probable dementia of the Alzheimer type were treated for 6 months with a new nootropic drug, aniracetam (Ro 13-5057) in a double-blind randomized study versus placebo. The two treatment groups were comparable at baseline for demographic and behaviourial parameters and symptomatology. Patients underwent clinical, behaviourial and psychometric evaluation every other month. The aniracetam group differed significantly from the placebo group by the end of the study and also showed a statistically significant improvement versus baseline in the psychobehavioural parameters, while in the placebo group a steady deterioration was observed. Tolerability to aniracetam was excellent.

Placebo-controlled study of the mite allergen-reducing effect of tannic acid plus benzyl benzoate on carpets in homes of children with house dust mite sensitization and asthma.

PubMed

Lau, Susanne; Wahn, Julia; Schulz, Gabriele; Sommerfeld, Christine; Wahn, Ulrich

2002-02-01

We studied the effect of a spray containing 1% benzyl benzoate, an acaricide, and 1% tannic acid ('Lowal'; a protein-denaturing substance), on concentrations of major allergens from house dust mite (HDM) species Dermatophagoides pteronyssinus and D. farinae (Der p 1 and Der f 1, respectively) in carpets. In a double-blind, placebo-controlled study with crossover design, 30 homes of children with HDM sensitization and asthma were included. All houses showed > or = 400 ng/g of Der p 1 + Der f 1 in carpet dust. The first treatment was performed on day 0 (group 1 active treatment, n = 15; group 2 placebo treatment, n = 15). After 2 and 8 weeks, dust samples were collected for quantification of mite allergens. After a 2-week washout period, the second treatment was performed (group 1 placebo treatment; group 2 active treatment). Again, carpet dust was collected after 2 and 8 weeks. Twenty-two of 30 families completed the trial: 14/15 in group 1 and eight of 15 in group 2. On day 0, there was no significant difference in mite allergen exposure between group 1 and group 2 (1,498 vs. 2,239 ng/g of Der p 1 + Der f 1, respectively). In group 1, the geometric mean for the difference of mite allergen concentration comparing day 0 and week 6 was 196 ng/g (95% CI: -7,161 and 8,401) for the first treatment (active) and 15 ng/g (95% CI: -1,079 and 1,292) for the second treatment (control). In group 2, the difference was 66 ng/g (95% CI: -398 and 1,515) for the first treatment (control) and 609 ng/g (95% CI: 186 and 9,264) for the second treatment (active). Comparing placebo and active treatment in total, there was a significant decrease following placebo treatment after 14 days (p = 0.026). After 8 weeks, active treatment was superior to placebo treatment (p = 0.049), but the allergen reduction achieved was < 20% (median 1,500 ng/g on day 0 vs. 1,250 ng/g after 8 weeks). We conclude that the slight mite allergen reduction on carpets achieved by the treatment with 'Lowal' is unlikely to achieve worthwhile clinical benefit either in the treatment of mite-sensitive patients or in primary or secondary prophylaxis.

A randomized, controlled, double-blind trial of the adjunct use of Clebopride in polyethylene glycol electrolyte (PEG) solution for colonoscopy preparation.

PubMed

Abdullah, Murdani; Rani, A Aziz; Fauzi, Achmad; Syam, Ari Fahrial; Makmun, Dadang; Simadibrata, Marcellus; Manan, Chudahman; Harjodisastro, Daldiyono

2010-01-01

To study the benefit of Clebopride as an adjuvant in polyethylene glycol electrolyte (PEG) solution for colonoscopy preparation. Eighty one adult patients who underwent colonoscopy examination were recruited in this randomized double blind controlled study. First group received PEG and placebo, whereas second group received PEG and Clebopride. Two litres of PEG was taken at night before colonoscopy. The acceptability and tolerability of bowel preparation were assessed through interview method. The efficacy of bowel preparation was assessed using Aronchick's Criteria. In terms of acceptability, 64 patients (31 patients from placebo group vs 33 patients from Clebopride group) were able to drink two litres of PEG solution. Sixty patients (29 patients from placebo group and 31 patients from Clebopride group) were willing to accept PEG solution for their next bowel preparation. On the term of tolerability, nausea, abdominal distension, and borborygmus were more frequent in the placebo group (34.2% vs 27.9%; 44.7% vs 32.6%; 26.3% vs 4.6% respectively). However, only the difference at the incidence of borborygmus that was statistically significant (p<0.05). On the terms of efficacy, both groups showed a comparable bowel preparation quality with 88.4% of bowel preparation in Clebopride group and 81.6% of bowel preparation in placebo group were optimal (p = 0.585). The adjunct use of Clebopride in PEG solution for colonoscopy preparations tends to increase the acceptability, tolerability, and efficacy. The presence of borborygmus was significantly lower in the Clebopride group.

A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.

PubMed

Ikeda, S; Takano, Y; Cynshi, O; Tanaka, R; Christ, A D; Boerlin, V; Beyer, U; Beck, A; Ciorciaro, C; Meyer, M; Kadowaki, T

2015-10-01

To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). In a 12-week, multicentre, multinational, randomized, double-blind, parallel-group, placebo-controlled, dose-finding study, patients with inadequate glycaemic control from diet and exercise alone, or from diet and exercise plus a stable dose of metformin, were randomized to one of five doses of tofogliflozin (2.5, 5, 10, 20, or 40 mg) or placebo. The primary efficacy endpoint was absolute change at week 12 from baseline in glycated haemoglobin (HbA1c), minus the change in the placebo group. Statistically significant dose-dependent reductions in HbA1c were shown in all treated groups except the 2.5-mg dose group, with a maximum reduction of 0.56% (placebo-subtracted) at the 40-mg dose, along with increased urinary glucose excretion. Metformin treatment had no substantial influence on tofogliflozin efficacy. Dose-dependent reductions in fasting plasma glucose and body weight were observed, and glucose intolerance was improved, with a trend towards blood pressure reduction. Slight increases were observed for mean ketone bodies with no abnormal change in ketone body ratio. No deaths or treatment-related serious adverse events were reported. The incidence of adverse events was similar in the placebo (37.9%) to that in the tofogliflozin group (35.9-46.3%). Withdrawal because of adverse events was rare (≤2 patients per treatment group), with similar rates of withdrawal in the placebo and tofogliflozin groups. A once-daily dose of tofogliflozin for 12 weeks was an effective, safe and well-tolerated treatment for T2DM. © 2015 John Wiley & Sons Ltd.

Tacrolimus in the treatment of myasthenia gravis in patients with an inadequate response to glucocorticoid therapy: randomized, double-blind, placebo-controlled study conducted in China.

PubMed

Zhou, Lei; Liu, Weibin; Li, Wei; Li, Haifeng; Zhang, Xu; Shang, Huifang; Zhang, Xu; Bu, Bitao; Deng, Hui; Fang, Qi; Li, Jimei; Zhang, Hua; Song, Zhi; Ou, Changyi; Yan, Chuanzhu; Liu, Tao; Zhou, Hongyu; Bao, Jianhong; Lu, Jiahong; Shi, Huawei; Zhao, Chongbo

2017-09-01

To determine the efficacy of low-dose, immediate-release tacrolimus in patients with myasthenia gravis (MG) with inadequate response to glucocorticoid therapy in a randomized, double-blind, placebo-controlled study. Eligible patients had inadequate response to glucocorticoids (GCs) after ⩾6 weeks of treatment with prednisone ⩾0.75 mg/kg/day or 60-100 mg/day. Patients were randomized to receive 3 mg tacrolimus or placebo daily (orally) for 24 weeks. Concomitant glucocorticoids and pyridostigmine were allowed. Patients continued GC therapy from weeks 1-4; from week 5, the dose was decreased at the discretion of the investigator. The primary efficacy outcome measure was a reduction, relative to baseline, in quantitative myasthenia gravis (QMG) score assessed using a generalized linear model; supportive analyses used alternative models. Of 138 patients screened, 83 [tacrolimus ( n = 45); placebo ( n = 38)] were enrolled and treated. The change in adjusted mean QMG score from baseline to week 24 was -4.9 for tacrolimus and -3.3 for placebo (least squares mean difference: -1.7, 95% confidence interval: -3.5, -0.1; p = 0.067). A post-hoc analysis demonstrated a statistically significant difference for QMG score reduction of ⩾4 points in the tacrolimus group (68.2%) versus the placebo group (44.7%; p = 0.044). Adverse event profiles were similar between treatment groups. Tacrolimus 3 mg treatment for patients with MG and inadequate response to GCs did not demonstrate a statistically significant improvement in the primary endpoint versus placebo over 24 weeks; however, a post-hoc analysis demonstrated a statistically significant difference for QMG score reduction of ⩾4 points in the tacrolimus group versus the placebo group. This study was limited by the low number of patients, the absence of testing for acetylcholine receptor antibody and the absence of stratification by disease duration (which led to a disparity between the two groups). ClinicalTrials.gov identifier: NCT01325571.

Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients.

PubMed

Abe, Koji; Itoyama, Yasuto; Sobue, Gen; Tsuji, Shoji; Aoki, Masashi; Doyu, Manabu; Hamada, Chikuma; Kondo, Kazuoki; Yoneoka, Takatomo; Akimoto, Makoto; Yoshino, Hiide

2014-12-01

Our objective was to confirm the efficacy and safety of edaravone in amyotrophic lateral sclerosis (ALS) patients. We conducted a 36-week confirmatory study, consisting of 12-week pre-observation period followed by 24-week treatment period. Patients received placebo or edaravone i.v. infusion over 60 min for the first 14 days in cycle 1, and for 10 of the first 14 days during cycles 2 to 6. The efficacy primary endpoint was changed in the revised ALS functional rating scale (ALSFRS-R) scores during the 24-week treatment. Patients were treated with placebo (n = 104) and edaravone (n = 102). Changes in ALSFRS-R during the 24-week treatment were -6.35 ± 0.84 in the placebo group (n = 99) and -5.70 ± 0.85 in the edaravone group (n = 100), with a difference of 0.65 ± 0.78 (p = 0.411). Adverse events amounted to 88.5% (92/104) in the placebo group and 89.2% (91/102) in the edaravone group. In conclusion, the reduction of ALSFRS-R was smaller in the edaravone group than in the placebo group, but efficacy of edaravone for treatment of ALS was not demonstrated. Levels and frequencies of reported adverse events were similar in the two groups.

Repaglinide improves blood glucose control in sulphonylurea-naive type 2 diabetes.

PubMed

Van Gaal, L F; Van Acker, K L; De Leeuw, I H

2001-09-01

The prandial glucose regulator repaglinide has a rapid onset of action, a short half-life and is metabolised mainly by the liver. Here we report the findings of a 10-week, double-blind, parallel, placebo controlled, randomised trial with repaglinide in 25 diet-treated, sulphonylurea-naïve patients with Type 2 diabetes. Repaglinide was titrated, based on capillary blood glucose, from 0.5 mg to a maximum of 4 mg, preprandially with breakfast and dinner. After 10 weeks, repaglinide was associated with a decrease in HbA(1c) of 2.3%Hb relative to the placebo group (P=0.018). This reflected a 30% decrease within the repaglinide group from a mean HbA(1c) of 7.0 to 4.9%Hb (P<0.002). Repaglinide was also associated with a decrease in fructosamine, by 0.88 mmol/l, relative to placebo (P<0.001), with a 20% decrease (from 3.80 to 3.04 mmol/l) within the repaglinide group (P<0.001). Fasting and postprandial blood glucose concentrations decreased in association with repaglinide by 3.6 and 6.4 mmol/l, respectively, relative to placebo (P<0.001 in each case). Within the repaglinide group fasting and postprandial blood glucose decreased by 3.9 and 6.2 mmol/l, respectively (P<0.001 in each case). The number of patients reporting hypoglycaemia in the repaglinide group was similar to placebo (15 vs. 20, respectively; NS). Test meal assessments confirmed that repaglinide effectively controls glucose levels by stimulating mealtime insulin secretion. Fasting serum insulin concentration was not raised compared to baseline or placebo during repaglinide therapy, albeit that fasting glucose levels were decreased by repaglinide. Twice-daily meal-related insulin secretagogue therapy with repaglinide, a new short and rapid-acting prandial glucose regulator, is capable of improving all measures of glycaemic control without increased hypoglycaemia or fasting hyperinsulinaemia.

Comparison of lidocaine spray and paracervical block application for pain relief during first-trimester surgical abortion: A randomised, double-blind, placebo-controlled trial.

PubMed

Aksoy, Huseyin; Aksoy, Ulku; Ozyurt, Sezin; Ozoglu, Nil; Acmaz, Gokhan; Aydın, Turgut; İdem Karadağ, Özge; Tayyar, Ahter Tanay

2016-07-01

Surgical abortion is one of the most frequently performed gynaecological procedures and its associated pain has always been a problem in gynaecology. Here we studied the analgesic efficacy of lidocaine spray and paracervical block (PCB) in patients undergoing first-trimester surgical abortion. A randomised double-blind placebo-controlled study was conducted on 108 women requesting pregnancy termination. The subjects were randomly assigned into four groups: Group 1 (PCB plus lidocaine spray) (n=27), Group 2 (PCB) (n=27), Group 3 (lidocaine spray) (n=27) and Group 4 (placebo) (n=27). Intra-procedural and post-procedural pain scores were measured with a standard visual analogue scale (VAS). The median VAS scores during procedure in placebo, lidocaine spray, PCB plus lidocaine spray and PCB groups were 8 (7-9), 5 (4-8), 4 (3-4) and 5 (3-5), respectively. The most effective method of pain relief during first-trimester abortion can be achieved through a combined use of PCB plus lidocaine spray. Therefore, lidocaine spray is a non-invasive complementary anaesthetic method versus traditional PCB for first-trimester surgical abortion.

Double-blind, placebo-controlled trial on the effect of piracetam on breath-holding spells.

PubMed

Sawires, Happy; Botrous, Osama

2012-07-01

Breath-holding spells (BHS) are apparently frightening events occurring in otherwise healthy children.The aim of this study was to evaluate the efficacy of piracetam in the treatment of breath-holding spells. Forty patients with BHS (who were classified into two groups)were involved in a double-blinded placebo-controlled prospective study. Piracetam was given to group A while group B received placebo. Patients were followed monthly for a total period of 4 months. The numbers of attacks/month before and monthly after treatment were documented, and the overall number of attacks/month after treatment was calculated in both groups. The median number of attacks/month before treatment in the two groups was 5.5 and 5,respectively, while after the first month of treatment, it was 2 and 5, respectively. The median overall number of attacks/month after treatment in both groups was 1 and 5, respectively.There was a significant decline of number of attacks after piracetam treatment compared to placebo (p value<0.001). There were no reported side effects of the piracetam throughout the study period. In conclusion, piracetam is a safe and effective drug for the treatment of breath-holding spells in children.

Teacher Response to the Methylphenidate (Ritalin) versus Placebo Status of Hyperactive Boys in the Classroom.

ERIC Educational Resources Information Center

Whalen, Carol K.; And Others

1981-01-01

Teacher behaviors toward hyperactive boys on methylphenidate (ritalin), toward hyperactive boys on placebo, and toward normal comparison peers were compared. Teachers were more intense and controlling toward hyperactive boys on placebo, but no differences emerged between comparison and medicated groups. Need for broader monitoring of treatment…

Controlled trial of anti-tuberculous chemotherapy for two years in Crohn's disease.

PubMed Central

Swift, G L; Srivastava, E D; Stone, R; Pullan, R D; Newcombe, R G; Rhodes, J; Wilkinson, S; Rhodes, P; Roberts, G; Lawrie, B W

1994-01-01

One hundred and thirty patients with active symptoms of Crohn's disease were treated in a double blind randomised controlled trial with rifampicin, isoniazid, and ethambutol, or identical placebos for up to two years. All other treatment considered necessary was continued. Analyses were based on 126 patients, 63 in each treatment group. Thirty seven in the active and 30 in the placebo group had previous surgical procedures. There was no difference in concomitant treatment between the two groups. Thirty in the active and 46 in the placebo groups were taking corticosteroids at entry to the trial. Forty eight of 63 patients in the active and 49 of 63 in the placebo group, completed at least 12 months' therapy. Reasons for early withdrawal included pregnancy, adverse reaction, and failure to comply. There was no significant difference in the mean number of months completed between the two groups. Nineteen adverse reactions were recorded for 17 patients in the active group compared with three reactions in patients on placebo. All of the nine patients withdrawn early because of adverse reactions were in the active group. Fifteen patients on active treatment and 14 on placebo had surgery during the trial with no difference in the type of surgery required between the groups. Radiological assessments based on 98 patients at the end of the trial showed no significant differences between groups in changes of extent of disease. More patients developed strictures on placebo compared with active treatment but without a statistically significant difference. No differences were found between groups for the total prednisolone dose or the number of days on which prednisolone dose was 10 mg or above. Serial measurements of body weight and Crohn's disease activity index (CDAI) together with blood values for albumin, haemoglobin, white cell count, and platelets showed no consistent different differences between groups. There were occasional significant differences for some of these values between groups, which were not sustained. The trail provides little evidence of tangible benefit from the trail treatment. PMID:8150348

Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial.

PubMed

McInnes, Iain B; Kavanaugh, Arthur; Gottlieb, Alice B; Puig, Lluís; Rahman, Proton; Ritchlin, Christopher; Brodmerkel, Carrie; Li, Shu; Wang, Yuhua; Mendelsohn, Alan M; Doyle, Mittie K

2013-08-31

Many patients with psoriasis develop psoriatic arthritis, a chronic inflammatory disease that afflicts peripheral synovial, axial, and entheseal structures. The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis. We did a randomised, placebo-controlled, phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis. In this phase 3, multicentre, double-blind, placebo-controlled trial at 104 sites in Europe, North America, and Asia-Pacific, adults with active psoriatic arthritis (≥5 tender and ≥5 swollen joints, C-reactive protein ≥3·0 mg/L) were randomly assigned (1:1:1, by dynamic central randomisation based on an algorithm implemented by an interactive voice-web response system) to 45 mg ustekinumab, 90 mg ustekinumab, or placebo at week 0, week 4, and every 12 weeks thereafter. At week 16, patients with less than 5% improvement in both tender and swollen joint counts entered masked early-escape and were given 45 mg ustekinumab (if in the placebo group) or 90 mg ustekinumab (if in the 45 mg group). At week 24, all remaining patients in the placebo group received ustekinumab 45 mg, which they continued at week 28 and every 12 weeks thereafter. Our primary endpoint was 20% or greater improvement in American College of Rheumatology (ACR20) criteria at week 24. This trial is registered with ClinicalTrials.gov (NCT01009086) and EudraCT (2009-012264-14). Between Nov 30, 2009, and March 30, 2011, 615 patients were randomly assigned-206 to placebo, 205 to 45 mg ustekinumab, and 204 to 90 mg ustekinumab. More ustekinumab-treated (87 of 205 [42·4%] in the 45 mg group and 101 of 204 [49·5%] in the 90 mg group) than placebo-treated (47 of 206 [22·8%]) patients achieved ACR20 at week 24 (p<0·0001 for both comparisons); responses were maintained at week 52. At week 16, proportions of patients with adverse events were similar in the ustekinumab and placebo groups (171 of 409 [41·8%] vs 86 of 205 [42·0%]). Ustekinumab significantly improved active psoriatic arthritis compared with placebo, and might offer an alternative therapeutic mechanism of action to approved biological treatments. Janssen Research & Development. Copyright © 2013 Elsevier Ltd. All rights reserved.

Combined Diosmectite and Mesalazine Treatment for Mild-to-Moderate Ulcerative Colitis: A Randomized, Placebo-Controlled Study

PubMed Central

Jiang, Xue-Liang; Wang, Hua-Hong; Cui, Hui-Fei

2015-01-01

Background The relapse rate of ulcerative colitis (UC) is high. The efficacy of combined diosmectite and mesalazine treatment for active mild-to-moderate UC was investigated. Material/Methods A total of 120 patients with UC were enrolled in this randomized, single-blind, placebo-controlled study. Sixty patients were assigned to the Diosmectite group (diosmectite and mesalazine) and 60 were assigned to Placebo group (placebo and mesalazine). In the induction phase, the primary end point was the clinical remission rate at 8 weeks; secondary end points were clinical response, endothelial mucosal healing, Mayo score, erythrocyte sedimentation rate, C-reactive protein levels, and defecation frequency. In the maintenance phase, the primary end point was clinical remission at 52 weeks; secondary end points were clinical response, endothelial mucosal healing, Mayo score, erythrocyte sedimentation rate, and defecation frequency. Results At 8 weeks, the Diosmectite group had a significantly higher clinical remission rate (68.3% vs. 50%) and mucosal healing rate (66.7% vs. 48.3%) compared with the Placebo group. There were no significant differences in clinical response rates, Mayo score, erythrocyte sedimentation rate, C-reactive protein, or defecation frequency. At 52 weeks, the Diosmectite group had a significantly higher clinical remission rate (61.7% vs. 40%) and mucosal healing rate (60% vs. 38.3%) compared with the Placebo group. Defecation frequency was lower, but this was not significant. Conclusions Combined diosmectite and mesalazine treatment successfully induced and maintained the treatment of active mild-to-moderate UC as indicated by higher rates of clinical remission and mucosal healing. PMID:25582578

Pneumococcal vaccination in patients with systemic lupus erythematosus: A multicenter placebo-controlled randomized double-blind study.

PubMed

Grabar, Sophie; Groh, Matthieu; Bahuaud, Mathilde; Le Guern, Véronique; Costedoat-Chalumeau, Nathalie; Mathian, Alexis; Hanslik, Thomas; Guillevin, Loïc; Batteux, Frédéric; Launay, Odile

2017-09-05

Invasive pneumococcal disease and respiratory tract infections are both frequent and severe in patients with systemic lupus erythematosus (SLE). This study aimed to compare the immunological efficacy and safety of pneumococcal vaccination with the 23-valent polysaccharide (PPS) vaccine alone to a sequential immunization with the 7-valent pneumococcal conjugate (PnCj) vaccine followed by PPS in patients with SLE and stable diseaase. Multicenter randomized placebo-controlled double-blind trial: PPS vaccine alone (placebo-PPS group) or PnCj vaccine followed by PPS vaccine (PnCj-PPS group) 24weeks later. The primary endpoint was the rate of responders at week 28 to at least 5 of the 7 serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) shared by both PPS and PnCj. Pneumococcal IgG antibodies' opsonophagocytic activity (OPA) were also assessed. Twenty-five patients in the placebo-PPS group and 17 in the PnCj-PPS group were included in a modified intention-to-treat analysis. The primary endpoint was reached in 72% (18/25) in the placebo-PPS and 76% (13/17) in the PnCj-PPS group (p=0.75). There was no difference in the rates of responders with OPA. At week 52, 13/18 (72%) patients in the placebo-PPS group and 10/13 (77%) patients in the PnCj-PPS group (p=0.77) that met the primary endpoint at week 28 were still responders to ≥5/7 serotypes shared by both PPS and PnCj vaccines. Nine SLE flares were reported in 6 patients (4 in the placebo-PPS and 2 in the PnCj-PPS groups respectively, p=0.70). Sequential administration of PnCj vaccine followed by PPS vaccine is safe and shows short-term immunological efficacy in patients with SLE but was not superior to the PPS vaccine alone. www.clinicaltrials.gov, NCT NCT00611663. Copyright © 2017 Elsevier Ltd. All rights reserved.

Residual Limb Hyperhidrosis and RimabotulinumtoxinB: A Randomized Placebo-Controlled Study.

PubMed

Pasquina, Paul F; Perry, Briana N; Alphonso, Aimee L; Finn, Sacha; Fitzpatrick, Kevin F; Tsao, Jack W

2016-05-01

To investigate the use of rimabotulinumtoxinB (BoNT/B [Myobloc]) compared with placebo in treating hyperhidrosis in the residual limbs of individuals with amputation. Randomized, double-blind, placebo-controlled pilot study. Military medical center. Male participants (N=9) with 11 major amputations of the lower limbs and who complained of excessive sweating in their residual limbs were enrolled in the study between September 24, 2008 to October 28, 2011. Participants' lower limbs were randomly assigned to receive injections of either BoNT/B (n=7) or placebo (n=4). BoNT/B. The primary efficacy variable was a minimum of 50% reduction in sweat production 4 weeks after the injection as measured via gravimetric sweat analysis after 10 minutes of physical exertion. Secondary analyses were performed on prosthetic function and pain. All volunteers (100%; 7) in the BoNT/B group achieved a minimum of 50% reduction in sweat production as compared with only 50% (2) in the placebo group. The percent reduction was significantly greater for the BoNT/B group than for the placebo group (-72.7%±15.7% vs -32.7%±39.2%; P<.05). Although both groups subjectively self-reported significant sweat reduction and improved prosthetic function (P<.05 for both), objective gravimetric sweat analyses significantly decreased only for the BoNT/B group (2.3±2.3g vs 0.7±1.1g; P<.05). Neither group reported a change in phantom limb pain or residual limb pain (P>.05 for both). BoNT/B successfully reduces sweat production in individuals with residual limb hyperhidrosis, but does not affect pain. No differences were found in perceived effect on prosthetic use between BoNT/B and placebo groups. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Memantine for Prophylactic Treatment of Migraine Without Aura: A Randomized Double-Blind Placebo-Controlled Study.

PubMed

Noruzzadeh, Rezvan; Modabbernia, Amirhossein; Aghamollaii, Vajiheh; Ghaffarpour, Majid; Harirchian, Mohammad Hossein; Salahi, Sarvenaz; Nikbakht, Nikta; Noruzi, Nahid; Tafakhori, Abbas

2016-01-01

Uncontrolled studies in human have suggested that memantine might be a suitable option for migraine prophylaxis. To assess the efficacy and tolerability of memantine for migraine prophylaxis. This was a 12-week randomized double-blind placebo-controlled parallel-group study. Sixty patients with migraine without aura were randomized using a computer-generated list to receive memantine (10 mg/day) or placebo for 12 weeks. The primary outcome was the difference in change from baseline in the monthly attack frequency at week 12 between the two groups (using migraine diary). Secondary efficacy measures were assessed using several clinical, functional, and psychological instruments. We performed both complete case (CC) and intention-to-treat analyses (ITT). Twenty-five patients in the memantine group and 27 patients in the placebo group completed the study. Patients in the memantine group showed significantly greater reduction (mean change; 3.4; 95%CI, 2.3-4.4) in the monthly attack frequency than the placebo group (mean change, 1.0; 95%CI, 0.3-1.7) (mean difference [MD], 2.3; 95%CI, 1.1-3.5, P < .001). Both CC (MD, 4.9; 95%CI, 2.6-7.2 days), and ITT analyses (MD, 5.2; 95%CI, 2.0-8.5) showed significantly higher reduction in the mean number of migraine days in the memantine group than the placebo group (P < .01). Patients in the memantine group experienced greater reduction in the number of work absence days, severity, and disability score than the patients in the placebo group in both ITT and CC analyses. Changes in quality of life, sleep, depression, and anxiety did not differ between the two groups. Three patients in the memantine group complained of sedation, mild vertigo and nausea, and drowsiness. In the placebo group, one patient complained of nausea and another patient discontinued treatment after 2 weeks due to vertigo. Memantine might be a tolerable and efficacious option for prophylaxis in patients with migraine without aura. Tolerability, short duration required for titration, and safety profile in pregnancy might give memantine an advantage over other antimigraine medications. The study was registered in the Iranian Registry of Clinical Trials (Registration number: IRCT2013120115616N1). © 2015 American Headache Society.

Vildagliptin as add-on therapy to insulin improves glycemic control without increasing risk of hypoglycemia in Asian, predominantly Chinese, patients with type 2 diabetes mellitus.

PubMed

Ning, Guang; Wang, Weiqing; Li, Ling; Ma, Jianhua; Lv, Xiaofeng; Yang, Ming; Wang, Wei; Woloschak, Michael; Lukashevich, Valentina; Kothny, Wolfgang

2016-05-01

The aim of the present study was to investigate the efficacy and safety of vildagliptin added onto insulin with or without metformin in an Asian, predominantly Chinese, population with type 2 diabetes mellitus (T2DM). In this 24-week, multicenter, double-blind, placebo-controlled trial, patients with T2DM inadequately controlled (HbA1c 7.5%-11.0%) on stable therapy with long-acting, intermediate-acting, or premixed insulin, with or without concomitant metformin, were randomized to receive vildagliptin 50 mg b.i.d. or placebo. Of 293 patients randomized, 146 received vildagliptin and 147 received placebo treatment. At baseline, the overall mean age of patients was 58.1 years, mean T2DM duration was 11.3 years, and mean HbA1c was 8.7%. The adjusted mean (±SE) change in HbA1c at Week 24 in the vildagliptin and placebo groups was -1.08 ± 0.12% and -0.38 ± 0.12%, respectively (between-treatment difference -0.70 ± 0.16%; P < 0.001). The between-group difference in fasting plasma glucose was -0.43 ± 0.38 mmol/L (P = 0.259). Significantly, more patients achieved HbA1c <7.0% with vildagliptin than with placebo (23.6% vs. 11.2%; P = 0.006). The incidence of adverse events in the vildagliptin and placebo groups was 43.8% and 46.3%, whereas that of serious adverse events was 3.4% and 6.8%, respectively. The frequency of hypoglycemia was lower in the vildagliptin than placebo group (2.7% vs. 5.4%). The addition of vildagliptin 50 mg b.i.d. significantly improved glycemic control without an increased risk of hypoglycemia in Asian, predominantly Chinese, patients with T2DM inadequately controlled on insulin, with or without metformin. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley Sons Australia, & Ltd.

A Double-Blind, Placebo-Controlled Study of Selegiline Transdermal System in Depressed Adolescents

PubMed Central

Hochadel, Thomas J.; Portland, Kimberly Blanchard; Azzaro, Albert J.; Katic, Alain; Khan, Arif; Emslie, Graham

2014-01-01

Abstract Objective: A randomized, double-blind, placebo-controlled flexible-dose, parallel group trial was conducted at 26 clinical investigational sites in the United States to examine the safety and efficacy of the selegiline transdermal system (STS) (EMSAM®) in adolescents (ages 12–17 years) meeting American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for moderate to severe major depressive disorder (MDD) without psychotic features. Methods: Adolescents (n=308) with moderate to severe MDD were randomized to either STS (n=152) or placebo (n=156). Two hundred and fifteen (69.8%) subjects completed the study and 17 (5.5%) reported discontinuation because of adverse events (AEs). The primary efficacy outcome measure was the mean change from baseline to end of study (week 12 last observation carried forward [LOCF]) in the Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary outcome measures included end-point Clinical Global Impressions – Severity (CGI-S) and Clinical Global Impressions – Improvement (CGI-I). Results: Patients on STS or placebo had a significant decline from baseline (p<0.001) on their CDRS-R total score with mean reductions±SD as follows: STS 21.4±16.6; placebo 21.5±16.5. Both groups had similar response rates (58.6% vs. 59.3%) defined as CGI-I of 1 or 2 at study end. However, these between-group efficacy findings were without statistical significance. The overall incidence of reported AEs was 62.5% for STS-treated patients and 57.7% for placebo-treated patients. Most commonly reported AEs in STS or placebo groups were application site reactions (STS=24.3%; placebo=21.8%), headache (STS=17.1%; placebo=16.7%), and nausea (STS=7.2%; placebo=7.7%). Treatment groups did not differ on any laboratory parameters, vital signs, or electrocardiogram (ECG) findings. No suspected hypertensive crises were reported in the trial. Conclusions: These data demonstrated that the STS was safe and well tolerated in this adolescent sample. However, both STS-treated and placebo-treated subjects demonstrated a decline from baseline in depressive symptoms (CDRS-R total score) over the length of the study, without statistical superiority by either group. PMID:24955812

Safety of Russian-backbone seasonal trivalent, live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh.

PubMed

Ortiz, Justin R; Goswami, Doli; Lewis, Kristen D C; Sharmeen, Amina Tahia; Ahmed, Moshtaq; Rahman, Mustafizur; Rahman, Mohammed Z; Feser, Jodi; Neuzil, Kathleen M; Brooks, W Abdullah

2015-06-26

Live-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings. We conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations. Three hundred children were randomized and administered LAIV (n=150) or placebo (n=150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n=13 vs. n=16, p=0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p=0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events. In this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Double-Blind, Placebo-Controlled, Randomized Trial of Selenium in Graves Hyperthyroidism.

PubMed

Kahaly, George J; Riedl, Michaela; König, Jochem; Diana, Tanja; Schomburg, Lutz

2017-11-01

Supplemental selenium (Se) may affect the clinical course of Graves disease (GD). Evaluate efficacy of add-on Se on medical treatment in GD. Double-blind, placebo-controlled, randomized supplementation trial. Academic endocrine outpatient clinic. Seventy untreated hyperthyroid patients with GD. Additionally to methimazole (MMI), patients received for 24 weeks either sodium selenite 300 µg/d po or placebo. MMI was discontinued at 24 weeks in euthyroid patients. Response rate (week 24), recurrence rate (week 36), and safety. A response was registered in 25 of 31 patients (80%) and in 27 of 33 (82%) at week 24 [odds ratio (OR) 0.93; 95% confidence interval (CI), 0.26 to 3.25; P = 0.904] in the Se (+MMI) and placebo (+MMI) groups, respectively. During a 12-week follow-up, 11 of 23 (48%) and 12 of 27 (44%) relapsed (OR 1.13; 95% CI, 0.29 to 2.66; P = 0.81) in the Se and placebo groups, respectively. Serum concentrations of Se and selenoprotein P were unrelated to response or recurrence rates. At week 36, 12 of 29 (41%) and 15 of 33 (45%) were responders and still in remission in the Se and placebo groups, respectively (OR 0.85; 95% CI, 0.31 to 2.32; P = 0.80). Serum levels of free triiodothyronine/free tetraiodothyronine, thyroid-stimulating hormone receptor antibody, prevalence of moderate to severe Graves orbitopathy, thyroid volume, and MMI starting dose were significantly lower in responders than in nonresponders. A total of 56 and 63 adverse events occurred in the Se and placebo groups, respectively (P = 0.164), whereas only one drug-related side effect (2.9%) was noted in 35 patients on placebo + MMI. Supplemental Se did not affect response or recurrence rates in GD. Copyright © 2017 Endocrine Society

The efficacy of cetirizine hydrochloride on the pruritus of cats with atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Wildermuth, Kerstin; Zabel, Sonja; Rosychuk, Rod A W

2013-12-01

Various antihistamines have been used in the management of feline atopic dermatitis, with variable reported benefit. To date, there have been no randomized, double-blind, placebo-controlled, crossover clinical trials on the use of this drug class in cats. To evaluate the clinical efficacy of cetirizine hydrochloride for the control of pruritus and dermatitis in cats diagnosed with atopic dermatitis. In this randomized, double-blind, placebo-controlled crossover clinical trial, 21 client-owned cats diagnosed with mild to moderate nonseasonal atopic dermatitis were randomly assigned to two groups. Cats in each group received either 1 mg/kg cetirizine hydrochloride or placebo once daily per os for 28 days followed by a 14 day wash-out period. Treatments were then crossed over, and cats received placebo or cetirizine hydrochloride for another 28 days. Owners marked a pruritus severity scale before inclusion in the study and weekly throughout the entire study period. Lesions were scored by the clinician using a Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03 modified for the cat before enrolment and at day 28 of each treatment. Nineteen cats completed the study. There were no statistically significant differences between treatment with cetirizine hydrochloride and placebo for modified CADESI-03 or pruritus scores. This study suggests that cetirizine hydrochloride cannot be recommended for the management of feline atopic dermatitis. © 2013 ESVD and ACVD.

Effects of Kivia powder on gut health in patients with occasional constipation: a randomized, double-blind, placebo-controlled study.

PubMed

Udani, Jay K; Bloom, David W

2013-06-08

To evaluate the efficacy of Kivia powder on supporting overall gut health through the relief of the discomfort of occasional constipation. Randomized, double-blind, placebo-controlled, parallel-group trial. The investigational product for this study was Kivia powder (Vital Food Processors Ltd., Auckland, New Zealand), containing the active ingredient Zyactinase™, 5.5 g taken daily for four weeks. One hundred thirty-eight subjects reporting occasional constipation were screened and 87 were randomized to placebo (n = 44) and product (n = 43). Bowel movement frequency, as measured by both average daily spontaneous bowel movements (SBM) and complete spontaneous bowel movements (CSBM), were the same in both groups at baseline. There were significant increases in spontaneous bowel movements at week 1 (p = 0.001), week 2 (p = 0.001), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. SBM demonstrated significant differences between the treatment group and the placebo group at week 3 (p = 0.000), and week 4 (p = 0.020). The treatment group demonstrated a significantly higher rate of SBM at week 3 (p = 000) and from baseline to week 4 (p = 0.019). Significant increases in complete spontaneous bowel movements were observed at week 1 (p = 0.000), week 2 (p = 0.000), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. Moreover, CSBM was significantly higher for the treatment group compared to placebo at week 2 (p = 0.001). The change in average daily CSBM from baseline to week 2 was significantly higher in the treatment group than in the placebo group (p = 0.004).Abdominal discomfort or pain demonstrated significant differences between groups at week 1 (p = 0.044) and week 3 (p = 0.026). Flatulence was significantly lower for active group compared to placebo at week 2 (p = 0.047) and week 3 (p = 0.023). The number of bowel movements associated with urgency was significantly lower in the treatment group compared to the placebo group at week 3 (p = 0.048). In addition, it was decreased from baseline to week 1 (p = 0.040) and from baseline to week 3 (p = 0.024) in the treatment group, while the placebo group did not report any reductions in bowel urgency. Bowel movements in the treatment arm were significantly smoother and softer by week 2 (p = 0.020) and week 3 (p = 0.041). Treatment with Kivia powder, an extract of kiwifruit containing Zyactinase™, for four weeks was well tolerated and more effective than placebo in gently enhancing bowel movement frequency and reducing abdominal pain and flatulence in subjects with occasional constipation. ISRCTN: ISRCTN49036618.

Effect of vitamin D, calcium and multiple micronutrient supplementation on vitamin D and bone status in Bangladeshi premenopausal garment factory workers with hypovitaminosis D: a double-blinded, randomised, placebo-controlled 1-year intervention.

PubMed

Islam, Md Zahirul; Shamim, Abu Ahmed; Viljakainen, Heli T; Akhtaruzzaman, Mohammad; Jehan, Atia H; Khan, Habib Ullah; Al-Arif, Ferdaus Ahmad; Lamberg-Allardt, Christel

2010-07-01

Due to little outdoor activity and low dietary intake of vitamin D (VD), Bangladeshi low-income women are at risk for osteoporosis at an early age. The present study assessed the effect of VD, Ca and multiple micronutrient supplementation on VD and bone status in Bangladeshi young female garment factory workers. This placebo-controlled 1-year intervention randomly assigned 200 apparently healthy subjects (aged 16-36 years) to four groups: VD group, daily 10 microg VD; VD and Ca (VD-Ca) group, daily 10 microg VD+600 mg Ca; multiple micronutrient and Ca (MMN-Ca) group, 10 microg VD and other micronutrients+600 mg Ca; a placebo group. Serum 25-hydroxyvitamin D (S-25OHD), intact parathyroid hormone (S-iPTH), Ca, phosphate and alkaline phosphatase were measured. Bone mineral density and bone mineral content were measured by dual-energy X-ray absorptiometry. All measurements were made at baseline and at 12 months. Significantly (P < 0.001) higher S-25OHD concentrations were observed in the supplemented groups than in the placebo group after the intervention. Supplementation had an effect (P < 0.001) on S-iPTH in the VD-Ca and MMN-Ca groups compared with the placebo group. Bone mineral augmentation increased at the femur in the supplemented groups. Supplementation with VD-Ca should be recommended as a strategic option to reduce the risk of osteomalacia and osteoporosis in these subjects. MMN-Ca may have analogous positive health implications with additional non-skeletal benefits.

Brief Report: A Randomized, Placebo-Controlled Proof-of-Concept Trial of Adjunctive Topiramate for Alcohol Use Disorders in Bipolar Disorder

PubMed Central

Sylvia, Louisa G.; Gold, Alexandra K.; Stange, Jonathan P.; Peckham, Andrew D.; Deckersbach, Thilo; Calabrese, Joseph R.; Weiss, Roger D.; Perlis, Roy H.; Nierenberg, Andrew A.; Ostacher, Michael J.

2016-01-01

Background and Objectives Topiramate is effective for alcohol use disorders (AUDs) among non-psychiatric patients. We examined topiramate for treating comorbid AUDs in bipolar disorder (BD). Methods Twelve participants were randomized to topiramate or placebo for 12 weeks. Results The topiramate group, with two out of five participants (40%) completing treatment, experienced less improvement in drinking patterns than the placebo group, with five out of seven participants (71%) completing treatment. Discussion and Conclusions Topiramate did not improve drinking behavior and was not well-tolerated. This study failed to recruit adequately. Problems surrounding high attrition, a small study sample, and missing data preclude interpretation of study findings. Scientific Significance This is the first randomized, placebo-controlled trial of topiramate for AUDs in BD. PMID:26894822

An Investigation of the Hypoalgesic Effects of TENS Delivered by a Glove Electrode

PubMed Central

Cowan, Stephen; McKenna, Joanne; McCrum-Gardner, Evie; Johnson, Mark I.; Sluka, Kathleen A.; Walsh, Deirdre M.

2009-01-01

This randomized, placebo-controlled, blinded study investigated the hypoalgesic effects of high-frequency transcutaneous electrical nerve stimulation (TENS) delivered via a glove electrode compared with standard self-adhesive electrodes. Fifty-six TENS-naïve, healthy individuals (18 to 50 years old; 28 men, 28 women) were randomly allocated to 1 of 4 groups (n = 14 per group): glove electrode; placebo TENS using a glove electrode; standard electrode; and no treatment control. Active TENS (continuous stimulus, 100 Hz, strong but comfortable intensity) was applied to the dominant forearm/hand for 30 minutes. Placebo TENS was applied using a burst stimulus, 100-Hz frequency, 5-second cycle time for 42 seconds, after which the current amplitude was automatically reset to 0 mA. Pressure pain thresholds (PPTs) were recorded from 3 points on the dominant and nondominant upper limbs before and after TENS. Statistical analyses of dominant PPT data using between-within groups ANOVA showed significant differences between groups at all 3 recording points (P = .01). Post hoc Scheffe tests indicated no significant difference between the standard electrode and glove electrode groups. There was a significant hypoalgesic effect in the standard electrode group compared with the control group and between the glove electrode group and both the control and placebo TENS groups. There was no significant interactive effect between time and group at any of the recording points (P > .05). Perspective This study presents a comparison of the hypoalgesic effects of 2 different types of TENS electrode, a novel glove electrode and standard self-adhesive rectangular electrodes. The glove electrode provides a larger contact area with the skin, thereby stimulating a greater number of nerve fibers. The results show that both electrodes have similar hypoalgesic effects and therefore give the clinician another choice in electrode. PMID:19398378

Nitroglycerin 0.4% ointment vs placebo in the treatment of pain resulting from chronic anal fissure: a randomized, double-blind, placebo-controlled study

PubMed Central

2013-01-01

Background Complications of chronic anal fissure (CAF) treatments are prompting interest in lower-risk therapies. This study was conducted to compare nitroglycerin (NTG) 0.4% ointment with placebo for pain associated with CAF. Methods In this randomized, double-blind, placebo-controlled trial, patients with one CAF and moderate-to-severe pain (≥50 mm on a 100 mm visual analog scale [VAS]) received 375 mg NTG 0.4% (1.5 mg active ingredient) or 375 mg placebo ointment applied anally every 12 hours for 21 days. The primary end point was change from baseline VAS score in 24-hour pain averaged over days 14–18. Review of data from patients who withdrew early was blinded to treatment. To control for the confounding effects of analgesics, all patients received 650 mg acetaminophen for headache prophylaxis before each application. Results A total of 247 patients were enrolled (NTG, n = 123; placebo, n = 124). The prespecified baseline observation carried forward (BOCF) analysis found no significant difference between groups; however, a last observation carried forward (LOCF) analysis showed a significant advantage for NTG. A post hoc analysis (LOCF/BOCF hybrid) demonstrated a significant adjusted mean difference of −7.0 mm in favor of NTG 0.4% (95% CI −13.6, –0.4; P = .038). Headache was the most common adverse event in the NTG (69.9%) and placebo (47.6%) groups. Conclusions This was the first placebo-controlled study that also controlled for the confounding effects of analgesics used to treat NTG-induced headache. In patients with moderate-to-severe CAF pain, NTG 0.4% ointment effectively reduced CAF pain compared with placebo. Trial registration ClinicalTrials.gov, NCT00522041 PMID:23815124

Do placebo effects associated with sham osteopathic procedure occur in newborns? Results of a randomized controlled trial.

PubMed

Martelli, Marta; Cardinali, Lucia; Barlafante, Gina; Pizzolorusso, Gianfranco; Renzetti, Cinzia; Cerritelli, Francesco

2014-04-01

Placebo effect has been largely studied and debated in medicine. Research focused mainly on children and adults but not on newborns. In osteopathy, few studies documented this effect and no research has been conducted in newborns. To assess the presence of placebo effect in newborns using sham osteopathic manipulative treatment. Randomized control trial. Neonatal Intensive Care Unit in Italy. Two groups (103 patients each) of preterm infants aged 29-36 weeks without medical complications received routine pediatric care and osteopathic sham therapy was administrated to the study group only for the entire period of hospitalization. Primary end point was the mean reduction of length of stay at discharge. Secondary objective was the change in daily weight gain. 206 newborns entered the study. No difference between sham and control group was found for the primary outcome length of stay (30.0±20.3; 28.8±18.9; p=0.70). Multivariate analysis showed no difference between study and control group on length of stay. A negative association was found for gestational age (-2.33; 95% CI -3.81 to -0.85; p=0.002), birth weight (-0.01; 95% CI -0.02 to -0.01; p<0.001) and milk volume at study enrollment (-0.02; 95% CI -0.05 to -0.01; p=0.01). To the best of our knowledge, this study is the first in the field showing no placebo effect on newborns. Further discussions are opened concerning the age when placebo effect starts. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Effect of Saffron on Depression among Recovered Consumers of Methamphetamine Living with HIV/AIDS.

PubMed

Jalali, Farzad; Hashemi, Seyedeh Fatemeh

2018-03-15

From one hand, depression is one of the symptoms that occur after abstinence from methamphetamine. On the other people living with HIV/AIDS are in isolation due to the nature of their illness and depression is one of the most common mental health problems they experience. This study was aimed at determining the effectiveness of saffron on reducing depression among recovered consumers of methamphetamine living with HIV/AIDS. The design of this study was semi-experimental with pre-test, post-test and control (placebo) groups. The statistical population consisted of all recovered consumers of methamphetamine living with HIV/AIDS who were referred to the Positive Club. Fifty-seven (57) recovered consumers of methamphetamine, living with HIV/AIDS, were selected by convenience sampling method. They were randomly assigned to an experimental (saffron) group and a control (placebo) group. The experimental group received 30 ml of saffron per day for 8 weeks, whereas the control (placebo) group received placebo the same way. BDI-II was used in this study as a measurement instrument. ANCOVA models were used for statistical inference. The findings showed that saffron and its ingredients had been effective in reducing depression among this group (P < 0.05). In fact, saffron with its active ingredients (Crusin and Saffranal) by serotonin and dopamine secretion in the brain, help in reducing depression among recovered consumers of methamphetamine living with HIV/AIDS.

Effects of vibration training in reducing risk of slip-related falls among young adults with obesity.

PubMed

Yang, Feng; Munoz, Jose; Han, Long-Zhu; Yang, Fei

2017-05-24

This study examined the effects of controlled whole-body vibration training on reducing risk of slip-related falls in people with obesity. Twenty-three young adults with obesity were randomly assigned into either the vibration or placebo group. The vibration and placebo groups respectively received 6-week vibration and placebo training on a side-alternating vibration platform. Before and after the training, the isometric knee extensors strength capacity was measured for the two groups. Both groups were also exposed to a standardized slip induced by a treadmill during gait prior to and following the training. Dynamic stability and fall incidences responding to the slip were also assessed. The results indicated that vibration training significantly increased the muscle strength and improved dynamic stability control at recovery touchdown after the slip occurrence. The improved dynamic stability could be resulted from the enhanced trunk segment movement control, which may be attributable to the strength increment caused by the vibration training. The decline of the fall rates from the pre-training slip to the post-training one was greater among the vibration group than the placebo group (45% vs. 25%). Vibration-based training could be a promising alternative or additional modality to active exercise-based fall prevention programs for people with obesity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Combined citalopram and methylphenidate improved treatment response compared to either drug alone in geriatric depression: a randomized double-blind, placebo-controlled trial

PubMed Central

Lavretsky, Helen; Reinlieb, Michelle; Cyr, Natalie St.; Siddarth, Prabha; Ercoli, Linda M.; Senturk, Damla

2015-01-01

Objective We evaluated the potential of methylphenidate to improve antidepressant response to citalopram in elderly depressed patients with respect to clinical and cognitive outcomes. Methods We conducted a 16-week randomized double-blind placebo-controlled trial for geriatric depression in 143 older outpatients diagnosed with major depression comparing treatment response in three groups: 1) methylphenidate and placebo (N=48); 2) citalopram and placebo (N=48); 3) methylphenidate and citalopram (N=47). Primary outcome was defined as the change in depression severity. Remission was defined as Hamilton Depression Rating Scale (HDRS-24) score of 6 or below. Secondary outcomes included measures of anxiety, apathy, quality of life, and cognition. Results Citalopram daily doses ranged between 20–60 mg (mean 32 mg); methylphenidate daily doses ranged between 5–40 mg (mean 16 mg). All groups showed significant improvement in the severity of depression. However, the improvement in depression severity and the clinical global impression was more prominent in the methylphenidate and citalopram group compared to methylphenidate and placebo and citalopram and placebo (P<0.05). Additionally, the rate of improvement in the methylphenidate and citalopram group was significantly faster than that in the citalopram and placebo in the first 4 weeks of the trial. The groups did not differ on cognitive improvement or the number of side-effects. Conclusions Combined treatment with citalopram and methylphenidate demonstrated an enhanced clinical response profile in the mood and wellbeing, and the rate of response compared to either drug. All treatments led to an improvement in cognitive functioning, without additional benefit from the use of methylphenidate. PMID:25677354

Cognitive Factors Mediate Placebo Responses in Patients with House Dust Mite Allergy

PubMed Central

Benson, Sven; Rueckert, Annika; Hillen, Uwe; Schadendorf, Dirk; Schedlowski, Manfred

2013-01-01

Background Placebo effects have been reported in type I allergic reactions. However the neuropsychological mechanisms steering placebo responses in allergies are largely unknown. The study analyzed whether and to what extend a conditioned placebo response is affecting type I allergic reactions and whether this response can be reproduced at multiple occasions. Methods 62 patients with house dust mite allergy were randomly allocated to either a conditioned (n = 25), sham-conditioned (n = 25) or natural history (n = 12) group. During the learning phase (acquisition), patients in the conditioned group received the H1-receptor antagonist desloratadine (5mg) (unconditioned stimulus/US) together with a novel tasting gustatory stimulus (conditioned stimulus/CS). Patients in the sham-conditioned control group received the CS together with a placebo pill. After a wash out time of 9 days patients in the conditioned and sham-conditioned group received placebo pills together with the CS during evocation. Allergic responses documented by wheal size after skin prick test and symptom scores after nasal provocation were analyzed at baseline, after last desloratadine treatment and after the 1st and 5th CS re-exposure. Results Both conditioned and sham-conditioned patients showed significantly decreased wheal sizes after the 1st CS-evocation and significantly decreased symptom scores after the 1st as well as after the 5th evocation compared to the natural history control group. Conclusions These results indicate that placebo responses in type I allergy are not primarily mediated by learning processes, but seemed to be induced by cognitive factors such as patients’ expectation, with these effects not restricted to a single evocation. PMID:24260254

Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial.

PubMed

Costello, John M; Dunbar-Masterson, Carolyn; Allan, Catherine K; Gauvreau, Kimberlee; Newburger, Jane W; McGowan, Francis X; Wessel, David L; Mayer, John E; Salvin, Joshua W; Dionne, Roger E; Laussen, Peter C

2014-07-01

We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes. In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ≤5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics, and operative factors were similar among treatment groups. No significant treatment group differences were found for median days alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum to maximum, 0-24]; milrinone, 18 [0-23]; placebo, 20 [0-23]; P=0.38). Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events. Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery. http://www.clinicaltrials.gov. Unique identifier: NCT00543309. © 2014 American Heart Association, Inc.

Efficacy evaluation of a pollen blocker cream against dust-mite allergy: A multicenter, randomized, double-blind, placebo-controlled crossover trial.

PubMed

Li, Yanqing; Cheng, Lei; Chen, Xiaoning; Yang, Beibei; Wang, Dehui

2015-01-01

To further evaluate the efficacy and safety of a pollen blocker cream against dust-mite allergy. A multicenter, randomized, double-blind, placebo-controlled, crossover trial was conducted in a Chinese population. Patients diagnosed with perennial allergic rhinitis, sensitive to dust-mite allergy including Dermatophagoides farinae and Dermatophagoides pteronyssinus were randomly allocated to receive a pollen blocker cream or placebo, which was applied and spread evenly to the lower internal nose region three times daily for a total of 30 days. The primary outcome measurements for efficacy were total nasal symptom score (TNSS) and individual nasal symptom score (iNSS). Adverse events were also monitored. After application of a pollen blocker, the mean TNSS decreased from 23.1 to 13.8, the decrease of the pollen blocker group (9.3) was highly significant compared with the placebo group (5.2; p < 0.001). Similarly, the decreases in iNSSs (rhinorrhea, congestion, sneezing, and itching) between the pollen blocker group and the placebo group were also significant (p < 0.05). In addition, in adults, the pollen blocker led to a remarkably significant decrease in TNSS (9.5) compared with placebo (5.4; p < 0.001); in children, the pollen blocker led to a significant decrease in TNSS (8.6) compared with placebo (4.8; p < 0.05). No statistical difference was found in the incidence of adverse events between the two groups (p > 0.05), and no severe systematic reactions were observed. Pollen Blocker is a safe and effective alternative to the drugs for treatment of AR, especially for Chinese people allergic to dust-mite allergy.

Intravenous iron isomaltoside 1000 (Monofer®) reduces postoperative anaemia in preoperatively non-anaemic patients undergoing elective or subacute coronary artery bypass graft, valve replacement or a combination thereof: a randomized double-blind placebo-controlled clinical trial (the PROTECT trial).

PubMed

Johansson, P I; Rasmussen, A S; Thomsen, L L

2015-10-01

This trial explores whether intravenous iron isomaltoside 1000 (Monofer®) results in a better regeneration of haemoglobin levels and prevents anaemia compared to placebo in preoperative non-anaemic patients undergoing cardiac surgery. The trial is a prospective, double-blind, comparative, placebo-controlled trial of 60 non-anaemic patients undergoing cardiac surgery. The patients were randomized 1:1 to either 1000 mg intravenous iron isomaltoside 1000 administered perioperatively by infusion or placebo. Mean preoperative haemoglobin in the active treatment group was 14·3 g/dl vs. 14·0 g/dl in the placebo group. At discharge 5 days after surgery, haemoglobin levels were reduced to 10·7 and 10·5 g/dl, respectively. One month after surgery, haemoglobin concentration had increased to an average of 12·6 g/dl vs. 11·8 g/dl (p = 0·012) and significantly more patients were non-anaemic in the intravenous iron isomaltoside 1000-treated group compared to the placebo group (38·5% vs. 8·0%; p = 0·019). There were no differences in side-effects between the groups. A single perioperative 1000 mg dose of intravenous iron isomaltoside 1000 significantly increased the haemoglobin level and prevented anaemia 4 weeks after surgery, with a short-term safety profile similar to placebo. Future trials on potential clinical benefits of preoperative treatment with intravenous iron in non-anaemic patients are needed. © 2015 The Authors ISBT Science Series published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

Antidepressant Efficacy of the Antimuscarinic Drug Scopolamine

PubMed Central

Furey, Maura L.; Drevets, Wayne C.

2010-01-01

Context The need for improved therapeutic agents that more quickly and effectively treat depression is critical. In a pilot study we evaluated the role of the cholinergic system in cognitive symptoms of depression and unexpectedly observed rapid reductions in depression severity following the administration of the antimuscarinic drug scopolamine hydrobromide (4 μg/kg intravenously) compared with placebo (P=.002). Subsequently a clinical trial was designed to assess more specifically the antidepressant efficacy of scopolamine. Objective To evaluate scopolamine as a potential antidepressant agent. Design Two studies were conducted: a double-blind, placebo-controlled, dose-finding study followed by a double-blind, placebo-controlled, crossover clinical trial. Setting The National Institute of Mental Health. Patients Currently depressed outpatients aged 18 to 50 years meeting DSM-IV criteria for recurrent major depressive disorder or bipolar disorder. Of 39 eligible patients, 19 were randomized and 18 completed the trial. Interventions Multiple sessions including intravenous infusions of placebo or scopolamine hydrobromide (4 μg/kg). Individuals were randomized to a placebo/ scopolamine or scopolamine/placebo sequence (series of 3 placebo sessions and series of 3 scopolamine sessions). Sessions occurred 3 to 5 days apart. Main Outcome Measures Psychiatric evaluations using the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were performed to assess antidepressant and antianxiety responses to scopolamine. Results The placebo/scopolamine group showed no significant change during placebo infusion vs baseline; reductions in depression and anxiety rating scale scores (P<.001 for both) were observed after the administration of scopolamine compared with placebo. The scopolamine/placebo group also showed reductions in depression and anxiety rating scale scores (P<.001 for both) after the administration of scopolamine, relative to baseline, and these effects persisted as they received placebo. In both groups, improvement was significant at the first evaluation after scopolamine administration (P≤.002). Conclusion Rapid, robust antidepressant responses to the antimuscarinic scopolamine occurred in currently depressed patients who predominantly had poor prognoses. PMID:17015814

Alpha lipoic acid efficacy in burning mouth syndrome. A controlled clinical trial

PubMed Central

Palacios-Sánchez, Begoña; Cerero-Lapiedra, Rocío; Llamas-Martínez, Silvia; Esparza-Gómez, Germán

2015-01-01

Background A double-blind placebo-controlled trial was conducted in order to evaluate the efficacy of alpha lipoic acid (ALA) and determine the statistical significance of the outcome variables. Burning mouth syndrome (BMS) is defined as an oral burning sensation in the absence of clinical signs which could justify the syndrome. Recent studies suggest the existence of neurological factors as a possible cause of the disease. Material and Methods 60 patients with BMS, in two groups: case group with 600 mg/day and placebo as control group; with follow up of 2 months. Results 64% of ALA patients reported some level of improvement, with a level of maintenance of 68.75% one month after treatment. 27.6% of the placebo group also demonstrated some reduction in BMS symptoms. Conclusions Long-term evolution and the intensity of symptoms are variables that reduce the probability of improvement with ALA treatment. Key words: Burning mouth syndrome, neuropathy, alpha lipoic acid. PMID:26034927

A Randomized, Double-Blind, Placebo-Controlled Trial of Pleconaril for the Treatment of Neonates With Enterovirus Sepsis.

PubMed

Abzug, Mark J; Michaels, Marian G; Wald, Ellen; Jacobs, Richard F; Romero, José R; Sánchez, Pablo J; Wilson, Gregory; Krogstad, Paul; Storch, Gregory A; Lawrence, Robert; Shelton, Mark; Palmer, April; Robinson, Joan; Dennehy, Penelope; Sood, Sunil K; Cloud, Gretchen; Jester, Penelope; Acosta, Edward P; Whitley, Richard; Kimberlin, David

2016-03-01

Neonatal enterovirus sepsis has high mortality. Antiviral therapy is not available. Neonates with suspected enterovirus sepsis (hepatitis, coagulopathy, and/or myocarditis) with onset at ≤15 days of life were randomized 2:1 to receive oral pleconaril or placebo for 7 days. Serial virologic (oropharynx, rectum, urine, serum), clinical, pharmacokinetic, and safety evaluations were performed. Sixty-one subjects were enrolled (43 treatment, 18 placebo), of whom 43 were confirmed enterovirus infected (31 treatment, 12 placebo). There was no difference in day 5 oropharyngeal culture positivity (primary endpoint; 0% in both groups). However, enterovirus-infected subjects in the treatment group became culture negative from all anatomic sites combined faster than placebo group subjects (median 4.0 versus 7.0 days, P = .08), and fewer subjects in the treatment group remained polymerase chain reaction (PCR)-positive from the oropharynx when last sampled (23% versus 58%, P = .02; median, 14.0 days). By intent to treat, 10/43 (23%) subjects in the treatment group and 8/18 (44%) in the placebo group died (P = .02 for 2-month survival difference); among enterovirus-confirmed subjects, 7/31 (23%) in the treatment group died versus 5/12 (42%) in the placebo group (P = .26). All pleconaril recipients attained concentrations greater than the IC90 after the first study day, but 38% were less than the IC90 during the first day of treatment. One subject in the treatment group and three in the placebo group had treatment-related adverse events. Shorter times to culture and PCR negativity and greater survival among pleconaril recipients support potential efficacy and warrant further evaluation. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Are There Scenarios When the Use of Non-Placebo-Control Groups in Experimental Trial Designs Increase Expected Value to Society?

PubMed

Uyei, Jennifer; Braithwaite, R Scott

2016-01-01

Despite the benefits of the placebo-controlled trial design, it is limited by its inability to quantify total benefits and harms. Such trials, for example, are not designed to detect an intervention's placebo or nocebo effects, which if detected could alter the benefit-to-harm balance and change a decision to adopt or reject an intervention. In this article, we explore scenarios in which alternative experimental trial designs, which differ in the type of control used, influence expected value across a range of pretest assumptions and study sample sizes. We developed a decision model to compare 3 trial designs and their implications for decision making: 2-arm placebo-controlled trial ("placebo-control"), 2-arm intervention v. do nothing trial ("null-control"), and an innovative 3-arm trial design: intervention v. do nothing v. placebo trial ("novel design"). Four scenarios were explored regarding particular attributes of a hypothetical intervention: 1) all benefits and no harm, 2) no biological effect, 3) only biological effects, and 4) surreptitious harm (no biological benefit or nocebo effect). Scenario 1: When sample sizes were very small, the null-control was preferred, but as sample sizes increased, expected value of all 3 designs converged. Scenario 2: The null-control was preferred regardless of sample size when the ratio of placebo to nocebo effect was >1; otherwise, the placebo-control was preferred. Scenario 3: When sample size was very small, the placebo-control was preferred when benefits outweighed harms, but the novel design was preferred when harms outweighed benefits. Scenario 4: The placebo-control was preferred when harms outweighed placebo benefits; otherwise, preference went to the null-control. Scenarios are hypothetical, study designs have not been tested in a real-world setting, blinding is not possible in all designs, and some may argue the novel design poses ethical concerns. We identified scenarios in which alternative experimental study designs would confer greater expected value than the placebo-controlled trial design. The likelihood and prevalence of such situations warrant further study. © The Author(s) 2015.

Evaluating the efficiency of a combination of Pygeum africanum and stinging nettle (Urtica dioica) extracts in treating benign prostatic hyperplasia (BPH): double-blind, randomized, placebo controlled trial.

PubMed

Melo, Ezer A; Bertero, Eduardo B; Rios, Luiz A S; Mattos, Demerval

2002-01-01

In spite of its historical use, published data about phytotherapic products is characterized by the absence of well conducted studies, leading to conflictive and indefinite results about efficiency and safety of theses drugs. In that sense, we have analyzed the results of a combination of Pygeum africanum and stinging nettle (Urtica dioica) extracts in patients with benign prostatic hyperplasia (BPH), based in a double-blind, randomized, placebo-controlled protocol. We have selected, according to inclusion and exclusion criteria, only patients with >or=50 years, presenting urinary symptoms assessed by the International Prostatic Symptoms Score (IPSS), with minimum score of 12, and Quality of Life (QoL) index of at least 3 points, rectal examination consistent with BPH, and maximum urinary flow rate (Q(max)) between 5 and 15 mL/s. Phytotherapic and placebo groups were formed by 27 and 22 patients, respectively. The major variables analyzed during the study were IPSS variation, Q(max), and side effects. Reduction of >or=30% and >or=50% in IPSS were the parameters used to define a clinically significant response (CSR). We have also analyzed >or=30% and >or=50% Q(max) increases. After six months of treatment we did not observe significant differences in clinical improvement potential between the phytotherapic combination and placebo groups. Percent IPSS drop of 21.6% in the phytotherapic group was similar to 19.7% obtained in the placebo group (p=0.928). Neither we observed any difference (p=0.530) for QoL improvement between phytotherapic (9.26%) and placebo (5.98%) groups. The alterations of Q(max) followed the trend line observed in clinical data, with no significant difference (p=0.463) in Q(max) increasing percent between phytotherapic (17.2%) and placebo (13.3%) groups. The CSR evaluation of clinical and urodynamic data was also similar between the groups. The combination of 25mg Pygeum africanum and 300mg stinging nettle extracts produced clinical and urodynamic effects similar to placebo in a group of HBP patients.

The effect of zonisamide on antipsychotic-associated weight gain in patients with schizophrenia: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Ghanizadeh, Ahmad; Nikseresht, Mohammad Saeed; Sahraian, Ali

2013-06-01

Many patients with schizophrenia suffer from metabolic symptoms and weight gain in which predispose them to obesity, diabetes, and cardiovascular problems. This trial examines the efficacy and safety of zonisamide on weight and body mass index in patients with schizophrenia being administered with atypical antipsychotics. In this 10-week, double blind randomized placebo controlled clinical trial, forty one patients with schizophrenia diagnosed according to DSM-IV-TR criteria who were taking a stable dose of atypical antipsychotic are allocated into one of the two groups of zonisamide or placebo group. Weight, body mass index, waist circumference, and adverse effects were assessed. The two groups were not statistically different regarding baseline characteristics on age, gender, education, diagnosis, weight, body mass index, daily cigarette smoking, and the duration of illness. After 10 weeks, the patients in the placebo group had significantly gained weight, while the patients in the zonisamide group lost weight (mean=1.9, SD=2.2 versus mean=-1.1 kg, SD=1.4). The changes of body mass index in the two groups were significantly different. Body mass index decreased in the zonisamide group (mean=-0.3, SD=0.4) while it increased in the placebo group (mean=2.2, SD=6.9). There was a significance difference between the two groups regarding waist circumference at the end of trial (P<0.0001), too. The waist increased in the placebo group while it decreased in the zonisamide group (mean=1.1, SD=1.7 versus mean=-0.7, SD=1.2, respectively), as well. The frequencies of adverse effects were not significantly different between the two groups and zonisamide was tolerated well. Zonisamide as an adjuvant treatment is tolerated well and markedly affect on the weight loss of patients with schizophrenia being treated with atypical antipsychotics. Copyright © 2013 Elsevier B.V. All rights reserved.

EDTA Chelation Therapy Alone and in Combination with Oral High-Dose Multivitamins and Minerals for Coronary Disease: The Factorial Group Results of the Trial to Assess Chelation Therapy

PubMed Central

Lamas, Gervasio A.; Boineau, Robin; Goertz, Christine; Mark, Daniel B.; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L.; Chappell, L. Terry; Lindblad, Lauren; Lewis, Eldrin F.; Drisko, Jeanne; Lee, Kerry L.

2014-01-01

Background Disodium ethylene diamine tetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. Objective This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes. Methods Double-blind placebo-controlled 2 × 2 factorial multicenter randomized trial of 1708 post-MI patients ≥ 50 years and creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitaminmultimineral mixture or placebo. Primary endpoint was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina. Results Median age was 65 years, 18% female, 94% Caucasian, 37% diabetic, 83% prior coronary revascularization, and 73% on statins. Five-year Kaplan-Meier estimates for the primary endpoint in the chelation + high-dose vitamin group was 31.9%, in the chelation + placebo vitamin group 33.7%, in the placebo infusion + active vitamin group 36.6%, and in the placebo infusions + placebo vitamin group 40.2 %. The reduction in primary endpoint by double active treatment compared with double placebo was significant (HR 0.74, 95% CI (0.57,0.95); p=0.016). In patients with diabetes, the primary endpoint reduction of double active compared with double placebo was more pronounced (HR 0.49, 95% CI (0.33,0.75), p<0.001). Conclusions In stable post- MI patients on evidence-based medical therapy, the combination of oral high-dose vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance. PMID:24952858

A double-blind placebo-controlled study into the efficacy of a homeopathic remedy for fear of firework noises in the dog (Canis familiaris).

PubMed

Cracknell, Nina R; Mills, Daniel S

2008-07-01

Seventy-five dogs that showed a fear response to fireworks participated in a double-blinded, placebo-controlled clinical trial to assess the efficacy of a homeopathic remedy for the alleviation of their behavioural signs. Dogs were randomly assigned to one of two treatments; the homeopathic treatment or the placebo treatment. At the baseline assessments the owners identified the behavioural signs of fear that their dogs normally displayed in response to fireworks, rated their frequency and intensity, and assessed the global severity of their dog's responses. These measures were repeated at the final assessment and owners also completed weekly diaries for the length of the trial. There were significant improvements in the owners' rating of 14/15 behavioural signs of fear in the placebo treatment group and all 15 behavioural signs in the homeopathic treatment group. Both treatment groups also showed significant improvement in the owners' rating of the global severity of their dog's responses. However, there was no significant difference in the response seen between the two treatment groups.

Palmitoylethanolamide as adjunctive therapy in major depressive disorder: A double-blind, randomized and placebo-controlled trial.

PubMed

Ghazizadeh-Hashemi, Maryam; Ghajar, Alireza; Shalbafan, Mohammad-Reza; Ghazizadeh-Hashemi, Fatemeh; Afarideh, Mohsen; Malekpour, Farzaneh; Ghaleiha, Ali; Ardebili, Mehrdad Eftekhar; Akhondzadeh, Shahin

2018-05-01

Experimental studies provide evidence for antidepressant effects of Palmitoylethanolamide (PEA) in animal models of depression. We aimed to evaluate the efficacy and tolerability of PEA add-on therapy in treatment of patients with major depressive disorder (MDD). In a randomized double-blind, and placebo-controlled study, 58 patients with MDD (DSM-5) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were randomized to receive either 600 mg twice daily Palmitoylethanolamide or placebo in addition to citalopram for six weeks. Patients were assessed using the HAM-D scale at baseline and weeks 2, 4, and 6. Fifty-four individuals completed the trial. At week 2, patients in the PEA group demonstrated significantly greater reduction in HAM-D scores compared to the placebo group (8.30 ± 2.41 vs. 5.81 ± 3.57, P = .004). The PEA group also demonstrated significantly greater improvement in depressive symptoms [F (3, 156) = 3.35, P = .021] compared to the placebo group throughout the trial period. The patients in the PEA group experienced more response rate (≥ 50% reduction in the HAM-D score) than the placebo group (100% vs. 74% respectively, P = .01) at the end of the trial. Baseline parameters and frequency of side effects were not significantly different between the two groups. The population size in this study was small and the follow-up period was relatively short. Palmitoylethanolamide adjunctive therapy to citalopram can effectively improve symptoms of patients (predominantly male gender) with major depressive disorder. PEA showed rapid-onset antidepressant effects which need further investigation. Copyright © 2018 Elsevier B.V. All rights reserved.

Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial.

PubMed

Ehrhardt, Stephan; Guo, Nan; Hinz, Rebecca; Schoppen, Stefanie; May, Jürgen; Reiser, Markus; Schroeder, Maximilian Philipp; Schmiedel, Stefan; Keuchel, Martin; Reisinger, Emil C; Langeheinecke, Andreas; de Weerth, Andreas; Schuchmann, Marcus; Schaberg, Tom; Ligges, Sandra; Eveslage, Maria; Hagen, Ralf M; Burchard, Gerd D; Lohse, Ansgar W

2016-01-01

Background.  Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Data on the efficacy of probiotics to prevent AAD and CDAD are unclear. We aimed to evaluate the efficacy of Saccharomyces boulardii to prevent AAD and CDAD in hospitalized adult patients. Methods.  We conducted a multicenter, phase III, double-masked, randomized, placebo-controlled trial in hospitalized patients who received systemic antibiotic treatment in 15 hospitals in Germany between July 2010 and October 2012. Participants received Perenterol forte 250 mg capsules or matching placebo twice per day within 24 hours of initiating antibiotic treatment, continued treatment for 7 days after antibiotic discontinuation, and were then observed for 6 weeks. Results.  Two thousand four hundred forty-four patients were screened. The trial was stopped early for futility after inclusion of 477 participants. Two hundred forty-six patients aged 60.1 ± 16.5 years and 231 patients aged 56.5 ± 17.8 were randomized to the S boulardii group and the placebo group, respectively, with 21 and 19 AADs in the respective groups (P = .87). The hazard ratio of AAD in the S boulardii group compared with the placebo group was 1.02 (95% confidence interval, .55-1.90; P = .94). Clostridium difficile-associated diarrhea occurred in 0.8% of participants (4 of 477). Nine serious adverse events were recorded in the S boulardii group, and 3 serious adverse events were recorded in the placebo group. None were related to study participation. Conclusions.  We found no evidence for an effect of S boulardii in preventing AAD or CDAD in a population of hospitalized patients without particular risk factors apart from systemic antibiotic treatment. ClinicalTrials.gov Identifier.  NCT01143272.

Topiramate as an adjuvant treatment for obsessive compulsive symptoms in patients with bipolar disorder: a randomized double blind placebo controlled clinical trial.

PubMed

Sahraian, Ali; Bigdeli, Mohammad; Ghanizadeh, Ahmad; Akhondzadeh, Shahin

2014-09-01

It has not been examined trialed whether obsessive compulsive symptoms in patients with bipolar disorder respond to topiramate as an adjuvant treatment. This 4-month double-blind placebo-controlled randomized clinical trial examined the efficacy and safety of augmentation with topiramat for treating the patients with bipolar disorder, manic phase type-I, and obsessive compulsive disorder symptoms. Both groups received lithium+olanzapine+clonazepam. However, one group received topiramate and the other group placebo as adjuvant medications. Yale Brown obsessive compulsive behavior scale was used to assess the outcome. Adverse effects were also recorded. A total of 32 patients completed this trial. The mean score decreased from 24.2(4.8) to 17.6(8.7) in the topiramate group (P<0.003) and from 20.9(2.9) to 9.6(3.5) in the placebo group during this trial (P<0.0001). Additionally, 9(52.9%) out of 17 patients in the topiramate group and 2(12.5%) out of 16 patients in the placebo group showed more than 34% decline in YBOC score (x2=6.0, df=1, P<0.01). No serious adverse effects were detected. The limitations of the present study were its small sample size and the fact that it was conducted in a single center. The combination of lithium+olanzapine+clonazepam decreased the symptoms of obsessive compulsive disorder in the patients with bipolar disorder type I. However, topiramate had a more significant effect than placebo on improvement of the patients with bipolar disorder and obsessive compulsive symptoms. This combination seems to be without serious adverse effects. Copyright © 2014 Elsevier B.V. All rights reserved.

Oral Administration of Polymer Hyaluronic Acid Alleviates Symptoms of Knee Osteoarthritis: A Double-Blind, Placebo-Controlled Study over a 12-Month Period

PubMed Central

Tashiro, Toshiyuki; Seino, Satoshi; Sato, Toshihide; Matsuoka, Ryosuke; Masuda, Yasunobu; Fukui, Naoshi

2012-01-01

This study was conducted to investigate the efficacy of oral hyaluronic acid (HA) administration for osteoarthritis (OA) in knee joints. Sixty osteoarthritic subjects (Kellgren-Lawrence grade 2 or 3) were randomly assigned to the HA or placebo group. The subjects in the HA group were given 200 mg of HA once a day everyday for 12 months, while the subjects in the placebo group were given placebo. The subjects in both groups were requested to conduct quadriceps strengthening exercise everyday as part of the treatment. The subjects' symptoms were evaluated by the Japanese Knee Osteoarthritis Measure (JKOM) score. The symptoms of the subjects as determined by the JKOM score improved with time in both the HA and placebo groups. This improvement tended to be more obvious with the HA group, and this trend was more obvious with the subjects aged 70 years or less. For these relatively younger subjects, the JKOM score was significantly better than the one for the placebo group at the 2nd and 4th months after the initiation of administration. Oral administration of HA may improve the symptoms of knee OA in patients aged 70 years or younger when combined with the quadriceps strengthening exercise. PMID:23226979

The effect of vilazodone on sexual function during the treatment of major depressive disorder.

PubMed

Clayton, Anita H; Kennedy, Sidney H; Edwards, John B; Gallipoli, Susan; Reed, Carol R

2013-10-01

  Sexual dysfunction is common in major depressive disorder (MDD), and many serotonergic antidepressants adversely affect sexual function. Vilazodone, a novel serotonin (5-HT) reuptake inhibitor and 5-HT1A partial agonist approved for MDD, exerts its effects at the 5-HT transporter and at both presynaptic and postsynaptic 5-HT1A receptors. This mechanism may limit sexual dysfunction.   To summarize effects of vilazodone (40 mg/day, with food) on sexual function in adults with MDD.   Data sources were three Phase III studies: two 8-week, placebo-controlled studies (NCT00285376 and NCT00683592) and a 52-week open-label study (NCT00644358). Sexual function was assessed by analyzing changes from baseline to end of treatment (EOT) using validated measures.   Arizona Sexual Experience Scale or Changes in Sexual Functioning Questionnaire.   Population included 869 patients (vilazodone, 436; placebo, 433) from placebo-controlled studies and 599 patients from the open-label study. Sexual dysfunction prevalence was high (50%, men; 68%, women) before treatment and declined during treatment in vilazodone and placebo groups, indicating improvement on average. At EOT, stable/improved sexual function was observed in ≥91% of patients in placebo-controlled studies; treatment group differences in sexual dysfunction at EOT were not statistically significant for either sex. Differences vs. placebo in changes from baseline of sexual function scores were small and were generally not statistically significant; effect sizes (Cohen's D) were generally of low magnitude. In the placebo-controlled studies, 8.0% of vilazodone-treated patients and 0.9% of placebo-treated patients reported ≥1 sexual-function-related treatment-emergent adverse event (P<0.001).   Half of men and two thirds of women with MDD had sexual dysfunction at baseline; sexual function improved on average in both vilazodone and placebo groups. Results suggest that vilazodone may have a small adverse impact on sexual function in adults with MDD relative to the high prevalence of sexual dysfunction at baseline. © 2012 International Society for Sexual Medicine.

A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of the extended-release tramadol hydrochloride/acetaminophen fixed-dose combination tablet for the treatment of chronic low back pain.

PubMed

Lee, Jae Hyup; Lee, Chong-Suh

2013-11-01

Chronic low back pain is a common condition that is often difficult to treat. The combination of tramadol hydrochloride and acetaminophen in an extended-release formulation has been shown to provide rapid and long-lasting analgesic effects resulting from the synergistic activity of these 2 active ingredients. The goal of this study was to evaluate the efficacy and safety of extended-release tramadol hydrochloride 75-mg/acetaminophen 650-mg fixed-dose combination tablets (TA-ER) for the treatment of chronic low back pain. This Phase III, double-blind, placebo-controlled, parallel-group study enrolled 245 patients with moderate to severe (≥4 cm on a 10-cm visual analog scale) chronic (≥3 months') low back pain insufficiently controlled by previous NSAIDs or cyclooxygenase-2-selective inhibitors and randomly assigned them to receive 4 weeks of either TA-ER or placebo. The primary efficacy end point was the percentage of patients with a pain intensity change rate ≥30% from baseline to final evaluation. Secondary end points included quality of life (Korean Short Form-36), functionality (Korean Oswestry Disability Index), and adverse events. The percentage of patients with a pain intensity change rate ≥30% was significantly higher (P < 0.05) in the TA-ER group than in the placebo group for both the full analysis set and the per-protocol population. Pain relief success rate from baseline was significantly higher with TA-ER versus placebo at days 8 and 15 but not at the final visit. Patients in the TA-ER group had significant improvements versus placebo in role-physical, general health, and reported health transition domains of the Korean Short Form-36 and significantly higher functional improvements in the personal care section of the Korean Oswestry Disability Index. Patient assessment of overall pain control as "very good" was also significantly higher with TA-ER than with placebo. Adverse events were reported more frequently with TA-ER than with placebo; the most common adverse events reported were nausea, dizziness, constipation, and vomiting. TA-ER was significantly more effective than placebo in providing pain relief, functional improvements, and improved quality of life. It exhibited a predictable safety profile in patients with chronic low back pain. ClinicalTrials.gov identifier: NCT01112267. © 2013 The Authors. Published by Elsevier HS Journals, Inc. All rights reserved.

Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM.

PubMed

Penno, G; Chaturvedi, N; Talmud, P J; Cotroneo, P; Manto, A; Nannipieri, M; Luong, L A; Fuller, J H

1998-09-01

We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.

Evaluation of a multi-herb supplement for erectile dysfunction: a randomized double-blind, placebo-controlled study.

PubMed

Shah, Gaurang R; Chaudhari, Manojkumar V; Patankar, Suresh B; Pensalwar, Shrikant V; Sabale, Vilas P; Sonawane, Navneet A

2012-09-15

Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP) - a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study. 78 men aged 25-50 years of age; suffering from mild to moderate erectile dysfunction (ED), participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF) was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone, Semen analysis, Investigator's Global assessment and Subjects' opinion. In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd) IIEF-EF score at baseline increased from 16.08 (2.87) to 25.08 (4.56) in the VXP group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P < 0.0001). Similar results were observed in each of the remaining four domains of the IIEF (orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction).There was a significant difference for VXP versus placebo comparison of mean (sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53) and partners :(82.75(9.8) vs 18.50(9.44);P < 0.001. Thirty-five out of 39 (90%) subjects from the VXP group and one (3%) from the placebo group wished to continue with the treatment they received. Investigator's global assessment rated VXP therapy as very good to excellent in more than 50% patients and placebo therapy as fair to good in about 25% of patients. Incidence of side effects and subject's rating for tolerability of treatment was similar in both groups. VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men. Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009.

The safety profile of parecoxib for the treatment of postoperative pain: a pooled analysis of 28 randomized, double-blind, placebo-controlled clinical trials and a review of over 10 years of postauthorization data

PubMed Central

Schug, Stephan A; Parsons, Bruce; Li, Chunming; Xia, Feng

2017-01-01

Background Nonselective, nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors are associated with safety issues including cardiovascular, renal, and gastrointestinal (GI) events. Objective To examine the safety of parecoxib, a COX-2 inhibitor, for the management of postoperative pain. Design Pooled analysis of 28 placebo-controlled trials of parecoxib and review of postauthorization safety data. Main outcome measures Prespecified safety events commonly associated with COX-2 inhibitors and/or NSAIDs. In the clinical trial analysis, the frequency of each event was compared between treatment groups using a chi-square test. In the postauthorization review, the number of confirmed cases, along with outcome, was presented for each event. Results In the clinical trial analysis, GI-related events occurred in ~0.2% of patients in the parecoxib and placebo groups. Renal failure and impairment was similar between parecoxib (1.0%) and placebo (0.9%). The occurrence of arterial (parecoxib=0.3%; placebo=0.2%) and venous (parecoxib=0.2%; placebo=0.1%) cardiovascular embolic and thrombotic events was similar between groups. Hypersensitivity reactions including anaphylactic reactions (parecoxib=8.7%; placebo=8.6%), hypotension (parecoxib=2.6%; placebo=2.1%), angioedema (parecoxib=2.5%; placebo=2.8%), and severe cutaneous adverse reactions (0% in both groups) were similar between groups. Incision site or other skin/tissue infections occurred in <0.1% of patients in both groups. The occurrence of these events (total reports/serious reports) in the postauthorization database, based on 69,567,300 units of parecoxib, was as follows: GI ulceration-related events (35/35), renal failure and impairment (77/68), cardiovascular embolic and thrombotic events (66/64), hypersensitivity reactions including hypotension-related events (32/25) and severe cutaneous adverse events (17/17), and masking signs of inflammation (18/18). A majority of reported outcomes were classified as recovered or recovering. Conclusions Potentially serious safety events occur infrequently with parecoxib, which high-lights its safety in patients with postoperative pain. PMID:29066931

The safety profile of parecoxib for the treatment of postoperative pain: a pooled analysis of 28 randomized, double-blind, placebo-controlled clinical trials and a review of over 10 years of postauthorization data.

PubMed

Schug, Stephan A; Parsons, Bruce; Li, Chunming; Xia, Feng

2017-01-01

Nonselective, nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors are associated with safety issues including cardiovascular, renal, and gastrointestinal (GI) events. To examine the safety of parecoxib, a COX-2 inhibitor, for the management of postoperative pain. Pooled analysis of 28 placebo-controlled trials of parecoxib and review of postauthorization safety data. Prespecified safety events commonly associated with COX-2 inhibitors and/or NSAIDs. In the clinical trial analysis, the frequency of each event was compared between treatment groups using a chi-square test. In the postauthorization review, the number of confirmed cases, along with outcome, was presented for each event. In the clinical trial analysis, GI-related events occurred in ~0.2% of patients in the parecoxib and placebo groups. Renal failure and impairment was similar between parecoxib (1.0%) and placebo (0.9%). The occurrence of arterial (parecoxib=0.3%; placebo=0.2%) and venous (parecoxib=0.2%; placebo=0.1%) cardiovascular embolic and thrombotic events was similar between groups. Hypersensitivity reactions including anaphylactic reactions (parecoxib=8.7%; placebo=8.6%), hypotension (parecoxib=2.6%; placebo=2.1%), angioedema (parecoxib=2.5%; placebo=2.8%), and severe cutaneous adverse reactions (0% in both groups) were similar between groups. Incision site or other skin/tissue infections occurred in <0.1% of patients in both groups. The occurrence of these events (total reports/serious reports) in the postauthorization database, based on 69,567,300 units of parecoxib, was as follows: GI ulceration-related events (35/35), renal failure and impairment (77/68), cardiovascular embolic and thrombotic events (66/64), hypersensitivity reactions including hypotension-related events (32/25) and severe cutaneous adverse events (17/17), and masking signs of inflammation (18/18). A majority of reported outcomes were classified as recovered or recovering. Potentially serious safety events occur infrequently with parecoxib, which high-lights its safety in patients with postoperative pain.

Novel sublingual low-dose zolpidem tablet reduces latency to sleep onset following spontaneous middle-of-the-night awakening in insomnia in a randomized, double-blind, placebo-controlled, outpatient study.

PubMed

Roth, Thomas; Krystal, Andrew; Steinberg, Frank J; Singh, Nikhilesh N; Moline, Margaret

2013-02-01

To evaluate efficacy and safety of 3.5-mg zolpidem tartrate sublingual tablets (ZST) on latency to sleep onset after middle-of-the-night (MOTN) awakenings in patients with insomnia characterized by difficulty returning to sleep after MOTN awakenings. Multicenter randomized, double-blind, placebo-controlled, parallel-group. Outpatient. There were 295 adults (median age 43 y; 68.1% female) with primary insomnia and difficulty returning to sleep after MOTN awakenings (three or more MOTN awakenings/wk during screening). After a 2-wk, single-blind placebo eligibility period, participants were randomized 1:1 to as-needed MOTN dosing with 3.5 mg ZST or placebo for 28 nights. An interactive voice response system determined if the study drug could be taken and recorded sleep/wake efficacy measures. ZST significantly (P < 0.0001) decreased latency to sleep onset over 4 wk (baseline 68.1 min; ZST 38.2 min) compared with placebo (baseline 69.4 min; placebo 56.4 min). Ratings of morning sleepiness/alertness significantly (P = 0.0041) favored the ZST group on nights medication was taken but not on other nights. Participants in the ZST group took the study drug on 62% of nights during the 4 wk; members of the placebo group took study medication on 64% of nights. Adverse events were generally mild and at the same rate (19.3% of participants) in both groups. There were no treatment-related serious adverse events (SAEs), and one adverse event-related study discontinuation from the placebo group. Dosing/week did not increase across the study. 3.5 mg ZST used as needed significantly reduced latency to return to sleep in comparison with placebo in these patients with insomnia. Sleep quality was improved, and morning sleepiness/alertness scores also improved. ZST was well tolerated. These data demonstrate the utility of a sleep-promoting agent when used as needed in the MOTN. NCT00466193: "A Study of Zolpidem Tartrate Tablet in Adult Patients with Insomnia" http://www.clinicaltrials.gov/ct2/show/NCT00466193?spons=%22Transcept+Pharmaceuticals%22&spons_ex=Y&rank=2

Weight changes in obese adults 6-months after discontinuation of double-blind zonisamide or placebo treatment

PubMed Central

Shin, J.H.; Gadde, K.M.; Øtbye, T.; Bray, Bray

2014-01-01

We evaluated weight changes in obese patients at 6-months after they ended participation in a 12-month randomized controlled trial in which they received daily placebo, zonisamide 200 mg, or zonisamide 400 mg, in addition to lifestyle counseling. Of the originally randomized 225 patients, 218 completed month-12 when study interventions were discontinued. For the 154 patients who returned for 6-month follow-up off-treatment, weight changes between month-12 and month-18 for placebo (n=53), zonisamide 200 mg (n=49), and zonisamide 400 mg groups (n=52) were 0.5 kg (95% CI, −0.8 to 1.8; 0.7%), 1.5 kg (0.2 to 2.8; 1.6%; p=0.26 vs placebo) and 2.4 kg (1.1 to 3.7; 2.6%; p=0.04 vs placebo), respectively. Our results suggest that although zonisamide 400 mg daily for 12-months resulted in greater weight loss than with placebo, weight regain after discontinuation of interventions was greater in the zonisamide 400 mg group than placebo group. PMID:25123600

Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial.

PubMed

Blay, Jean-Yves; Pápai, Zsuzsanna; Tolcher, Anthony W; Italiano, Antoine; Cupissol, Didier; López-Pousa, Antonio; Chawla, Sant P; Bompas, Emmanuelle; Babovic, Nada; Penel, Nicolas; Isambert, Nicolas; Staddon, Arthur P; Saâda-Bouzid, Esma; Santoro, Armando; Franke, Fabio A; Cohen, Patrick; Le-Guennec, Solenn; Demetri, George D

2015-05-01

Ombrabulin (AVE8062) disrupts the vasculature of established tumours and has shown preclinical synergistic anti-tumour activity when combined with cisplatin. In this phase 3 trial, we aimed to assess the efficacy and safety of ombrabulin plus cisplatin compared with placebo plus cisplatin in patients with advanced soft-tissue sarcomas. We did this multinational, randomised, double-blind, placebo-controlled phase 3 study at 44 centres in ten countries. Patients aged 18 years and older with metastatic soft-tissue sarcomas, an Eastern Cooperative Oncology Group performance status of 0-2, and who had previously received treatment with anthracycline and ifosfamide were randomly assigned (1:1) to intravenous infusion of ombrabulin 25 mg/m(2) plus cisplatin 75 mg/m(2) or intravenous infusion of placebo plus cisplatin 75 mg/m(2) every 3 weeks. Patients were allocated to treatment using a permuted blocks randomisation scheme (block size of four) via an interactive voice-response system, and stratified by histological subtype. Patients, medical staff, study investigators, and individuals who handled and analysed the data were masked to treatment assignment. Our primary endpoint was median progression-free survival in the intention-to-treat population. Safety analyses were done on all randomised patients who received at least one dose of study drug. This trial is now closed, and is registered with ClinicalTrials.gov, number NCT00699517. Between June 13, 2008, and April 26, 2012, we randomly assigned 355 patients to ombrabulin plus cisplatin (n=176) or placebo plus cisplatin (n=179). Median duration of follow-up was 27·9 (IQR 20·9-33·2) in the placebo group and 30·5 months (20·7-37·6) in the ombrabulin group. Progression-free survival was slightly, but significantly, improved in the ombrabulin group compared with the placebo group (median 1·54 months [95% CI 1·45-2·69] vs 1·41 [1·38-1·58] months; hazard ratio 0·76 [95% CI 0·59-0·98]; p=0·0302). Grade 3 or 4 adverse events occurred more frequently in individuals in the ombrabulin group than in those in the placebo group and included neutropenia (34 [19%] in the ombrabulin group vs 14 [8%] in the placebo group) and thrombocytopenia (15 [8%] vs six [3%] for placebo). Adverse events leading to death occurred in 18 patients in the ombrabulin group and 10 patients in the placebo group. The combination of ombrabulin and cisplatin significantly improved progression-free survival; however, it did not show a sufficient clinical benefit in patients with advanced soft-tissue sarcomas to support its use as a therapeutic option. Predictive biomarkers are needed for the rational clinical development of tumour vascular-disrupting drugs for soft-tissue sarcomas. Sanofi. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial.

PubMed

Bruix, Jordi; Takayama, Tadatoshi; Mazzaferro, Vincenzo; Chau, Gar-Yang; Yang, Jiamei; Kudo, Masatoshi; Cai, Jianqiang; Poon, Ronnie T; Han, Kwang-Hyub; Tak, Won Young; Lee, Han Chu; Song, Tianqiang; Roayaie, Sasan; Bolondi, Luigi; Lee, Kwan Sik; Makuuchi, Masatoshi; Souza, Fabricio; Berre, Marie-Aude Le; Meinhardt, Gerold; Llovet, Josep M

2015-10-01

There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation. We undertook this phase 3, double-blind, placebo-controlled study of patients with hepatocellular carcinoma with a complete radiological response after surgical resection (n=900) or local ablation (n=214) in 202 sites (hospitals and research centres) in 28 countries. Patients were randomly assigned (1:1) to receive 400 mg oral sorafenib or placebo twice a day, for a maximum of 4 years, according to a block randomisation scheme (block size of four) using an interactive voice-response system. Patients were stratified by curative treatment, geography, Child-Pugh status, and recurrence risk. The primary outcome was recurrence-free survival assessed after database cut-off on Nov 29, 2013. We analysed efficacy in the intention-to-treat population and safety in randomly assigned patients receiving at least one study dose. The final analysis is reported. This study is registered with ClinicalTrials.gov, number NCT00692770. We screened 1602 patients between Aug 15, 2008, and Nov 17, 2010, and randomly assigned 1114 patients. Of 556 patients in the sorafenib group, 553 (>99%) received the study treatment and 471 (85%) terminated treatment. Of 558 patients in the placebo group, 554 (99%) received the study treatment and 447 (80%) terminated treatment. Median duration of treatment and mean daily dose were 12·5 months (IQR 2·6-35·8) and 577 mg per day (SD 212·8) for sorafenib, compared with 22·2 months (8·1-38·8) and 778·0 mg per day (79·8) for placebo. Dose modification was reported for 497 (89%) of 559 patients in the sorafenib group and 206 (38%) of 548 patients in the placebo group. At final analysis, 464 recurrence-free survival events had occurred (270 in the placebo group and 194 in the sorafenib group). Median follow-up for recurrence-free survival was 8·5 months (IQR 2·9-19·5) in the sorafenib group and 8·4 months (2·9-19·8) in the placebo group. We noted no difference in median recurrence-free survival between the two groups (33·3 months in the sorafenib group vs 33·7 months in the placebo group; hazard ratio [HR] 0·940; 95% CI 0·780-1·134; one-sided p=0·26). The most common grade 3 or 4 adverse events were hand-foot skin reaction (154 [28%] of 559 patients in the sorafenib group vs four [<1%] of 548 patients in the placebo group) and diarrhoea (36 [6%] vs five [<1%] in the placebo group). Sorafenib-related serious adverse events included hand-foot skin reaction (ten [2%]), abnormal hepatic function (four [<1%]), and fatigue (three [<1%]). There were four (<1%) drug-related deaths in the sorafenib group and two (<1%) in the placebo group. Our data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study.

PubMed

Kudo, Masatoshi; Cheng, Ann-Lii; Park, Joong-Won; Park, Jae Hyung; Liang, Po-Chin; Hidaka, Hisashi; Izumi, Namiki; Heo, Jeong; Lee, Youn Jae; Sheen, I-Shyan; Chiu, Chang-Fang; Arioka, Hitoshi; Morita, Satoshi; Arai, Yasuaki

2018-01-01

Orantinib is an oral multi-kinase inhibitor. This study was done to evaluate the efficacy of orantinib combined with conventional transcatheter arterial chemoembolisation (cTACE) in patients with unresectable hepatocellular carcinoma. This randomised, double-blind, placebo-controlled, phase 3 study was done at 75 sites in Japan, South Korea, and Taiwan. Patients with unresectable hepatocellular carcinoma, no extra-hepatic tumour spread, and Child-Pugh score of 6 or less were randomly assigned (1:1) by interactive web response system using a computer-generated sequence to receive orantinib or placebo, within 28 days of cTACE. Randomisation was stratified by region, Child-Pugh score (5 vs 6), alpha fetoprotein concentrations (<400 ng/mL vs ≥400 ng/mL), and size of the largest lesion (≤50 mm vs >50 mm). Orantinib at 200 mg, twice per day, or placebo was given orally until TACE failure or unacceptable toxicity. The patients, investigators, and study personnel were masked to treatment assignment. The primary endpoint was overall survival, analysed in the full analysis set (patients who had received at least one dose of study drug). This study is registered at ClinicalTrials.gov, number NCT01465464, and has been terminated. Between Dec 10, 2010, and Nov 21, 2013, 889 patients were randomly assigned to receive either orantinib (445 patients; 444 treated) or placebo (444 patients; all treated). The study was ended at interim analysis for futility evaluation. Median follow-up was 17·3 months (IQR 11·3-26·4). There was no improvement in overall survival with orantinib compared with placebo (median 31·1 months [95% CI 26·5-34·5] vs 32·3 months [28·4-not reached]; hazard ratio 1·090, 95% CI 0·878-1·352; p=0·435). The main adverse events in the orantinib group were oedema, ascites, and elevation of aspartate and alanine aminotransferases. The most frequent adverse events of grade 3 or worse in the orantinib group included elevated aspartate aminotransferase (189 [43%] patients in the oratinib group, 161 [36%] patients in the placebo group), elevated alanine aminotransferase (150 [34%] patients in the oratinib group, 132 (30%) patients in the placebo group), and hypertension (47 [11%] patients in the oratinib group, 39 [9%] patients in the placebo group). Serious adverse events were reported in 200 (45%) patients in the orantinib group and 134 (30%) patients in the placebo group. Orantinib combined with cTACE did not improve overall survival in patients with unresectable hepatocellular carcinoma. Taiho Pharmaceutical. Copyright © 2018 Elsevier Ltd. All rights reserved.

Plant-Based Nutraceutical Increases Plasma Catalase Activity in Healthy Participants: A Small Double-Blind, Randomized, Placebo-Controlled, Proof of Concept Trial.

PubMed

Sweazea, Karen L; Johnston, Carol S; Knurick, Jessica; Bliss, Courtney D

2017-03-04

Oxidative stress resulting from dietary, lifestyle and environmental factors is strongly associated with tissue damage and aging. It occurs when there is either an overproduction of reactive oxygen species (i.e., oxidants) or decreased bioavailability of antioxidants that can scavenge them. The objective of this 12-week double-blind placebo-controlled study was to assess the efficacy of a nutraceutical at augmenting antioxidant status. Healthy adults (25-45 y) were randomized to either a treatment group (Product B, n = 23) or a placebo group (control, n = 20). No significant effect of Product B was observed for anthropometric variables or markers of glucose and lipid regulation. Biomarkers of oxidative stress were likewise not altered following the 12-week intervention. Plasma catalase concentrations were significantly elevated following 12 weeks of Product B as compared to the control group (+6.1 vs. -10.3 nmol/min/mL, p = 0.038), whereas other measures of antioxidant capacity were not significantly different between the groups. Product B effectively augmented concentrations of the anti-aging antioxidant catalase in healthy adults.

Vitamin D supplementation affects serum high-sensitivity C-reactive protein, insulin resistance, and biomarkers of oxidative stress in pregnant women.

PubMed

Asemi, Zatollah; Samimi, Mansooreh; Tabassi, Zohreh; Shakeri, Hossein; Esmaillzadeh, Ahmad

2013-09-01

Unfavorable metabolic profiles and oxidative stress in pregnancy are associated with several complications. This study was conducted to determine the effects of vitamin D supplementation on serum concentrations of high-sensitivity C-reactive protein (hs-CRP), metabolic profiles, and biomarkers of oxidative stress in healthy pregnant women. This randomized, double-blind, placebo-controlled clinical trial was conducted in 48 pregnant women aged 18-40 y old at 25 wk of gestation. Participants were randomly assigned to receive either 400 IU/d cholecalciferol supplements (n = 24) or placebo (n = 24) for 9 wk. Fasting blood samples were taken at study baseline and after 9 wk of intervention to quantify serum concentrations of hs-CRP, lipid concentrations, insulin, and biomarkers of oxidative stress. After 9 wk of intervention, the increases in serum 25-hydroxyvitamin D and calcium concentrations were greater in the vitamin D group (+3.7 μg/L and +0.20 mg/dL, respectively) than in the placebo group (-1.2 μg/L and -0.12 mg/dL, respectively; P < 0.001 for both). Vitamin D supplementation resulted in a significant decrease in serum hs-CRP (vitamin D vs. placebo groups: -1.41 vs. +1.50 μg/mL; P-interaction = 0.01) and insulin concentrations (vitamin D vs. placebo groups: -1.0 vs. +2.6 μIU/mL; P-interaction = 0.04) and a significant increase in the Quantitative Insulin Sensitivity Check Index score (vitamin D vs. placebo groups: +0.02 vs. -0.02; P-interaction = 0.006), plasma total antioxidant capacity (vitamin D vs. placebo groups: +152 vs. -20 mmol/L; P-interaction = 0.002), and total glutathione concentrations (vitamin D vs. placebo groups: +205 vs. -32 μmol/L; P-interaction = 0.02) compared with placebo. Intake of vitamin D supplements led to a significant decrease in fasting plasma glucose (vitamin D vs. placebo groups: -0.65 vs. -0.12 mmol/L; P-interaction = 0.01), systolic blood pressure (vitamin D vs. placebo groups: -0.2 vs. +5.5 mm Hg; P-interaction = 0.01), and diastolic blood pressure (vitamin D vs. placebo groups: -0.4 vs. +3.1 mm Hg; P-interaction = 0.01) compared with placebo. In conclusion, vitamin D supplementation for 9 wk among pregnant women has beneficial effects on metabolic status.

Homeopathic pathogenetic trials produce specific symptoms different from placebo.

PubMed

Möllinger, Heribert; Schneider, Rainer; Walach, Harald

2009-04-01

Homeopathy uses information gathered from healthy volunteers taking homeopathic substances (pathogenetic trials) for clinical treatment. It is controversial whether such studies produce symptoms different from those produced by placebo. To test whether homeopathic preparations produce different symptoms than placebo in healthy volunteers. Three armed, double-blind, placebo controlled randomised experimental pathogenetic study in 25 healthy volunteers who took either one of two homeopathic remedies, Natrum muriaticum and Arsenicum album in 30CH or identical placebo. Main outcome parameter was the number of remedy-specific symptoms per group. On average, 6 symptoms typical for Arsenicum album were experienced by participants taking arsenicum album, 5 symptoms typical for Natrum muriaticum by those taking natrum muriaticum, and 11 non-specific symptoms by those in the placebo group. Differences were significant overall (Kruskall Wallis test, p = 0.0002,) and significantly different from placebo (Mann-Whitney test, p = 0.001). Homeopathic remedies produce different symptoms than placebo. Copyright (c) 2009 S. Karger AG, Basel.

Effect of hyoscine-N-butyl bromide rectal suppository on labor progress in primigravid women: randomized double-blind placebo-controlled clinical trial.

PubMed

Makvandi, Somayeh; Tadayon, Mitra; Abbaspour, Mohammadreza

2011-04-15

To determine the effects of hyoscine-N-butyl bromide (HBB) rectal suppository on labor progress in primigravid women. A randomized double-blind placebo-controlled clinical trial was carried out on 130 primigravid women admitted for spontaneous labor. The women were recruited based on the inclusion and exclusion criteria and randomized into the experimental (n=65) and control group (n=65). In the beginning of the active phase of labor, 20 mg of HBB rectal suppository was administered to the experimental group, while a placebo suppository was administered to the control group. Cervical dilatation and duration of active phase and second stage of labor were recorded. The rate of cervical dilatation was 2.6 cm/h in the experimental and 1.5 cm/h in the control group (P<0.001). The active phase and the second stage of labor were significantly shorter in the experimental group (P=0.001 and P<0.001, respectively). There was no significant difference between the two groups in the fetal heart rate, maternal pulse rate, blood pressure, and the APGAR score 1 and 5 minutes after birth. Use of HBB rectal suppository in the active management of labor can shorten both the active phase and second stage of labor without significant side-effects.

Intravenous dexamethasone versus ketamine gargle versus intravenous dexamethasone combined with ketamine gargle for evaluation of post-operative sore throat and hoarseness: A randomized, placebo-controlled, double blind clinical trial

PubMed Central

Safavi, Mohammadreza; Honarmand, Azim; Fariborzifar, Arghavan; Attari, Mohammadali

2014-01-01

Background: Sore throat and hoarseness are the most frequent subjective complaints after tracheal intubation for general anesthesia. We conducted a prospective, randomized, double-blind, placebo controlled study to evaluate the efficacy of intravenous (IV) dexamethasone plus ketamine gargle for reducing the incidence and severity of post-operative sore throat (POST) and hoarseness. Materials and Methods: 140 patients (aged 16-65 year) scheduled for elective surgery were enrolled. Patients were randomly allocated into four groups of 35 subjects each: Group K, gargled 40 mg ketamine in 30 ml saline; Group D, were infused 0.2 mg/kg IV dexamethasone; Group KD, gargled 40 mg ketamine in 30 ml saline plus 0.2 mg/kg IV dexamethasone; Group P (placebo) that received saline (gargle and IV). POST was graded at 0, 2, 4, 8, 16 and 24 h after operation on a four-point scale (0-3). Results: The incidence and severity of POST were significantly lower in Group KD, compared with the other groups at all times after tracheal extubation for up to 24 h (P < 0.05). Also the incidence and severity of hoarseness were significantly lower in each Groups of KD and K and D compared with group placebo (P < 0.05). Conclusion: The prophylactic use of 0.2 mg/kg of IV dexamethasone plus ketamine gargle significantly reduced the incidence and severity of POST compared with using each of these drugs alone or using placebo. PMID:25371869

Effects of Transdermal Testosterone on Natriuretic Peptide Levels in Women: A Randomized Placebo-Controlled Pilot Study

PubMed Central

Lin, Eleanor; McCabe, Elizabeth; Newton-Cheh, Christopher; Bloch, Kenneth; Buys, Emmanuel; Wang, Thomas; Miller, Karen K.

2011-01-01

Objective To investigate whether testosterone administration alters natriuretic peptide levels in women. Design Three-month, double-blind, randomized, placebo-controlled study. Setting Clinical research center. Patients 51 women with hypoandrogenemia due to hypopituitarism. Intervention Transdermal testosterone (300 mcg daily) or placebo patch. Main Outcome Measure N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Results NT-proBNP levels decreased in the transdermal testosterone group compared with placebo over three months (p = 0.009). The difference between groups remained significant after controlling for baseline age, systolic blood pressure, body mass index, and homeostasis model of assessment-insulin resistance (p = 0.008). Change in NT-proBNP over three months was inversely associated with change in free testosterone levels (ρ = −0.41, p = 0.01). Conclusions Testosterone administration to women results in decreased natriuretic peptide levels, suggesting that testosterone may be an inverse regulator of the natriuretic peptide system. Clinical Trials Registration Number NCT00027430 PMID:22137497

Do randomized clinical trials with inadequate blinding report enhanced placebo effects for intervention groups and nocebo effects for placebo groups? A protocol for a meta-epidemiological study of PDE-5 inhibitors

PubMed Central

2012-01-01

Background Patients’ expectations of treatment effects may contribute to positive (placebo) and negative (nocebo) outcomes. The effect of patient expectations may be pronounced in subjectively assessed conditions, such as male erectile dysfunction. The aim of this project is to examine the magnitude of expectancy in trials of phosphodiesterase-5 inhibitors. We hypothesize that randomized controlled trials with inadequate blinding will report enhanced placebo effects for intervention groups and nocebo effects for placebo groups, compared with adequately blinded studies. Methods/design We will quantify the magnitude of expectancy by comparing the effect estimates of trials with inadequate and adequate blinding. Blinding will be assessed using four domains from the Cochrane ‘risk-of-bias’ tool: allocation concealment; blinding of patient; caregiver; and outcome assessor. Our secondary aim is to identify factors that can modify expectations, such as prior experience with the intervention and drug side effects. We will perform an electronic search using a combination of controlled vocabulary and free text words in the following databases: MEDLINE, EMBASE, CENTRAL, and a clinical trials register. We will include randomized controlled trials, with either parallel or crossover design, that compare one phosphodiesterase-5 inhibitor with a placebo. The study’s primary aim should be to investigate the efficacy of phosphodiesterase-5 inhibitors for treating male erectile dysfunction. Screening will take place at two levels: abstracts and titles, followed by full text reports. Two reviewers will independently extract data on the primary outcome and assess risk of bias. We will meta-analyze treatment effects, if appropriate, to assess the magnitude of enhanced placebo effects and nocebo effects in intervention and placebo groups, respectively. We will explore possible mediators of placebo and nocebo effects with subgroup and meta-regression analyses. Discussion Treatments may confer significant costs and risk of adverse effects; it is important, therefore, to determine whether the effects of treatments are larger than expectancy alone. If treatment expectations can be used in a non-deceptive way to produce clinically advantageous outcomes, then it may be possible to incorporate such mechanisms into evidence-based healthcare decision-making. PMID:23151403

Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial.

PubMed

Al-Lamee, Rasha; Thompson, David; Dehbi, Hakim-Moulay; Sen, Sayan; Tang, Kare; Davies, John; Keeble, Thomas; Mielewczik, Michael; Kaprielian, Raffi; Malik, Iqbal S; Nijjer, Sukhjinder S; Petraco, Ricardo; Cook, Christopher; Ahmad, Yousif; Howard, James; Baker, Christopher; Sharp, Andrew; Gerber, Robert; Talwar, Suneel; Assomull, Ravi; Mayet, Jamil; Wensel, Roland; Collier, David; Shun-Shin, Matthew; Thom, Simon A; Davies, Justin E; Francis, Darrel P

2018-01-06

Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy. NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre. Copyright © 2018 Elsevier Ltd. All rights reserved.

A randomized, double-blinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury.

PubMed

Kurokawa, Sei; Katsuki, Shinichi; Fujita, Tomoki; Saitoh, Yusuke; Ohta, Hidetoshi; Nishikawa, Kouji; Sato, Yasushi; Sato, Yasuhiro; Ohira, Koji; Yamada, Masataka; Kato, Mototsugu

2014-02-01

It is not clear what kind of drug is appropriate to heal NSAID-induced enteropathy. Several reports showed the preventive effect of prostaglandin analogue or inducer using healthy subjects who took NSAIDs. However there was no report for healing effect and for patients. The aim of this study was to evaluate the healing effect of rebamipide in patients with NSAIDs-induced enteropathy. In addition, we evaluated for nutritional parameter. This study was conducted as a randomized, double-blinded, placebo-controlled, multicenter trial. Study protocol was approved by each hospital's ethical committees. Patients with LDA and/or NSAID more than 3 months were enrolled. Patients with enteropathy were divided into the placebo and the rebamipide groups. Rebamipide 100 mg three times daily was administered during 4 weeks. Capsule endoscopies were performed at 0 and 4 week. The number of small intestinal ulcer and erosion were evaluated. Total protein was analyzed as nutritional parameter. Sixty one participants were completed this study. Change in number of small intestinal erosion in the rebamipide group was -2.5 ± 3.4, and 2.1 ± 3.9 in the placebo group (P < 0.0001). Change in number of small intestinal ulcer in the rebamipide group was -0.5 ± 1.6, and 0.1 ± 0.7 in the placebo group (P = 0.024). Change in serum total protein levels in the rebamipide group was 0.06 ± 0.36, and -0.27 ± 0.34 in the placebo group (P = 0.0005). Rebamipide has not only the healing effect for NSAIDs-induced enteropathy compared with placebo, but the improvement of nutritional condition. These results showed a tentative therapeutical strategy for chronic NSAIDs users.

Comparison between lornoxicam quick-release and parecoxib for post-operative analgesia after laparoscopic cholecystectomy: A prospective randomized, placebo-controlled trial.

PubMed

Kouroukli, Irene; Zompolas, Vasilios; Tsekoura, Vasiliki; Papazoglou, Ioannis; Louizos, Antonis; Panaretou, Venetiana

2013-10-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are valuable for post-operative pain as they reduce the use of opioids. Cyclooxygenase-2 inhibitors and traditional NSAIDs can be used. This is a prospective, randomized, placebo-controlled trial to study the efficacy and the safety of the oral administration of lornoxicam quick release tablets versus intravenously administered parecoxib for the management of pain after laparoscopic cholecystectomy (LC). One hundred and eight patients, American Society of Anesthesiologists I-II, were randomized to either group A (n = 36): Lornoxicam quick-release 8 mg PO, group B (n = 36): Parecoxib 40 mg intravenous (IV) or group C (n = 36) placebo, for post-operative analgesia, 30 min before the operation and 12 and 24 h post-operatively. All patients received a standard dose of meperidine 1 mg/kg intramuscularly before the incision and post-operatively as rescue analgesia, when visual analog scale (VAS) pain score was <4. Pain at rest and on movement was assessed at 20 min, 3, 6, 12, 18 and 24 h post-operatively. Total meperidine administration and adverse events were also recorded. There were significantly lower VAS pain scores at 20 min, 3, 6, 12 and 18 h at rest or with movement in the lornoxicam quick release and parecoxib groups compared with the placebo group. The number of patients requiring rescue analgesia (meperidine) was significantly higher in the placebo group (P = 0.001). The average dose of meperidine administered was significantly higher in the placebo group, both at 20 min (P = 0.013/0.007) and 24 h (P = 0.037/0.023) post-operatively. VAS scores and meperidine requirements were similar in patients who received lornoxicam or parecoxib. Parecoxib 40 mg IV and lornoxicam quick-release 8 mg PO every 12 h are equivalent adjuvant analgesics with a greater efficacy than placebo for post-operative analgesia in patients undergoing LC.

Effects of Boron-Based Gel on Radiation-Induced Dermatitis in Breast Cancer: A Double-Blind, Placebo-Controlled Trial.

PubMed

Aysan, Erhan; Idiz, Ufuk Oguz; Elmas, Leyla; Saglam, Esra Kaytan; Akgun, Zuleyha; Yucel, Serap Baskaya

2017-06-01

This study is aimed to evaluate the effects of boron on radiation-induced skin reactions (RISR) in breast cancer patients. After 47 patients with invasive ductal carcinoma underwent radiotherapy, 23 (49%) received a boron-based gel, and 24 (51%) received placebo. Assessments were performed according to the Radiation Therapy Oncology Group (RTOG) skin scale and a Five-Point Horizontal Scale (FPHS). At the end of the fifth week of radiotherapy, the RTOG scores in the boron group were significantly lower than those in the placebo group (p = .024). The FPHS score was higher in the placebo group than in the boron group, and this difference was not statistically significant (p = .079). Using the RTOG scoring system, we revealed that the application of a boron-based gel diminished RISR. The mechanism of action is unclear but may be related to antioxidant, wound healing, and thermal degradation effects of boron.

The Effect of Ginger on Breast Milk Volume in the Early Postpartum Period: A Randomized, Double-Blind Controlled Trial.

PubMed

Paritakul, Panwara; Ruangrongmorakot, Kasem; Laosooksathit, Wipada; Suksamarnwong, Maysita; Puapornpong, Pawin

2016-09-01

In Thailand, ginger is a popular natural galactagogue among breastfeeding women. However, there has never been evidence to support the effectiveness of ginger in increasing the breast milk volume. To compare breast milk volume on the third and seventh day postpartum between lactating mothers who receive 500 mg dried ginger capsules twice daily with those receiving placebo. A randomized, double-blind controlled trial was conducted. Women who deliver a term baby were randomly assigned to receive dried ginger or placebo for 7 days postpartum. Breast milk volume was measured on third day postpartum using test weight method for a period of 24 hours and on seventh day postpartum using 1 hour milk production. We also compared the third day serum prolactin level between the two groups. Data from 63 women were available for analysis, 30 from the ginger group and 33 from the placebo group. The two groups were similar regarding baseline characteristics. Women in the ginger group have higher milk volume than the placebo group (191.0 ± 71.2 mL/day versus 135.0 ± 61.5 mL/day, p < 0.01). However, the seventh day milk volume in the ginger group does not differ from the placebo group (80.0 ± 58.5 mL versus 112.1 ± 91.6 mL, p = 0.24). The mean serum prolactin levels were similar in both groups (321.5 ± 131.8 ng/L in the ginger group, and 331.4 ± 100.7 ng/L in the placebo group, p = 0.74). No side effect was reported in this study. Ginger is a promising natural galactagogue to improve breast milk volume in the immediate postpartum period without any notable side effect.

Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease.

PubMed

Sato, Yoshihiro; Honda, Yoshiaki; Iwamoto, Jun

2007-03-20

There is a high incidence of hip fractures in patients with Parkinson disease (PD). Bone mineral density (BMD) is decreased in patients with PD, correlating with the immobilization-induced bone resorption and hypovitaminosis D with compensatory hyperparathyroidism. To evaluate the effectiveness of risedronate, an inhibitor of bone resorption, on osteoporosis and the risk of hip fractures in elderly men with PD. This was a 2-year, randomized, double-blind, placebo-controlled trial. In a prospective study of patients with PD, 121 patients received a daily dose of 2.5 mg risedronate and vitamin D2 1,000 IU for 2 years, and the remaining 121 received placebo and vitamin D2 1,000 IU. Incidence of hip fractures was compared between the two groups. Nine patients sustained hip fractures in the placebo group, and three hip fractures occurred in the risedronate group. The relative risk of a hip fracture in the risedronate group vs the placebo group was 0.33 (95% CI, 0.09 to 1.20). BMD increased by 2.2% in the risedronate group and decreased by 2.9% in the placebo group (p < 0.0001). Urinary deoxypyridinoline, a bone resorption marker, decreased by 46.7% in the risedronate group and by 33.0% in the placebo group. Treatment with risedronate and vitamin D2 increases bone mineral density in elderly men with Parkinson disease and reduces the risk of hip fractures.

Oral sumatriptan for migraine in children and adolescents: a randomized, multicenter, placebo-controlled, parallel group study.

PubMed

Fujita, Mitsue; Sato, Katsuaki; Nishioka, Hiroshi; Sakai, Fumihiko

2014-04-01

The objective of this article is to evaluate the efficacy and tolerability of two doses of oral sumatriptan vs placebo in the acute treatment of migraine in children and adolescents. Currently, there is no approved prescription medication in Japan for the treatment of migraine in children and adolescents. This was a multicenter, outpatient, single-attack, double-blind, randomized, placebo-controlled, parallel-group study. Eligible patients were children and adolescents aged 10 to 17 years diagnosed with migraine with or without aura (ICHD-II criteria 1.1 or 1.2) from 17 centers. They were randomized to receive sumatriptan 25 mg, 50 mg or placebo (1:1:2). The primary efficacy endpoint was headache relief by two grades on a five-grade scale at two hours post-dose. A total of 178 patients from 17 centers in Japan were enrolled and randomized to an investigational product in double-blind fashion. Of these, 144 patients self-treated a single migraine attack, and all provided a post-dose efficacy assessment and completed the study. The percentage of patients in the full analysis set (FAS) population who report pain relief at two hours post-treatment for the primary endpoint was higher in the placebo group than in the pooled sumatriptan group (38.6% vs 31.1%, 95% CI: -23.02 to 8.04, P  = 0.345). The percentage of patients in the FAS population who reported pain relief at four hours post-dose was higher in the pooled sumatriptan group (63.5%) than in the placebo group (51.4%) but failed to achieve statistical significance ( P  = 0.142). At four hours post-dose, percentages of patients who were pain free or had complete relief of photophobia or phonophobia were numerically higher in the sumatriptan pooled group compared to placebo. Both doses of oral sumatriptan were well tolerated. No adverse events (AEs) were serious or led to study withdrawal. The most common AEs were somnolence in 6% (two patients) in the sumatriptan 25 mg treatment group and chest discomfort in 7% (three patients) in the sumatriptan 50 mg treatment group. There was no statistically significant improvement between the sumatriptan pooled group and the placebo group for pain relief at two hours. Oral sumatriptan was well tolerated.

Randomized controlled trial of benzocaine versus placebo spray for pain relief at hysterosalpingogram

PubMed Central

Bachman, Emelia Argyropoulos; Senapati, Suneeta; Sammel, Mary D.; Kalra, Suleena Kansal

2016-01-01

Many women experience pain during hysterosalpingogram (HSG). This prospective, randomized, double-blinded, placebo-controlled study assessed whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, parity, pre-procedure oral analgesic use and history of dysmenorrhoea and/or chronic pelvic pain. Median change in pain score from baseline to procedure was 50.6 mm (−7.4 to 98.8 mm) in the benzocaine group and 70.4 mm (19.8 to 100 mm) in the placebo group. There was no difference between groups after adjusting for history of dysmenorrhoea. There was no difference in resolution of pain in benzocaine versus placebo groups at 5 min post procedure – median pain score difference – 11.1 (−90.1 to 18.5) versus −37.0 (−100 to 1.2) – or at 30 min post procedure. Satisfaction scores did not differ by treatment and did not correlate with pain score during the procedure (rho = 0.005). The use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain. PMID:24745839

Effects of a Proprietary Freeze-Dried Water Extract of Eurycoma longifolia (Physta) and Polygonum minus on Sexual Performance and Well-Being in Men: A Randomized, Double-Blind, Placebo-Controlled Study

PubMed Central

Udani, Jay K.; George, Annie A.; Musthapa, Mufiza; Pakdaman, Michael N.; Abas, Azreena

2014-01-01

Background. Physta is a proprietary product containing a freeze-dried water extract of Eurycoma longifolia (tongkat ali), which is traditionally used as an energy enhancer and aphrodisiac. We aim to evaluate a 300 mg combination of Physta and Polygonum minus, an antioxidant, with regard to sexual performance and well-being in men. Methods. Men that aged 40–65 years were screened for this 12-week randomized, double-blind, placebo-controlled, parallel-group study. Outcome measures included validated questionnaires that aimed to evaluate erectile function, satisfaction with intervention, sexual intercourse performance, erectile hardness, mood, and overall quality of life. Results. 12 subjects in the active group and 14 in the placebo group completed the study. Significant improvements were noted in scores for the Sexual Intercourse Attempt diary, Erection Hardness Scale, Sexual Health Inventory of Men, and Aging Male Symptom scale (P < 0.05 for all). Three adverse events were reported in the active group and four in the placebo group, none of which were attributed to study product. Laboratory evaluations, including liver and kidney function testing, showed no clinically significant abnormality. Conclusion. Supplementation for twelve weeks with Polygonum minus and the proprietary Eurycoma longifolia extract, Physta, was well tolerated and more effective than placebo in enhancing sexual performance in healthy volunteers. PMID:24550993

Effects of a Proprietary Freeze-Dried Water Extract of Eurycoma longifolia (Physta) and Polygonum minus on Sexual Performance and Well-Being in Men: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Udani, Jay K; George, Annie A; Musthapa, Mufiza; Pakdaman, Michael N; Abas, Azreena

2014-01-01

Background. Physta is a proprietary product containing a freeze-dried water extract of Eurycoma longifolia (tongkat ali), which is traditionally used as an energy enhancer and aphrodisiac. We aim to evaluate a 300 mg combination of Physta and Polygonum minus, an antioxidant, with regard to sexual performance and well-being in men. Methods. Men that aged 40-65 years were screened for this 12-week randomized, double-blind, placebo-controlled, parallel-group study. Outcome measures included validated questionnaires that aimed to evaluate erectile function, satisfaction with intervention, sexual intercourse performance, erectile hardness, mood, and overall quality of life. Results. 12 subjects in the active group and 14 in the placebo group completed the study. Significant improvements were noted in scores for the Sexual Intercourse Attempt diary, Erection Hardness Scale, Sexual Health Inventory of Men, and Aging Male Symptom scale (P < 0.05 for all). Three adverse events were reported in the active group and four in the placebo group, none of which were attributed to study product. Laboratory evaluations, including liver and kidney function testing, showed no clinically significant abnormality. Conclusion. Supplementation for twelve weeks with Polygonum minus and the proprietary Eurycoma longifolia extract, Physta, was well tolerated and more effective than placebo in enhancing sexual performance in healthy volunteers.

Oral intake of Boesenbergia pandurata extract improves skin hydration, gloss, and wrinkling: A randomized, double-blind, and placebo-controlled study.

PubMed

Kim, Do Un; Chung, Hee Chul; Kim, Changhee; Hwang, Jae-Kwan

2017-12-01

Photoaging is a severe skin damage that occurs as a result of exposure to external elements, primarily ultraviolet (UV) irradiation. Chronically, UV-irradiated skin exhibits the signs of sunburn and hyperpigmentation with the destruction of connective tissues. Previously, Boesenbergia pandurata (B. pandurata) and its active compound panduratin A showed antiphotoaging activities in vitro and in vivo. The aim of this study was to investigate the clinical efficacy of B. pandurata intake on skin hydration, gloss, wrinkling, and elasticity. A double-blind, placebo-controlled trial was conducted to clinically evaluate the effect of B. pandurata ethanol extract (BPE) containing 8% of panduratin A on human skin hydration, gloss, wrinkling, and elasticity. Ninety-two subjects were randomly assigned to receive tablets containing either BPE or placebo for 12 weeks. The test group had significantly increased skin hydration and gloss and decreased wrinkling compared to the placebo group at 12 weeks. There was no significant difference in skin elasticity between the two groups; however, the increment rate in the test group was higher than that in the placebo group at 12 weeks. None of the subjects developed adverse symptoms during the study period. These results suggest that BPE can be used as a nutraceutical or nutricosmetic material for improving human skin hydration, gloss, and wrinkling. © 2017 Wiley Periodicals, Inc.

Evaluation of an ultra-low-dose oral contraceptive for dysmenorrhea: a placebo-controlled, double-blind, randomized trial.

PubMed

Harada, Tasuku; Momoeda, Mikio

2016-12-01

To evaluate the efficacy and safety of an ultra-low-dose oral contraceptive (NPC-01; 0.02 mg ethinyl estradiol and 1 mg norethisterone) in subjects with dysmenorrhea. Placebo-controlled, double-blind, randomized trial. Clinical trial sites. Two hundred fifteen subjects with dysmenorrhea. Subjects were randomly assigned to receive NPC-01, placebo, or IKH-01 (0.035 mg ethinyl estradiol and 1 mg norethisterone) for four cycles. Total dysmenorrhea score (verbal rating scale) assessing pain on the basis of limited ability to work and need for analgesics. The reductions of total dysmenorrhea score and visual analog scale score after the treatment were significantly higher in the NPC-01 group than in the placebo group. Furthermore, the efficacy of NPC-01 was comparable to that of IKH-01. The overall incidence of side effects was significantly higher in the NPC-01 group than in the placebo group. All side effects that occurred in the NPC-01 group were previously reported in patients receiving IKH-01. No serious side effects occurred. The ultra-low-dose contraceptive NPC-01 relieved dysmenorrhea as effectively as IKH-01. Thus, NPC-01 could represent a new option for long-term treatment of dysmenorrhea. NCT01129102. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The Effect of Trimethoprim on Serum Folate Levels in Humans: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Meidahl Petersen, Kasper; Eplov, Kasper; Kjær Nielsen, Torben; Jimenez-Solem, Espen; Petersen, Morten; Broedbaek, Kasper; Daugaard Popik, Sara; Kallehave Hansen, Lina; Enghusen Poulsen, Henrik; Trærup Andersen, Jon

2016-01-01

Trimethoprim antagonize the actions of folate by inhibition of dihydrofolate reductase. This could diminish serum folate levels in humans and causes folate deficiency in some patients. We conducted a randomized, double-blind, placebo-controlled trial, to investigate the effect of trimethoprim on serum folate levels in healthy participants after a 7-day trial period. Thirty young, healthy males were randomly allocated to receive trimethoprim, 200 mg twice daily, and 30 were randomly allocated to placebo. Before trial initiation, participant numbers were given randomly generated treatment allocations within sealed opaque envelopes. Participants and all staff were kept blinded to treatment allocations during the trial. Serum folate was measured at baseline and at end of trial. In the 58 participants analyzed (30 in the trimethoprim group and 28 in the placebo group), 8 had folate deficiency at baseline. Within the trimethoprim group, serum folate was significantly decreased (P = 0.018) after the trial. We found a mean decrease in serum folate among trimethoprim exposed of 1.95 nmol/L, compared with a 0.21 nmol/L mean increase in the placebo group (P = 0.040). The proportion of folate-deficient participants increased significantly within the trimethoprim group (P = 0.034). No serious adverse events were observed. In conclusion, we found that a daily dose of 400 mg trimethoprim for 7 days significantly lowered serum folate levels in healthy study participants.

The effect of different dosage regimens of tranexamic acid on blood loss in bimaxillary osteotomy: a randomized, double-blind, placebo-controlled study.

PubMed

Apipan, B; Rummasak, D; Narainthonsaenee, T

2018-05-01

The purpose of this study was to compare the effects of three dosage regimens of intravenous tranexamic acid and normal saline placebo on blood loss and the requirement for transfusion during bimaxillary osteotomy. A prospective, randomized, double-blind, placebo-controlled study was performed. Eighty patients scheduled for elective bimaxillary osteotomy were divided into four groups: a placebo group and three groups receiving a single dose of tranexamic acid 10, 15, or 20mg/kg body weight after the induction of anaesthesia. Demographic data, the anaesthetic time, the operative time, and the experience of the surgical team were similar in the four groups. Patients receiving placebo had increased blood loss compared to those receiving tranexamic acid. No significant difference in blood loss was found among those who received 10, 15, or 20mg/kg body weight of tranexamic acid. There was no significant difference in transfusion requirement, amount of 24-h postoperative vacuum drainage, length of hospital stay, or complications among the four groups. Prophylactic tranexamic acid decreased bleeding during bimaxillary osteotomy. Of the three dosages of tranexamic acid studied, the most efficacious and cost-effective dose to reduce bleeding was 10mg/kg body weight. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

A randomized controlled trial comparing Ametop™ with placebo for reducing pain associated with local anesthetic skin infiltration before neuraxial anesthesia in parturients.

PubMed

Kavanagh, T; Dube, A; Albert, A; Gunka, V

2016-08-01

Between 10-22% of the general population experience needle phobia. Needle phobic parturients are at increased risk of adverse outcomes. We assessed the efficacy of topical Ametop™ (tetracaine 4%) gel in reducing the pain associated with local anesthetic skin infiltration before neuraxial block in non-laboring women. This was a prospective, randomized, double-blind, placebo-controlled study. Ametop™ or placebo was applied to the skin of the lower back at least 20min before neuraxial block using a standardized technique with 1% lidocaine skin infiltration. The primary outcome was numeric pain score (0-10) 30s after lidocaine infiltration. Groups were compared using Welch's t-test. Thirty-six subjects in each group were analyzed. There was a statistically significant difference in the mean (standard deviation) pain score between the Ametop™ and the placebo groups: 2.36±1.80 and 3.51±2.22, respectively (P=0.019). There were no significant adverse events. The mean numeric pain score in the Ametop™ group was 33% lower compared to the placebo group. Topical Ametop™ gel applied at least 20min before local anesthetic infiltration of the skin prior to neuraxial block in elective cesarean delivery may be a useful adjunct in needle phobic women. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia

PubMed Central

Kennedy, S.B.; Bolay, F.; Kieh, M.; Grandits, G.; Badio, M.; Ballou, R.; Eckes, R.; Feinberg, M.; Follmann, D.; Grund, B.; Gupta, S.; Hensley, L.; Higgs, E.; Janosko, K.; Johnson, M.; Kateh, F.; Logue, J.; Marchand, J.; Monath, T.; Nason, M.; Nyenswah, T.; Roman, F.; Stavale, E.; Wolfson, J.; Neaton, J.D.; Lane, H.C.

2017-01-01

BACKGROUND The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. METHODS We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSVΔG-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated. RESULTS A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSVΔG-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (P<0.001 for all comparisons); these differences were not seen at 1 month. Serious adverse events within 12 months after injection were seen in 40 participants (8.0%) in the ChAd3-EBO-Z group, in 47 (9.4%) in the rVSVΔG-ZEBOV-GP group, and in 59 (11.8%) in the placebo group. By 1 month, an antibody response developed in 70.8% of the participants in the ChAd3-EBO-Z group and in 83.7% of those in the rVSVΔG-ZEBOV-GP group, as compared with 2.8% of those in the placebo group (P<0.001 for both comparisons). At 12 months, antibody responses in participants in the ChAd3-EBO-Z group (63.5%) and in those in the rVSVΔG-ZEBOV-GP group (79.5%) remained significantly greater than in those in the placebo group (6.8%, P<0.001 for both comparisons). CONCLUSIONS A randomized, placebo-controlled phase 2 trial of two vaccines that was rapidly initiated and completed in Liberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407.) PMID:29020589

Investigating the effect of therapeutic touch on the intensity of acute chemotherapy-induced vomiting in breast cancer women under chemotherapy

PubMed Central

Matourypour, Pegah; Vanaki, Zohreh; Zare, Zahra; Mehrzad, Valiolah; Dehghan, Mojtaba; Ranjbaran, Mehdi

2016-01-01

Background: Nausea and vomiting are the worst and the most prevalent complications experienced by 70–80% of patients. Complementary treatments including therapeutic touch are cost-effective and low-risk, independent nursing interventions. Present research aims at investigating the effect of therapeutic touch on the intensity of acute chemotherapy-induced vomiting in these patients. Materials and Methods: As a single-blind, randomized clinical trial, the present research was carried out on women with breast cancer undergoing chemotherapy in Isfahan, Iran. The subjects were divided into three groups of control, placebo, and intervention. The intervention was applied to each patient once for 20 min on the aura (human energy field) focusing on solar chakra. Data gathering instruments included demographic questionnaire and acute vomiting intensity scale. Results: There was a significant difference among the three groups (and also after the intervention) (P < 0.0001). Paired comparisons among the groups using Mann–Whitney test showed that there was a statistically significant difference between the control group and the intervention group and between the control group and the placebo group (P < 0.0001). However, there was no significant difference between the placebo and intervention groups (P = 0.07). Conclusions: Therapeutic touch was effective in reducing vomiting in the intervention group. However, the patients experienced lower-intensity vomiting which may be because of presence of a therapist and probably the reduced anxiety related to an additional intervention. So, further research is recommended considering the placebo group and employing another person in addition to the therapist, who is not skilled for this technique. PMID:27186202

Investigating the effect of therapeutic touch on the intensity of acute chemotherapy-induced vomiting in breast cancer women under chemotherapy.

PubMed

Matourypour, Pegah; Vanaki, Zohreh; Zare, Zahra; Mehrzad, Valiolah; Dehghan, Mojtaba; Ranjbaran, Mehdi

2016-01-01

Nausea and vomiting are the worst and the most prevalent complications experienced by 70-80% of patients. Complementary treatments including therapeutic touch are cost-effective and low-risk, independent nursing interventions. Present research aims at investigating the effect of therapeutic touch on the intensity of acute chemotherapy-induced vomiting in these patients. As a single-blind, randomized clinical trial, the present research was carried out on women with breast cancer undergoing chemotherapy in Isfahan, Iran. The subjects were divided into three groups of control, placebo, and intervention. The intervention was applied to each patient once for 20 min on the aura (human energy field) focusing on solar chakra. Data gathering instruments included demographic questionnaire and acute vomiting intensity scale. There was a significant difference among the three groups (and also after the intervention) (P < 0.0001). Paired comparisons among the groups using Mann-Whitney test showed that there was a statistically significant difference between the control group and the intervention group and between the control group and the placebo group (P < 0.0001). However, there was no significant difference between the placebo and intervention groups (P = 0.07). Therapeutic touch was effective in reducing vomiting in the intervention group. However, the patients experienced lower-intensity vomiting which may be because of presence of a therapist and probably the reduced anxiety related to an additional intervention. So, further research is recommended considering the placebo group and employing another person in addition to the therapist, who is not skilled for this technique.

Interferon-alpha and transfer factor in the treatment of multiple sclerosis: a double-blind, placebo-controlled trial. AUSTIMS Research Group.

PubMed Central

1989-01-01

The role of interferon-alpha (IFN-alpha) and transfer factor (TF) in the treatment of multiple sclerosis was investigated in a prospective, multi-centric, three year, double-blind, placebo-controlled trial. One hundred and eighty two patients with clinically definite multiple sclerosis were randomised into three treatment groups whose compositions were found to be similar for demographic and prognostic variables including HLA status. Subcutaneous injections of IFN-alpha (3 x 10(6) units), TF (0.5 units) manufactured from leucocytes of cohabiting donors, or placebo were given twice weekly for two months, once weekly for 10 months then fortnightly for 24 months. One hundred and fifty three patients completed the injection regimen. There was no significant difference in the progression of disability for multiple sclerosis patients in either the IFN-alpha or TF-treated groups compared with the placebo group. Similarly, change in visual evoked responses (VER), and in number of oligoclonal bands (OCB) and the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) over the trial period did not differ significantly between the three groups. However, the IFN-alpha-treated group had significantly more reported adverse drug reactions and patient withdrawals than either of the other two groups. PMID:2659737

A Comparison of Alprazolam and Behavior Therapy in Treatment of Panic Disorder.

ERIC Educational Resources Information Center

Klosko, Janet S.; And Others

1990-01-01

Compared panic control treatment (PCT), behavior therapy for panic disorders, with alprazolam medication, placebo, and waiting-list control groups. Percentage of clients (N=57) completing study who were free of panic attacks following PCT was 87 percent, compared with 50 percent for alprazolam, 36 percent for placebo, and 33 percent for…

Social Mishap Exposures for Social Anxiety Disorder: An Important Treatment Ingredient

ERIC Educational Resources Information Center

Fang, Angela; Sawyer, Alice T.; Asnaani, Anu; Hofmann, Stefan G.

2013-01-01

Conventional cognitive-behavioral therapy for social anxiety disorder, which is closely based on the treatment for depression, has been shown to be effective in numerous randomized placebo-controlled trials. Although this intervention is more effective than waitlist control group and placebo conditions, a considerable number of clients do not…

Prophylactic effect of artemether on human schistosomiasis mansoni among Egyptian children: A randomized controlled trial.

PubMed

Elmorshedy, Hala; Tanner, Marcel; Bergquist, Robert N; Sharaf, Soraya; Barakat, Rashida

2016-06-01

A double-blind, randomized controlled trial was conducted in an endemic focus for Schistosoma mansoni in Kafr El-Sheikh Governorate, Northern Nile Delta, Egypt, to evaluate the prophylactic effect of artemether (ART) given in conjunction with praziquantel (PZQ). The study encompassed 913 primary school children randomly assigned to two treatment groups PZQ/ART and PZQ/ART-placebo. At baseline, both groups received 40 mg/kg body weight of PZQ twice four weeks apart, after which one group received 6 mg/kg body weight of ART every 3 weeks in 5 cycles during the transmission season and the other group received ART-placebo. At the end of the study, prevalence of infection among the PZQ/ART was approximately half that of the PZQ/ART-placebo group, i.e. 6.7% versus 11.6%, and incidence of new infections for the PZQ/ART was 2.7% versus 6.5% for the PZQ/ART-placebo. In conclusion, PZQ/ART combined therapy might be considered as an adjunct measure against human schistosomiasis, by specifically reducing transmission and therefore contribute to disease elimination. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Radiochromium (chromium-51) evaluation of gastrointestinal blood loss associated with placebo, aspirin, and nabumetone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lussier, A.; LeBel, E.

Gastrointestinal blood loss is one of the most serious clinical events induced by drugs. To date, almost no nonsteroidal anti-inflammatory drug has been shown to be devoid of that side effect in a strictly controlled study. The objective of this study was to assess quantitatively, by use of radioactive chromium (chromium-51)-labeled red blood cells, gastrointestinal blood loss associated with nabumetone (1000 mg daily), aspirin (3.6 g daily), and placebo. A total of 37 normal subjects, divided among the three treatment groups and a fourth group that received no treatment, were assessed clinically and quantitatively for gastrointestinal blood loss over amore » period of 28 days of active treatment. The results with chromium-51, analyzed on a logarithmic scale, revealed no statistically significant differences between the nabumetone, placebo, and control groups. Gastrointestinal blood loss in the aspirin group, however, was elevated when compared with all other groups at a high level of statistical significance (p less than 0.001). It is concluded that, under conditions in which aspirin causes substantial gastrointestinal microbleeding, nabumetone is not significantly different from placebo.« less

Naproxen or estradiol for bleeding and spotting with the levonorgestrel intrauterine system: a randomized controlled trial.

PubMed

Madden, Tessa; Proehl, Sarah; Allsworth, Jenifer E; Secura, Gina M; Peipert, Jeffrey F

2012-02-01

The purpose of this study was to evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women who are initiating the levonorgestrel-releasing intrauterine system. We conducted a randomized controlled trial of naproxen, estradiol, or placebo that was administered over the first 12 weeks of levonorgestrel-releasing intrauterine system use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis. There were 129 women who were assigned randomly to naproxen (n = 42 women), estradiol (n = 44 women), or placebo (n = 43 women). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared with placebo (42.9% vs 16.3%; P = .03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (adjusted relative risk, 0.90; 95% confidence interval, 0.84-0.97) compared with placebo. More frequent bleeding and spotting was observed in the estradiol group (adjusted relative risk, 1.25; 95% confidence interval, 1.17-1.34). The administration of naproxen resulted in a reduction in bleeding and spotting days compared with placebo. Copyright © 2012 Mosby, Inc. All rights reserved.

Amoxicillin-clavulanate for patients with acute exacerbation of chronic rhinosinusitis: a prospective, double-blinded, placebo-controlled trial.

PubMed

Sabino, Henrique Augusto Cantareira; Valera, Fabiana Cardoso Pereira; Aragon, Davi Casale; Fantucci, Marina Zilio; Titoneli, Carolina Carneiro; Martinez, Roberto; Anselmo-Lima, Wilma T; Tamashiro, Edwin

2017-02-01

The management of acute exacerbation of chronic rhinosinusitis (AECRS) is still under debate, especially because there are no adequate studies to support a best-evidence treatment for this condition. Antibiotic use for AECRS has been recommended based on extrapolation of data from acute rhinosinusitis (ARS) or non-placebo-controlled studies. This study aimed to evaluate whether antibiotic therapy modifies the course of AECRS in a randomized, placebo-controlled study. Patients with AECRS were randomized in a double-blinded manner (2:1 ratio) to receive either amoxicillin-clavulanate 875 mg/125 mg twice daily (BID) (AMX-CLAV, n = 21) or placebo capsules (n = 11) during 14 days. All patients were also treated with mometasone furoate and nasal washes with saline. Global sinonasal symptoms (Severity Symptom Assessment [SSA]), quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), nasal endoscopic score (Lund-Kennedy), and microbiological evaluation were compared to evaluate the efficacy of antibiotic therapy in AECRS. Despite the majority of bacteria cultured from the middle meatus swab were sensitive for AMX-CLAV (84%), both AMX-CLAV and placebo-treated groups presented the same clinical course, with no difference between groups. Both groups exhibited overall improvement of symptoms on day 14 compared to day 0 (p < 0.01), especially the items "nasal secretion" and "nasal obstruction" (p < 0.05). We also observed the same evolution of nasal endoscopic and quality of life scores between placebo and AMX-CLAV. We concluded that AMX-CLAV for 14 days did not change the clinical course of AECRS compared with placebo. The addition of an oral antibiotic to ongoing topical intranasal steroid spray may not provide additional benefit during management of AECRS. © 2016 ARS-AAOA, LLC.

A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes.

PubMed

Goldberg, R B; Einhorn, D; Lucas, C P; Rendell, M S; Damsbo, P; Huang, W C; Strange, P; Brodows, R G

1998-11-01

The objective of the study was to assess the efficacy and safety of repaglinide compared with placebo in the treatment of patients with type 2 diabetes. This was a phase II multicenter, double-blind, placebo-controlled, randomized, dose-adjustment and maintenance trial. After screening and a 2-week washout period, 99 patients were randomized to receive either repaglinide (n = 66) or placebo (n = 33). Patients underwent 6 weeks of dose adjustment followed by 12 weeks of dose maintenance. Fasting and stimulated glycosylated hemoglobin (HbA1c), plasma glucose, insulin, and C-peptide were measured at predetermined intervals. Adverse events and hypoglycemic episodes were recorded. From baseline to last visit, mean HbA1c decreased from 8.5 to 7.8% in patients treated with repaglinide and increased from 8.1 to 9.3% in patients receiving placebo, with a statistically significant difference of - 1.7% (P < 0.0001) between treatment groups at the last visit. Mean fasting plasma glucose and postprandial glucose increased in patients receiving placebo and decreased in patients treated with repaglinide, with statistically significant (P < 0.01) differences between groups at the last visit. Concentrations of fasting and postprandial insulin and C-peptide were lower at the last visit compared with baseline for patients treated with placebo and higher for patients treated with repaglinide, and the differences between groups were statistically significant (P < 0.05). Overall, repaglinide was well tolerated. This study demonstrated that repaglinide was safe and efficacious in lowering blood glucose concentrations. In addition to overall improvement in glycemic control noted with repaglinide in both sulfonylurea-treated patients and oral hypoglycemic agent-naive patients, repaglinide had a potent glucose-lowering effect in the postprandial period.

Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial.

PubMed

Bruera, Eduardo; Valero, Vicente; Driver, Larry; Shen, Loren; Willey, Jie; Zhang, Tao; Palmer, J Lynn

2006-05-01

To evaluate the effectiveness of patient-controlled methylphenidate as compared with placebo in cancer patients with fatigue, as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F). Patients with a fatigue score of at least 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) and hemoglobin level of at least 10 g/dL were included. Patients were randomly assigned to receive 5 mg methylphenidate or placebo every 2 hours as needed (maximum of four capsules a day), for 7 days. Patients completed a daily diary including study drug record and fatigue intensity. A research nurse telephoned patients daily to assess toxicity and fatigue level. All patients were offered open-label methylphenidate for 4 weeks. FACIT-F and the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 15, and 36. The FACIT-F fatigue subscore on day 8 was considered the primary end point. Of 112 patients randomly assigned, 52 patients in the methylphenidate and 53 in the placebo group were assessable for analysis. Fatigue intensity improved significantly on day 8 in both the methylphenidate and placebo groups. However, there was no significant difference in fatigue improvement by FACIT-F (P = .31) or ESAS (P = .14) between groups. In open-label phase, fatigue intensity maintained low as compared with baseline. No significant toxicities were observed. Both methylphenidate and placebo resulted in significant symptom improvement. Methylphenidate was not significantly superior to placebo after 1 week of treatment. Longer study duration is justified. The role of daily telephone calls from a research nurse should be explored as a palliative care intervention.

Effect of a gastro-protective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: a double-blind placebo-controlled study in Japan.

PubMed

Miwa, Hiroto; Osada, Taro; Nagahara, Akihito; Ohkusa, Toshifumi; Hojo, Mariko; Tomita, Toshihiko; Hori, Kazutoshi; Matsumoto, Takayuki; Sato, Nobuhiro

2006-12-01

Although mucosal protective agents have been used frequently for treatment of symptomatic gastritis, there has been no well-controlled study of functional dyspepsia. The aim of this study was to assess the efficacy of a 4-week treatment with rebamipide for the relief of overall dyspeptic symptoms and the improvement in quality of life from an untreated baseline in Japanese patients with functional dyspepsia. In a double-blinded, randomized, placebo-controlled, single-center study, 81 patients with functional dyspepsia were recruited and treated with rebamipide (100 mg, t.i.d.) or placebo for 4 weeks. Symptoms were assessed at baseline and at the end of the study period by a symptom questionnaire. Quality of life was evaluated by the QPD 32. Data was analyzed for symptoms from 38 patients who received rebamipide and 33 patients who received placebo treatment. Overall symptoms were significantly improved in both the rebamipide and placebo treatment groups from the untreated baseline after 4 weeks of treatment, and the mean changes in overall symptoms were not significantly different between the groups. However, the improvement in symptom score was significantly greater in the treatment arm than in the placebo arm for three items, which were bloating, belching, and pain or discomfort that was relieved after a meal. Regarding quality of life, social restriction and pain intensity were significantly improved in the rebamipide treatment group in per-protocol analysis (P = 0.048 and P = 0.031, respectively). Although rebamipide was not significantly better than placebo in reducing overall symptoms by 4 weeks' treatment, it may partially improve the symptoms. It may also be beneficial in improvement of quality of life in Japanese patients with functional dyspepsia.

Efficacy of misoprostol in the treatment of tinnitus in patients with diabetes and/or hypertension.

PubMed

Akkuzu, Babur; Yilmaz, Ismail; Cakmak, Ozcan; Ozluoglu, Levent N

2004-09-01

To determine the efficacy of the prostaglandin E1 analogue misoprostol in the treatment of tinnitus in diabetic and/or hypertensive patients. Double-blind, randomized, placebo-controlled trial. Tertiary care referral center. The subjects were 42 patients with hypertension and/or diabetes mellitus who had chronic tinnitus and had experienced tinnitus symptoms for a minimum of 6 months. Twenty-eight patients were randomly assigned to Group I (misoprostol treatment), and 14 patients to the Group II (placebo treatment). Misoprostol therapy was started at 200 microg per day, and was increased 200 microg every 7 days until a dose of 800 microg per day was reached. The same numbers of placebo tablets were given to the control group using the same schedule. Both groups were treated for 1 month. The changes in objective and subjective tinnitus findings from baseline to 1 month were assessed, and the group results were compared. The chi(2)-test, student's t-test and paired-samples t-test were used to analyze the study. At the completion of treatment, objective assessment showed that tinnitus loudness decreased in 13 (46%) of the 28 patients in the experimental group, whereas this was observed in only two (14%) of the 14 subjects in the placebo group. Subjective tinnitus scoring revealed improvement rates of 29 and 14% for the misoprostol and placebo groups, respectively. When t-test relating to difference between rates were performed, the difference between improvement rate for tinnitus loudness of the experimental group and control group was found to be statistically significant (P = 0.05), but difference between improvement rate based on subjective tinnitus scoring was insignificant (P = 0.22). Misoprostol is an effective and safe treatment for chronic tinnitus in hypertensive and/or diabetic patients. Our results are encouraging, but further studies of larger series are needed.

The Effects of Metformin and Weight Loss on Biomarkers Associated With Breast Cancer Outcomes.

PubMed

Patterson, Ruth E; Marinac, Catherine R; Sears, Dorothy D; Kerr, Jacqueline; Hartman, Sheri J; Cadmus-Bertram, Lisa; Villaseñor, Adriana; Flatt, Shirley W; Godbole, Suneeta; Li, Hongying; Laughlin, Gail A; Oratowski-Coleman, Jesica; Parker, Barbara A; Natarajan, Loki

2018-05-18

This study investigated the effects of metformin and weight loss on biomarkers associated with breast cancer prognosis. Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomly assigned to metformin vs placebo and to a weight loss intervention vs control (ie, usual care). The 2 × 2 factorial design allows a single randomized trial to investigate the effect of two factors and interactions between them. Outcomes were changes in fasting insulin, glucose, C-reactive protein (CRP), estradiol, testosterone, and sex-hormone binding globulin (SHBG). The trial was powered for a main effects analysis of metformin vs placebo and weight loss vs control. All tests of statistical significance were two-sided. A total of 313 women (94.0%) completed the six-month trial. High prescription adherence (ie, ≥80% of pills taken) ranged from 65.9% of participants in the metformin group to 81.3% of those in the placebo group (P < .002). Mean percent weight loss was statistically significantly higher in the weight loss group (-5.5%, 95% confidence interval [CI] = -6.3% to -4.8%) compared with the control group (-2.7%, 95% CI = -3.5% to -1.9%). Statistically significant group differences (ie, percent change in metformin group minus placebo group) were -7.9% (95% CI = -15.0% to -0.8%) for insulin, -10.0% (95% CI = -18.5% to -1.5%) for estradiol, -9.5% (95% CI = -15.2% to -3.8%) for testosterone, and 7.5% (95% CI = 2.4% to 12.6%) for SHBG. Statistically significant group differences (ie, percent change in weight loss group minus placebo group) were -12.5% (95% CI = -19.6% to -5.3%) for insulin and 5.3% (95% CI = 0.2% to 10.4%) for SHBG. As adjuvant therapy, weight loss and metformin were found to be a safe combination strategy that modestly lowered estrogen levels and advantageously affected other biomarkers thought to be on the pathway for reducing breast cancer recurrence and mortality.

A double-blind, placebo-controlled trial of epsilon-aminocaproic acid for reducing blood loss in coronary artery bypass grafting surgery.

PubMed

Kikura, Mutsuhito; Levy, Jerrold H; Tanaka, Kenichi A; Ramsay, James G

2006-02-01

Epsilon-aminocaproic acid is a plasmin inhibitor that potentially reduces perioperative bleeding when administered prophylactically to cardiac surgery patients. To evaluate the efficacy of epsilon-aminocaproic acid, a prospective placebo-controlled trial was conducted in patients undergoing primary coronary artery bypass grafting surgery. One hundred patients were randomly assigned to receive either epsilon-aminocaproic acid (100 mg/kg before skin incision followed by 1 g/hour continuous infusion until chest closure, 10 g in cardiopulmonary bypass circuit) or placebo, and the efficacy of epsilon-aminocaproic acid was evaluated by the reduction in postoperative thoracic-drainage volume and in donor-blood transfusion up to postoperative day 12. Postoperative thoracic-drainage volume was significantly lower in the epsilon-aminocaproic acid group compared with the placebo group (epsilon-aminocaproic acid, 649 +/- 261 mL; versus placebo, 940 +/- 626 mL; p=0.003). There were no significant differences between the epsilon-aminocaproic acid and placebo groups in the percentage of patients requiring donor red blood cell transfusions (epsilon-aminocaproic acid, 24%; versus placebo, 18%; p=0.62) or in the number of units of donor red blood cells transfused (epsilon-aminocaproic acid, 2.2 +/- 0.8 U; versus placebo, 1.9 +/- 0.8 U; p=0.29). Epsilon-aminocaproic acid did not reduce the risk of donor red blood cell transfusions compared with placebo (odds ratio: 1.2, 95% confidence interval; 0.4 to 3.2, p=0.63). Prophylactic administration of epsilon-aminocaproic acid reduces postoperative thoracic-drainage volume by 30%, but it may not be potent enough to reduce the requirement and the risk for donor blood transfusion in cardiac surgery patients. This information is useful for deciding on a therapy for hemostasis in cardiac surgery.

A randomized, double-blind, placebo-controlled clinical trial of megestrol acetate as an appetite stimulant in children with weight loss due to cancer and/or cancer therapy.

PubMed

Cuvelier, Geoff D E; Baker, Tina J; Peddie, Elaine F; Casey, Linda M; Lambert, Pascal J; Distefano, Dianne S; Wardle, Marlene G; Mychajlunow, Beth A; Romanick, Marcel A; Dix, David B; Wilson, Beverly A

2014-04-01

Megestrol acetate (MA) is an appetite stimulant with efficacy in promoting weight gain in adults with cancer-associated anorexia-cachexia. Studies documenting MA efficacy in children, however, are limited. We present the first randomized, double-blind, placebo-controlled clinical trial of MA versus placebo in children with cancer and weight loss. Subjects <18 years of age with weight loss (minimum 5% from highest previous weight; or %ideal body weight <90%) due to cancer and/or cancer therapy were randomized to either MA (7.5 mg/kg/day) or placebo for a planned study duration of 90 days. Primary outcome was the difference between groups in mean percent weight change from beginning to end of the study period. Secondary outcomes included effects on anthropometrics, body composition, need for tube feeding or parenteral nutrition, and toxicities. Twenty-six patients were randomly assigned (13 MA, 13 placebo). The MA group experienced a mean weight gain of +19.7% compared to a mean weight loss of -1.2% in the placebo group, for a difference of +20.9% (95%CI: +11.3% to +30.5%, P = 0.003) in favor of MA over placebo. MA subjects experienced significant increases in weight for age z-scores, body mass index z-scores, and mid upper arm circumference compared to placebo. DXA scanning suggested disproportionate increases in fat accrual. Adrenal suppression was the main toxicity of MA. In children with high-risk malignancies, MA resulted in significant increases in mean percent weight change compared to placebo. Further studies of MA should be pursued to better delineate the effect on nutritional status. © 2013 Wiley Periodicals, Inc.

[Dexpanthenol nasal spray as an effective therapeutic principle for treatment of rhinitis sicca anterior].

PubMed

Kehrl, W; Sonnemann, U

1998-09-01

Controlled clinical studies on medical treatment of rhinitis sicca anterior have not yet been published. Therapy recommendations are based on experiences but not on results of controlled clinical studies. The aim of this study was to examine the efficacy and tolerance of a new form of application of Dexpanthenol in physiologic saline solution (Nasicur). A randomized comparison of parallel groups was performed. One group was treated with the nasal spray while the control group received a placebo. The assessment of nasal breathing resistance and the extent of crust formation according to scores were defined as target parameters. Statistical analysis was carried out according to Wilcoxon at alpha < or = 0.05. Forty-eight outpatients diagnosed with rhinitis sicca anterior were included in this study. Twenty-four received the medication, and 29 were treated with a placebo. The superiority of the dexpanthenol nasal spray in comparison to the placebo medication was demonstrated for both target parameters as clinically relevant and statistically significant. The placebo spray showed clinical improvement of the other treatment outcome parameters. Dexpanthenol nasal spray showed no statistically significant difference in comparison to placebo. The clinically proven efficacy is emphasized by good tolerance of both treatments which was validated by the objective rhinoscopy findings. Good compliance was confirmed. The result of the controlled clinical study confirms that the dexpanthenol nasal spray is an effective medicinal treatment of rhinitis sicca anterior and is more effective than common medications.

Randomised controlled trial of the effect of long-term selenium supplementation on plasma cholesterol in an elderly Danish population.

PubMed

Cold, Frederik; Winther, Kristian H; Pastor-Barriuso, Roberto; Rayman, Margaret P; Guallar, Eliseo; Nybo, Mads; Griffin, Bruce A; Stranges, Saverio; Cold, Søren

2015-12-14

Although cross-sectional studies have shown a positive association between Se and cholesterol concentrations, a recent randomised controlled trial in 501 elderly UK individuals of relatively low-Se status found that Se supplementation for 6 months lowered total plasma cholesterol. The Danish PRECISE (PREvention of Cancer by Intervention with Selenium) pilot study (ClinicalTrials.gov ID: NCT01819649) was a 5-year randomised, double-blinded, placebo-controlled trial with four groups (allocation ratio 1:1:1:1). Men and women aged 60-74 years (n 491) were randomised to 100 (n 124), 200 (n 122) or 300 (n 119) μg Se-enriched yeast or matching placebo-yeast tablets (n 126) daily for 5 years. A total of 468 participants continued the study for 6 months and 361 participants, equally distributed across treatment groups, continued for 5 years. Plasma samples were analysed for total and HDL-cholesterol and for total Se concentrations at baseline, 6 months and 5 years. The effect of different doses of Se supplementation on plasma lipid and Se concentrations was estimated by using linear mixed models. Plasma Se concentration increased significantly and dose-dependently in the intervention groups after 6 months and 5 years. Total cholesterol decreased significantly both in the intervention groups and in the placebo group after 6 months and 5 years, with small and nonsignificant differences in changes in plasma concentration of total cholesterol, HDL-cholesterol, non-HDL-cholesterol and total:HDL-cholesterol ratio between intervention and placebo groups. The effect of long-term supplementation with Se on plasma cholesterol concentrations or its sub-fractions did not differ significantly from placebo in this elderly population.

Pregabalin versus tramadol for postoperative pain management in patients undergoing lumbar laminectomy: a randomized, double-blinded, placebo-controlled study

PubMed Central

Kumar, Koramutla Pradeep; Kulkarni, Dilip Kumar; Gurajala, Indira; Gopinath, Ramachandran

2013-01-01

Prevention and treatment of postoperative pain continues to be a major challenge in postoperative care. Opioid analgesics, with their well-known side effects, continue to represent a cornerstone in postoperative pain control. Anticonvulsant medications are established treatments for neuropathic pain. Pregabalin (S-[+]-3-isobutylgaba), a structural analog of gamma-Aminobutyric acid, has been used for the treatment of various neuropathic pain and also as an adjunctive therapy for adults with partial onset seizures. This study was thus taken up to primarily assess and compare the analgesic and anxiolytic effects of administering pregabalin and tramadol preoperatively for patients undergoing elective decompressive lumbar laminectomy. The study group included 75 patients between the ages of 20–60 years belonging to American Society of Anesthesiology-1 (ASA) and ASA-2 patients. The patients were randomly allocated into three groups of 25 patients each. The placebo group received a placebo capsule, the tramadol group received a 100 mg capsule, while the pregabalin group received a 150 mg capsule orally 1 hour before anesthetic induction. Pregabalin showed statistically significant analgesic effects compared to placebo, but the effect was found to be less prevalent compared to tramadol. The need for rescue analgesia was the least prevalent in tramadol patients followed by pregabalin patients, and reached a maximum in the control group. Pregabalin showed statistically significant anxiolytic effects compared to placebo, and this was associated with less sedation in comparison to tramadol. Pregabalin had fewer numbers of postoperative complications of nausea, vomiting, and drowsiness in comparison to tramadol. The results of this study support the clinical use of pregabalin in the postsurgical setting for pain relief, as it is well tolerated, and usually presents with transient adverse effects. PMID:23837006

Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: a randomized, double-blind, placebo-controlled trial.

PubMed

Sagheb, Mohammad Mahdi; Dormanesh, Banafshe; Fallahzadeh, Mohammad Kazem; Akbari, Hamideh; Sohrabi Nazari, Sahar; Heydari, Seyed Taghi; Behzadi, Saeed

2012-05-01

Restless legs syndrome (RLS) is a common disorder in hemodialysis patients that leads to insomnia and impaired quality of life. Because high oxidative stress has been implicated in the pathogenesis of RLS, we sought to evaluate the efficacy of vitamins C and E and their combination in reducing the severity of RLS symptoms in hemodialysis patients in this randomized, double-blind, placebo-controlled, four-arm parallel trial. Sixty stable hemodialysis patients who had all four diagnostic criteria for RLS developed by the International Restless Legs Syndrome Group with no acute illness or history of renal stone were randomly allocated to four fifteen-patient parallel groups to receive vitamin C (200 mg) and vitamin E (400 mg), vitamin C (200 mg) and placebo, vitamin E (400 mg) and placebo, and double placebo daily for eight weeks. International Restless Legs Scale (IRLS) scores were measured for all patients at baseline and at the end of treatment phase. The primary outcome was absolute change in IRLS sum score from baseline to the end of treatment phase. Means of IRLS sum score decreased significantly in the vitamins C and E (10.3 ± 5.3, 95% CI: 7.4-13.3), vitamin C and placebo (10 ± 3.5, 95% CI: 8.1-11.9), and vitamin E and placebo groups (10.1 ± 6, 95% CI: 6.8-13.5) compared with the double placebo group (3.1 ± 3, 95% CI: 1.5-4.8), (P<0.001); however, no differences were observed between these treatment groups. Vitamins C and E and their combination are safe and effective treatments for reducing the severity of RLS in hemodialysis patients over the short-term. Copyright © 2012 Elsevier B.V. All rights reserved.

Remifentanil analgesia during external cephalic version for breech presentation in nulliparous women at term: A randomized controlled trial.

PubMed

Wang, Zhi-Hong; Yang, Yi; Xu, Gui-Ping

2017-03-01

The aim of the study was to assess the efficacy and safety of remifentanil for pain relief during external cephalic version (ECV) for breech presentation in nulliparous women at term. A total of 144 nulliparous women with singleton breech presentation were randomly divided into the intervention group and the placebo group, with 72 subjects in each group. The subjects in the intervention group received remifentanil (infused at 0.1 μg kg min with demand boluses of 0.1 μg/kg), whereas those in the placebo group were given saline placebo. This study was conducted from May 2013 to April 2016. The outcomes measures include pain (measured with the visual analog scale, VAS), success rate of ECV, maternal satisfaction for ECV, and adverse events. A total of 137 participants completed the study. The intervention with remifentanil showed greater efficacy than did placebo in decreasing the VAS score immediately after ECV (intervention group 4.3 ± 2.2 vs placebo group 6.4 ± 2.5, P < 0.01). A significant difference in the ECV success rate was also found between the 2 groups (intervention group 56.9% vs placebo group 38.9%, P = 0.03). In addition, a significant difference in the satisfaction score was also detected (intervention group 9.3 ± 0.9 vs placebo group 6.7 ± 1.2, P < 0.01). The observed adverse events were similar between the 2 groups. This study shows that remifentanil could decrease pain, improve the ECV success rate, and improve satisfaction in nulliparous women at term during the period of ECV. Furthermore, it is also well tolerated with few adverse events.

Efficacy of combination therapy with probiotics and mosapride in patients with IBS without diarrhea: a randomized, double-blind, placebo-controlled, multicenter, phase II trial.

PubMed

Choi, C H; Kwon, J G; Kim, S K; Myung, S-J; Park, K S; Sohn, C-I; Rhee, P-L; Lee, K J; Lee, O Y; Jung, H-K; Jee, S R; Jeen, Y T; Choi, M-G; Choi, S C; Huh, K C; Park, H

2015-05-01

Probiotics can be beneficial in irritable bowel syndrome (IBS). Mosapride citrate, a selective 5-HT4 receptor agonist, stimulates gastrointestinal motility. We investigated the efficacy of combination therapy with probiotics and mosapride for non-diarrheal-type IBS. Two hundred and eighty-five IBS patients were randomly assigned to either a combination of probiotics (Bacillus subtilis and Streptococcus faecium) and mosapride at one of four different doses or a placebo for 4 weeks. The primary outcome was the proportion of patients experiencing adequate relief (AR) of global IBS symptoms at week 4. The secondary outcomes included subject's global assessment (SGA) of IBS symptom relief, individual symptoms, stool parameters, and IBS-quality of life. The proportion of AR at week 4 was significantly higher in all treatment groups compared to the placebo group (53.7% in group 1, 55.0% in group 2, 55.2% in group 3, 53.6% in group 4 [the highest dose], and 35.1% in placebo group, respectively, p < 0.05). The proportion of patients reporting 'completely or considerably relieved' in the SGA was higher in the treatment groups than in the placebo group. The abdominal pain/discomfort score in the treatment group 4 was more prominently improved compared with that of the placebo group. In patients with constipation-predominant IBS, the improvements in stool frequency and consistency were significantly higher in the treatment groups 4 and 1, respectively, than those in the placebo group. Combination therapy with probiotics and mosapride is effective for relief of symptoms in patients with non-diarrheal-type IBS. The study has been registered in the US National Library of Medicine (http://www.clinicaltrials.gov, NCT01505777). © 2015 John Wiley & Sons Ltd.

Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients.

PubMed

Tarumi, Yoko; Wilson, Mitchell P; Szafran, Olga; Spooner, G Richard

2013-01-01

The stool softener docusate is widely used in the management of constipation in hospice patients. There is little experimental evidence to support this practice, and no randomized trials have been conducted in the hospice setting. To assess the efficacy of docusate in hospice patients. This was a 10-day, prospective, randomized, double-blind, placebo-controlled trial of docusate and sennosides vs. placebo and sennosides in hospice patients in Edmonton, Alberta. Patients were included if they were age 18 years or older, able to take oral medications, did not have a gastrointestinal stoma, and had a Palliative Performance Scale score of 20% or more. The primary outcome measures were stool frequency, volume, and consistency. Secondary outcomes were patient perceptions of bowel movements (difficulty and completeness of evacuation) and bowel-related interventions. A total of 74 patients were randomized into the study (35 to the docusate group and 39 to the placebo group). There were neither significant differences between the groups in stool frequency, volume, or consistency, nor in difficulty or completeness of evacuation. On the Bristol Stool Form Scale, more patients in the placebo group had Type 4 (smooth and soft) and Type 5 (soft blobs) stool, whereas in the docusate group, more had Type 3 (sausage like) and Type 6 (mushy) stool (P=0.01). There was no significant benefit of docusate plus sennosides compared with placebo plus sennosides in managing constipation in hospice patients. Docusate use should be considered on an individual basis. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

A Randomized, Placebo-Controlled Trial of Latrepirdine in Huntington Disease

PubMed Central

Kieburtz, Karl; McDermott, Michael P.; Voss, Tiffini S.; Corey-Bloom, Jody; Deuel, Lisa M.; Dorsey, E. Ray; Factor, Stewart; Geschwind, Michael D.; Hodgeman, Karen; Kayson, Elise; Noonberg, Sarah; Pourfar, Michael; Rabinowitz, Karen; Ravina, Bernard; Sanchez-Ramos, Juan; Seely, Lynn; Walker, Francis; Feigin, Andrew

2014-01-01

Objectives To evaluate the safety and tolerability of latrepirdine in Huntington disease (HD) and explore its effects on cognition, behavior, and motor symptoms. Design Double-blind, randomized, placebo-controlled trial. Setting Multicenter outpatient trial. Participants Ninety-one participants with mild to moderate HD enrolled at 17 US and UK centers from July 18, 2007, through July 16, 2008. Intervention Latrepirdine, 20 mg 3 times daily (n=46), or matching placebo (n=45) for a 90-day treatment period. Main Outcome Measures The primary outcome variable was tolerability, defined as the ability to complete the study at the assigned drug dosage. Secondary outcome variables included score changes from baseline to day 90 on the Unified Huntington's Disease Rating Scale (UHDRS), the Mini-Mental State Examination (MMSE), and the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog). Results Latrepirdine was well tolerated (87% of the patients given latrepirdine completed the study vs 82% in the placebo group), and adverse event rates were comparable in the 2 groups (70% in the latrepirdine group and 80% in the placebo group). Treatment with latrepirdine resulted in improved mean MMSE scores compared with stable performance in the placebo group (treatment effect, 0.97 points; 95% confidence interval, 0.10-1.85; P=.03). No significant treatment effects were seen on the UHDRS or the ADAS-cog. Conclusions Short-term administration of latrepirdine is well tolerated in patients with HD and may have a beneficial effect on cognition. Further investigation of latrepirdine is warranted in this population with HD. PMID:20142523

The positive effects of Xueshuan Xinmai tablets on brain functional connectivity in acute ischemic stroke: a placebo controlled randomized trial.

PubMed

Wei, Dongfeng; Xie, Daojun; Li, He; Chen, Yaojing; Qi, Di; Wang, Yujiao; Zhang, Yangjun; Chen, Kewei; Li, Chuanfu; Zhang, Zhanjun

2017-11-10

Through a placebo controlled randomized study, the purpose of this report was to investigate the effects of Xueshuan Xinmai tablets (XXMT) on neurologic deficits, quality of life and brain functional connectivity in acute ischemic stroke patients and to explore the mechanism of action of XXMT. In total, 44 acute ischemic stroke patients were randomly divided to the XXMT treatment group (n = 22) or the placebo group (n = 22) in a 2-week trial. Before and after the treatment, the neurological assessment and functional magnetic resonance imaging examinations were carried out. Compared to the placebo group, the scores of the National Institutes of Health Stroke Scale (NIHSS) and Stroke-Specific Quality of Life Scale (SSQOL) significantly improved in the treatment group. In addition, XXMT-treated patients demonstrated significantly enhanced functional connectivity within the default mode, frontal-parietal, and motor control networks. Furthermore, the changed connectivity in the left precuneus was positively correlated to the improvement of NIHSS and SSQOL scores. The present study indicated that XXMT treatment significantly improved the neurologic deficit and quality of life of acute ischemic stroke patients and that the therapeutic effect may be based on the modulation of XXMT on the functional connectivity of brain networks.

Efficacy of botulinum toxin in treating myofascial pain in bruxers: a controlled placebo pilot study.

PubMed

Guarda-Nardini, Luca; Manfredini, Daniele; Salamone, Milena; Salmaso, Luigi; Tonello, Stefano; Ferronato, Giuseppe

2008-04-01

The present investigation is a preliminary double-blind, controlled placebo, randomized clinical trial with a six month follow-up period. The study aimed to assess the efficacy of type A botulinum toxin (Botox, Allergan, Inc. Irvine, CA) to treat myofascial pain symptoms and to reduce muscle hyperactivity in bruxers. Twenty patients (ten males, ten females; age range 25-45) with a clinical diagnosis of bruxism and myofascial pain of the masticatory muscles were enrolled in a double-blind, controlled placebo, randomized clinical trial, with a treatment group (ten subjects treated with botulinum toxin injections- BTX-A) and a control group (ten subjects treated with saline placebo injections). A number of objective and subjective clinical parameters (pain at rest and during chewing; mastication efficiency; maximum nonassisted and assisted mouth opening, protrusive and laterotrusive movements; functional limitation during usual jaw movements; subjective efficacy of the treatment; tolerance of the treatment) were assessed at baseline time and at one week, one month, and six months follow-up appointments. Descriptive analysis showed that improvements in both objective (range of mandibular movements) and subjective (pain at rest; pain during chewing) clinical outcome variables were higher in the Botox treated group than in the placebo treated subjects. Patients treated with BTX-A had a higher subjective improvement in their perception of treatment efficacy than the placebo subjects. Differences were not significant in some cases due to the small sample size. Results from the present study supported the efficacy of BTX-A to reduce myofascial pain symptoms in bruxers, and provided pilot data which need to be confirmed by further research using larger samples.

Ketorolac for Pain Control With Intrauterine Device Placement: A Randomized Controlled Trial

PubMed Central

Ngo, Lynn L.; Ward, Kristy K.; Mody, Sheila K.

2015-01-01

Objective To evaluate intramuscular ketorolac compared to placebo saline injection for pain control with intrauterine device (IUD) placement. Methods We conducted a randomized, double-blind, placebo controlled trial between July 2012 and March 2014. Patients received ketorolac 30mg or placebo saline intramuscular injection 30 minutes prior to IUD placement. The primary outcome was pain with IUD placement on a 10cm visual analog scale (VAS). Sample size was calculated to provide 80% power to show a 2.0cm difference (α=0.05) in the primary outcome. Secondary outcomes included pain with study drug injection, speculum insertion, tenaculum placement, uterine sounding, and at 5 and 15 minutes after IUD placement. Results A total of 67 women participated in the study, 33 in the ketorolac arm and 34 in the placebo arm. There were no differences in baseline demographics including age, BMI, and race. There were no differences in median pain scores for IUD placement in the placebo versus ketorolac groups (5.2cm vs 3.6cm, p=0.99). There was a decrease in median pain scores at 5 minutes (2.2cm vs 0.3cm, p=<0.001) and 15 minutes (1.6cm vs 0.1cm, p=<0.001) after IUD placement but no difference for all other time points. Nulliparous participants (n=16, 8 per arm) had a decrease in pain scores with IUD placement (8.1cm vs 5.4cm, p=0.02). In this study, 22% of participants in the placebo group and 18% in the ketorolac group reported injection pain was as painful as IUD placement. Conclusions Ketorolac does not reduce pain with IUD placement but does reduce pain at 5 and 15 minutes after placement. PMID:26241253

Ketorolac for Pain Control With Intrauterine Device Placement: A Randomized Controlled Trial.

PubMed

Ngo, Lynn L; Ward, Kristy K; Mody, Sheila K

2015-07-01

To evaluate intramuscular ketorolac compared with placebo saline injection for pain control with intrauterine device (IUD) placement. We conducted a randomized, double-blind, placebo-controlled trial between July 2012 and March 2014. Patients received 30 mg ketorolac or placebo saline intramuscular injection 30 minutes before IUD placement. The primary outcome was pain with IUD placement on a 10-cm visual analog scale. Sample size was calculated to provide 80% power to show a 2.0-cm difference (α=0.05) in the primary outcome. Secondary outcomes included pain with study drug injection, speculum insertion, tenaculum placement, uterine sounding, and at 5 and 15 minutes after IUD placement. A total of 67 women participated in the study, 33 in the ketorolac arm and 34 in the placebo arm. There were no differences in baseline demographics including age, body mass index, and race. There were no differences in median pain scores for IUD placement in the placebo compared with ketorolac groups (5.2 compared with 3.6 cm, P=.99). There was a decrease in median pain scores at 5 minutes (2.2 compared with 0.3 cm, P≤.001) and 15 minutes (1.6 compared with 0.1 cm, P≤.001) after IUD placement but no difference for all other time points. Nulliparous participants (n=16, eight per arm) had a decrease in pain scores with IUD placement (8.1 compared with 5.4 cm, P=.02). In this study, 22% of participants in the placebo group and 18% in the ketorolac group reported injection pain was as painful as IUD placement. Ketorolac does not reduce pain with IUD placement but does reduce pain at 5 and 15 minutes after placement. ClinicalTrials.gov; www.clinicaltrials.gov, NCT01664559. I.

Hyoscine N-Butylbromide for Preventing Propofol Injection Pain: A Randomized, Placebo-Controlled and Double-Blind Study

PubMed Central

Sargın, Mehmet; Uluer, Mehmet Selçuk; Aydoğan, Eyüp

2018-01-01

Objective In this study, the aim was to investigate the effect of hyoscine N-butylbromide (HnBB) pretreatment on pain during propofol injection. Subjects and Methods In this prospective, randomized, placebo-controlled and double-blind trial, 60 patients scheduled to undergo routine outpatient surgery under general anesthesia were randomly allocated to 2 groups, the HnBB (n = 30) and sodium chloride (n = 30) groups. Twenty seconds after the injection of 20 mg HnBB or 0.9 % sodium chloride, a 50-mg dose of propofol was injected in 2–3 s. Ten seconds later, the pain intensity was assessed using a 4-point scale: no pain (0), mild (1), moderate (2), and severe (3) pain. The Student t test was used for the analysis of parametric data and the Pearson χ2 test for categorical data. Results The occurrence of pain in the HnBB group (43.3%) was significantly lower than the control group (73.3%) (p < 0.018). Of the 30 patients in each group, 10 in the control group and 3 in the HnBB group experienced severe pain (p = 0.001). Conclusions Pretreatment with 20 mg HnBB significantly reduced propofol injection pain compared to placebo. PMID:29402789

Blueberries improve endothelial function, but not blood pressure, in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Stull, April J; Cash, Katherine C; Champagne, Catherine M; Gupta, Alok K; Boston, Raymond; Beyl, Robbie A; Johnson, William D; Cefalu, William T

2015-05-27

Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus -0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome.

Blueberries Improve Endothelial Function, but Not Blood Pressure, in Adults with Metabolic Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

PubMed Central

Stull, April J.; Cash, Katherine C.; Champagne, Catherine M.; Gupta, Alok K.; Boston, Raymond; Beyl, Robbie A.; Johnson, William D.; Cefalu, William T.

2015-01-01

Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus −0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome. PMID:26024297

A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study.

PubMed

2002-12-01

Monotherapy with rasagiline mesylate may be useful in early Parkinson disease (PD). To evaluate the safety and efficacy of the selective monoamine oxidase type B inhibitor rasagiline. Multicenter, 26-week, parallel-group, randomized, double-blind, placebo-controlled clinical trial. Academically based movement disorders clinics. Patients with early PD not requiring dopaminergic therapy (n = 404). Research participants were randomized to rasagiline mesylate at dosages of 1 mg or 2 mg per day or matching placebo. A 1-week escalation period was followed by a 25-week maintenance period. The primary prespecified measure of efficacy was the change in the total Unified Parkinson's Disease Rating Scal score between baseline and 26 weeks of treatment, comparing each active treatment group with the placebo group. Monotherapy with rasagiline was effective in this 26-week study. The adjusted effect size for the total Unified Parkinson's Disease Rating Scale was -4.20 units comparing 1 mg of rasagiline and placebo (95% confidence interval, -5.66 to -2.73 units; P<.001) and -3.56 units comparing a 2-mg dosage and placebo (95% confidence interval, -5.04 to -2.08 units; P<.001). There were no meaningful differences in the frequency of adverse events or premature withdrawals among the treatment groups. Rasagiline is effective as monotherapy for patients with early PD. The 2 dosages in this trial were both effective relative to placebo. Further study is warranted to evaluate the longer-term effects of rasagiline in PD.

Folic acid supplementation inhibits recurrence of colorectal adenomas: A randomized chemoprevention trial

PubMed Central

Jaszewski, Richard; Misra, Sabeena; Tobi, Martin; Ullah, Nadeem; Naumoff, Jo Ann; Kucuk, Omer; Levi, Edi; Axelrod, Bradley N; Patel, Bhaumik B; Majumdar, Adhip PN

2008-01-01

AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonic adenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a significant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia. PMID:18680228

Nocebo in chronic inflammatory demyelinating polyneuropathy; a systematic review and meta-analysis of placebo-controlled clinical trials.

PubMed

Zis, Panagiotis; Hadjivassiliou, Marios; Sarrigiannis, Ptolemaios G; Jenkins, Thomas M; Mitsikostas, Dimos-Dimitrios

2018-05-15

Nocebo is very prevalent among neurological disorders, resulting in low adherence and treatment outcome. We sought to examine the adverse events (AE) following placebo administration in placebo-controlled randomized clinical trials (RCTs) for chronic inflammatory demyelinating polyneuropathy (CIDP). After a systematic literature search for RCTs for CIDP pharmacotherapy treatments, we assessed the number of AE in the placebo groups and the number discontinuations because of placebo intolerance. Our literature search strategy revealed 82 papers. Data were extracted from three RCTs fulfilling our inclusion criteria. Approximately two in five placebo-treated patients (42.0%) reported at least one AE and approximately one in fifty placebo-treated patients discontinued placebo treatment because of AEs (2.1%). All patients participating in the CIDP trials reported similar AEs independently of the study arm they belonged. Compared to other neurological diseases the nocebo effect in CIDP is significantly smaller. Copyright © 2018 Elsevier B.V. All rights reserved.

Randomized controlled trial of benzocaine versus placebo spray for pain relief at hysterosalpingogram.

PubMed

Bachman, E A; Senapati, S; Sammel, M D; Kalra, S K

2014-06-01

Many women experience pain during hysterosalpingogram (HSG). This prospective, randomized, double-blinded, placebo-controlled study assessed whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, parity, pre-procedure oral analgesic use and history of dysmenorrhoea and/or chronic pelvic pain. Median change in pain score from baseline to procedure was 50.6mm (-7.4 to 98.8mm) in the benzocaine group and 70.4mm (19.8 to 100mm) in the placebo group. There was no difference between groups after adjusting for history of dysmenorrhoea. There was no difference in resolution of pain in benzocaine versus placebo groups at 5 min post procedure--median pain score difference -11.1 (-90.1 to 18.5) versus -37.0 (-100 to 1.2)--or at 30 min post procedure. Satisfaction scores did not differ by treatment and did not correlate with pain score during the procedure (rho=0.005). The use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain. Many women experience pain during hysterosalpingogram (HSG), which is a test used to evaluate the uterine cavity and fallopian tube. We conducted a prospective, randomized, double-blinded, placebo-controlled study to assess whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, previous pregnancies, pre-procedure oral analgesic use and history of dysmenorrhoea (painful periods) and/or chronic pelvic pain. There was no difference in pain scores or resolution of pain between the two groups. Satisfaction scores did not differ by treatment group and did not correlate with the pain score during the procedure. We conclude that the use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Lavender-thymol as a new topical aromatherapy preparation for episiotomy: A randomised clinical trial.

PubMed

Marzouk, T; Barakat, R; Ragab, A; Badria, F; Badawy, A

2015-01-01

The objective of this study was to evaluate the effectiveness of topical lavender-thymol in promoting episiotomy healing. This placebo-controlled, single-blinded, randomised clinical trial involved 60 primiparous women. REEDA score was used to evaluate the outcome of the trial. On the 7th post-partum day, women in Placebo-treated group had worse Redness, Edema, Ecchymosis, Discharge and Approximation (REEDA) score of 3.93 ± 3.65 compared with those in Lavender-thymol-treated group (2.03 ± 1.7) with significant difference (P = 0.013). Visual analogue Scale (VAS) score for pain at episiotomy in Lavender-thymol-treated group was 3.5 ± 1.9, whereas in Placebo-treated group it was 2.1 ± 2.2 (p = 0.011) for dyschezia, 3.8 ± 1.7 and 2.8 ± 1.6 in Placebo- and Lavender-thymol-treated women, respectively (p = 0.023). At 7th post-partum week, dyspareunia was more severe in Placebo-treated group compared with that in Lavender-thymol-treated group (5.3 ± 2.7 vs 2.7 ± 1.5 and p < 0.001). Topical aromatherapy using lavender-thymol was highly effective, suitable and safe for episiotomy wound care with little or no expected side effects compared with that using placebo.

Effects of guar gum ingestion on postprandial blood pressure in older adults.

PubMed

Jang, A L; Hwang, S K; Kim, D U

2015-03-01

The aim of this study was to investigate the effects of guar gum on postprandial blood pressure in older people. A randomized, double-blind, placebo-controlled, cross-over design. Community senior centers in B city, South Korea. Twenty-two older female adults aged 67 to 88 with postprandial hypotension. The participants were randomly assigned to guar gum (semi-fluid food with 9 gram) or placebo intervention during the first treatment phase. After a washout period of 1 week, the two interventions were switched to the other in the second treatment phase. Blood pressure was measured during both phases before having a meal and every 15 minutes during 120 minutes after a meal with automated sphygmomanometer. Change in systolic blood pressure (SBP) over time was significantly different between guar gum and placebo groups (F=4.07, p=0.001). Compared with placebo group, guar gum group had significantly low prevalence of postprandial hypotension (PPH) (guar gum group=18.2% vs. placebo group=72.7%; χ² =13.20, p<0.001). It also had significant difference in change of diastolic blood pressure (DBP) over time between guar gum and placebo groups (F=2.49, p=0.027). This findings show that guar gum could be effective on postprandial drops in blood pressure in older female adults.

Double-blinded, placebo-controlled study to evaluate an antipruritic shampoo for dogs with allergic pruritus.

PubMed

Schilling, J; Mueller, R S

2012-07-28

Shampoo therapy is frequently used on pruritic dogs. However, there are few double-blinded, placebo-controlled studies of this form of therapy. This randomised, double-blinded, placebo-controlled study evaluated the efficacy of a commercial medicated shampoo (DermaTopic; Almapharm) containing chlorhexidine, lactoferrin, piroctone olamine, chitosan and essential fatty acids in 27 dogs with mild to moderate allergic pruritus without secondary skin infections. All dogs received shampoo therapy with either DermaTopic or a shampoo vehicle as placebo twice weekly for four weeks. The extent of pruritus was evaluated before the study and then on a daily basis by the owners using a visual analogue scale. Before beginning the treatment and after four weeks, the skin lesions were evaluated by an experienced clinician with a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index - CADESI). The pruritus was reduced significantly by both DermaTopic and placebo. However, there was no significant difference between both groups. There was no statistically significant difference in the CADESI scores pre- and post-treatment in either group or between the two types of treatment. This study provides further evidence of the benefit of shampoo therapy for pruritic dogs.

Metabolic management in overweight subjects with naive impaired fasting glycaemia by means of a highly standardized extract from Cynara scolymus: a double-blind, placebo-controlled, randomized clinical trial.

PubMed

Rondanelli, Mariangela; Opizzi, Annalisa; Faliva, Milena; Sala, Patrizio; Perna, Simone; Riva, Antonella; Morazzoni, Paolo; Bombardelli, Ezio; Giacosa, Attilio

2014-01-01

The aim of this study is to evaluate the efficacy of a dietary supplementation with an extract from Cynara scolymus (Cs) on the glucose pattern in a group of patients with naïve impaired fasting glycaemia (IFG). A randomized, double-blind, placebo-controlled trial has been performed in 55 overweight subjects with IFG (fasting blood glucose [FBG]: 6.11 ± 0.56 mmol/l). These subjects were randomly assigned to supplement their diet with either an extract from Cs (600 mg/d) (26 subjects) or placebo (29 matched subjects) for 8 weeks. The decrease of FBG was the primary endpoint. The assessment of Homeostatic Metabolic Assessment (HOMA), glycosylated haemoglobin, A1c-Derived Average Glucose (ADAG), lipidic pattern and anthropometric parameters were the secondary endpoints. The within groups and percent changes from baseline were analyzed by the signed rank test. The comparison between groups was performed by Wilcoxon's two sample test. The supplemented group had significant decreases of: FBG (-9.6%), HOMA (-11.7%), glycosylated haemoglobin (-2.3%), ADAG (-3.1%) and lipidic pattern. The placebo group did not show any significant difference. Compared with the placebo, the supplemented group showed a significant difference in FBG, HOMA and lipidic pattern. These data demonstrate the efficacy of Cs extract on the reduction of glycometabolic parameters in overweight subjects with IFG. Copyright © 2013 John Wiley & Sons, Ltd.

Effect of fennel vaginal cream on sexual function in postmenopausal women: A double blind randomized controlled trial

PubMed Central

Abedi, Parvin; Najafian, Mahin; Yaralizadeh, Masumeh; Namjoyan, Foroogh

2018-01-01

Objective: The aim of this study was to assess the effect of fennel on sexual function in postmenopausal women. It was a randomized controlled trial in 60 postmenopausal women with sexual dysfunction who were randomly assigned to two groups receiving either fennel vaginal cream (n=30) or placebo (n=30). Vaginal atrophy in the women was assessed using symptoms such as pallor, dryness, dyspareunia, itching and burning. The pH of the vagina and cytology of the vaginal mucosa were also measured at baseline and 8 weeks after the intervention. All participants were requested to fill out the Female Sexual Function Index (FSFI) at baseline and after 8 weeks. The intervention group was requested to use fennel vaginal cream (5 grams) every night, while the control group used placebo each night for 8 weeks. The data were analyzed using the independent t-test and Chi-square, Mann-Whitney and Wilcoxon tests. All areas of sexual function including arousal, lubrication, orgasm, sexual satisfaction and pain improved in both fennel and placebo groups after 8 weeks; however, the differences in the fennel group were more evident (p<0.05). The total FSFI score was significantly higher in the fennel group compared to the control group (8.2 ±9.4 and 8.03±10.36 before the intervention and changing to 33.79±0.7 and 18.99±1.09 after the intervention in the fennel and placebo groups, respectively; p<0.001). Discussion: According to our results, fennel vaginal cream is an effective means of improving sexual activity in postmenopausal women. The use of this product in women who have sexual dysfunction and contraindications for hormone therapy is recommended. PMID:29696061

Raloxifene Plus Antipsychotics Versus Placebo Plus Antipsychotics in Severely Ill Decompensated Postmenopausal Women With Schizophrenia or Schizoaffective Disorder: A Randomized Controlled Trial.

PubMed

Weiser, Mark; Levi, Linda; Burshtein, Shimon; Hagin, Michal; Matei, Valentin P; Podea, Delia; Micluția, Ioana; Tiugan, Alexandru; Păcală, Bogdan; Grecu, Iosif Gabos; Noy, Adam; Zamora, Daisy; Davis, John M

2017-07-01

Several single-center studies have found raloxifene, an estrogen agonist, to be effective in ameliorating symptoms of schizophrenia in stable patients as augmentation of antipsychotics. This multicenter study assessed whether raloxifene plus antipsychotic treatment, in comparison to placebo plus antipsychotics, improves symptoms or cognition in severely ill decompensated schizophrenia patients. In this 16-week, double-blind, randomized, placebo-controlled study, 200 severely ill, decompensated postmenopausal women who met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder were recruited from January 2011 to December 2012 and were randomized to receive either raloxifene 120 mg/d plus antipsychotics or placebo plus antipsychotics. The primary outcome measure was Positive and Negative Syndrome Scale (PANSS) total score at the end of the trial. The placebo plus antipsychotics group experienced statistically significant improvement in PANSS total score (P < .001) compared to the raloxifene plus antipsychotics group, using mixed models for repeated measures, with results favoring placebo by 4.5 points (95% CI, 2.3-6.7). These results were clearly outside the 95% confidence interval. This negative effect was more pronounced in patients who had more frequent relapses and in those with baseline PANSS scores of 100 or higher. There were no differences between groups in Clinical Global Impression Scale-Severity scores or Composite Brief Assessment of Cognition in Schizophrenia scores at 16 weeks (P > .3). Baseline follicle-stimulating hormone and estradiol levels did not alter the drug-placebo differences. Individuals in the active treatment arm showed worse outcome than those in the placebo arm, most likely as a result of chance variation, but the results unequivocally show no benefit of antipsychotics plus raloxifene versus antipsychotics plus placebo in this large randomized, double-blind, placebo-controlled trial in postmenopausal women. These data do not support the use of raloxifene in severely decompensated schizophrenia patients until reliable research identifies what subgroup of patients or domain of outcome is benefited. ClinicalTrials.gov identifier: NCT01280305. © Copyright 2017 Physicians Postgraduate Press, Inc.

Skin adhesive low-level light therapy for dysmenorrhoea: a randomized, double-blind, placebo-controlled, pilot trial.

PubMed

Shin, Yong-Il; Kim, Nam-Gyun; Park, Kyoung-Jun; Kim, Dong-Wook; Hong, Gi-Youn; Shin, Byung-Cheul

2012-10-01

The cause of dysmenorrhoea is an abnormal function of smooth muscles in the uterus due to long-term deficient blood supply into smooth muscle tissue. The purpose of this study was to evaluate the effectiveness of skin adhesive low-level light therapy (LLLT) in participants with dysmenorrhoea. Thirty-one women were included in this randomized, double-blind, placebo-controlled, pilot trial. Twenty-one women were treated with active LLLT and ten women were treated with placebo one. The therapy was performed in a laboratory room for 20 min a day over a period of 5 days prior to the expected onset of menstruation. The outcome was measured using a visual analog scale (VAS) for each participant's dysmenorrhoeal pain severity. VAS of each subject was measured every month for 6 months. In the active LLLT group, 16 women reported successful results during their first menstrual cycle just after active LLLT and 5 women had successful results from the second menstrual cycle after active LLLT. The pain reduction rate was 83 % in the active LLLT group, whereas there was only a slight and temporary reduction in pain in the placebo LLLT group. Changes of VAS within 6 months of LLLT showed statistical significance (p = 0.001) over placebo control. Our study suggests that skin adhesive LLLT on acupuncture points might be an effective, simple and safe non-pharmacological treatment for dysmenorrhoea.

Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia.

PubMed

Rolnik, Daniel L; Wright, David; Poon, Liona C; O'Gorman, Neil; Syngelaki, Argyro; de Paco Matallana, Catalina; Akolekar, Ranjit; Cicero, Simona; Janga, Deepa; Singh, Mandeep; Molina, Francisca S; Persico, Nicola; Jani, Jacques C; Plasencia, Walter; Papaioannou, George; Tenenbaum-Gavish, Kinneret; Meiri, Hamutal; Gizurarson, Sveinbjorn; Maclagan, Kate; Nicolaides, Kypros H

2017-08-17

Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia. In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle. A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events. Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29 ; Current Controlled Trials number, ISRCTN13633058 .).

Topiramate for the management of methamphetamine dependence: a pilot randomized, double-blind, placebo-controlled trial.

PubMed

Rezaei, Farzin; Ghaderi, Ebrahim; Mardani, Roya; Hamidi, Seiran; Hassanzadeh, Kambiz

2016-06-01

To date, no medication has been approved as an effective treatment for methamphetamine dependence. Topiramate has attracted considerable attention as a treatment for the dependence on alcohol and stimulants. Therefore, this study aimed to evaluate the effect of topiramate for methamphetamine dependence. This study was a double-blind, randomized, placebo-controlled trial. In the present investigation, 62 methamphetamine-dependent adults were enrolled and randomized into two groups, and received topiramate or a placebo for 10 weeks in escalating doses from 50 mg/day to the target maintenance dose of 200 mg/day. Addiction severity index (ASI) and craving scores were registered every week. The Beck questionnaire was also given to each participant at baseline and every 2 weeks during the treatment. Urine samples were collected at baseline and every 2 weeks during the treatment. Fifty-seven patients completed 10 weeks of the trial. There was no significant difference between both groups in the mean percentage of prescribed capsules taken by the participants. At week six, the topiramate group showed a significantly lower proportion of methamphetamine-positive urine tests in comparison with the placebo group (P = 0.01). In addition, there were significantly lower scores in the topiramate group in comparison with the placebo group in two domains of ASI: drug use severity (P < 0.001) and drug need (P < 0.001). Furthermore, the craving score (duration) significantly declined in the topiramate patients compared to those receiving the placebo. In conclusion, the results of this trial suggest that topiramate may be beneficial for the treatment of methamphetamine dependence. © 2016 Société Française de Pharmacologie et de Thérapeutique.

The role of G-CSF in recurrent implantation failure: A randomized double blind placebo control trial.

PubMed

Davari-Tanha, Fatemeh; Shahrokh Tehraninejad, Ensieh; Ghazi, Mohadese; Shahraki, Zahra

2016-12-01

Recurrent implantation failure (RIF) is the absence of implantation after three consecutive In Vitro Fertilization (IVF) cycles with transferring at least four good quality embryos in a minimum of three fresh or frozen cycles in a woman under 40 years. The definition and management of RIF is under constant scrutiny. To investigate the effects of Granulocyte colony stimulating factor (G-CSF) on RIF, pregnancy rate, abortion rate and implantation rates. A double blind placebo controlled randomized trial was conducted at two tertiary university based hospitals. One hundred patients with the history of RIF from December 2011 until January 2014 were recruited in the study. G-CSF 300µg/1ml was administered at the day of oocyte puncture or day of progesterone administration of FET cycle. Forty patients were recruited at G-CSF group, 40 in saline and 20 in placebo group. The mean age for whole study group was 35.3±4.2 yrs (G-CSF 35.5±4.32, saline 35.3±3.98, placebo 35.4±4.01, respectively). Seventeen patients had a positive pregnancy test after embryo transfer [10 (25%) in G-CSF; 5 (12.5%) in saline; and 2 (10%) in placebo group]. The mean of abortion rates was 17.6% (3), two of them in G-CSF, one in saline group. The implantation rate was 12.3% in G-CSF, 6.1% in saline and 4.7% in placebo group. G-CSF may increase chemical pregnancy and implantation rate in patients with recurrent implantation failure but clinical pregnancy rate and abortion rate was unaffected.

Inhaled budesonide and oral dexamethasone prevent acute mountain sickness.

PubMed

Zheng, Cheng-Rong; Chen, Guo-Zhu; Yu, Jie; Qin, Jun; Song, Pan; Bian, Shi-Zhu; Xu, Bai-Da; Tang, Xu-Gang; Huang, Yong-Tao; Liang, Xiao; Yang, Jie; Huang, Lan

2014-10-01

This double-blind, randomized controlled trial aimed to investigate inhaled budesonide and oral dexamethasone compared with placebo for their prophylactic efficacy against acute mountain sickness after acute high-altitude exposure. There were 138 healthy young male lowland residents recruited and randomly assigned to receive inhaled budesonide (200 μg, twice a day [bid]), oral dexamethasone (4 mg, bid), or placebo (46 in each group). They traveled to 3900 m altitude from 400 m by car. Medication started 1 day before high-altitude exposure and continued until the third day of exposure. Primary outcome measure was the incidence of acute mountain sickness after exposure. One hundred twenty-four subjects completed the study (42, 39, and 43 in the budesonide, dexamethasone, and placebo groups, respectively). Demographic characteristics were comparable among the 3 groups. After high-altitude exposure, significantly fewer participants in the budesonide (23.81%) and dexamethasone (30.77%) groups developed acute mountain sickness compared with participants receiving placebo (60.46%) (P = .0006 and P = .0071, respectively). Both the budesonide and dexamethasone groups had lower heart rate and higher pulse oxygen saturation (SpO2) than the placebo group at altitude. Only the budesonide group demonstrated less deterioration in forced vital capacity and sleep quality than the placebo group. Four subjects in the dexamethasone group reported adverse reactions. Both inhaled budesonide (200 μg, bid) and oral dexamethasone (4 mg, bid) were effective for the prevention of acute mountain sickness, especially its severe form, compared with placebo. Budesonide caused fewer adverse reactions than dexamethasone. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The challenges of control groups, placebos and blinding in clinical trials of dietary interventions.

PubMed

Staudacher, Heidi M; Irving, Peter M; Lomer, Miranda C E; Whelan, Kevin

2017-08-01

High-quality placebo-controlled evidence for food, nutrient or dietary advice interventions is vital for verifying the role of diet in optimising health or for the management of disease. This could be argued to be especially important where the benefits of dietary intervention are coupled with potential risks such as compromising nutrient intake, particularly in the case of exclusion diets. The objective of the present paper is to explore the challenges associated with clinical trials in dietary research, review the types of controls used and present the advantages and disadvantages of each, including issues regarding placebos and blinding. Placebo-controlled trials in nutrient interventions are relatively straightforward, as in general placebos can be easily produced. However, the challenges associated with conducting placebo-controlled food interventions and dietary advice interventions are protean, and this has led to a paucity of placebo-controlled food and dietary advice trials compared with drug trials. This review appraises the types of controls used in dietary intervention trials and provides recommendations and nine essential criteria for the design and development of sham diets for use in studies evaluating the effect of dietary advice, along with practical guidance regarding their evaluation. The rationale for these criteria predominantly relate to avoiding altering the outcome of interest in those delivered the sham intervention in these types of studies, while not compromising blinding.

Randomized, controlled trial of rasagiline as an add-on to dopamine agonists in Parkinson's disease.

PubMed

Hauser, Robert A; Silver, Dee; Choudhry, Azhar; Eyal, Eli; Isaacson, Stuart

2014-07-01

Dopamine agonists (DA) are often used as first-line monotherapy for the symptomatic control of Parkinson's disease (PD). However, DA monotherapy typically becomes inadequate within a few years, at which time the DA dosage must be increased or other antiparkinsonian medications added. Adding a monoamine oxidase-B (MAO-B) inhibitor to DA monotherapy might improve symptomatic control while maintaining good safety and tolerability. We conducted an 18-week, randomized, double-blind, placebo-controlled trial of rasagiline 1 mg/d as an add-on to DA therapy (ropinirole ≥ 6 mg/d or pramipexole ≥ 1.0 mg/d) in early PD patients whose conditions were not adequately controlled on their current treatment regimen. The primary efficacy variable was the change in total Unified Parkinson Disease Rating Scale (UPDRS) score (sum of parts I, II, and III) from baseline to week 18, comparing rasagiline and placebo groups. The modified intent-to-treat (ITT) population included 321 subjects whose mean ± SD age was 62.6 ± 9.7, and duration of PD was 2.1 ± 2.1 years. Results demonstrated a significantly greater improvement in total UPDRS scores from baseline to week 18 in the rasagiline group compared with the placebo group (least squares [LS] mean difference ± SE, -2.4 ± 0.95; 95% confidence interval [CI], -4.3, -0.5; P = 0.012). Mean improvement (LS mean ± SE) was -3.6 ± 0.68 in the rasagiline group and -1.2 ± 0.68 in the placebo group. Rasagiline was well tolerated, and the most common adverse events (AEs; rasagiline vs. placebo) were dizziness (7.4% vs. 6.1%), somnolence (6.8% vs. 6.7%), and headache (6.2% vs. 4.3%). Rasagiline 1 mg/d provided statistically significant improvement when added to dopamine agonist therapy and was well tolerated. © 2014 International Parkinson and Movement Disorder Society.

A Randomized Placebo-Controlled Trial of Oral Ramosetron for Prevention of Post Operative Nausea and Vomiting after Intrathecal Morphine in Patients Undergoing Gynecological Surgery.

PubMed

Wangnamthip, Suratsawadee; Chinachoti, Thitima; Amornyotin, Somchai; Wongtangman, Karuna; Sukantarat, Numphung; Noitasaeng, Papiroon

2016-05-01

The incidence of postoperative nausea and vomiting (PONV) after intrathecal morphine is high. Ramosetron is a 5-HT₃ antagonist that has been shown to reduce PONV in general anesthesia. The objective of this study was to evaluate the efficacy of Ramosetron in preventing PONV MATERIAL AND METHOD: 165 patients undergoing elective gynecological surgery under spinal anesthesia were randomly allocated to two groups: the Ramosetron group (0.1 mg orally, n = 82), and the placebo group (oral corn starch, n = 83). The incidence of PONV severity of nausea and use of rescue antiemetic during the first 24 hour after surgery were evaluated. The incidence of PONV was significantly lower in the Ramosetron group compared with the placebo group (24.4% vs. 44.6%, number needed to treat (NNT) = 5.0). The severity of nausea was significantly lower in the Ramosetron group compared with the placebo group (20.7% vs. 39.8%, NNT = 6.0) in the 24 hour period. Oral Ramosetron 0.1 mg was more effective than placebo in PONV prevention and reduced the incidence of moderate to severe nausea after intrathecal morphine in the first 24 hour after gynecological surgery.

Thrombopoietin-receptor agonists for children with immune thrombocytopenia: a systematic review.

PubMed

Zhang, Jiaxing; Liang, Yi; Ai, Yuan; Xie, Juan; Li, Youping; Zheng, Wenyi

2017-10-01

We conducted a systematic review to assess the efficacy and safety of Thrombopoietin-receptor agonists (TPOras) for pediatric immune thrombocytopenia (ITP). We searched PubMed, Embase and Cochrane Library from their earliest records to January 2017. Randomized controlled trials (RCTs) were included. Primary outcomes were durable response and clinically significant bleeding. Secondary outcomes were overall response, overall bleeding events, the use of rescue medication and adverse events (AEs). Five randomized RCTs (261participants) were included. Compared with placebo group, the proportion of patients achieving durable platelet response was significantly higher in Eltrombopag (P = 0.0004) or Romiplostim (P = 0.002) group, so was the overall response in Eltrombopag [RR = 2.64, 95% CI (1.58, 4.44)] or Romiplostim [RR = 5.05, 95% CI (2.21, 11.53)] group. Both clinically significant bleeding (P = 0.04) and total bleeding (P = 0.01) in Eltrombopag group were significantly less frequent than those in placebo group, while no significant difference between Romiplostim and placebo group. The proportion of patients receiving rescue medication, the incidence of overall AEs and serious AEs between TPO-receptor agonists and placebo group were not significantly different. TPOras might improve both durable and overall platelet response in pediatric ITP, compared with placebo.

Placebo-controlled trial of mianserin and maprotiline in primary depressive illness

PubMed Central

Edwards, J. Guy; Goldie, Ann

1983-01-01

1 Preliminary results of a double-blind placebo-controlled trial of mianserin and maprotiline carried out in 58 outpatients with primary depressive illness are reported. 2 Patients received six weeks' treatment with 30 to 90 mg mianserin, 75 to 225 mg maprotiline or one to three capsules of placebo, all medication being taken at night. 3 There were statistically significant improvements in each treatment group and a better response to mianserin than to placebo or maprotiline on the Hamilton Rating Scale for Depression, after one week's treatment. 4 Neither mianserin nor maprotiline was superior to placebo after two or four weeks' treatment and relatively few patients completed six weeks' treatment because of a generally unsatisfactory response. 5 Unwanted effects were not particularly troublesome, though mianserin and maprotiline caused more drowsiness and blurred vision than did placebo, while maptrotiline produced more constipation than either of the other two treatments. 6 The importance of placebo-controlled trials of antidepressants is emphasized and the precautions that should be taken when they are carried out in outpatients are described. PMID:6337611

An investigation of the effects of therapeutic touch plan on acute chemotherapy-induced nausea in women with breast cancer in Isfahan, Iran, 2012–2013

PubMed Central

Matourypour, Pegah; Zare, Zahra; Mehrzad, Valiolah; Musarezaie, Amir; Dehghan, Mojtaba; Vanaki, Zohre

2015-01-01

Introduction: Nausea is the worst and most prevalent chemotherapy-induced complication experienced by 70–80% of patients despite mediation therapy. Reduction of nausea is one of the most important roles of oncologist nurses. Today, complementary therapies in addition to classic medicine, because of their lower costs, receive much attention. Nonetheless, their safety and effectiveness are not yet proven. The purpose of this research was to investigate the effect of therapeutic touch plan as a complementary therapy on acute nausea in women with breast cancer in 2012–2013 in Isfahan, Iran. Materials and Methods: A quasi-experimental, single-blind, randomized control trial with three groups (control, placebo and intervention) was performed at the Isfahan Seyedolshohada (AS) Teaching Hospital, Isfahan, in 2012–2013. The intervention was therapeutic touch plan on women with breast cancer, with the three groups receiving the same medicine regimen. Information was recorded by a checklist after infusion of chemotherapy drugs. Data analysis was performed by SPSS, ANOVA and Kruskal–Wallis tests. Results: The ANOVA test showed that the therapeutic touch plan was significantly effective in reducing the duration of nausea compared with the control and placebo groups (P < 0.001). The Kruskal–Wallis test showed that the frequency of occurrence of nausea was also reduced in the intervention and placebo groups compared with the control group (P < 0.001). The therapeutic touch plan was significantly effective in delaying the onset of nausea compared with the control and placebo groups (P < 0.001). Conclusion: This research showed that the therapeutic touch plan is effective in reducing acute chemotherapy-induced nausea; thus, education and implementation of the therapeutic touch plan is proposed for clinical nurses. PMID:26430688

An investigation of the effects of therapeutic touch plan on acute chemotherapy-induced nausea in women with breast cancer in Isfahan, Iran, 2012-2013.

PubMed

Matourypour, Pegah; Zare, Zahra; Mehrzad, Valiolah; Musarezaie, Amir; Dehghan, Mojtaba; Vanaki, Zohre

2015-01-01

Nausea is the worst and most prevalent chemotherapy-induced complication experienced by 70-80% of patients despite mediation therapy. Reduction of nausea is one of the most important roles of oncologist nurses. Today, complementary therapies in addition to classic medicine, because of their lower costs, receive much attention. Nonetheless, their safety and effectiveness are not yet proven. The purpose of this research was to investigate the effect of therapeutic touch plan as a complementary therapy on acute nausea in women with breast cancer in 2012-2013 in Isfahan, Iran. A quasi-experimental, single-blind, randomized control trial with three groups (control, placebo and intervention) was performed at the Isfahan Seyedolshohada (AS) Teaching Hospital, Isfahan, in 2012-2013. The intervention was therapeutic touch plan on women with breast cancer, with the three groups receiving the same medicine regimen. Information was recorded by a checklist after infusion of chemotherapy drugs. Data analysis was performed by SPSS, ANOVA and Kruskal-Wallis tests. The ANOVA test showed that the therapeutic touch plan was significantly effective in reducing the duration of nausea compared with the control and placebo groups (P < 0.001). The Kruskal-Wallis test showed that the frequency of occurrence of nausea was also reduced in the intervention and placebo groups compared with the control group (P < 0.001). The therapeutic touch plan was significantly effective in delaying the onset of nausea compared with the control and placebo groups (P < 0.001). This research showed that the therapeutic touch plan is effective in reducing acute chemotherapy-induced nausea; thus, education and implementation of the therapeutic touch plan is proposed for clinical nurses.

A systematic review and meta-analysis assessing adverse event profile and tolerability of nicergoline.

PubMed

Fioravanti, Mario; Nakashima, Taku; Xu, Jun; Garg, Amit

2014-07-30

To evaluate the safety profile of nicergoline compared with placebo and other active agents from published randomised controlled trials. Systematic review and meta-analysis of nicergoline compared with placebo and other active agents across various indications. MEDLINE, Medline-in-process, Cochrane, EMBASE, EMBASE alerts, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR) and Cochrane Methodology Register (CMR) for all the randomised controlled trials, open-label or blinded, in adults treated with nicergoline. Studies published until August 2013 were included. 29 studies were included for data extraction. The studies included in this review were majorly from European countries and mostly in cerebrovascular disease (n=15) and dementia (n=8). The treatment withdrawals were comparatively lower in the nicergoline group as compared with the placebo group (RR=0.92; 95% CI 0.7 to 1.21) and other active comparators (RR=0.45; 95% CI 0.10 to 1.95), but the difference was non-significant. Incidence of any adverse events (AEs) was slightly higher (RR=1.05; 95% CI 0.93 to 1.2) while incidence of serious AEs was lower (RR=0.85; 95% CI 0.50 to 1.45) in the nicergoline compared with placebo group. Frequency of anxiety was significantly lower in nicergoline as compared with placebo (p=0.01). Other AEs including diarrhoea, gastric upset, dizziness and drowsiness were less frequent in the nicergoline group when compared with placebo/active drugs, but the difference was non-significant. Frequency of hypotension and hot flushes was slightly higher in the nicergoline group but the difference was non-significant. None of the studies reported any incidence of fibrosis or ergotism with nicergoline treatment. Nicergoline is an ergot derivative, but its safety profile is better than other ergot derivatives like ergotamine and ergotoxine. This systematic review and meta-analysis suggests that nicergoline has a good safety profile. None of the studies included in this systematic review reported any incidence of fibrosis or ergotism with nicergoline. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Safety of Flibanserin in Women Treated With Antidepressants: A Randomized, Placebo-Controlled Study.

PubMed

Clayton, Anita H; Croft, Harry A; Yuan, James; Brown, Louise; Kissling, Robert

2018-01-01

Depression is often associated with sexual dysfunction, and pharmacologic treatment for hypoactive sexual desire disorder can be considered in women receiving treatment for depression. To evaluate the safety of flibanserin in women treated for depression with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. In this double-blinded, randomized, placebo-controlled trial, women with remitted or mild depression treated with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors who were not postmenopausal and were experiencing symptoms of hypoactive sexual desire disorder (ie, decreased sexual desire and related distress) received flibanserin 50 mg at bedtime (qhs) for 2 weeks and up-titrated to 100 mg qhs, flibanserin 100 mg qhs for the entire treatment period, or placebo for up to 12 weeks. Safety assessment included adverse events and symptoms of depression and anxiety. 73 patients were randomly assigned to flibanserin (both dose groups combined) and 38 to placebo. The sponsor terminated the study early at discontinuation of the development of flibanserin. Treatment duration was at least 8 weeks for 84.9% and 94.7% of patients in the flibanserin and placebo groups, respectively. The most common adverse events (incidence ≥ 2% in the flibanserin group and higher than that in the placebo group) included dry mouth (5.5% for flibanserin vs 2.6% for placebo), insomnia (5.5% vs 2.6%), back pain (4.1% vs 2.6%), and dizziness (4.1% vs 0.0%). There were no serious adverse events and no instances of suicidal ideation or behavior. The proportions of patients with symptom worsening in the flibanserin and placebo groups, respectively, were 6.9% and 21.6% for depression and 1.4% and 2.7% for anxiety. Remission of depression at study end point, as measured by the Quick Inventory of Depressive Symptomatology-Self Report, was experienced by 19.4% of flibanserin-treated patients and 10.8% of patients receiving placebo; remission of anxiety based on the Beck Anxiety Inventory was noted in 16.4% and 2.7% of patients, respectively. The results of this study support the safety of flibanserin in premenopausal women being treated with a serotonergic antidepressant. No increased risks were observed when adding flibanserin to a stable selective serotonin reuptake inhibitor or serotonin and norepinephrine reuptake inhibitor treatment regimen. This was a well-designed, randomized, placebo-controlled trial. The primary limitation was the early study discontinuation by the sponsor, which decreased the sample size and duration of treatment. In this small trial, flibanserin 100 mg qhs was generally safe and well tolerated in premenopausal women with mild or remitted depression taking a serotonergic antidepressant. Clayton AH, Croft HA, Yuan J, et al. Safety of Flibanserin in Women Treated With Antidepressants: A Randomized, Placebo-Controlled Study. J Sex Med 2018;15:43-51. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A study of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer after two or more implantation failures.

PubMed

Huang, Pinxiu; Wei, Lihong; Li, Xinlin

2017-01-01

To investigate the effect of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer (FET) after two or more implantation failures (TIFs). The study was a prospective randomized single-blind study of 161 cycles in patients undergoing FET who had TIFs. The intervention group received an intrauterine injection of 1000 IU of hCG before embryo transfer (ET) (n = 62). A placebo group (n = 49) received an intrauterine injection of physiological saline before ET. A control group (n = 50) did not receive an intrauterine injection. Clinical pregnancy rates, abortion rates, and ongoing pregnancy rates were compared between the three groups. The clinical pregnancy rates were 59.68%, 53.06%, and 32.00% in the hCG group, placebo group, and control group, respectively. The clinical pregnancy rates were significantly higher in the hCG and placebo groups than in the control group. There were no significant differences in the abortion rates among the three groups. An intrauterine administration of hCG before FET significantly improved the pregnancy rates after TIFs. But local injury caused by the operation of intrauterine perfusion may play an important role in improving clinical pregnancy rates.

Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial

PubMed Central

Pandya, K J; Morrow, G R; Roscoe, J A; Hickok, J T; Zhao, H; Pajon, E; Sweeney, T J; Banerjee, T K; Flynn, P J

2005-01-01

Summary Background Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer. Methods 420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat. Findings Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity. Interpretation Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer. PMID:16139656

Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial.

PubMed

Vellas, Bruno; Coley, Nicola; Ousset, Pierre-Jean; Berrut, Gilles; Dartigues, Jean-François; Dubois, Bruno; Grandjean, Hélène; Pasquier, Florence; Piette, François; Robert, Philippe; Touchon, Jacques; Garnier, Philippe; Mathiex-Fortunet, Hélène; Andrieu, Sandrine

2012-10-01

Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints. In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer's disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov, number NCT00276510. Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer's disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio [HR] 0·84, 95% CI 0·60-1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69-1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77-1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups. Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer's disease compared with placebo. Ipsen. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of daily Chlorella consumption on serum lipid and carotenoid profiles in mildly hypercholesterolemic adults: a double-blinded, randomized, placebo-controlled study

PubMed Central

2014-01-01

Background High level of serum cholesterol is considered to be a major risk factor for cardiovascular disease (CVD). A double-blinded, randomized, placebo-controlled trial was performed to test the hypothesis that a daily intake of Chlorella may improve serum lipid profile through enhancement of serum carotenoid concentration in mildly hypercholesterolemic subjects. Methods Eligible subjects (n = 63) were randomized to either Chlorella (5 g/day) or placebo for a double-blinded trial with a 2-week lead-in period and a 4-week intervention period. Serum triglycerides, total cholesterol, lipoproteins, apolipoproteins and carotenoids were assessed at the beginning and the end of the trial. Results Compared with the control group, the Chlorella group exhibited remarkable changes in total cholesterol (Chlorella −1.6%; placebo 0.03%; P = 0.036), triglycerides (Chlorella −10.3%; placebo 11.9%; P = 0.002), lutein/zeaxanthin (Chlorella 89.6%; placebo −1.7%; P < 0.0001), and α-carotene (Chlorella 163.6%; placebo 15%; P < 0.0001). Improvement of serum lipids was supported by significant reductions of very low-density lipoprotein cholesterol (Chlorella −11%; placebo 11.8%; P = 0.006), apolipoprotein B (Chlorella −1.5%; placebo 1.7%; P = 0.044), non high-density lipoprotein (Chlorella −2.6%; placebo −0.5%; P = 0.032), and high-density lipoprotein/triglycerides (Chlorella 4.0%; placebo −9.5%; P = 0.023), suggesting an inhibitory effect of Chlorella on the intestinal absorption of dietary and endogenous lipids. Further, the changes of serum lipids appeared to be associated with the changes of serum carotenoids. Conclusion Daily consumption of Chlorella supplements provided the potential of health benefits reducing serum lipid risk factors, mainly triglycerides and total cholesterol, in mildly hypercholesterolemic subjects. The effect was related to carotenoid consumption. Trial registration WHO International Clinical Trials Registry Platform KCT0000259. PMID:24920270

Impact of daily Chlorella consumption on serum lipid and carotenoid profiles in mildly hypercholesterolemic adults: a double-blinded, randomized, placebo-controlled study.

PubMed

Ryu, Na Hee; Lim, Yeni; Park, Ji Eeun; Kim, Joohee; Kim, Ji Yeon; Kwon, Sung Won; Kwon, Oran

2014-06-11

High level of serum cholesterol is considered to be a major risk factor for cardiovascular disease (CVD). A double-blinded, randomized, placebo-controlled trial was performed to test the hypothesis that a daily intake of Chlorella may improve serum lipid profile through enhancement of serum carotenoid concentration in mildly hypercholesterolemic subjects. Eligible subjects (n = 63) were randomized to either Chlorella (5 g/day) or placebo for a double-blinded trial with a 2-week lead-in period and a 4-week intervention period. Serum triglycerides, total cholesterol, lipoproteins, apolipoproteins and carotenoids were assessed at the beginning and the end of the trial. Compared with the control group, the Chlorella group exhibited remarkable changes in total cholesterol (Chlorella -1.6%; placebo 0.03%; P = 0.036), triglycerides (Chlorella -10.3%; placebo 11.9%; P = 0.002), lutein/zeaxanthin (Chlorella 89.6%; placebo -1.7%; P < 0.0001), and α-carotene (Chlorella 163.6%; placebo 15%; P < 0.0001). Improvement of serum lipids was supported by significant reductions of very low-density lipoprotein cholesterol (Chlorella -11%; placebo 11.8%; P = 0.006), apolipoprotein B (Chlorella -1.5%; placebo 1.7%; P = 0.044), non high-density lipoprotein (Chlorella -2.6%; placebo -0.5%; P = 0.032), and high-density lipoprotein/triglycerides (Chlorella 4.0%; placebo -9.5%; P = 0.023), suggesting an inhibitory effect of Chlorella on the intestinal absorption of dietary and endogenous lipids. Further, the changes of serum lipids appeared to be associated with the changes of serum carotenoids. Daily consumption of Chlorella supplements provided the potential of health benefits reducing serum lipid risk factors, mainly triglycerides and total cholesterol, in mildly hypercholesterolemic subjects. The effect was related to carotenoid consumption. WHO International Clinical Trials Registry Platform KCT0000259.

Antibiotics for acute maxillary sinusitis in adults.

PubMed

Ahovuo-Saloranta, Anneli; Rautakorpi, Ulla-Maija; Borisenko, Oleg V; Liira, Helena; Williams, John W; Mäkelä, Marjukka

2014-02-11

Sinusitis is one of the most common diagnoses among adults in ambulatory care, accounting for 15% to 21% of all adult outpatient antibiotic prescriptions. However, the role of antibiotics for sinusitis is controversial. To assess the effects of antibiotics in adults with acute maxillary sinusitis by comparing antibiotics with placebo, antibiotics from different classes and the side effects of different treatments. We searched CENTRAL 2013, Issue 2, MEDLINE (1946 to March week 3, 2013), EMBASE (1974 to March 2013), SIGLE (OpenSIGLE, later OpenGrey (accessed 15 January 2013)), reference lists of the identified trials and systematic reviews of placebo-controlled studies. We also searched for ongoing trials via ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). We imposed no language or publication restrictions. Randomised controlled trials (RCTs) comparing antibiotics with placebo or antibiotics from different classes for acute maxillary sinusitis in adults. We included trials with clinically diagnosed acute sinusitis, confirmed or not by imaging or bacterial culture. Two review authors independently screened search results, extracted data and assessed trial quality. We calculated risk ratios (RRs) for differences between intervention and control groups in whether the treatment failed or not. All measures are presented with 95% confidence intervals (CIs). We conducted the meta-analyses using either the fixed-effect or random-effects model. In meta-analyses of the placebo-controlled studies, we combined data across antibiotic classes. Primary outcomes were clinical failure rates at 7 to 15 days and 16 to 60 days follow-up. We used GRADEpro to assess the quality of the evidence. We included 63 studies in this updated review; nine placebo-controlled studies involving 1915 participants (seven of the studies clearly conducted in primary care settings) and 54 studies comparing different classes of antibiotics (10 different comparisons). Five studies at low risk of bias comparing penicillin or amoxicillin to placebo provided information on the main outcome: clinical failure rate at 7 to 15 days follow-up, defined as a lack of full recovery or improvement, for participants with symptoms lasting at least seven days. In these studies antibiotics decreased the risk of clinical failure (pooled RR of 0.66, 95% CI 0.47 to 0.94, 1084 participants randomised, 1058 evaluated, moderate quality evidence). However, the clinical benefit was small. Cure or improvement rates were high in both the placebo group (86%) and the antibiotic group (91%) in these five studies. When clinical failure was defined as a lack of full recovery (n = five studies), results were similar: antibiotics decreased the risk of failure (pooled RR of 0.73, 95% CI 0.63 to 0.85, high quality evidence) at 7 to 15 days follow-up.Adverse effects in seven of the nine placebo-controlled studies (comparing penicillin, amoxicillin, azithromycin or moxicillin to placebo) were more common in antibiotic than in placebo groups (median of difference between groups 10.5%, range 2% to 23%). However, drop-outs due to adverse effects were rare in both groups: 1.5% in antibiotic groups and 1% in control groups.In the 10 head-to-head comparisons, none of the antibiotic preparations were superior to another. However, amoxicillin-clavulanate had significantly more drop-outs due to adverse effects than cephalosporins and macrolides. There is moderate evidence that antibiotics provide a small benefit for clinical outcomes in immunocompetent primary care patients with uncomplicated acute sinusitis. However, about 80% of participants treated without antibiotics improved within two weeks. Clinicians need to weigh the small benefits of antibiotic treatment against the potential for adverse effects at both the individual and general population levels.

Liposomal Bupivacaine Block at the Time of Cesarean Delivery to Decrease Postoperative Pain: A Randomized Controlled Trial.

PubMed

Prabhu, Malavika; Clapp, Mark A; McQuaid-Hanson, Emily; Ona, Samsiya; OʼDonnell, Taylor; James, Kaitlyn; Bateman, Brian T; Wylie, Blair J; Barth, William H

2018-07-01

To evaluate whether a liposomal bupivacaine incisional block decreases postoperative pain and represents an opioid-minimizing strategy after scheduled cesarean delivery. In a single-blind, randomized controlled trial among opioid-naive women undergoing cesarean delivery, liposomal bupivacaine or placebo was infiltrated into the fascia and skin at the surgical site, before fascial closure. Using an 11-point numeric rating scale, the primary outcome was pain score with movement at 48 hours postoperatively. A sample size of 40 women per group was needed to detect a 1.5-point reduction in pain score in the intervention group. Pain scores and opioid consumption, in oral morphine milligram equivalents, at 48 hours postoperatively were summarized as medians (interquartile range) and compared using the Wilcoxon rank-sum test. Between March and September 2017, 249 women were screened, 103 women enrolled, and 80 women were randomized. One woman in the liposomal bupivacaine group was excluded after randomization as a result of a vertical skin incision, leaving 39 patients in the liposomal bupivacaine group and 40 in the placebo group. Baseline characteristics between groups were similar. The median (interquartile range) pain score with movement at 48 hours postoperatively was 4 (2-5) in the liposomal bupivacaine group and 3.5 (2-5.5) in the placebo group (P=.72). The median (interquartile range) opioid use was 37.5 (7.5-60) morphine milligram equivalents in the liposomal bupivacaine group and 37.5 (15-75) morphine milligram equivalents in the placebo group during the first 48 hours postoperatively (P=.44). Compared with placebo, a liposomal bupivacaine incisional block at the time of cesarean delivery resulted in similar postoperative pain scores in the first 48 hours postoperatively. ClinicalTrials.gov, NCT02959996.

Efficacy of Glutamate Modulators in Tic Suppression: A Double-Blind, Randomized Control Trial of D-serine and Riluzole in Tourette Syndrome.

PubMed

Lemmon, Monica E; Grados, Marco; Kline, Tina; Thompson, Carol B; Ali, Syed F; Singer, Harvey S

2015-06-01

It has been hypothesized that glutamatergic transmission may be altered in Tourette syndrome. In this study, we explored the efficacy of a glutamate agonist (D-serine) and antagonist (riluzole) as tic-suppressing agents in children with Tourette syndrome. We performed a parallel three-arm, 8-week, double-blind, randomized placebo-controlled treatment study in children with Tourette syndrome. Each child received 6 weeks of treatment with D-serine (maximum dose 30 mg/kg/day), riluzole (maximum dose 200 mg/day), or placebo, followed by a 2-week taper. The primary outcome measure was effective tic suppression as determined by the differences in the Yale Global Tic Severity Scale score; specifically, the total tic score and the combined score (total tic score + global impairment) between treatment arms after 6 weeks of treatment. Mann-Whitney U tests were performed to analyze differences between each group and the placebo group. Twenty-four patients (males = 21, ages 9-18) enrolled in the study; one patient dropped out before completion. Combined Yale Global Tic Severity Scale score and total tic scores improved in all groups. The 6-week mean percent improvement of the riluzole (n = 10), D-serine (n = 9), and placebo (n = 5) groups in the combined Yale Global Tic Severity Scale score were 43.7, 39.5, and 30.2 and for total tic scores were 38.0, 25.0, and 34.0, respectively. There were no significant differences in Yale Global Tic Severity Scale score or total tic score, respectively, between the riluzole and placebo (P = 0.35, 0.85) or D-serine and placebo (P = 0.50, 0.69) groups. Tics diminished by comparable percentages in the riluzole, D-serine, and placebo groups. These preliminary data suggest that D-serine and riluzole are not effective in tic suppression. Copyright © 2015 Elsevier Inc. All rights reserved.

Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis: the placebo-controlled SEDUCE study

PubMed Central

Hachulla, Eric; Hatron, Pierre-Yves; Carpentier, Patrick; Agard, Christian; Chatelus, Emmanuel; Jego, Patrick; Mouthon, Luc; Queyrel, Viviane; Fauchais, Anne-Laure; Michon-Pasturel, Ulrique; Jaussaud, Roland; Mathian, Alexis; Granel, Brigitte; Diot, Elisabeth; Farge-Bancel, Dominique; Mekinian, Arsène; Avouac, Jérôme; Desmurs-Clavel, Hélène; Clerson, Pierre

2016-01-01

Objective To assess the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc). Methods Randomised, placebo-controlled study in patients with SSc to assess the effect of sildenafil 20 mg or placebo, three times daily for 12 weeks, on ischaemic DU healing. The primary end point was the time to healing for each DU. Time to healing was compared between groups using Cox models for clustered data (two-sided tests, p=0.05). Results Intention-to-treat analysis involved 83 patients with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to 1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28) (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was lower in the sildenafil group compared with the placebo group at week (W) 8 (1.23±1.61 vs 1.79±2.40 p=0.04) and W12 (0.86±1.62 vs 1.51±2.68, p=0.01) resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12). Conclusions The primary end point was not reached in intention-to-treat, partly because of an unexpectedly high healing rate in the placebo group. We found a significant decrease in the number of DUs in favour of sildenafil compared with placebo at W8 and W12, confirming a sildenafil benefit. Trial registration number NCT01295736. PMID:25995322

A double-blind, placebo-controlled clinical trial of the effect of chlorpheniramine on the response of the nasal airway, middle ear and eustachian tube to provocative rhinovirus challenge.

PubMed

Doyle, W J; McBride, T P; Skoner, D P; Maddern, B R; Gwaltney, J M; Uhrin, M

1988-03-01

This paper presents the results of a randomized, double-blind, placebo-controlled study of the efficacy of chlorpheniramine in relieving the symptoms and attenuating the pathophysiologic correlates of a rhinovirus "common cold." Forty healthy, adult, nonatopic subjects were randomly assigned to one of two treatment groups: active drug and placebo. On study Day 0, all subjects were challenged intranasally with rhinovirus type 39 (dose = 100 TCID50). Subjects were cloistered from Day 2 to Day 7, at which time they were treated with either chlorpheniramine or placebo. From 3 days before challenge to study Day 19, subjects had nasal patency assessed by rhinomanometry, eustachian tube function assessed by the 9-step test and sonotubometry, middle ear pressure assessed by tympanometry and nasal clearance assessed by the dyed-saccharin technique. Symptom diaries were maintained throughout the period of follow-up. During cloister, symptoms also were scored by interview, nasal secretions were quantified and nasal washings were performed for viral culture. Results showed that 19 (95%) subjects in the active-treatment group and 18 (90%) subjects in the placebo-treatment group shed virus. Symptomatic colds were observed in 63% of the active-treated and 83% of the placebo-treated subjects. Symptoms increased on Day 1 and peaked at Days 4 to 5. Detrimental changes in other measured functions consistent with those previously reported were observed. During the period of treatment, significant differences in the average symptom scores favoring the active-treatment group were observed for sneezing. Also, weight of expelled secretions was greater and mucociliary clearance rate less on some cloister days for the placebo-treated group. No significant differences between treatment groups in the objective measures of nasal congestion or the response of the middle ear and eustachian tube were documented.

Randomized Controlled Trial on the Effect of Channa striatus Extract on Measurement of the Uterus, Pulsatility Index, Resistive Index of Uterine Artery and Superficial Skin Wound Artery in Post Lower Segment Caesarean Section Women.

PubMed

Abu Bakar, Mohd Rizal; Abdul Kadir, Azidah; Abdul Wahab, Siti Zubaidah; Abdul Karim, Ahmad Helmy; Nik Hussain, Nik Hazlina; Mohd Noor, Norhayati; Omar, Julia; Bin Bai Bae, Saringat; Wan Mahmood, Wan Haslindawani; Abdul Razak, Asrenee; Yunus, Rohaizan

2015-01-01

To compare the mean of anteroposterior (AP) measurements of the uterus in longitudinal and oblique transverse planes, and the pulsatility index (PI) and resistive index (RI) of the uterine artery and superficial skin wound artery between patients taking Channa striatus and placebo. Channa striatus, also known as haruan, is a fresh water snakehead fish consumed in many parts of Southeast Asia. Channa striatus is also normally consumed by women postpartum to promote wound healing as well as to reduce post-operative pain. This study is a randomised, double blind, placebo-controlled study conducted in women after Lower Segment Caesarean Section (LSCS). Subjects were randomised to either a Channa striatus or a placebo group and were given a daily dosage of 500 mg of Channa striatus extract or 500 mg maltodextrin, respectively, for six weeks post LSCS. The anteroposterior measurements of the uterus in the longitudinal and oblique transverse planes, and the pulsatility index (PI) and resistive index (RI) of the uterine and superficial skin wound arteries were assessed using pelvic Gray-scale ultrasound and Doppler ultrasound at baseline (Day 3) and at two weeks, four weeks and six weeks post-operatively. Sixty-six subjects were randomised into the study with 33 in the Channa striatus group and 33 in the placebo group. No significant differences were detected in terms of the pulsatility index (PI) and the resistive index (RI) of the uterine and superficial skin wound arteries between the Channa striatus and placebo groups. However, in the Channa striatus group, the AP measurements of the uterus on the longitudinal and oblique transverse planes were significantly lower compared to the placebo group (p<0.05 and p<0.001, respectively). Daily intake of Channa striatus extract results in marked differences compared to placebo in terms of uterine involution and recovery in women post LSCS. www.isrctn.com 11960786.

Prophylactic antibiotics to prevent pneumonia and other complications after measles: community based randomised double blind placebo controlled trial in Guinea-Bissau.

PubMed

Garly, May-Lill; Balé, Carlitos; Martins, Cesário Lourenco; Whittle, Hilton C; Nielsen, Jens; Lisse, Ida M; Aaby, Peter

2006-12-16

To investigate whether prophylactic antibiotics can prevent complications of measles. Community based, randomised, double blind, placebo controlled trial. Bandim Health Project study area in Bissau, Guinea-Bissau, west Africa. 84 patients with measles during a measles epidemic in Bissau in 1998 (fewer than originally planned owing to interruption by war). Sulfamethoxazole-trimethoprim (co-trimoxazole) or placebo for seven days. Pneumonia and admission to hospital. Also weight change during the first month of infection, diarrhoea, severe fever, oral thrush, stomatitis, conjunctivitis, and otitis media. The median age of the patients with measles was 5.4 (range 0.49-24.8) years. One of 46 participants who received co-trimoxazole developed pneumonia, in contrast to six of 38 participants who received placebo (odds ratio 0.08 (95% confidence interval 0 to 0.56), adjusted for age group). The number needed to treat was 7 (4 to 48). All three participants admitted to hospital had received placebo (P=0.09). The weight gain during the first month after inclusion was 15 (2-29) g/day in the placebo group and 32 (23-42) g/day in the co-trimoxazole group (P=0.04, adjusted for age group, weight for age at inclusion, measles vaccination status, and duration of disease). Significantly less conjunctivitis occurred among recipients of co-trimoxazole than placebo, as well as a non-significant tendency to less diarrhoea, severe fever, oral thrush, and stomatitis. Complications of otitis media were the same in the two groups. The group that received prophylactic antibiotics had less pneumonia and conjunctivitis and had significantly higher weight gains in the month after inclusion. The results indicate that prophylactic antibiotics may have an important role in the management of measles infection in low income countries. Clinical trials NCT00168532.

Efficacy of vitamin C vaginal tablets in the treatment of bacterial vaginosis: a randomised, double blind, placebo controlled clinical trial.

PubMed

Petersen, Eiko E; Genet, Margherita; Caserini, Maurizio; Palmieri, Renata

2011-01-01

A randomised, double blind, parallel groups, placebo controlled clinical trial was conducted to assess the efficacy and safety profile of 250 mg ascorbic acid (Vit. C, Vagi C) in women with bacterial vaginosis (BV). Overall, 277 out-patients with at least three of the following signs (white discharge that smoothly coats the vaginal walls, pH of vaginal fluid > 4.5, a fishy odour of vaginal discharge before or after addition of 10% KOH and presence of clue cells on microscopic examination) were randomised to apply a tablet deeply into the vagina once daily for 6 days. The primary efficacy endpoint was the cure rate, defined as the recovery of all inclusion criteria. In the intent-to-treat (ITT) population, cure was achieved by 55.3% of patients with Vit. C (n=141) and by 25.7% of patients with placebo (n=136). The between-group difference was 29.6% (p < 0.001). In the per-protocol (PP) population, cure rate was 66.4% with Vit. C (n=116) and 27.1% with placebo (n = 118), respectively. Between-group difference was 39.3% (p < 0.001). In a subset of patients with centralised evaluation of the vaginal swab, cure in ITT was achieved by 86.3% of patients with Vit. C (n=51) and by 7.6% of patients with placebo (n=53), the between-group difference was 78.7% (p < 0.0001). Cure rate in PP was 86.0% with Vit. C (n=50) and 6.1% with placebo (n=49), between-group difference was 79.9% (p < 0.0001). Both Vit. C and placebo were well tolerated and no differences in safety profile were evident between groups. The results support an effective and safe use of silicon-coated Vit. C vaginal tablets in the management of BV.

Use of Low Level of Continuous Heat as an Adjunct to Physical Therapy Improves Knee Pain Recovery and the Compliance for Home Exercise in Patients With Chronic Knee Pain: A Randomized Controlled Trial.

PubMed

Petrofsky, Jerrold S; Laymon, Michael S; Alshammari, Faris S; Lee, Haneul

2016-11-01

Petrofsky, JS, Laymon, MS, Alshammari, FS, and Lee, H. Use of low level of continuous heat as an adjunct to physical therapy improves knee pain recovery and the compliance for home exercise in patients with chronic knee pain: a randomized controlled trial. J Strength Cond Res 30(11): 3107-3115, 2016-This study examined if the use of low level continuous heat (LLCH) wraps at home between physical therapy sessions at a clinic resulted in better therapy outcomes in patients with chronic knee pain. Fifty individuals with chronic nonspecific knee pain was randomly allocated to 2 groups: the LLCH group and the placebo group. All subjects underwent 1 hour of conventional physical therapy twice per week for 2 weeks at the outpatient clinic and they were asked to accomplish 1 hour of therapeutic exercise at home each day between sessions. The LLCH group applied LLCH knee wraps for 6 hours at home before home exercise while placebo group took a placebo ibuprofen. (This was done since placebo heat is impossible to use since subjects would notice that the wraps were cold) Before, during, and after intervention, pain intensity, active range of motion of the knee (AROM), knee strength, and home exercise compliance were measured. The LLCH group showed pain attenuation after 2 weeks of therapy sessions (p ≤ 0.05). AROM and strength of the knee significantly improved over time compared to the placebo group. Home exercise compliance was significantly higher in the LLCH group than placebo group (p ≤ 0.05). These results indicated that the use of LLCH as an adjunct to conventional physical therapy for chronic knee pain significantly improved pain attenuation and recovery of strength and movement in patients with chronic knee pain.

Efficacy of lycopene in the treatment of gingivitis: a randomised, placebo-controlled clinical trial.

PubMed

Chandra, Rampalli Viswa; Prabhuji, M L Venkatesh; Roopa, D Adinarayana; Ravirajan, Sandhya; Kishore, Hadal C

2007-01-01

The aim of the present study was to compare the effect of systemically administered lycopene (LycoRed) as a monotherapy and as an adjunct to scaling and root planing in gingivitis patients. Twenty systemically healthy patients showing clinical signs of gingivitis were involved in a randomised, double-blind, parallel, split-mouth study. The subjects were randomly distributed between the two treatment groups: experimental group (n = 10), 8 mg lycopene/day for 2 weeks; and controls (n = 10), placebo for 2 weeks. Quadrant allocation within each group was randomised with two quadrants treated with oral prophylaxis (OP) and two quadrants not receiving any form of treatment (non-OP). Bleeding index (SBI) and non-invasive measures of plaque (PI) and gingivitis (GI) were assessed at baseline, 1 and 2 weeks. Salivary uric acid levels were also measured. All the treatment groups demonstrated statistically significant reductions in the GI, SBI and PI. Treatment with OP-lycopene resulted in a statistically significant decrease in GI when compared with OP-placebo (p < 0.05) and non-OP-placebo (p < 0.01). Treatment with non-OP-lycopene resulted in a statistically significant decrease in GI when compared with non-OP-placebo (p < 0.01). The OP-lycopene group showed a statistically significant reduction in SBI values when compared with the non-OP-lycopene group (p < 0.05) and the non-OP-placebo group (p < 0.001). There was a strong negative correlation between the salivary uric acid levels and the percentage reduction in GI at 1 and 2 weeks in the OP-lycopene group (r = -0.852 and -0.802 respectively) and in the non-OP-lycopene group (r = -0.640 and -0.580 respectively). The results presented in this study suggest that lycopene shows great promise as a treatment modality in gingivitis. The possibility of obtaining an additive effect by combining routine oral prophylaxis with lycopene is also an exciting possibility, which deserves further study.

An Approach to Assess Generalizability in Comparative Effectiveness Research: A Case Study of the Whole Systems Demonstrator Cluster Randomized Trial Comparing Telehealth with Usual Care for Patients with Chronic Health Conditions.

PubMed

Steventon, Adam; Grieve, Richard; Bardsley, Martin

2015-11-01

Policy makers require estimates of comparative effectiveness that apply to the population of interest, but there has been little research on quantitative approaches to assess and extend the generalizability of randomized controlled trial (RCT)-based evaluations. We illustrate an approach using observational data. Our example is the Whole Systems Demonstrator (WSD) trial, in which 3230 adults with chronic conditions were assigned to receive telehealth or usual care. First, we used novel placebo tests to assess whether outcomes were similar between the RCT control group and a matched subset of nonparticipants who received usual care. We matched on 65 baseline variables obtained from the electronic medical record. Second, we conducted sensitivity analysis to consider whether the estimates of treatment effectiveness were robust to alternative assumptions about whether "usual care" is defined by the RCT control group or nonparticipants. Thus, we provided alternative estimates of comparative effectiveness by contrasting the outcomes of the RCT telehealth group and matched nonparticipants. For some endpoints, such as the number of outpatient attendances, the placebo tests passed, and the effectiveness estimates were robust to the choice of comparison group. However, for other endpoints, such as emergency admissions, the placebo tests failed and the estimates of treatment effect differed markedly according to whether telehealth patients were compared with RCT controls or matched nonparticipants. The proposed placebo tests indicate those cases when estimates from RCTs do not generalize to routine clinical practice and motivate complementary estimates of comparative effectiveness that use observational data. Future RCTs are recommended to incorporate these placebo tests and the accompanying sensitivity analyses to enhance their relevance to policy making. © The Author(s) 2015.

Effects of Low Dose Metformin in Adolescents with Type I Diabetes Mellitus: A Randomized, Double-Blinded Placebo-Controlled Study

PubMed Central

Nadeau, Kristen; Chow, Kelsey; Alam, Lyla; Lindquist, Kara; Cambell, Sarah; McFann, Kim; Klingensmith, Georgeanna; Walravens, Phillipe

2014-01-01

Background Insulin resistance increases during adolescence in those with type 1 diabetes (T1DM), complicating glycemic control and potentially increasing cardiovascular disease (CVD) risk. Metformin, typically used in type 2 diabetes (T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity. Objective We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. Design, Setting, and Participants This randomized, double-blinded, placebo-controlled trial included 74 pubertal adolescents (ages 13–20 years) with T1DM. Participants were randomized to receive either metformin or placebo for six months. HbA1c, insulin dose, waist circumference, BMI, and blood pressure were measured at baseline, 3 and 6 months, with fasting lipids measured at baseline and 6 months. Results Total daily insulin dose, BMI Z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants. In placebo group, total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months. No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group. Conclusions Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose. The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM. Further studies with higher metformin doses and more detailed measurements are needed to confirm these results, their underlying mechanisms, and potential impact on CVD in T1DM youth. PMID:24698216

One-year efficacy and safety of saxagliptin add-on in patients receiving dapagliflozin and metformin.

PubMed

Matthaei, S; Aggarwal, N; Garcia-Hernandez, P; Iqbal, N; Chen, H; Johnsson, E; Chin, A; Hansen, L

2016-11-01

Greater reductions in glycated haemoglobin (HbA1c) with saxagliptin, a dipeptidyl peptidase-4 inhibitor, versus placebo add-on in patients with type 2 diabetes who had inadequate glycaemic control with dapagliflozin 10 mg/d plus metformin were demonstrated after 24 weeks of treatment. Results over 52 weeks of treatment were assessed in this analysis. Patients (mean baseline HbA1c 7.9%) receiving open-label dapagliflozin 10 mg/d plus metformin were randomized to double-blind saxagliptin 5 mg/d or placebo add-on. The adjusted mean change from baseline to week 52 in HbA1c was greater with saxagliptin than with placebo add-on -0.38% vs 0.05%; difference -0.42% (95% confidence interval -0.64, -0.20)]. More patients achieved the HbA1c target of <7% with saxagliptin than with placebo add-on (29% vs 13%), and fewer patients were rescued or discontinued the study for lack of glycaemic control with saxagliptin than with placebo add-on (19% vs 28%). Reductions from baseline in body weight (≤1.5 kg) occurred in both groups. Similar proportions of patients reported ≥1 adverse event with saxagliptin (58.2%) and placebo add-on (58.0%); no new safety signals were detected. Hypoglycaemia was infrequent in both treatment groups (≤2.5%), with no major episodes. The rate of urinary tract infections was similar in the saxagliptin and placebo add-on groups (7.8% vs 7.4%). The incidence of genital infections was 3.3% with saxagliptin versus 6.2% with placebo add-on. Triple therapy with saxagliptin add-on to dapagliflozin plus metformin for 52 weeks resulted in sustained improvements in glycaemic control without an increase in body weight or increased risk of hypoglycaemia. © 2016 John Wiley & Sons Ltd.

Individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP study): a randomized, double-dummy, double-blind, placebo-controlled trial.

PubMed

Macías-Cortés, Emma Del Carmen; Llanes-González, Lidia; Aguilar-Faisal, Leopoldo; Asbun-Bojalil, Juan

2015-01-01

Perimenopausal period refers to the interval when women's menstrual cycles become irregular and is characterized by an increased risk of depression. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. The aim of this study was to assess efficacy and safety of individualized homeopathic treatment versus placebo and fluoxetine versus placebo in peri- and postmenopausal women with moderate to severe depression. A randomized, placebo-controlled, double-blind, double-dummy, superiority, three-arm trial with a 6 week follow-up study was conducted. The study was performed in a public research hospital in Mexico City in the outpatient service of homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed with major depression according to DSM-IV (moderate to severe intensity) were included. The outcomes were: change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression, Beck Depression Inventory and Greene Scale, after 6 weeks of treatment, response and remission rates, and safety. Efficacy data were analyzed in the intention-to-treat population (ANOVA with Bonferroni post-hoc test). After a 6-week treatment, homeopathic group was more effective than placebo by 5 points in Hamilton Scale. Response rate was 54.5% and remission rate, 15.9%. There was a significant difference among groups in response rate definition only, but not in remission rate. Fluoxetine-placebo difference was 3.2 points. No differences were observed among groups in the Beck Depression Inventory. Homeopathic group was superior to placebo in Greene Climacteric Scale (8.6 points). Fluoxetine was not different from placebo in Greene Climacteric Scale. Homeopathy and fluoxetine are effective and safe antidepressants for climacteric women. Homeopathy and fluoxetine were significantly different from placebo in response definition only. Homeopathy, but not fluoxetine, improves menopausal symptoms scored by Greene Climacteric Scale. ClinicalTrials.gov NCT01635218. https://clinicaltrials.gov/ct2/show/NCT01635218 [corrected].

Individualized Homeopathic Treatment and Fluoxetine for Moderate to Severe Depression in Peri- and Postmenopausal Women (HOMDEP-MENOP Study): A Randomized, Double-Dummy, Double-Blind, Placebo-Controlled Trial

PubMed Central

Macías-Cortés, Emma del Carmen; Llanes-González, Lidia; Aguilar-Faisal, Leopoldo; Asbun-Bojalil, Juan

2015-01-01

Background Perimenopausal period refers to the interval when women's menstrual cycles become irregular and is characterized by an increased risk of depression. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. The aim of this study was to assess efficacy and safety of individualized homeopathic treatment versus placebo and fluoxetine versus placebo in peri- and postmenopausal women with moderate to severe depression. Methods/Design A randomized, placebo-controlled, double-blind, double-dummy, superiority, three-arm trial with a 6 week follow-up study was conducted. The study was performed in a public research hospital in Mexico City in the outpatient service of homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed with major depression according to DSM-IV (moderate to severe intensity) were included. The outcomes were: change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression, Beck Depression Inventory and Greene Scale, after 6 weeks of treatment, response and remission rates, and safety. Efficacy data were analyzed in the intention-to-treat population (ANOVA with Bonferroni post-hoc test). Results After a 6-week treatment, homeopathic group was more effective than placebo by 5 points in Hamilton Scale. Response rate was 54.5% and remission rate, 15.9%. There was a significant difference among groups in response rate definition only, but not in remission rate. Fluoxetine-placebo difference was 3.2 points. No differences were observed among groups in the Beck Depression Inventory. Homeopathic group was superior to placebo in Greene Climacteric Scale (8.6 points). Fluoxetine was not different from placebo in Greene Climacteric Scale. Conclusion Homeopathy and fluoxetine are effective and safe antidepressants for climacteric women. Homeopathy and fluoxetine were significantly different from placebo in response definition only. Homeopathy, but not fluoxetine, improves menopausal symptoms scored by Greene Climacteric Scale. Trial Registration ClinicalTrials.gov NCT01635218 Protocol Publication http://www.trialsjournal.com/content/14/1/105. PMID:25768800

Phase 3 randomized study of the efficacy and safety of inhaled dry powder mannitol for the symptomatic treatment of non-cystic fibrosis bronchiectasis.

PubMed

Bilton, Diana; Daviskas, Evangelia; Anderson, Sandra D; Kolbe, John; King, Gregory; Stirling, Rob G; Thompson, Bruce R; Milne, David; Charlton, Brett

2013-07-01

Inhaled dry powder mannitol enhanced mucus clearance and improved quality of life over 2 weeks in non-cystic fibrosis bronchiectasis. This study's objective was to investigate the efficacy and safety of dry powder mannitol over 12 weeks. Patients with bronchiectasis confirmed by high-resolution CT (HRCT) scan, aged 15 to 80 years, with FEV1≥50% predicted and ≥1 L participated in a randomized, placebo-controlled, double-blind study. Patients with a negative mannitol provocation test were randomized to inhale 320 mg mannitol (n=231) or placebo (n=112) bid for 12 weeks. To further assess safety, the same mannitol dose/frequency was administered to a patient subset in an open-label extension over 52 weeks. Primary end points were changes from baseline at 12 weeks in 24-h sputum weight and St. George's Respiratory Questionnaire (SGRQ) score. There was a significant difference of 4.3 g in terms of change in sputum weight over 12 weeks (95% CI, 1.64-7.00; P=.002) between mannitol and placebo; however, this was largely driven by a decrease in sputum weight in the placebo group. This was associated, in turn, with more antibiotic use in the placebo group (50 of 112 [45%]) than in the inhaled mannitol group (85 of 231 [37%]). There was no statistical difference between the groups (P=.304) in total SGRQ score (mannitol, -3.4 points [95% CI, -4.81 to -1.94] vs placebo, -2.1 points [95% CI, -4.12 to -0.09]). In a subgroup study (n=82), patients receiving mannitol showed less small airway mucus plugging on HRCT scan at 12 weeks compared with patients receiving placebo (P=.048). Compliance rates were high, and mannitol was well tolerated with adverse events similar to those of placebo. Because the difference in sputum weights appears to be associated with increased antibiotic use in the placebo group, a larger controlled study is now required to investigate the long-term mannitol effect on pulmonary exacerbations and antibiotic use. ClinicalTrials.gov; No.: NCT0027753; URL: www.clinicaltrials.gov.

Effect of latanoprost/timolol and dorzolamide/tiomolol on intraocular pressure after phacoemulsification surgery

PubMed Central

Erdogan, Haydar; Ozec, Ayse Vural; Caner, Cengiz; Toker, Mustafa Ilker; Arici, Mustafa Kemal; Topalkara, Aysen

2011-01-01

AIM To evalaute the effect of fixed-combination latanoprost 0.005%/timolol maleate 0.5% and dorzolamide hydrochloride 2%/timolol maleate 0.5% on postoperative intraocular pressure after phacoemulsification cataract surgery. METHODS This study is a prospective, randomized, double-masked and placebo-controlled. The study included 90 eyes of 90 patients which were scheduled to have phacoemulsification surgery. Patients were randomly assigned preoperatively to 1 of 3 groups (30 eyes of 30 patients). Two hour before surgery, the patients received one drop latanoprost/timolol (group 1), dorzolamide/timolol (group 2) and placebo (group 3, control group). The IOPs were measured at preoperative and postoperative 4, 8, and 24 hours. RESULTS The preoperative mean intraocular pressure was not statistically significant between both drug groups and control group. In group 1 and 2, the postoperative mean IOP [group1: (14.03±3.15)mmHg and group 2: (14.16±4.43)mmHg] at 24 hours were significantly lower than the control group [(16.93±3.70)mmHg, (P<0.05)]. In addition, the postoperative mean IOP of group 1 [(14.90±3.69)mmHg] at 8 hours was significantly lower than the control group [(17.70±3.89)mmHg, (P<0.05)], but there was no significant difference between group 2 [(16.16±5.23)mmHg] and control group at 8 hours (P>0.05). CONCLUSION When compared with placebo, the use of preoperative fixed combination of latanoprost/timolol and dorzolamide/timolol is an effective method for preventing intraocular pressure elevation in 24 hours after phacoemulsification surgery, but did not completely prevent IOP spikes. PMID:22553640

Effects of kivia powder on Gut health in patients with occasional constipation: a randomized, double-blind, placebo-controlled study

PubMed Central

2013-01-01

Objective To evaluate the efficacy of Kivia powder on supporting overall gut health through the relief of the discomfort of occasional constipation. Design Randomized, double-blind, placebo-controlled, parallel-group trial. Interventions The investigational product for this study was Kivia powder (Vital Food Processors Ltd., Auckland, New Zealand), containing the active ingredient Zyactinase™, 5.5 g taken daily for four weeks. Results One hundred thirty-eight subjects reporting occasional constipation were screened and 87 were randomized to placebo (n = 44) and product (n = 43). Bowel movement frequency, as measured by both average daily spontaneous bowel movements (SBM) and complete spontaneous bowel movements (CSBM), were the same in both groups at baseline. There were significant increases in spontaneous bowel movements at week 1 (p = 0.001), week 2 (p = 0.001), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. SBM demonstrated significant differences between the treatment group and the placebo group at week 3 (p = 0.000), and week 4 (p = 0.020). The treatment group demonstrated a significantly higher rate of SBM at week 3 (p = 000) and from baseline to week 4 (p = 0.019). Significant increases in complete spontaneous bowel movements were observed at week 1 (p = 0.000), week 2 (p = 0.000), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. Moreover, CSBM was significantly higher for the treatment group compared to placebo at week 2 (p = 0.001). The change in average daily CSBM from baseline to week 2 was significantly higher in the treatment group than in the placebo group (p = 0.004). Abdominal discomfort or pain demonstrated significant differences between groups at week 1 (p = 0.044) and week 3 (p = 0.026). Flatulence was significantly lower for active group compared to placebo at week 2 (p = 0.047) and week 3 (p = 0.023). The number of bowel movements associated with urgency was significantly lower in the treatment group compared to the placebo group at week 3 (p = 0.048). In addition, it was decreased from baseline to week 1 (p = 0.040) and from baseline to week 3 (p = 0.024) in the treatment group, while the placebo group did not report any reductions in bowel urgency. Bowel movements in the treatment arm were significantly smoother and softer by week 2 (p = 0.020) and week 3 (p = 0.041). Conclusions Treatment with Kivia powder, an extract of kiwifruit containing Zyactinase™, for four weeks was well tolerated and more effective than placebo in gently enhancing bowel movement frequency and reducing abdominal pain and flatulence in subjects with occasional constipation. Trial registration ISRCTN: ISRCTN49036618 PMID:23758673

Rebamipide (OPC-12759) in the treatment of dry eye: a randomized, double-masked, multicenter, placebo-controlled phase II study.

PubMed

Kinoshita, Shigeru; Awamura, Saki; Oshiden, Kazuhide; Nakamichi, Norihiro; Suzuki, Hiroyuki; Yokoi, Norihiko

2012-12-01

To investigate the dose response for efficacy of 1% and 2% rebamipide ophthalmic suspension compared with placebo in patients with dry eye. A randomized, double-masked, multicenter, placebo-controlled, parallel-group, dose-response phase II study. A total of 308 patients with dry eye. After a 2-week screening period, patients were randomized to receive placebo or 1% rebamipide or 2% rebamipide administered as 1 drop in each eye 4 times daily for 4 weeks. The primary objective end point was change in fluorescein corneal staining (FCS) score from baseline to last observation carried forward (LOCF). Secondary objective end points were lissamine green conjunctival staining (LGCS) score, tear film break-up time (TBUT), and the Schirmer's test. Secondary subjective end points included dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision) score and patients' overall treatment impression score. Rebamipide dose response was observed in FCS, LGCS, and TBUT scores. Both 1% and 2% rebamipide were significantly more effective than the placebo in terms of the change from baseline to LOCF for FCS, LGCS, and TBUT scores. There was no significant difference between the rebamipide and placebo groups from baseline to LOCF in Schirmer's test values, and dose response was not observed. In the predefined dry eye subpopulation with a baseline FCS score of 10 to 15, the mean change from baseline in the 2% rebamipide group was larger than that in the 1% rebamipide group. Change from baseline to LOCF for all 5 dry eye-related ocular symptom scores and patients' overall treatment impression showed significant improvements in the 1% and 2% rebamipide groups compared with the placebo group, except for photophobia in the 1% rebamipide group. No deaths or drug-related serious adverse events occurred in any treatment group. The incidence of ocular abnormalities was similar across the rebamipide and placebo groups. Rebamipide was effective in treating both objective signs and subjective symptoms of dry eye and were well tolerated in this 4-week study. Although 1% and 2% rebamipide were both efficacious, 2% rebamipide may be more effective than 1% rebamipide in some measures. Proprietary or commercial disclosure may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Fluoxetine, Smoking, and History of Major Depression: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Spring, Bonnie; Doran, Neal; Pagoto, Sherry; McChargue, Dennis; Cook, Jessica Werth; Bailey, Katherine; Crayton, John; Hedeker, Donald

2007-01-01

The study was a randomized placebo-controlled trial testing whether fluoxetine selectively enhances cessation for smokers with a history of depression. Euthymic smokers with (H+, n = 109) or without (H-, n = 138) a history of major depression received 60 mg fluoxetine or placebo plus group behavioral quit-smoking treatment for 12 weeks. Fluoxetine…

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study.

PubMed

Tanaka, Yoshiya; Emoto, Kahaku; Cai, Zhihong; Aoki, Takehiro; Schlichting, Douglas; Rooney, Terence; Macias, William

2016-03-01

To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX). This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult-onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events. A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p < 0.001). Significant improvements in disease activity, remission, and physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of ≥ 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses ≤ 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group. In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.gov NCT01469013).

Impact of different concentrations of an octenidine dihydrochloride mouthwash on salivary bacterial counts: a randomized, placebo-controlled cross-over trial.

PubMed

Lorenz, Katrin; Jockel-Schneider, Yvonne; Petersen, Nicole; Stölzel, Peggy; Petzold, Markus; Vogel, Ulrich; Hoffmann, Thomas; Schlagenhauf, Ulrich; Noack, Barbara

2018-03-02

This bi-centric, placebo-controlled, randomized, evaluator-blinded, incomplete cross-over clinical phase II trial was initialized to identify the most appropriate concentration of octenidine dihydrochloride (OCT) in mouth rinses. Rinses of 0.10, 0.15, and 0.20% OCT were compared to a saline placebo rinse regarding the reduction of salivary bacterial counts (SBCs) in 90 gingivitis patients over 4 days. Changes in plaque (PI) and gingival index (GI), taste perception, and safety issues were evaluated. At baseline, the first OCT (0.10, 0.15, 0.20%) rinse resulted in a decrease of SBC (reduction by 3.63-5.44 log 10 colony forming units [CFU]) compared to placebo (p < 0.001). Differences between OCT concentrations were not verified. After 4 days, the last OCT rinse again resulted in a significant SBC decrease (3.69-4.22 log 10 CFU) compared to placebo (p < 0.001). Overall, SBC reduction between baseline and day 4 was significantly higher in OCT 0.15 and 0.20% groups compared to OCT 0.10% and placebo. Mean GI/PIs were significantly lower in OCT groups than in the placebo group (p < 0.001). Differences in GI/PI between OCT groups were not verified. Adverse effects increased with increasing OCT concentrations. Considering antibacterial efficacy, frequency of adverse events, and user acceptance, 0.10% OCT was identified as the preferred concentration to be used in future clinical trials. Due to its low toxicity and pronounced antibacterial properties, octenidine dihydrochloride (OCT) is a promising candidate for the use in antiseptic mouth rinses. OCT concentrations of 0.10% are recommended for future clinical trials evaluating the plaque-reducing properties of OCT mouth rinses. ( www.clinicaltrials.gov , NCT022138552).

Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer's disease.

PubMed

Feldman, Howard H; Lane, Roger

2007-10-01

To evaluate the efficacy and safety of rapidly titrated rivastigmine administered twice (BID) or three times (TID) daily in patients with mild to moderate Alzheimer's disease (AD). This was a 26 week international, randomised, double blind, placebo controlled study in which 678 patients with probable AD received placebo or rivastigmine 2-12 mg/day BID or TID. Primary outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog) and categorical analysis of the Clinician Interview Based Impression of Change incorporating caregiver information (CIBIC-Plus). Secondary outcomes were the CIBIC-Plus change from baseline, Progressive Deterioration Scale, ADAS-cogA, Mini-Mental State Examination and Global Deterioration Scale. At week 26, mean rivastigmine dose was 9.6 (2.76) mg/day in the TID group and 8.9 (2.93) mg/day in the BID group. Mean ADAS-cog changes from baseline in the TID and BID rivastigmine treated groups were -0.2 (SD 7.3) and 1.2 (SD 7.2) versus 2.8 (SD 7.2) for the placebo group (p<0.05). Differences between rivastigmine TID and placebo on the CIBIC-Plus categorical responder analysis were significant (31% vs 19%; p<0.05, intention to treat). No significant differences were seen between BID and placebo for this outcome measure. Adverse events were predominantly gastrointestinal, occurring mainly during dose titration. Withdrawal because of adverse events accounted for 17% of BID, 11% of TID and 9% of placebo patients. Rivastigmine administered as a BID or TID regimen significantly benefited cognitive, function and global performances in AD patients. The TID regimen showed a tendency for superior tolerability and permitted titration to higher doses, an outcome that is significant as the efficacy of rivastigmine is dose related.

A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults.

PubMed

Gray, Kevin M; Sonne, Susan C; McClure, Erin A; Ghitza, Udi E; Matthews, Abigail G; McRae-Clark, Aimee L; Carroll, Kathleen M; Potter, Jennifer S; Wiest, Katharina; Mooney, Larissa J; Hasson, Albert; Walsh, Sharon L; Lofwall, Michelle R; Babalonis, Shanna; Lindblad, Robert W; Sparenborg, Steven; Wahle, Aimee; King, Jacqueline S; Baker, Nathaniel L; Tomko, Rachel L; Haynes, Louise F; Vandrey, Ryan G; Levin, Frances R

2017-08-01

Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18-50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio=1.00, 95% confidence interval 0.63-1.59, p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. In contrast with prior findings in adolescents, there is no evidence that NAC 1200mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors. Copyright © 2017 Elsevier B.V. All rights reserved.

Blood pressure-lowering effects of long chain n-3 fatty acids from meals enriched with liquid fish oil and from microencapsulated powder.

PubMed

Sveinsdottir, Kolbrun; Martinsdottir, Emilia; Ramel, Alfons

2016-12-01

Diet plays an important role in the etiology of hypertension. Blood pressure (BP)-lowering properties of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) are promising. The aim was to investigate whether different formulations of fish oil differently affect blood pressure in community-dwelling adults. The hypothesis was that fish oil formulations would improve BP in comparison with a placebo. In this 4-week randomized, placebo-controlled, doubly-blinded dietary intervention study, participants (N = 99, >50 years) from the capital area of Iceland were randomized into three groups. Group 1 (n = 38) received 6 meals/week fortified with a liquid fish oil and placebo powder. Group 2 (n = 30) received conventional (unfortified) meals and microencapsulated powder. Group 3 (n = 31) was the control group which received conventional meals and placebo powder. Calculated on a weekly basis, the amount of EPA + DHA provided was 1.5 g/d. Systolic (SBP) and diastolic BP (DBP) were measured before and after the intervention period. Seventy-seven subjects finished the study (77.8%). Drop-out rates were not different between groups. According to multivariate statistics, endpoint SBP was lower in Group 1 (-7.0 mmHg, p = 0.037) and in Group 2 (-7.2 mmHg, p = 0.037) as compared with Group 3. There was no significant difference in DBP between the groups. Our study shows that LC n-3 PUFA from microencapsulated powder are equally effective to meaningfully reduce SBP as LC n-3 PUFA from meals enriched with liquid fish oil in comparison with a control group.

Drug treatment of bothersome lower urinary tract symptoms after ureteric JJ-stent insertion: A contemporary, comparative, prospective, randomised placebo-controlled study, single-centre experience.

PubMed

Hekal, Ihab A

2016-12-01

To provide a guide for medication to alleviate bothersome lower urinary tract symptoms (LUTS) in patients after JJ ureteric stenting. Between June 2011 and June 2015, a prospective randomised placebo-controlled study was conducted on 200 consecutive cases of ureteric stones that required JJ stents. All patients had signed informed consent and JJ-stent placement confirmed by X-ray. The patients were randomised into five groups: A, solifenacin 5 mg; B, trospium chloride 20 mg; C, antispasmodic; and E, α-blocker; and a placebo group (D). A standard model was created to lessen patient selection bias. Eligible patients were enrolled and assessed for side-effects and bothersome LUTS using the validated Ureteric Stent Symptoms Questionnaire. Appropriate statistical analysis was carried out. In all, 150 male patients in the five groups were compared. LUTS were less in groups A and B ( P  < 0.05), while dry mouth was significantly reported in Group A. Individual comparisons with the placebo group showed a non-significant difference with Group C, while Group E had significant nocturia improvement. Selective comparison of two best groups (A and B) showed less frequency in Group B, while the other LUTS were less in Group A with comparable side-effects. In symptomatic patients following JJ-stent insertion, anti-muscarinic medication, namely solifenacin 5 mg or trospium chloride 20 mg, was the best. The advantage of trospium over solifenacin is in the control of frequency rather than the other symptoms. Addition of an α-blocker (alfuzosin 10 mg) is valuable when nocturia is the predominant symptom.

The use of a non-benzodiazepine hypnotic sleep-aid (Zolpidem) in patients undergoing ACL reconstruction: a randomized controlled clinical trial.

PubMed

Tompkins, Marc; Plante, Matthew; Monchik, Keith; Fleming, Braden; Fadale, Paul

2011-05-01

Previous studies have addressed post-operative pain management after ACL reconstruction by examining the use of intra-articular analgesia and/or modification of anesthesia techniques. To our knowledge, however, no previous studies have evaluated the effect of zolpidem on post-operative narcotic requirements, pain, and fatigue in patients undergoing outpatient arthroscopic ACL reconstruction. The purpose of this prospective, blinded, randomized, controlled clinical study was to evaluate the effect of zolpidem on post-operative narcotic requirements, pain, and fatigue in patients undergoing outpatient arthroscopic ACL reconstruction. Twenty-nine patients undergoing arthroscopic ACL reconstruction were randomized to a treatment group or placebo group. Both groups received post-operative hydrocodone/acetaminophen bitartrate (Vicodin ES). Patients in the treatment group received a single dose of zolpidem for the first seven post-operative nights. Patients in the placebo group received a gelatin capsule similar in appearance to zolpidem. The amount of Vicodin used in each group, the amount of post-operative pain, and the amount of post-operative fatigue were analyzed. Following ACL reconstruction, a 28% reduction was seen in the total amount of narcotic consumed with zolpidem (P = 0.047) when compared to placebo. There were no significant differences in post-operative pain or fatigue levels between zolpidem and placebo. Adding zolpidem to the post-operative medication regimen after arthroscopic ACL reconstruction helps to lower the amount of narcotic pain medication required for adequate analgesia. Randomized controlled clinical trial, Level I.

Ondansetron, granisetron, and dexamethasone compared for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy : A randomized placebo-controlled study.

PubMed

Erhan, Yamac; Erhan, Elvan; Aydede, Hasan; Yumus, Okan; Yentur, Alp

2008-06-01

Laparoscopic cholecystectomies are associated with an appreciably high rate of postoperative nausea and vomiting (PONV). This study was designed to compare the effectiveness of ondansetron, granisetron, and dexamethasone for the prevention of PONV in patients after laparoscopic cholecystectomy. A total of 80 American Society of Anesthesiologists (ASA) physical class I-II patients scheduled for laparoscopic cholecystectomy were included in this randomized, double blind, placebo-controlled study. All patients received a similar standardized anesthesia and operative treatment. Patients were randomly divided into four groups (n = 20 each). Group 1, consisting of control patients, received 0.9% NaCl; group 2 patients received ondansetron 4 mg i.v.; group 3 patients received granisetron 3 mg i.v.; and group 4 patients received dexamethasone 8 mg i.v., all before the induction of anesthesia. Both nausea and vomiting were assessed during the first 24 h after the procedure. The total incidence of PONV was 75% with placebo, 35% with ondansetron, 30% with granisetron, and 25% with dexamethasone. The incidence of PONV was significantly less frequent in groups receiving antiemetics (p < 0.05). The differences between dexamethasone, granisetron, and ondansetron were not significant. Prophylactic dexamethasone 8 mg i.v. significantly reduced the incidence of PONV in patients undergoing laparoscopic cholecystectomy. Dexamethasone 8 mg was as effective as ondansetron 4 mg and granisetron 3 mg, and it was more effective than placebo.

Vitamin C as an adjuvant for treating major depressive disorder and suicidal behavior, a randomized placebo-controlled clinical trial.

PubMed

Sahraian, Ali; Ghanizadeh, Ahmad; Kazemeini, Fereshteh

2015-03-14

There are some animal studies suggesting the possible role of vitamin C for treating depression. However, the efficacy of vitamin C for treating adult patients with major depressive disorder (MDD) has never been examined. This 8-week randomized double-blind placebo-controlled clinical trial included adult patients with major depressive disorder according to DSM-IV diagnostic criteria. Twenty-one patients in the treatment group received citalopram plus vitamin C and the 22 patients in the control group received citalopram plus placebo. The Hamilton Depression Rating Scale was used to measure depressive symptoms at baseline, week 2, week 4, and week 8. We also checked for the presence of adverse effects. While depression symptoms decreased in both groups during this trial, there was no statistically significant difference between the 2 groups (P = .5). The rate of remission, partial response, and complete response was not different between the two groups. The rate of adverse effects were not different between the two groups. Adding vitamin C to citalopram did not increase the efficacy of citalopram in MDD patients. Vitamin C plus citalopram is as effective as placebo plus citalopram for treating adult patients with suicidal behavior. No serious adverse effect for this combination was identified during this trial. This trial was registered at http://www.irct.ir . The registration number of this trial was: IRCT201312263930N31 . Date registered: 5 July 2014.

Citalopram, methylphenidate, or their combination in geriatric depression: a randomized, double-blind, placebo-controlled trial.

PubMed

Lavretsky, Helen; Reinlieb, Michelle; St Cyr, Natalie; Siddarth, Prabha; Ercoli, Linda M; Senturk, Damla

2015-06-01

The authors evaluated the potential of methylphenidate to improve antidepressant response to citalopram, as assessed by clinical and cognitive outcomes, in elderly depressed patients. The authors conducted a 16-week randomized double-blind placebo-controlled trial for geriatric depression in 143 older outpatients diagnosed with major depression comparing treatment response in three treatment groups: methylphenidate plus placebo (N=48), citalopram plus placebo (N=48), and citalopram plus methylphenidate (N=47). The primary outcome measure was change in depression severity. Remission was defined as a score of 6 or less on the Hamilton Depression Rating Scale. Secondary outcomes included measures of anxiety, apathy, quality of life, and cognition. Daily doses ranged from 20 mg to 60 mg for citalopram (mean=32 mg) and from 5 mg to 40 mg for methylphenidate (mean=16 mg). All groups showed significant improvement in depression severity and in cognitive performance. However, the improvement in depression severity and the Clinical Global Impressions improvement score was more prominent in the citalopram plus methylphenidate group compared with the other two groups. Additionally, the rate of improvement in the citalopram plus methylphenidate group was significantly higher than that in the citalopram plus placebo group in the first 4 weeks of the trial. The groups did not differ in cognitive improvement or number of side effects. Combined treatment with citalopram and methylphenidate demonstrated an enhanced clinical response profile in mood and well-being, as well as a higher rate of remission, compared with either drug alone. All treatments led to an improvement in cognitive functioning, although augmentation with methylphenidate did not offer additional benefits.

Efficacy of a Probiotic-Prebiotic Supplement on Incidence of Diarrhea in a Dog Shelter: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Rose, L; Rose, J; Gosling, S; Holmes, M

2017-03-01

Diarrhea is the most frequent morbidity affecting kenneled dogs in animal shelters. Diarrhea impacts animal welfare and the finances of the shelter as they must treat, clean, and house affected animals until recovered. Supplementing dogs entering an animal shelter with a probiotic-prebiotic, known as a synbiotic, will decrease the incidence of diarrhea. Seven hundred and seventy-three dogs entering an animal shelter in the United Kingdom. A prospective double-blind, randomized, placebo-controlled trial. Statistical difference was found between the groups across 3 measures of diarrhea incidence. First, the mean percentage of scored days per dog that were scored as diarrhea throughout their stay was 2.0% in the synbiotic group and 3.2% in the placebo group (P = .0022). Second, the occurrence of diarrhea within the first 14 days' stay was 18.8% in the synbiotic product group and 27.2% in the placebo group (P = .0008). Third, the occurrence of ≥2 consecutive days of diarrhea within the first 14 days' stay was 4.6% in the synbiotic product group and 8.0% in the placebo group (P = .0300). Supplementing healthy dogs entering an animal shelter with a synbiotic supplement significantly decreased the incidence of diarrhea in this trial. Animal shelters can use synbiotic supplements to improve animal welfare and decrease costs involved in cleaning and housing animals as well as potentially decreasing veterinary intervention. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Improvement of skin conditions by ingestion of Aspergillus kawachii (Koji) extract containing 14-dehydroergosterol in a randomized, double-blind, controlled trial.

PubMed

Sugihara, Yoshihiko; Ikushima, Shigehito; Miyake, Mika; Kirisako, Takayoshi; Yada, Yukihiro; Fujiwara, Daisuke

2018-01-01

The present study examined the effect of ingestion of Koji extract containing 14-dehydroergosterol (14-DHE), prepared from Aspergillus kawachii NBRC4308, on improvement of skin conditions among healthy volunteers. In a randomized, double-blind, placebo-controlled, parallel-group study, 70 healthy adult women who felt that their skin was dry ingested either a placebo dietary supplement or Koji extract (200 mg/day) supplement containing 0.1% 14-DHE for 12 weeks. Throughout the treatment period and for 4 weeks afterward, objective indicators - including moisture content of the stratum corneum, trans-epidermal water loss (TEWL), and skin wrinkles - were evaluated; in addition, the subjects answered a questionnaire on their skin conditions with ratings on a visual analog scale. Statistical analysis was conducted on the basis of differences from baseline scores. Compared with the placebo group, the Koji extract group showed significantly increased forearm moisture at 4, 8, and 16 weeks ( p < 0.05 on unpaired t -test). The questionnaire survey showed a marked improvement in skin conditions, particularly crow's feet, in the Koji extract group versus the placebo group at 8 weeks ( p < 0.05 by unpaired t -test). Furthermore, the Koji extract group showed a trend ( p < 0.10) toward improvement in skin moisture (at 4 weeks), dryness around the eyes/mouth (at 4 weeks), and overall skin condition (at 8 weeks) versus the placebo group. Ingestion of Koji extract containing 14-DHE was demonstrated to have positive effects toward improving skin conditions - in particular, on increasing skin moisture in the stratum corneum.

Twelve-week, multicenter, placebo-controlled, randomized, double-blind, parallel-group, comparative phase II/III study of benzoyl peroxide gel in patients with acne vulgaris: A secondary publication.

PubMed

Kawashima, Makoto; Sato, Shinichi; Furukawa, Fukumi; Matsunaga, Kayoko; Akamatsu, Hirohiko; Igarashi, Atsuyuki; Tsunemi, Yuichiro; Hayashi, Nobukazu; Yamamoto, Yuki; Nagare, Toshitaka; Katsuramaki, Tsuneo

2017-07-01

A placebo-controlled, randomized, double-blind, parallel-group, comparative, multicenter study was conducted to investigate the efficacy and safety of benzoyl peroxide (BPO) gel, administrated once daily for 12 weeks to Japanese patients with acne vulgaris. Efficacy was evaluated by counting all inflammatory and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. All 609 subjects were randomly assigned to receive the study products (2.5% and 5% BPO and placebo), and 607 subjects were included in the full analysis set, 544 in the per protocol set and 609 in the safety analyses. The median rates of reduction from baseline to the last evaluation of the inflammatory lesion counts, the primary end-point, in the 2.5% and 5% BPO groups were 72.7% and 75.0%, respectively, and were significantly higher than that in the placebo group (41.7%). No deaths or other serious adverse events were observed. The incidences of adverse events in the 2.5% and 5% BPO groups were 56.4% and 58.8%, respectively; a higher incidence than in the placebo group, but there was no obvious difference between the 2.5% and 5% BPO groups. All adverse events were mild or moderate in severity. Most adverse events did not lead to study product discontinuation. The results suggested that both 2.5% and 5% BPO are useful for the treatment of acne vulgaris. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd.

Efficacy and safety of canagliflozin in combination with insulin: a double-blind, randomized, placebo-controlled study in Japanese patients with type 2 diabetes mellitus.

PubMed

Inagaki, Nobuya; Harashima, Shin-Ichi; Maruyama, Nobuko; Kawaguchi, Yutaka; Goda, Maki; Iijima, Hiroaki

2016-06-18

Combination therapy with canagliflozin and insulin was investigated in a prescribed substudy of the canagliflozin Cardiovascular Assessment Study (CANVAS); however, it was not evaluated in Japanese patients with type 2 diabetes mellitus (T2DM). Since the usage profile of insulin therapy and pathologic features of Japanese patients differ from those of Caucasian patients, we determined the clinical benefit of such a combination therapy in Japanese patients. Patients who had inadequate glycemic control despite insulin, diet and exercise therapies were randomized into placebo (n = 70) and canagliflozin 100 mg (n = 76) groups that were administered once daily in addition to their prior insulin therapy in this double-blind, placebo-controlled study. The primary endpoint was the change in glycated hemoglobin (HbA1c) levels from the baseline to week 16. There was a statistically significant decrease in HbA1c levels from the baseline in the canagliflozin group (-0.97 ± 0.08 %) compared with the placebo group (0.13 ± 0.08 %) at week 16 [last observation carried forward (LOCF)]. The decrease in HbA1c levels in the canagliflozin group was independent of the insulin regimen (premixed, long-acting and long-acting plus rapid- or short-acting). Compared with the placebo group, canagliflozin significantly decreased fasting plasma glucose levels (-34.1 ± 4.8 vs -1.4 ± 5.0 mg/dL) and body weights (-2.13 ± 0.25 vs 0.24 ± 0.26 %), and significantly increased HDL cholesterol (3.3 ± 1.0 vs -0.5 ± 1.0 mg/dL) and HOMA2- %B (10.15 ± 1.37 vs 0.88 ± 1.42 %). The overall incidence of adverse events was similar between the two groups. The incidence and incidence per subject-year exposure of hypoglycemia (hypoglycemic symptoms and/or decreased blood glucose) were slightly higher in the canagliflozin group (40.0 % and 7.97) than in the placebo group (29.6 % and 4.51). However, hypoglycemic events in both groups were mild in severity and dose-reduction of insulin by <10 % from the baseline following hypoglycemic events decreased the incidence per subject-year exposure in the canagliflozin group. The incidence of hypoglycemia between the groups did not differ according to the insulin regimen. Canagliflozin in combination with insulin was effective in improving glycemic control and reducing body weight and well tolerated by Japanese patients with T2DM. Trial Registration ClinicalTrials.gov identifier: NCT02220920.

Double-blind study of mirtazapine and placebo in hospitalized patients with major depression.

PubMed

Vartiainen, H; Leinonen, E

1994-06-01

The purpose of the present 6-week multicenter dose finding study was to compare the efficacy and tolerability of mirtazapine (preferentially presynaptic alpha 2-adrenergic receptor blocker) to placebo in hospitalized patients with major depression. The clinical efficacy was evaluated with the Hamilton Depression Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Self-Rating Depression Scale, Global Assessment Scale (GAS), and Brief Psychiatric Rating Scale (BPRS). The side effects were recorded on a checklist of emergent symptoms (ROSE) and physical examinations, ECG, clinical chemistry, and hematology tests were carried out. The dosages of mirtazapine were gradually raised from 15 mg to 50 mg. One hundred and fourteen patients were included. Twenty-two patients (37%) in mirtazapine group and 24 (44%) in the placebo group were prematurely withdrawn from the study mainly due to inadequate efficacy. The decrease in HAM-D and MADRS was generally more pronounced in the mirtazapine group than in the placebo group. Minor side effects were reported in less than 15% of the patients in both groups. Only fatigue and faintness were slightly more pronounced in the mirtazapine group than in the placebo group. No significant changes were found in laboratory parameters. Because of methodological flaws like combining a dose finding study with a placebo controlled study, further conclusions should not be made on the efficacy of mirtazapine when treating depressive patients.

Clinical Evidence of Effects of Lactobacillus plantarum HY7714 on Skin Aging: A Randomized, Double Blind, Placebo-Controlled Study.

PubMed

Lee, Dong Eun; Huh, Chul-Sung; Ra, Jehyeon; Choi, Il-Dong; Jeong, Ji-Woong; Kim, Sung-Hwan; Ryu, Ja Hyun; Seo, Young Kyoung; Koh, Jae Sook; Lee, Jung-Hee; Sim, Jae-Hun; Ahn, Young-Tae

2015-12-28

The beneficial effects of probiotics are now widely reported, although there are only a few studies on their anti-aging effects. We have found that Lactobacillus plantarum HY7714 (HY7714) improves skin hydration and has anti-photoaging effects, and in the present study, we have further evaluated the anti-aging effect of HY7714 via a randomized, double blind, placebo-controlled clinical trial. The trial included 110 volunteers aged 41 and 59 years who have dry skin and wrinkles. Participants took 1 × 10(10) CFU/day of HY7714 (probiotic group) or a placebo (placebo group) for 12 weeks. Skin hydration, wrinkles, skin gloss, and skin elasticity were measured every 4 weeks during the study period. There were significant increases in the skin water content in the face (p < 0.01) and hands (p < 0.05) at week 12 in the probiotic group. Transepidermal water loss decreased significantly in both groups at weeks 4, 8, and 12 (p < 0.001 compared with baseline), and was suppressed to a greater extent in the face and forearm in the probiotic group at week 12. Volunteers in the probiotic group had a significant reduction in wrinkle depth at week 12, and skin gloss was also significantly improved by week 12. Finally, skin elasticity in the probiotic group improved by 13.17% (p < 0.05 vs. controls) after 4 weeks and by 21.73% (p < 0.01 vs. controls) after 12 weeks. These findings are preliminary confirmation of the anti-aging benefit to the skin of L. plantarum HY7714 as a nutricosmetic agent.

Do Montelukast Sodium and N-Acetylcysteine Have a Nephroprotective Effect on Unilateral Ureteral Obstruction? A Placebo Controlled Trial in a Rat Model.

PubMed

Sunay, Melih; Karakan, Tolga; Aydın, Arif; Koca, Gökhan; Börcek, Pınar; Öğüş, Elmas

2015-10-01

We assessed the nephroprotective effects of montelukast sodium and N-acetylcysteine on secondary renal damage due to unilateral ureteral obstruction in a rat model. In this study 30 Wistar albino male rats were randomized into 3 groups, including placebo, N-acetylcysteine and montelukast sodium. Three rats served as the control group. The left ureter of the rats was sutured with 4-zero polyglactin sutures. Medications were given 3 days before obstruction and continued for 15 days. Dimercaptosuccinic acid renal scintigraphy was performed before obstruction and on day 15. Rats were sacrificed on day 15 and histopathological examinations were done. We biochemically assessed oxidative stress markers (myeloperoxidase and malondialdehyde), sulfhydryl and total nitrite for lipid peroxidation, oxidative protein damage and antioxidant levels, respectively. On pathological examination inflammation and tubular epithelial damage in the N-acetylcysteine and montelukast sodium groups were less than in the placebo group (p <0.05). No difference was seen in normal kidneys. Myeloperoxidase, malondialdehyde and total nitrite levels in the N-acetylcysteine group, and myeloperoxidase and malondialdehyde levels in the montelukast sodium group were lower than in the placebo group (p <0.05). No statistical difference was seen in sulfhydryl levels (p >0.05) or among the N-acetylcysteine, montelukast sodium and placebo groups on scintigraphy (p >0.05). No pathological, chemical and scintigraphic differences were seen among the N-acetylcysteine, montelukast sodium and sham treated groups (p >0.05). N-acetylcysteine and montelukast sodium have a protective effect against obstructive damage of the kidney. However, further investigations are needed. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Efficacy and tolerability of vildagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes mellitus.

PubMed

Pan, C; Xing, X; Han, P; Zheng, S; Ma, J; Liu, J; Lv, X; Lu, J; Bader, G

2012-08-01

To investigate the efficacy and tolerability of vildagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. This was a 24-week, randomized, double-blind, placebo-controlled study. Patients with T2DM (N = 438) with haemoglobin A1c (HbA1c) of 7.0-10.0% and fasting plasma glucose (FPG) <15 mmol/l (<270 mg/dl) were randomized (1 : 1 : 1) to vildagliptin 50 mg bid, vildagliptin 50 mg qd or placebo in addition to metformin. The treatment groups were well balanced at baseline [mean HbA1c, 8.0%, FPG, 8.8 mmol/l (158 mg/dl); body mass index, 25.5 kg/m(2) ]. The adjusted mean change (AMΔ) in HbA1c at endpoint was -1.05 ± 0.08%, -0.92 ± 0.08% and -0.54 ± 0.08% in patients receiving vildagliptin 50 mg bid, 50 mg qd and placebo, respectively. The between-treatment difference (vildagliptin 50 mg bid-placebo) was -0.51 ± 0.11%, p < 0.001. A greater proportion of vildagliptin-treated patients met at least one responder criterion (82.1 and 70.7%) compared to placebo-treated patients (60.4%). The AMΔ at endpoint for FPG with vildagliptin 50 mg bid, -0.95 mmol/l (-17.1 mg/dl); 50 mg qd, -0.84 mmol/l (-15.1 mg/dl) was significantly different compared with the placebo -0.26 mmol/l (-4.68 mg/dl) (p ≤ 0.001). Adverse events (AEs) were reported as 34.2, 36.5 and 37.5% for patients receiving vildagliptin 50 mg bid, 50 mg qd or placebo, respectively. Two patients in the vildagliptin 50 mg qd and one in the placebo group reported serious AEs, which were not considered to be related to the study drug; one incidence of hypoglycaemic event was reported in the vildagliptin 50 mg bid group. Vildagliptin as add-on therapy to metformin improved glycaemic control and was well tolerated in Chinese patients who were inadequately controlled by metformin only. © 2012 Blackwell Publishing Ltd.

Z-drug for schizophrenia: A systematic review and meta-analysis.

PubMed

Kishi, Taro; Inada, Ken; Matsui, Yuki; Iwata, Nakao

2017-10-01

No systematic reviews and meta-analyses on the use of Z-drug for schizophrenia are available. Randomized, placebo-controlled, or non-pharmacological intervention-controlled trials published before 03/20/2017 were retrieved from major healthcare databases and clinical trial registries. A meta-analysis including only randomized, placebo-controlled trials was performed. Efficacy outcomes were measured as improvement in overall schizophrenia symptoms, total sleep time, and wake after sleep onset. Safety/acceptability outcomes were discontinuation rate and individual adverse events. Four trials [1 alpidem placebo-controlled study (n=66), 2 eszopiclone placebo-controlled studies (n=60), and 1 eszopiclone, shallow needling-controlled study (n=96)] were identified. The meta-analysis showed no significant differences in any outcome between pooled Z-drug and placebo treatment groups. For individual studies, alpidem was superior to placebo in improving the overall schizophrenia symptoms. One of the eszopiclone studies showed that eszopiclone was superior to placebo in improving the Insomnia Severity Index scores. Another eszopiclone study showed that eszopiclone did not differ from shallow needling therapy in improving both schizophrenia- and insomnia-related symptoms. Although this study failed to show significant benefits for the use of Z-drug in the treatment of schizophrenia, it showed that short-term use of eszopiclone is an acceptable method for treating persistent insomnia among these patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Gemfibrozil in late preterm and term neonates with moderate jaundice: a randomized controlled trial.

PubMed

Jaikrishan; Kumar, Praveen; Narang, Anil

2009-12-01

To determine, if oral Gemfibrozil is effective in decreasing the duration of phototherapy by at least 24 hours in neonates >34 weeks gestation with non-hemolytic jaundice, as compared to placebo. Double blind placebo controlled randomized controlled trial. Tertiary care neonatal unit in north India. Ninety seven neonates >34 weeks gestation with non-hemolytic jaundice within first 7 days of life requiring phototherapy. Two doses of Gemfibrozil (60 mg/kg/dose) or placebo, 12 hours apart. Babies were treated with single surface special blue light phototherapy. Serum total bilirubin (STB) was measured 8 hourly. Phototherapy was stopped if two consecutive STB values were below phototherapy zone. Duration of phototherapy. The median (IQR) duration of phototherapy was 40 (30, 60) hours in Gemfibrozil and 36 (19, 55) hours in the placebo group (P=0.13). The peak STB levels were 16.8 +/- 2.7 mg/dL and 16.3 +/- 2.3 mg/dL in Gemfibrozil and placebo groups, respectively. No side effect of the drug or placebo was noticed. Two doses of gemfibrozil (60 mg/kg/dose) given 12 hours apart were not able to reduce the duration of phototherapy, or peak bilirubin level in babies > 34 weeks gestation with non-hemolytic jaundice in the first week of life. Gemfibrozil was not associated with any side effects.

[Controlled clinical assay in Clonidine, arginine aspartate, alpha-ketoglutarate of Ornithine and Ciproheptadine as growth stimulants in children with short stature].

PubMed

Herranz Jordán, B; Moreno Romero, F; Cardesa García, J J; Santos Hurtado, I; Aparicio Palomino, A; Requena Guerrero, F

1993-06-01

Eighty-one healthy prepubertal children of short stature, between two and twelve years of age, were divided into four homogeneous groups. Each group was treated with a placebo for one year and for a second year with one of the following drugs (double blind): clonidine (CI), arginine asprate (AA), ornithine alphaketoglutare (OKG), or cyproheptadine (Cp). CI and OKG did not better the standard deviation of height. AA and Cp did, but to no greater extent than the placebo. The growth rate did not change in any group. The ratio of bone age/chronological age was significantly higher at the end of the OKG year than at the end of the year with placebo, a difference that was not found in any other group. The prognosis of adult height (TW2) did not change in any group. The standard deviation of weight increased in all groups, both with the placebo and the various drugs, without significant differences between the groups. The CI caused frequent clinical side effects, including a reversible increase in transaminases in one child. The Cp stimulated hunger. The AA and OKG did not produce side-effects and the placebo increased appetite in 11% of the children. Somatomedin C was significantly higher after one year with Cp than after one year with the placebo, significantly higher after the placebo than after CI and AA and there was no difference between the treatment with the placebo and OKG. Growth hormone values in a 24 hour urine sample were so scattered that we do not consider them helpful.(ABSTRACT TRUNCATED AT 250 WORDS)

A Rosa canina - Urtica dioica - Harpagophytum procumbens/zeyheri Combination Significantly Reduces Gonarthritis Symptoms in a Randomized, Placebo-Controlled Double-Blind Study.

PubMed

Moré, Margret; Gruenwald, Joerg; Pohl, Ute; Uebelhack, Ralf

2017-12-01

The special formulation MA212 (Rosaxan) is composed of rosehip ( Rosa canina L.) puree/juice concentrate, nettle ( Urtica dioica L.) leaf extract, and devil's claw ( Harpagophytum procumbens DC. ex Meisn. or Harpagophytum zeyheri Decne.) root extract and also supplies vitamin D. It is a food for special medical purposes ([EU] No 609/2013) for the dietary management of pain in patients with gonarthritis.This 12-week randomized, placebo-controlled double-blind parallel-design study aimed to investigate the efficacy and safety of MA212 versus placebo in patients with gonarthritis.A 3D-HPLC-fingerprint (3-dimensional high pressure liquid chromatography fingerprint) of MA212 demonstrated the presence of its herbal ingredients. Ninety-two randomized patients consumed 40 mL of MA212 (n = 46) or placebo (n = 44) daily. The Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality-of-life scores at 0, 6, and 12 weeks, and analgesic consumption were documented. Statistically, the initial WOMAC subscores/scores did not differ between groups. During the study, their means significantly improved in both groups. The mean pre-post change of the WOMAC pain score (primary endpoint) was 29.87 in the MA212 group and 10.23 in the placebo group. The group difference demonstrated a significant superiority in favor of MA212 (p U  < 0.001; p t  < 0.001). Group comparisons of all WOMAC subscores/scores at 6 and 12 weeks reached same significances. Compared to placebo, both physical and mental quality of life significantly improved with MA212. There was a trend towards reduced analgesics consumption with MA212, compared to placebo. In the final efficacy evaluation, physicians (p Chi  < 0.001) and patients (p Chi  < 0.001) rated MA212 superior to placebo. MA212 was well tolerated.This study demonstrates excellent efficacy for MA212 in gonarthritis patients. Georg Thieme Verlag KG Stuttgart · New York.

A randomized, double-blind, placebo-controlled study of the effects of pomegranate extract on rising PSA levels in men following primary therapy for prostate cancer.

PubMed

Pantuck, A J; Pettaway, C A; Dreicer, R; Corman, J; Katz, A; Ho, A; Aronson, W; Clark, W; Simmons, G; Heber, D

2015-09-01

The primary objective of this study was to compare the effects of pomegranate juice on PSA doubling times (PSADT) in subjects with rising PSA levels after primary therapy for prostate cancer. Double-blind, placebo-controlled multi-institutional study, evaluated the effects of pomegranate liquid extract on serum PSA levels. The primary end point of this study was change in serum PSADT. Additional secondary and exploratory objectives were to evaluate the safety of pomegranate juice and to determine the interaction of manganese superoxide dismutase (MnSOD) AA genotype and pomegranate treatment on PSADT. One-hundred eighty-three eligible subjects were randomly assigned to the active and placebo groups with a ratio of 2:1 (extract N=102; placebo N=64; juice N=17). The majority of adverse events were of moderate or mild grade. Median PSADT increased from 11.1 months at baseline to 15.6 months in the placebo group (P<0.001) compared with an increase from 12.9 months at baseline to 14.5 months in the extract group (P=0.13) and an increase from 12.7 at baseline to 20.3 in the juice group (P=0.004). However, none of these changes were statistically significant between the three groups (P>0.05). Placebo AA patients experienced a 1.8 month change in median PSADT from 10.9 months at baseline to 12.7 months (P=0.22), while extract patients experienced a 12 month change in median PSADT from 13.6 at baseline to 25.6 months (P=0.03). Compared with placebo, pomegranate extract did not significantly prolong PSADT in prostate cancer patients with rising PSA after primary therapy. A significant prolongation in PSADT was observed in both the treatment and placebo arms. Men with the MnSOD AA genotype may represent a group that is more sensitive to the antiproliferative effects of pomegranate on PSADT; however, this finding requires prospective hypothesis testing and validation.

Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period.

PubMed

Oe, Mariko; Sakai, Seigo; Yoshida, Hideto; Okado, Nao; Kaneda, Haruna; Masuda, Yasunobu; Urushibata, Osamu

2017-01-01

Hyaluronan (HA) has critical moisturizing property and high water retention capacity especially for human skin. This study aimed to evaluate the effect of oral intake of HA. The mean molecular weight (MW) of HA is 2 k and 300 k. Sixty Japanese male and female subjects aged 22-59 years who presented with crow's feet wrinkles were randomly assigned to the HA 2 k or HA 300 k at 120 mg/day or the placebo group. The subjects were administered HA at a rate of 120 mg/day or a placebo for 12 weeks. The skin wrinkles were evaluated by image analysis of skin wrinkle replicas, and their skin condition was evaluated using a questionnaire survey. During the study period, the HA groups showed better level of the whole sulcus volume ratio, wrinkle area ratio, and wrinkle volume ratio than the placebo group. After 8 weeks of ingestion, the HA 300 k group showed significantly diminished wrinkles compared with the placebo group. Skin luster and suppleness significantly improved after 12 weeks in all groups compared with the baseline. The results suggest that oral HA (both HA 2 k and HA 300 k) inhibits skin wrinkles and improves skin condition.

Participant experiences from chronic administration of a multivitamin versus placebo on subjective health and wellbeing: a double-blind qualitative analysis of a randomised controlled trial

PubMed Central

2012-01-01

Background While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported. Methods Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16), three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers) was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender). Usual experiences were categorised and discussed separately. Results Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022) and enhanced mood (p=.027). The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin group having minor digestive complaints. Conclusion This represents the first documented qualitative investigation of participants’ experience of chronic administration of a multivitamin. Results uncovered a range of subjective beneficial effects that are consistent with quantitative data from previously published randomised controlled trials examining the effects of multivitamins and B vitamin complexes on mood and well-being. Trial registration Prior to commencement this trial was registered with the Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au) ACTRN12611000092998 PMID:23241329

A randomized clinical trial of histamine 2 receptor antagonism in treatment-resistant schizophrenia.

PubMed

Meskanen, Katarina; Ekelund, Heidi; Laitinen, Jarmo; Neuvonen, Pertti J; Haukka, Jari; Panula, Pertti; Ekelund, Jesper

2013-08-01

Histamine has important functions as regulator of several other key neurotransmitters. Patients with schizophrenia have lower histamine H1 receptor levels. Since a case report in 1990 of an effect of the H2 antagonist famotidine on negative symptoms in schizophrenia, some open-label trials have been performed, but no randomized controlled trial. Recently, it was shown that clozapine is a full inverse agonist at the H2 receptor. We performed a researcher-initiated, academically financed, double-blind, placebo-controlled, parallel-group, randomized trial with the histamine H2 antagonist famotidine in treatment-resistant schizophrenia. Thirty subjects with schizophrenia were randomized to have either famotidine (100 mg twice daily, n = 16) or placebo (n = 14) orally, added to their normal treatment regimen for 4 weeks. They were followed up weekly with the Scale for the Assessment of Negative Symptoms (SANS), the PANSS (Positive and Negative Syndrome Scale), and Clinical Global Impression (CGI) Scale. In the famotidine group, the SANS score was reduced by 5.3 (SD, 13.1) points, whereas in the placebo group the SANS score was virtually unchanged (mean change, +0.2 [SD, 9.5]). The difference did not reach statistical significance (P = 0.134) in Mann-Whitney U analysis. However, the PANSS Total score and the General subscore as well as the CGI showed significantly (P < 0.05) greater change in the famotidine group than in the placebo group. No significant adverse effects were observed. This is the first placebo-controlled, randomized clinical trial showing a beneficial effect of histamine H2 antagonism in schizophrenia. H2 receptor antagonism may provide a new alternative for the treatment of schizophrenia.

Placebo-controlled clinical trial of use of 10% hydrogen peroxide whitening strips for medication-induced xerostomia.

PubMed

Papas, Athena S; Kugel, Gerard; Singh, Mabi; Barker, Matthew L; Gerlach, Robert W

2009-01-01

A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the effectiveness and safety of peroxide-containing strip-based tooth whitening among subjects with medication-induced hyposalivation. Eligibility for this tooth whitening study was limited to dentate adults taking xerogenic medications with an unstimulated salivary flow < or = 0.2 ml/min. After giving informed consent, 42 subjects were randomized using a 2:1 ratio to 10% hydrogen peroxide whitening strips (Crest Whitestrips Premium) or placebo strips without peroxide. Strips were used for 30 min twice daily for a 14-day period. Usage was unsupervised, and only the maxillary arch was treated. On days 8 and 15, efficacy was assessed from standard digital images of the anterior dentition and quantified using the Cielab color system, while safety was assessed from interviews and clinical examinations. At day 8, the peroxide group experienced significant (p < 0.001) color improvement relative to baseline and placebo. Adjusted means +/- standard errors for yellowness reduction were -1.65 +/- 0.115 units for the peroxide group and -0.32 +/- 0.170 units for the placebo group. For the increase in lightness, adjusted means +/- standard errors on day 8 were 1.53 +/- 0.130 units for the peroxide group and 0.37 +/- 0.191 units for the controls. Continued strip use through day 15 yielded incremental color improvement for the peroxide group. Mild and transient tooth sensitivity represented the most common adverse events. No subject discontinued treatment due to a product-related adverse event. Twice daily use of 10% hydrogen peroxide whitening strips by adults with medication-induced xerostomia was well tolerated, with significant tooth color improvement evident within 7 days. Copyright 2009 S. Karger AG, Basel.

Efficacy of cysteamine cream in the treatment of epidermal melasma, evaluating by Dermacatch as a new measurement method: a randomized double blind placebo controlled study.

PubMed

Farshi, Susan; Mansouri, Parvin; Kasraee, Behrooz

2018-03-01

Melasma is a difficult-to-treat hyperpigmentary disorder. Very few studies have been performed regarding the efficacy of cysteamine in the treatment of melasma. To determine the efficacy of cysteamine cream in the treatment of patients with epidermal melasma using Dermacatch ® as a more accurate skin colorimetric measurement tool. Participating patients (n = 40) received either placebo (n = 20) or cysteamine cream (n = 20) in a double-blind placebo controlled study. Cysteamine cream or placebo was applied on the lesions once a day at bedtime throughout the four-month study period. Treatment efficacy was determined through Dermacatch ® and Mexameter ® skin colorimetry, MASI scores, Investigator Global Assessments (IGAs), and patient questionnaires, all performed at baseline, 2-month, and 4-month examinations. Prior to the start of the protocol, the mean difference between pigmented and normal skin was calculated for cysteamine and placebo groups using both Dermacatch ® (72.3 ± 27.8 and 52.9 ± 16.4, respectively) and Mexameter ® (93.6 ± 42.6 and 65.4 ± 22.6, respectively). At 2 months, the mean differences were 38.1 ± 15.3 (Dermacatch ® ) and 49.9 ± 19 (Mexameter ® ) in the cysteamine group and 64.9 ± 25.3 (Dermacatch ® ) and 68 ± 26.2 (Mexameter ® ) in the placebo group. At 4 months, the mean differences were 23.8 ± 12.9 (Dermacatch ® ) and 35.5 ± 16.1 (Mexameter ® ) in the cysteamine group, and 50 ± 18 (Dermacatch ® ) and 51.2 ± 16.8 (Mexameter ® ) in the placebo group. Statistically significant differences were found between the cysteamine and placebo group outcomes at both time points (p = .01, p = .02). At the end of the treatment period, MASI scores were significantly lower in the cysteamine group versus placebo (8.03 ± 5.2 vs. 12.2 ± 7.4, p = .04). IGA scores and patient viewpoints indicated significant efficacy of cysteamine cream versus placebo. Cysteamine cream showed significant efficacy in decreasing melanin content of the lesions, as established by Dermacatch ® as a new measuring method.

Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.

PubMed

Andrieu, Sandrine; Guyonnet, Sophie; Coley, Nicola; Cantet, Christelle; Bonnefoy, Marc; Bordes, Serge; Bories, Lawrence; Cufi, Marie-Noëlle; Dantoine, Thierry; Dartigues, Jean-François; Desclaux, Françoise; Gabelle, Audrey; Gasnier, Yannick; Pesce, Alain; Sudres, Kristel; Touchon, Jacques; Robert, Philippe; Rouaud, Olivier; Legrand, Philippe; Payoux, Pierre; Caubere, Jean-Paul; Weiner, Michael; Carrié, Isabelle; Ousset, Pierre-Jean; Vellas, Bruno

2017-05-01

No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685). 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (-0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (-0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals. Copyright © 2017 Elsevier Ltd. All rights reserved.

A randomized trial of controlled-release oxycodone during inpatient rehabilitation following unilateral total knee arthroplasty.

PubMed

Cheville, A; Chen, A; Oster, G; McGarry, L; Narcessian, E

2001-04-01

Reliance on "as-needed" analgesia following total knee arthroplasty may lead to inadequate control of pain and delayed recovery of function. Preemptive use of controlled-release opioids may improve pain control, accelerate recovery, and reduce the need for inpatient rehabilitative services. This study was designed to determine whether controlled-release opioids enhance post-arthroplasty pain control and facilitate functional recovery during rehabilitation. Fifty-nine patients admitted for inpatient rehabilitation following unilateral total knee arthroplasty were randomized to receive OxyContin (controlled-release oxycodone) (twenty-nine patients) or a placebo (thirty patients) every twelve hours. Both groups could receive on-request, immediate-release oxycodone (5 mg every four hours). The dose of study medication was increased on the basis of the frequency of requests for immediate-release oxycodone. Measures of interest included pain ratings as determined with a visual-analog scale, changes in the range of motion of the knee and quadriceps strength, and improvements in selected Functional Independence Measure scores during the first eight physical therapy sessions. The duration of the hospital stay for rehabilitation also was compared between the two groups. Baseline demographic, clinical, and functional characteristics were similar between the OxyContin and placebo groups. Compared with the placebo group, the patients who received OxyContin reported significantly less pain as well as significantly greater range of motion of the knee (passive motion, p = 0.036; active motion, p< 0.001) and quadriceps strength (p = 0.001) by the eighth physical therapy session. The patients who received OxyContin also were discharged from the rehabilitation hospital at an average of 2.3 days earlier than the patients in the placebo group (p = 0.013). Preemptive use of controlled-release oxycodone during rehabilitation following total knee arthroplasty leads to improved pain control, more rapid functional recovery, and a reduced need for inpatient rehabilitative services.

Improvement of walking distance by defibrotide in patients with intermittent claudication--results of a randomized, placebo-controlled study (the DICLIS study). Defibrotide Intermittent CLaudication Italian Study.

PubMed

Violi, F; Marubini, E; Coccheri, S; Nenci, G G

2000-05-01

Defibrotide is an antithrombotic drug which enhances prostacyclin production and activates fibrinolytic system. The aim of this study was to investigate the improvement of walking distance in patients with intermittent claudication treated with defibrotide. DICLIS was a double blind, placebo-controlled study which included patients with walking distance autonomy at a standardized treadmill test < or =350 > or =100 meters. A total of 310 patients were randomly allocated to placebo (n = 101), defibrotide 800 mg/day (n = 104) or defibrotide 1200 mg/day (n = 105). During a one year follow-up, the Absolute Walking Distance (AWD) was measured six times (0, 30, 60, 90, 180, 360 days). Similar improvement in walking distance was found in the three groups until the 90th day; thereafter placebo group showed no further increase, while AWD continued to increase in the defibrotide groups. Between the 180th and 360th day visits, AWD was significantly higher (P <0.01) in patients given defibrotide than in patients given placebo. No difference in efficacy was observed between the two dosages of defibrotide. No differences in side effects were observed among the three groups. The results of the present trial suggest that long-term administration of defibrotide improves walking distance in patients with intermittent claudication.

Magnetic resonance therapy for knee osteoarthritis: a randomized, double blind placebo controlled trial.

PubMed

Gökşen, Nurgül; Çaliş, Mustafa; Doğan, Serap; Çaliş, Havva T; Özgöçmen, Salih

2016-08-01

Therapeutic nuclear magnetic resonance therapy (MRT) works based on the electromagnetic fields. To investigate efficacy of MRT in knee osteoarthritis (OA). Prospective, randomized, double-blind, placebo controlled trial. Outpatient clinic, university hospital. Patients who had mild to moderate knee OA at a single knee joint and between 30-75-years-old were randomized by blinded chip cards (1:1). The treatment group received ten sessions of one hour daily MRT, controls received placebo MRT. All patients underwent clinical examination at baseline, after 2 weeks, and 12 weeks. Imaging included blindly assessed ultrasonography and magnetic resonance (MR) of the knee. Ninety-seven patients completed the study. Both groups improved significantly but the average change from baseline in outcome parameters was similar in MRT group (on VAS-pain,-2.6; WOMAC-pain, -2.09; WOMAC-stiffness, -1.81; WOMAC-physical, -1.96) compared to placebo after two weeks (VAS-pain,-1.6; WOMAC-pain, -1.91; WOMAC-stiffness, -1.27; WOMAC-physical, -1.54). Also changes were quite similar at the 12th week after the treatment. SF-36 components at 12th week improved but changes were not significant. Imaging arm also failed to show significant differences between groups in terms of cartilage thickness on US and MR scores. No adverse events were recorded. MRT is safe, but not superior to placebo in terms of improvement in clinical or imaging parameters after a 10-day course of treatment in mild to moderate knee OA. The present study does not promote use of a 10-day course of MRT in mild to moderate knee OA.

Effect of vitamin D supplementation on selected inflammatory biomarkers in older adults: a secondary analysis of data from a randomised, placebo-controlled trial.

PubMed

Waterhouse, Mary; Tran, Bich; Ebeling, Peter R; English, Dallas R; Lucas, Robyn M; Venn, Alison J; Webb, Penelope M; Whiteman, David C; Neale, Rachel E

2015-09-14

Observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) levels are associated with inflammatory markers. Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups. Thus, we aimed to determine the effect of supplementary vitamin D using secondary data from a population-based, randomised, placebo-controlled, double-blind trial (Pilot D-Health trial 2010/0423). Participants were 60- to 84-year-old residents of one of the four eastern states of Australia. They were randomly selected from the electoral roll and were randomised to one of three trial arms: placebo (n 214), 750 μg (n 215) or 1500 μg (n 215) vitamin D3, each taken once per month for 12 months. Post-intervention blood samples for the analysis of C-reactive protein (CRP), IL-6, IL-10, leptin and adiponectin levels were available for 613 participants. Associations between intervention group and biomarker levels were evaluated using quantile regression. There were no statistically significant differences in distributions of CRP, leptin, adiponectin, leptin:adiponectin ratio or IL-10 levels between the placebo group and either supplemented group. The 75th percentile IL-6 level was 2·8 pg/ml higher (95 % CI 0·4, 5·8 pg/ml) in the 1500 μg group than in the placebo group (75th percentiles:11·0 v. 8·2 pg/ml), with a somewhat smaller, non-significant difference in 75th percentiles between the 750 μg and placebo groups. Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation, we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels, with the possible exception of IL-6.

Beneficial effects of Lactobacillus casei strain Shirota on academic stress-induced sleep disturbance in healthy adults: a double-blind, randomised, placebo-controlled trial.

PubMed

Takada, M; Nishida, K; Gondo, Y; Kikuchi-Hayakawa, H; Ishikawa, H; Suda, K; Kawai, M; Hoshi, R; Kuwano, Y; Miyazaki, K; Rokutan, K

2017-04-26

The present study examined whether Lactobacillus casei strain Shirota (LcS) improves sleep quality under psychological stress. A double-blind, placebo-controlled trial was conducted in healthy 4 th year medical students exposed to academic examination stress. The trial was repeated over two consecutive years in different groups of students, and the data were pooled. For 8 weeks prior to and 3 weeks after a national standardised examination, a total of 48 and 46 subjects received a daily dose of 100 ml of LcS-fermented milk or non-fermented placebo milk, respectively. Study measures included subjective anxiety, overnight single-channel electroencephalography (EEG) recordings, and the Oguri-Shirakawa-Azumi (OSA) sleep inventory scores of subjective sleep quality. Total OSA scores were significantly lower than baseline on the day before the exam and recovered after the exam, indicating a stress-induced decline in sleep quality. There was a significant positive effect of LcS treatment on OSA factors for sleepiness on rising and sleep length. Sleep latency measured by EEG lengthened as the exam approached in the placebo group but was significantly suppressed in the LcS group. The percentage of stage 3 non-REM (N3) sleep decreased in the placebo group as the exam approached, whereas it was maintained in the LcS group throughout the trial. Delta power during the first sleep cycle, measured as an index of sleep intensity, increased as the exam approached in the LcS group and was significantly higher than in the placebo group. These findings suggest that daily consumption of LcS may help to maintain sleep quality during a period of increasing stress. The observed retention of N3 sleep and increased delta power in the LcS group may have contributed to higher perceived sleep satisfaction.

The Acute Effect of Methylphenidate in Brazilian Male Children and Adolescents with ADHD: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Szobot, C. M.; Ketzer, C.; Parente, M. A.; Biederman, J.; Rohde, L. A.

2004-01-01

Objective: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. Method: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were…

Earlier triple therapy with pioglitazone in patients with type 2 diabetes.

PubMed

Charpentier, G; Halimi, S

2009-09-01

This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA(1c)) 6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA(1c) (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-B) were calculated. Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA(1c) and -2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA(1c) level of <8.5% achieved the HbA(1c) target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA(1c) level was >or= 8.5%, 13% achieved the HbA(1c) target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA(1c), FPG and surrogate measures of beta-cell function. Patients were more likely to reach target HbA(1c) levels (< 7.0%) with pioglitazone treatment if their baseline HbA(1c) levels were < 8.5%, highlighting the importance of early triple therapy.

Randomized placebo controlled trial of furosemide on subjective perception of dyspnoea in patients with pulmonary oedema because of hypertensive crisis.

PubMed

Holzer-Richling, Nina; Holzer, Michael; Herkner, Harald; Riedmüller, Eva; Havel, Christof; Kaff, Alfred; Malzer, Reinhard; Schreiber, Wolfgang

2011-06-01

To compare the administration of furosemide with placebo on the subjective perception of dyspnoea in patients with acute pulmonary oedema because of hypertensive crisis. Design  Randomized, controlled and double-blinded clinical trial. Municipal emergency medical service system and university-based emergency department. Fifty-nine patients with pulmonary oedema because of hypertensive crisis. Additional to administration of oxygen, morphine-hydrochloride and urapidil until the systolic blood pressure was below 160mmHg, the patients were randomized to receive furosemide 80mg IV bolus (furosemide group) or saline placebo (placebo group). The primary outcome was the subjective perception of dyspnoea as measured with a modified BORG scale at one hour after randomization. Secondary outcome parameters were the subjective perception of dyspnoea of patients as measured with a modified BORG scale and a visual analogue scale at 2, 3 and 6h after randomization of the patient; course of the systolic arterial pressure and peripheral oxygen saturation and lactate at admission and at 6h after admission. In 25 patients in the furosemide group and in 28 patients in the placebo group, a BORG score could be obtained. There was no statistically significant difference in the severity of dyspnoea at one hour after randomization (P=0·40). The median BORG score at 1h after randomization in the furosemide group was 3 (IQR 2 to 4) compared to 3 (IQR 2 to 7) in the placebo group (P=0·40). Those patients who were randomized to the placebo group needed higher doses of urapidil at 20min after randomization. There were no significant differences in the rate of adverse events, nonfatal cardiac arrests or death between the two groups. The subjective perception of dyspnoea in patients with hypertensive pulmonary oedema was not influenced by the application of a loop-diuretic. Therefore, additional furosemide therapy needs to be scrutinized in the therapy of these patients. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.

Captopril to Mitigate Chronic Renal Failure After Hematopoietic Stem Cell Transplantation: A Randomized Controlled Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, Eric P.; Irving, Amy A. B.A.; Drobyski, William R.

Purpose: To test whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure after hematopoietic stem cell transplantation (HSCT). Methods and Materials: A total of 55 subjects undergoing total body irradiation (TBI)-HSCT were enrolled in this randomized controlled trial. Captopril or identical placebo was started at engraftment and continued as tolerated until 1 year after HSCT. Results: The baseline serum creatinine and calculated glomerular filtration rate (GFR) did not differ between groups. The 1-year serum creatinine level was lower and the GFR higher in the captopril compared with the placebo group (p = 0.07 for GFR). Patientmore » survival was higher in the captopril compared with the placebo group, but this was also not statistically significant (p = 0.09). In study subjects who received the study drug for more than 2 months, the 1-year calculated GFRs were 92 mL/min and 80 mL/min, for the captopril and placebo groups, respectively (p = 0.1). There was no adverse effect on hematologic outcome. Conclusions: There is a trend in favor of captopril in mitigation of chronic renal failure after radiation-based HSCT.« less

Adding Paracetamol to Ibuprofen for the Treatment of Patent Ductus Arteriosus in Preterm Infants: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.

PubMed

Hochwald, Ori; Mainzer, Gur; Borenstein-Levin, Liron; Jubran, Huda; Dinur, Gil; Zucker, Meirav; Mor, Malka; Khoury, Asaad; Kugelman, Amir

2018-05-21

 The objective of this study was to compare the closure rate of hemodynamically significant patent ductus arteriosus (hsPDA) of intravenous ibuprofen + paracetamol (acetaminophen) versus ibuprofen + placebo, in preterm infants of 24 to 31 6/7 weeks postmenstrual age.  This is a single-center, double-blind, randomized controlled pilot study. Infants were assigned for treatment with either intravenous ibuprofen + paracetamol ( n  = 12) or ibuprofen + placebo ( n  = 12).  There was no statistical difference in baseline characteristics of the two groups. Echocardiography parameters were comparable before treatment in both groups. There was a trend toward higher hsPDA closure rate in the paracetamol group in comparison to the placebo group (83 vs. 42%, p  = 0.08). No adverse effects, clinical or laboratory, were associated with adding paracetamol.  Our pilot study was unable to detect a beneficial effect by adding intravenous paracetamol to ibuprofen for the treatment of hsPDA. Larger prospective studies are needed to explore the positive tendency suggested by our results and to assure safety. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial

PubMed Central

Boyle, Robert J; Pedroletti, Christophe; Wickman, Magnus; Bjermer, Leif; Valovirta, Erkka; Dahl, Ronald; Von Berg, Andrea; Zetterström, Olof

2011-01-01

Objective To determine whether environmental control using nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of patients with persistent atopic asthma. Design Randomised, double-blind, placebo-controlled, parallel-group trial. Setting Nineteen European asthma clinics. Participants 312 patients aged 7–70 with inadequately controlled persistent atopic asthma. Main outcome measure Proportion of patients with an increase of ≥0.5 points in asthma quality of life score after 1 year of treatment. Results TLA devices were successfully installed in the bedrooms of 282 (90%) patients included in the primary efficacy analysis. There was a difference in treatment response rate between active (143 of 189, 76%) and placebo (56 of 92, 61%) groups, difference 14.8% (95% CI 3.1 to 26.5, p=0.02).3 In patients aged ≥12, on whom the study was powered, the difference in response rate was similar-active 106 of 143 (74%), placebo 42 of 70 (60%), difference 14.1% (0.6 to 27.7, p=0.059). There was a difference between groups in fractional exhaled nitric oxide change of −7.1 ppb (−13.6 to −0.7, p=0.03). Active treatment was associated with less increase in cat-specific IgE than placebo. There was no difference in adverse event rates between treatment groups. Conclusion Inhalant exposure reduction with TLA improves quality of life, airway inflammation and systemic allergy in patients with persistent atopic asthma. TLA may be a treatment option for patients with inadequately controlled persistent atopic asthma. Trial registration number Clinical Trials NCT00986323. PMID:22131290

Urinary metabolites of histamine and leukotrienes before and after placebo-controlled challenge with ASA and food additives in chronic urticaria patients.

PubMed

Di Lorenzo, G; Pacor, M L; Vignola, A M; Profita, M; Esposito-Pellitteri, M; Biasi, D; Corrocher, R; Caruso, C

2002-12-01

The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU). Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine. For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P < 0.0001; A vs. B2, P < 0.0001; A vs. C1, P < 0.0001; A vs. C2, P < 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P < 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed significantly increased excretion rates of urinary LTE4 compared with the other groups challenged with placebo (A, B1, C1), or ASA (B2) (P < 0.0001). No significant correlation was seen between urinary LTE4 and methylhistamine excretion rate in any patients. Our results show that urinary excretion of N-MH and LTE4 is different for CU patients without ASA or food hypersensitivity, compared to those with CU with ASA or food additive hypersensitivity after specific challenge.

A randomized, double-blind, placebo-controlled study of rebamipide for gastric mucosal injury taking aspirin with or without clopidogrel.

PubMed

Tozawa, Katsuyuki; Oshima, Tadayuki; Okugawa, Takuya; Ogawa, Tomohiro; Ohda, Yoshio; Tomita, Toshihiko; Hida, Nobuyuki; Fukui, Hirokazu; Hori, Kazutoshi; Watari, Jiro; Nakamura, Shiro; Miwa, Hiroto

2014-08-01

Antithrombotic drugs, such as low-dose aspirin (LDA) and clopidogrel, can cause upper gastrointestinal complications. The goal of the present study was to investigate whether a mucosal-protective agent, rebamipide, could prevent gastric mucosal injuries induced by LDA with or without clopidogrel in healthy subjects. A randomized, double-blind, placebo-controlled trial was performed with 32 healthy male volunteers. Subjects were randomly assigned to a 14-day course of one of the following regimens: group A, placebo (tid) + LDA; group B, rebamipide (100 mg tid) + LDA (100 mg once-daily); group C, placebo + LDA + clopidogrel (75 mg once-daily); or group D, rebamipide + LDA + clopidogrel. The grade of gastric mucosal injuries was evaluated by esophagogastroduodenoscopy before and after dosing (on day 0 and day 14), and the grade of gastric mucosal injury was assessed according to the modified Lanza score. Subjective symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS). A rapid urease test was performed on day 0, and blood tests were performed on day 0 and day 14. Rebamipide significantly inhibited gastric mucosal injury induced by LDA alone or by LDA plus clopidogrel when compared with placebo in healthy subjects. GSRS score and hemoglobin level were not significantly different among the four groups. Rebamipide is useful for the primary prevention of gastric mucosal injury induced by LDA alone or by LDA plus clopidogrel in healthy subjects.

Antidepressants and ejaculation: a double-blind, randomized, placebo-controlled, fixed-dose study with paroxetine, sertraline, and nefazodone.

PubMed

Waldinger, M D; Zwinderman, A H; Olivier, B

2001-06-01

Antidepressant medication is often associated with sexual side effects. A double-blind, placebo-controlled study in men with lifelong rapid ejaculation was performed to assess the effects of two selective serotonin (5-HT) reuptake inhibitors--paroxetine and sertraline--and the 5-HT2 antagonist and 5-HT/noradrenaline reuptake inhibitor nefazodone on the latency to ejaculate. Forty-eight men with an intravaginal ejaculation latency time (IELT) of a maximum of 1 minute were randomly assigned to receive paroxetine (20 mg/day), sertraline (50 mg/day), nefazodone (400 mg/day), or placebo for 6 weeks. During the 1-month baseline and 6-week treatment period, IELTs were measured at home with a stopwatch. The trial was completed by 40 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was stable at approximately 20 seconds. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.002); the IELT after paroxetine and sertraline gradually increased to approximately 146 and 58 seconds, respectively, compared with 28 seconds in the nefazodone group. The paroxetine and sertraline groups differed significantly (p < 0.001 and p = 0.024, respectively) from placebo, but the nefazodone group did not (p = 0.85). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, whereas sertraline delayed it only moderately. There was no clinically relevant delay in ejaculation with nefazodone.

A randomized, double-blind, placebo-controlled trial of a Chinese herbal Sophora flower formula in patients with symptomatic haemorrhoids: a preliminary study.

PubMed

Man, Kee-Ming; Chen, Wen-Chi; Wang, Hwei-Ming; Chen, Huey-Yi; Shen, Jui-Lung; Chen, Lieh-Der; Tsai, Fuu-Jen; Chen, Yung-Hsiang; Yu, De-Xin; Chiang, Feng-Fan

2013-01-01

Dried flowers and buds of Sophora japonica (Huaihua) are used in China, Japan and Korea for treating haematemesis and bleeding haemorrhoids. This study compared the clinical safety and efficacy of a Sophora flower formula with a placebo for the conservative treatment of symptomatic haemorrhoids. The study was a prospective, double-blind, randomized placebo-controlled trial. The clinical effective rate, symptom score and the incidence of important clinical events were used as observation indices to evaluate the effect of the Sophora flower formula. The results showed that after 7 days of treatment, improvement was observed in 87.0% of the patients' major symptoms in the Sophora flower formula group compared with 81.8% of those in the placebo group. After 14 days, 78.2% patients in the Sophora flower formula group were asymptomatic, whereas 40.9% of those in the placebo group exhibited residual symptoms. However, the difference between both groups was not statistically significant. As the bowel habits of the patients improved and as the patients took sitz baths, their symptoms improved drastically, regardless of the use of the Sophora flower formula. These findings indicate that the traditional Chinese Sophora flower formula is clinically safe; however, its effects on haemorrhoids need to be studied in a larger sample size and with different dosages. The present study results may be a potential clinical reference for physicians prescribing medications for patients with symptomatic haemorrhoids.

Raloxifene for women with Alzheimer disease: A randomized controlled pilot trial.

PubMed

Henderson, Victor W; Ala, Tom; Sainani, Kristin L; Bernstein, Allan L; Stephenson, B Sue; Rosen, Allyson C; Farlow, Martin R

2015-12-01

To determine whether raloxifene, a selective estrogen receptor modulator, improves cognitive function compared with placebo in women with Alzheimer disease (AD) and to provide an estimate of cognitive effect. This pilot study was conducted as a randomized, double-blind, placebo-controlled trial, with a planned treatment of 12 months. Women with late-onset AD of mild to moderate severity were randomly allocated to high-dose (120 mg) oral raloxifene or identical placebo provided once daily. The primary outcome compared between treatment groups at 12 months was change in the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog). Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses (mean age 76 years, range 68-84), and 39 women contributed 12-month outcomes. ADAS-cog change scores at 12 months did not differ significantly between treatment groups (standardized difference 0.03, 95% confidence interval -0.39 to 0.44, 2-tailed p = 0.89). Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score. Caregiver burden and caregiver distress were similar in both groups. Results on the primary outcome showed no cognitive benefits in the raloxifene-treated group. This study provides Class I evidence that for women with AD, raloxifene does not have a significant cognitive effect. The study lacked the precision to exclude a small effect. © 2015 American Academy of Neurology.

[The efficacy of the complex medication Phyto-Hypophyson L in female, hormone-related sterility. A randomized, placebo-controlled clinical double-blind study].

PubMed

Bergmann, J; Luft, B; Boehmann, S; Runnebaum, B; Gerhard, I

2000-08-01

In a prospective, randomized, placebo-controlled, double-blind study, the effects of Phyto Hypophyson L (Steierl-Pharma GmbH, Herrsching, Germany), an Agnus castus-containing homeopathic preparation, were investigated in 67 women with fertility disorders. 37 women with oligomenorrhea and 30 women with amenorrhea received 50 drops of Phyto Hypophyson L or placebo 3 times a day over 3 months or 3 cycles. OUTCOME MEASURE AND RESULTS: The outcome measure being spontaneous menstruation, improved concentration of progesterone in the luteal phase, shortening of the cycle, earlier ovulation, and pregnancy was achieved in 38 out of 67 women. It was achieved more often from women with oligomenorrhea in the Phyto Hypophyson L group compared to the placebo group (82 versus 45%, p = 0.021). However, there was no significant effect when viewing the whole group. The baby take-home rate during the therapy and 6 months after the end of the therapy showed a ratio of 6 : 2 (18.7 : 6.4%). This result was not significant. Furthermore, in the oligomenorrhea verum group we observed a significant increase of progesterone during the luteal phase compared to the oligomenorrhea placebo group. Only very few undesirable drug effects were observed. In women with sterility and oligomenorrhea, a treatment with Phyto Hypophyson L can be recommended over a period of 3-6 months. Copyright 2000 S. Karger GmbH, Freiburg

Effects of Ganglioside on Working Memory and the Default Mode Network in Individuals with Subjective Cognitive Impairment: A Randomized Controlled Trial.

PubMed

Jeon, Yujin; Kim, Binna; Kim, Jieun E; Kim, Bori R; Ban, Soonhyun; Jeong, Jee Hyang; Kwon, Oran; Rhie, Sandy Jeong; Ahn, Chang-Won; Kim, Jong-Hoon; Jung, Sung Ug; Park, Soo-Hyun; Lyoo, In Kyoon; Yoon, Sujung

2016-01-01

This randomized, double-blind, placebo-controlled trial examined whether the administration of ganglioside, an active ingredient of deer bone extract, can improve working memory performance by increasing gray matter volume and functional connectivity in the default mode network (DMN) in individuals with subjective cognitive impairment. Seventy-five individuals with subjective cognitive impairment were chosen to receive either ganglioside (330[Formula: see text][Formula: see text]g/day or 660[Formula: see text][Formula: see text]g/day) or a placebo for 8 weeks. Changes in working memory performance with treatment of either ganglioside or placebo were assessed as cognitive outcome measures. Using voxel-based morphometry and functional connectivity analyses, changes in gray matter volume and functional connectivity in the DMN were also assessed as brain outcome measures. Improvement in working memory performance was greater in the ganglioside group than in the placebo group. The ganglioside group, relative to the placebo group, showed greater increases in gray matter volume and functional connectivity in the DMN. A significant relationship between increased functional connectivity of the precuneus and improved working memory performance was observed in the ganglioside group. The current findings suggest that ganglioside has cognitive-enhancing effects in individuals with subjective cognitive impairment. Ganglioside-induced increases in gray matter volume and functional connectivity in the DMN may partly be responsible for the potential nootropic effects of ganglioside. The clinical trial was registered with ClinicalTrials.gov (identifier: NCT02379481).

Myofascial trigger point-focused head and neck massage for recurrent tension-type headache: A randomized, placebo-controlled clinical trial

PubMed Central

Moraska, Albert F.; Stenerson, Lea; Butryn, Nathan; Krutsch, Jason P.; Schmiege, Sarah J.; Mann, J. Douglas

2014-01-01

Objective Myofascial trigger points (MTrPs) are focal disruptions in skeletal muscle that can refer pain to the head and reproduce the pain patterns of tension-type headache (TTH). The present study applied massage focused on MTrPs of subjects with TTH in a placebo-controlled, clinical trial to assess efficacy on reducing headache pain. Methods Fifty-six subjects with TTH were randomized to receive 12 massage or placebo (detuned ultrasound) sessions over six weeks, or to wait-list. Trigger point release (TPR) massage focused on MTrPs in cervical musculature. Headache pain (frequency, intensity and duration) was recorded in a daily headache diary. Additional outcome measures included self-report of perceived clinical change in headache pain and pressure-pain threshold (PPT) at MTrPs in the upper trapezius and sub-occipital muscles. Results From diary recordings, group differences across time were detected in headache frequency (p=0.026), but not for intensity or duration. Post hoc analysis indicated headache frequency decreased from baseline for both massage (p<0.0003) and placebo (p=0.013), but no difference was detected between massage and placebo. Subject report of perceived clinical change was a greater reduction in headache pain for massage than placebo or wait-list groups (p=0.002). PPT improved in all muscles tested for massage only (all p's<0.002). Discussion Two findings from this study are apparent: 1) MTrPs are important components in the treatment of TTH, and 2) TTH, like other chronic conditions, is responsive to placebo. Clinical trials on headache that do not include a placebo group are at risk for overestimating the specific contribution from the active intervention. PMID:25329141

Myofascial trigger point-focused head and neck massage for recurrent tension-type headache: a randomized, placebo-controlled clinical trial.

PubMed

Moraska, Albert F; Stenerson, Lea; Butryn, Nathan; Krutsch, Jason P; Schmiege, Sarah J; Mann, John D

2015-02-01

Myofascial trigger points (MTrPs) are focal disruptions in the skeletal muscle that can refer pain to the head and reproduce the pain patterns of tension-type HA (TTH). The present study applied massage focused on MTrPs of patients with TTH in a placebo-controlled, clinical trial to assess efficacy on reducing headache (HA) pain. Fifty-six patients with TTH were randomized to receive 12 massage or placebo (detuned ultrasound) sessions over 6 weeks, or to wait-list. Trigger point release massage focused on MTrPs in cervical musculature. HA pain (frequency, intensity, and duration) was recorded in a daily HA diary. Additional outcome measures included self-report of perceived clinical change in HA pain and pressure-pain threshold at MTrPs in the upper trapezius and suboccipital muscles. From diary recordings, group differences across time were detected in HA frequency (P=0.026), but not for intensity or duration. Post hoc analysis indicated that HA frequency decreased from baseline for both massage (P<0.0003) and placebo (P=0.013), but no difference was detected between massage and placebo. Patient report of perceived clinical change was greater reduction in HA pain for massage than placebo or wait-list groups (P=0.002). Pressure-pain threshold improved in all muscles tested for massage only (all P's<0.002). Two findings from this study are apparent: (1) MTrPs are important components in the treatment of TTH, and (2) TTH, like other chronic conditions, is responsive to placebo. Clinical trials on HA that do not include a placebo group are at risk for overestimating the specific contribution from the active intervention.

JinqiJiangtang tablets for pre-diabetes: A randomized, double-blind and placebo-controlled clinical trial.

PubMed

Wang, Hui; Guo, Liping; Shang, Hongcai; Ren, Ming; Wang, Xuemei; Wang, Dehui; Chen, Jianzong; Li, Shuanglei; Chen, Liming; Wang, Yue; Liu, Zhi; Zhai, Jingbo; Song, Yuzhen; Cao, Hongbo; Zhang, Junhua; Liu, Chunxiang; Sun, Xiao; Huo, Da; Mu, Wei; Zhang, Li; Zheng, Wenke; Yan, Xiaoyan; Yao, Chen

2017-09-11

This study observed the efficacy and safety of JinqiJiangtang tablets (JQJT tablets, a traditional Chinese patent medicine) for pre-diabetes. Four hundred patients with pre-diabetes at five centres were treated for 12months and followed for an additional 12months to investigate the preventative effects of JQJT tablets (Registration ID: ChiCTR-PRC-09000401). The incidence rate of diabetes mellitus was the primary endpoint. The risk of converting from pre-diabetes to diabetes was 0.58-fold less in the JQJT tablets group than in the placebo group [HR (95% CI): 0.58 (0.384, 0.876), P = 0.010]. Furthermore, the probability of achieving normalized blood glucose was 1.41-fold greater in the JQJT tablets group than in the placebo group [HR (95% CI): 1.41 (1.002, 1.996), P = 0.0049]. ITT analysis revealed that the incidence of diabetes upon treatment completion was 16.5% in the JQJT tablets group compared with 28.9% in the control group. The percentage of patients with normalized blood glucose upon 12-month intervention was 41.8% in the JQJT tablets group compared with 27.8% in the control group. JQJT tablets could be an effective intervention for preventative treatment of Type 2 diabetes mellitus.

Ineffectiveness of deanol in tardive dyskinesia: a placebo controlled study.

PubMed

de Montigny, C; Chouinard, G; Annable, L

1979-11-01

In a double-blind placebo-controlled study, deanol acetamidobenzoate, administered in doses up to 1.5 g q.d. for three weeks to chronic schizophrenic patients presenting moderate to severe tardive dyskinesia, failed to alleviate the dyskinetic movements. However, there was a tendency for a significant increase in the schizophrenic symptoms of the deanol-treated group relative to the control group. The ineffectiveness of deanol in alleviating tardive dyskinesia is consistent with its inability to enhance brain acetylcholine synthesis. The worsening of the schizophrenic symptoms may possibly result from an interference by deanol with central cholinergic function.

The Efficacy of Thai Herbal Prasaplai Formula for Treatment of Primary Dysmenorrhea: A Short-Term Randomized Controlled Trial

PubMed Central

Vannabhum, Manmas; Wongwananuruk, Thanyarat; Suwannatrai, Ueamphon; Dangrat, Chongdee; Apichartvorakit, Angkana; Booranasubkajorn, Suksalin; Laohapand, Tawee; Akaraserenont, Pravit

2016-01-01

This study aims to compare the efficacy of pain relief between a specific Thai herbal Prasaplai formula (PPF) and placebo in patients with primary dysmenorrhea. Forty women with primary dysmenorrhea symptoms were randomized into two groups. The experimental group received PPF capsules 1000 mg orally three times per day before meals for three days starting from the first day of menstruation. The placebo group received placebo as the same dose and time. Average pain intensity from the first day to the third day of cycle significantly decreased in both groups (p < 0.001), but with no statistically significant difference between groups. Using a pre- and posttreatment difference in NRS of at least 2, a greater proportion of patients in PPF group experienced pain relief compared to placebo during the first and second day of period. A greater proportion of PPF group also experienced no pain compared to the placebo group on day 1 and day 3 by using multidimensional scoring. The PPF demonstrates pain relief activity when used during menstruation in primary dysmenorrhea patients, with no adverse effects. However, further studies are needed in order to assess the value of PPF as a long-term prophylaxis for primary dysmenorrhea. PMID:27829860

Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial.

PubMed

Ludvik, Bernhard; Frías, Juan P; Tinahones, Francisco J; Wainstein, Julio; Jiang, Honghua; Robertson, Kenneth E; García-Pérez, Luis-Emilio; Woodward, D Bradley; Milicevic, Zvonko

2018-05-01

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms. We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors, with or without metformin. AWARD-10 was a phase 3b, double-blind, parallel-arm, placebo-controlled, 24-week study done at 40 clinical sites in Austria, Czech Republic, Germany, Hungary, Israel, Mexico, Spain, and the USA. Eligible adult patients (≥18 years) with inadequately controlled type 2 diabetes (HbA 1c concentration ≥7·0% [53 mmol/mol] and ≤9·5% [80 mmol/mol]), a BMI of 45 kg/m 2 or less, and taking stable doses (>3 months) of an SGLT2 inhibitor (with or without metformin) were randomly assigned (1:1:1) via an interactive web-response system to subcutaneous injections of either dulaglutide 1·5 mg, dulaglutide 0·75 mg, or placebo once per week for 24 weeks. Patients and investigators were masked to dulaglutide and placebo assignment, and those assessing outcomes were masked to study drug assignment. The primary objective was to test for the superiority of dulaglutide (1·5 mg or 0·75 mg) versus placebo for change in HbA 1c concentration from baseline at 24 weeks. All analyses were done in the intention-to-treat population, defined as all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02597049. Between Dec 7, 2015, and Feb 3, 2017, 424 patients were randomly assigned to dulaglutide 1·5 mg (n=142), dulaglutide 0·75 mg (n=142), and placebo (n=140). One patient in the dulaglutide 0·75 mg group was excluded from the analysis because they did not receive any dose of the study drug. The reduction in HbA 1c concentration at 24 weeks was larger in patients receiving dulaglutide (least squares mean [LSM] for dulaglutide 1·5 mg -1·34% [SE 0·06] or -14·7 mmol/mol [0·6]; dulaglutide 0·75 mg -1·21% [0·06] or -13·2 mmol/mol [0·6]) than in patients receiving placebo (-0·54% [0·06] or -5·9 mmol/mol [0·6]; p<0·0001 for both groups vs placebo). The LSM differences were -0·79% (95% CI -0·97 to -0·61) or -8·6 mmol/mol (-10·6 to -6·7) for dulaglutide 1·5 mg and -0·66% (-0·84 to -0·49) or -7·2 mmol/mol (-9·2 to -5·4) for dulaglutide 0·75 mg (p<0·0001 for both). Serious adverse events were reported for five (4%) patients in the dulaglutide 1·5 mg group, three (2%) patients in the dulaglutide 0·75 mg group, and five (4%) patients in the placebo group. Treatment-emergent adverse events were more common in patients treated with dulaglutide than in patients who received placebo, mainly because of an increased incidence of gastrointestinal adverse events. Nausea (21 [15%] patients in the dulaglutide 1·5 mg group vs seven [5%] in the dulaglutide 0·75 mg group vs five [4%] in the placebo group), diarrhoea (eight [6%] vs 14 [10%] vs four [3%]), and vomiting (five [4%] vs four [3%] vs one [1%]) were more common with dulaglutide than with placebo. One episode of severe hypoglycaemia was reported in the dulaglutide 0·75 mg group. Two (1%) patients receiving dulaglutide 1·5 mg died, but these deaths were not considered to be related to study drug; no deaths occurred in the other groups. Dulaglutide as add-on treatment to SGLT2 inhibitors (with or without metformin) resulted in significant and clinically relevant improvements in glycaemic control, with acceptable tolerability that is consistent with the established safety profile of dulaglutide. Eli Lilly and Company. Copyright © 2018 Elsevier Ltd. All rights reserved.

Does Long-Term Itraconazole Prophylaxis Result in In Vitro Azole Resistance in Mucosal Candida albicans Isolates from Persons with Advanced Human Immunodeficiency Virus Infection?

PubMed Central

Goldman, Mitchell; Cloud, Gretchen A.; Smedema, Melinda; LeMonte, Ann; Connolly, Patricia; McKinsey, David S.; Kauffman, Carol A.; Moskovitz, Bruce; Wheat, L. Joseph

2000-01-01

The effects of prolonged itraconazole exposure on the susceptibility of Candida albicans isolates to itraconazole and fluconazole have not been well characterized. A recent placebo-controlled study of long-term itraconazole antifungal prophylaxis in persons with advanced human immunodeficiency virus infection afforded the opportunity to address this question. Mucosal Candida sp. isolates were obtained from subjects who developed oropharyngeal or esophageal candidiasis, and in vitro susceptibilities of the last isolate obtained at removal from the study as a prophylaxis failure were compared in itraconazole and placebo recipients. More subjects in the placebo group (74 of 146 [51%]) than in the itraconazole group (51 of 149 [34%]) developed mucosal candidiasis (P = 0.004). A total of 112 isolates were recovered from 56 of the 74 (76%) subjects with mucosal candidiasis assigned to the placebo group, compared to 97 isolates from 45 of the 51 (88%) subjects in the itraconazole group. C. albicans accounted for 98% of isolates in the placebo group and 89% of isolates in the itraconazole group. The itraconazole MIC at which 50% of the isolates tested were inhibited (MIC50) for last-episode isolates from the itraconazole group was 0.125 μg/ml compared to 0.015 μg/ml for the placebo group subjects, P = 0.0001. The MIC50 of fluconazole for the last isolates from the itraconazole group was 1.5 μg/ml compared to 0.5 μg/ml for the placebo subjects (P = 0.005). A lower proportion of isolates recovered from subjects on itraconazole therapy were classified as susceptible to itraconazole (63%) compared to isolates from the placebo group (96%) (P = 0.001). Similarly, a lower proportion of C. albicans isolates from subjects on itraconazole therapy were susceptible to fluconazole (78%) compared to isolates from the placebo group (96%) (P = 0.01). Also, the proportion of isolates that were not fully susceptible to itraconazole or fluconazole was greater in patients assigned to the itraconazole group than the placebo group (itraconazole susceptibility, 37 and 4%, respectively (P = 0.001); fluconazole susceptibility, 23 and 4%, respectively (P = 0.01). In conclusion, long-term itraconazole prophylaxis in patients with AIDS is associated with reduction in susceptibility to itraconazole and cross-resistance to fluconazole. PMID:10817713

Effects of Hydroxychloroquine on Immune Activation and Disease Progression Among HIV-Infected Patients Not Receiving Antiretroviral Therapy A Randomized Controlled Trial

PubMed Central

Paton, Nicholas I.; Goodall, Ruth L.; Dunn, David T.; Franzen, Samuel; Collaco-Moraes, Yolanda; Gazzard, Brian G.; Williams, Ian G.; Fisher, Martin J.; Winston, Alan; Fox, Julie; Orkin, Chloe; Herieka, Elbushra A.; Ainsworth, Jonathan G.; Post, Frank A.; Wansbrough-Jones, Mark; Kelleher, Peter

2013-01-01

Context Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. Objective To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL. Intervention Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. Main Outcome Measures The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. Results There was no significant difference in CD8 cell activation between the 2 groups (−4.8% and −4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, −0.6%; 95% CI, −4.8% to 3.6%; P=.80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (−85 cells/μL vs −23 cells/μL at week 48; difference, −62 cells/μL; 95% CI, −115 to −8; P=.03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P=.003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P=.03). Conclusion Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication. Trial Registration isrctn.org Identifier: ISRCTN30019040 PMID:22820788

The 23-valent pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis: a double-blinded, randomized, placebo-controlled trial.

PubMed

Izumi, Yasumori; Akazawa, Manabu; Akeda, Yukihiro; Tohma, Shigeto; Hirano, Fuminori; Ideguchi, Haruko; Matsumura, Ryutaro; Miyamura, Tomoya; Mori, Shunsuke; Fukui, Takahiro; Iwanaga, Nozomi; Jiuchi, Yuka; Kozuru, Hideko; Tsutani, Hiroshi; Saisyo, Kouichirou; Sugiyama, Takao; Suenaga, Yasuo; Okada, Yasumasa; Katayama, Masao; Ichikawa, Kenji; Furukawa, Hiroshi; Kawakami, Kenji; Oishi, Kazunori; Migita, Kiyoshi

2017-01-25

Pneumococcal pneumonia is the most frequent form of pneumonia. We herein assessed the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in the prevention of pneumonia overall in rheumatoid arthritis (RA) patients at risk for infections. We hypothesized that PPSV23 vaccination is superior in preventing pneumococcal pneumonia compared with placebo in RA patients. A prospective, multicenter, double-blinded, randomized, placebo-controlled (1:1) trial was conducted across departments of rheumatology in Japanese National Hospital Organization hospitals. RA patients (n = 900) who had been treated with biological or immunosuppressive agents were randomly assigned PPSV23 or placebo (sodium chloride). The primary endpoints were the incidences of all-cause pneumonia and pneumococcal pneumonia. The secondary endpoint was death from pneumococcal pneumonia, all-cause pneumonia, or other causes. Cox regression models were used to estimate the risk of pneumonia overall for the placebo group compared with the vaccine group. Seventeen (3.7%) of 464 patients in the vaccine group and 15 (3.4%) of 436 patients in the placebo group developed pneumonia. There was no difference in the rates of pneumonia between the two study groups. The overall rate of pneumonia was 21.8 per 1000 person-years for patients with RA. The presence of interstitial pneumonia (hazard ratio: 3.601, 95% confidence interval: 1.547-8.380) was associated with an increased risk of pneumonia in RA patients. PPSV23 does not prevent against pneumonia overall in RA patients at relative risk for infections. Our results also confirm that the presence of interstitial lung disease is associated with pneumonia in Japanese patients with RA. UMIN-CTR UMIN000009566 . Registered 17 December 2012.

A randomized, placebo-controlled, phase 2 study of the efficacy and safety of droxidopa in patients with intradialytic hypotension.

PubMed

Vannorsdall, Mark D; Hariachar, Srinivas; Hewitt, L Arthur

2015-03-01

Intradialytic hypotension (IDH) is the most common complication of hemodialysis (HD), and it plays a significant role in the morbidity and mortality associated with maintenance HD. This was a placebo-controlled, parallel-group study evaluating efficacy and safety of droxidopa in improving intradialytic blood pressure (BP) responses in 85 adults with end-stage renal disease (ESRD) and prone to IDH. Following screening and baseline periods, patients received 400 mg or 600 mg droxidopa, or placebo, orally 1 hour before HD for 4 weeks. Primary outcome endpoint was the change between baseline and last 2 treatment weeks in average mean arterial pressure (MAP) during HD. Also assessed were changes from baseline in systolic BP (SBP) and diastolic BP (DBP) during and after HD; number of hypotension-induced interventions and symptoms; and adverse events. Increase in droxidopa intra-HD MAP were not significantly different from placebo, although droxidopa groups showed significant improvements in mean SBP after HD of +4.8 ± 11.6 mm Hg (600-mg) and +3.4 ± 13.1 (400-mg) compared with -4.4 ± 17.9 mm Hg in placebo, and the drop seen in mean nadir SBP pre- to intra-HD was also reduced. Changes in mean DBP pre- and post-HD, changes in mean nadir SBP post-HD, or intra-HD SBP were not significant over the treatment period. HD terminations decreased 5-fold in the 600-mg group and 2-fold in the 400-mg group, whereas the number of discontinuations stayed unchanged in the placebo group. Overall, treatment with 600-mg or 400-mg droxidopa was well tolerated in this population. These data suggest that droxidopa may have a role in reducing IDH complications in patients with ESRD on chronic HD.

Dietary supplementation with rice bran fermented with Lentinus edodes increases interferon-γ activity without causing adverse effects: a randomized, double-blind, placebo-controlled, parallel-group study.

PubMed

Choi, Ji-Young; Paik, Doo-Jin; Kwon, Dae Young; Park, Yongsoon

2014-04-22

The purpose of this study was to investigate the hypothesis that dietary supplementation with rice bran fermented with Lentinus edodes (rice bran exo-biopolymer, RBEP), a substance known to contain arabinoxylan, enhances natural killer (NK) cell activity and modulates cytokine production in healthy adults. This study was designed in a randomized, double-blind, placebo-controlled, and parallel-group format. Eighty healthy participants with white blood cell counts of 4,000-8,000 cells/μL were randomly assigned to take six capsules per day of either 3 g RBEP or 3 g placebo for 8 weeks. Three participants in the placebo group were excluded after initiation of the protocol; no severe adverse effects from RBEP supplementation were reported. NK cell activity of peripheral blood mononuclear cells was measured using nonradioactive cytotoxicity assay kits and serum cytokine concentrations included interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-10, and IL-12 were measured by Bio-Plex cytokine assay kit. This study was registered with the Clinical Research Information Service (KCT0000536). Supplementation of RBEP significantly increased IFN-γ production compared with the placebo group (P = 0.012). However, RBEP supplementation did not affect either NK cell activity or cytokine levels, including IL-2, IL-4, IL-10, IL-12, and TNF-α, compared with the placebo group. The data obtained in this study indicate that RBEP supplementation increases IFN-γ secretion without causing significant adverse effects, and thus may be beneficial to healthy individuals. This new rice bran-derived product may therefore be potentially useful to include in the formulation of solid and liquid foods designed for treatment and prevention of pathological states associated with defective immune responses.

A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury.

PubMed

Luangchosiri, Chote; Thakkinstian, Ammarin; Chitphuk, Sermsiri; Stitchantrakul, Wasana; Petraksa, Supanna; Sobhonslidsuk, Abhasnee

2015-09-23

Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown. We aimed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury (antiTB-DILI) in patients with tuberculosis. A double-blind randomized placebo-controlled trial was performed. Tuberculosis patients were randomly allocated to receive placebo or silymarin. The outcomes of interests were antiTB-DILI and the maximum liver enzymes at week 4. Antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione and malondialdehyde assays) were assessed. The risks of antiTB-DILI between the two groups were compared. A number need to treat was estimated. A total of 55 out of 70 expected numbers of patients were enrolled. There were 1/27 (3.7%) and 9/28 (32.1%) patients who developed antiTB-DILI in the silymarin and the placebo groups. Risk reduction was 0.28 (0.10, 0.47), i.e., receiving silymarin was 28% at lower risk for antiTB-DILI than placebo. This led to prevention of 28 patients from being antiTB-DILI among 100 treated patients. Median (IQR) of ALT levels at week 4 in the placebo and the silymarin group were 35.0 (15, 415) IU/L and 31.5 (20, 184) IU/L (p = 0.455). The decline of SOD level at week 4 in the silymarin group was less than the placebo group (p < 0.027). Silymarin reduced the incidence of antiTB-DILI. The benefit of silymarin may be explained from superoxide dismutase restoration. Larger clinical trials are required to confirm the result of our small study [Clinicaltrials.Gov Identifier Nct01800487].

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials

PubMed Central

Zhang, Zong Mei; Li, Wei; Jiang, Xue Liang

2016-01-01

Background/Aims To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy. Methods Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis. Results This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61). Conclusions ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA. PMID:26780088

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials.

PubMed

Zhang, Zong Mei; Li, Wei; Jiang, Xue Liang

2016-03-01

To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy. Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis. This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61). ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA.

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D).

PubMed

Lam, Ching; Tan, Wei; Leighton, Matthew; Hastings, Margaret; Lingaya, Melanie; Falcone, Yirga; Zhou, Xiaoying; Xu, Luting; Whorwell, Peter; Walls, Andrew F; Zaitoun, Abed; Montgomery, Alan; Spiller, Robin

2016-01-01

Immune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of 'satisfactory relief of IBS symptoms'. 136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (-0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up. This study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. NCT01316718. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Insulin resistance improvement by cinnamon powder in polycystic ovary syndrome: A randomized double-blind placebo controlled clinical trial.

PubMed

Hajimonfarednejad, Mahdie; Nimrouzi, Majid; Heydari, Mojtaba; Zarshenas, Mohammad Mehdi; Raee, Mohammad Javad; Jahromi, Bahia Namavar

2018-02-01

Our aim is to assess the effect of cinnamon powder capsules on insulin resistance, anthropometric measurements, glucose and lipid profiles, and androgens of women with polycystic ovarian syndrome (PCOS). Out of 80 women that were diagnosed as PCOS by Rotterdam Criteria, 66 were enrolled in this randomized double-blind placebo-controlled clinical trial. All of the PCOS women were taking medroxy progesterone acetate 10 mg/day for the last 10 days of their menstrual cycles. The cases were randomly allocated to 2 groups. The women in the first group were treated by cinnamon powder capsules 1.5 g/day in 3 divided doses for 12 weeks and the second group by similar placebo capsules. Anthropometric measurements, fasting blood sugar, fasting insulin, blood glucose 2 hr after taking 75 g oral glucose, HbA1c, testosterone, dehydroepiandrosterone sulphate, homeostatic model assessment for insulin resistance, triglyceride, and cholesterol (low-density lipoprotein, high-density lipoprotein, and total) before and after the intervention were evaluated and compared as outcome measures. Fasting insulin (p = .024) and homeostatic model assessment for insulin resistance (p = .014) were reduced after 12 weeks in the cinnamon group compared with the placebo. There was also a significant decrease in low-density lipoprotein in cinnamon group (p = .004) as compared with baseline that caused significant difference with placebo (p = .049). However, changes in other outcome measurements did not lead to statistically significant difference with placebo. The present results suggest that complementary supplementation of cinnamon significantly reduced fasting insulin and insulin resistance in women with PCOS. Copyright © 2017 John Wiley & Sons, Ltd.

Efficacy, Safety, and Tolerability of Fulranumab as an Adjunctive Therapy in Patients With Inadequately Controlled, Moderate-to-Severe Chronic Low Back Pain: A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Dose-loading Phase II Study.

PubMed

Sanga, Panna; Polverejan, Elena; Wang, Steven; Kelly, Kathleen M; Thipphawong, John

2016-06-01

Fulranumab is an investigational, fully human recombinant monoclonal antibody (IgG2) that neutralizes the biological actions of human nerve growth factor. Low back pain is a common cause of noncancer chronic pain and represents one of the most significant socioeconomic health-related problems in developed countries. This randomized, double-blind, placebo-controlled study was conducted to evaluate the analgesic effect of fulranumab in patients with moderate-to-severe chronic low back pain. Patients (aged 18-80 years) were randomized to receive subcutaneous injections every 4 weeks in 1 of 5 parallel treatment groups: placebo or fulranumab 1mg (1mgQ4wk), 3mg (3mgQ4wk), 3mg after a 6mg loading dose (6mgLD+3mgQ4wk), or 10mg (10mgQ4wk) every 4 weeks. A total of 385 patients (median age, 53 years; women, 54%) received at least 1 injection of study medication. No statistically significant differences were observed in improvement of pain intensity scores between the fulranumab treatment regimens and the placebo group at week 12 (primary end point; mean [SD], placebo: -2.0 [2.17], 1mgQ4wk: -1.9 [2.14], 3mgQ4wk: -2.2 [1.89], 6mgLD+3mgQ4wk: -2.0 [1.72] and 10mgQ4wk: -2.1 [2.18]). Results for secondary efficacy parameters (change in the Oswestry Disability Index, Brief Pain Inventory-Short Form, and Patient Global Assessment scales) were consistent with the primary outcome. A placebo effect was observed; the overall percentage of patients with treatment-emergent adverse events (TEAEs) was similar between the placebo (76%) and fulranumab treatment groups (77%-90%). Across all phases, the most common TEAEs in at least 10% of patients (combined fulranumab group vs placebo) were arthralgia (15% vs 12%), back pain (15% vs 18%), upper respiratory tract infection (15% vs 8%), paresthesia (14% vs 8%), diarrhea (12% vs 4%), headache (12% vs 8%), hypoesthesia (11% vs 5%), pain in extremity (11% vs 8%), sinusitis (10% vs 5%), and nasopharyngitis (10% vs 9%). Across all phases, neurologic TEAEs were less frequent in the placebo group (14%) versus the fulranumab treatment groups (25%). In the posttreatment phase, 8 patients had joint replacement operations, which were considered a result of normal progression of osteoarthritis. One case in the 10-mg group was determined to be rapid progession of osteoarthritis and was considered to be possibly related to study drug. Fulranumab did not demonstrate efficacy compared with placebo in patients with chronic low back pain but was generally well-tolerated. ClinicalTrials.gov identifier: NCT00973024. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain.

PubMed

Kosek, Eva; Rosen, Annelie; Carville, Serena; Choy, Ernest; Gracely, Richard H; Marcus, Hanke; Petzke, Frank; Ingvar, Martin; Jensen, Karin B

2017-07-01

Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and because placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. In our study we examined the placebo group (n = 37, mean age 45 years) from a 12-week, randomized, double-blind, placebo-controlled trial investigating the effects of milnacipran or placebo. Twenty-two patients were classified as placebo nonresponders and 15 as responders, according to the Patient Global Impression of Change scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (visual analog scale), FM effect (Fibromyalgia Impact Questionnaire), and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity (r = .689, P = .004), but not among nonresponders (r = -.348, P = .112). In our study we showed that FM duration influences endogenous pain regulation, because pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, because endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results. This study presents a novel perspective on placebo analgesia, because placebo responses among patients with chronic pain were analyzed. Long-term exposure to fibromyalgia pain was associated with lower placebo analgesia, and the results show the importance of taking pain duration into account when interpreting the results from placebo-controlled trials. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Modafinil effects on cognitive function in HIV+ patients treated for fatigue: a placebo controlled study.

PubMed

McElhiney, Martin; Rabkin, Judith; Van Gorp, Wilfred; Rabkin, Richard

2010-06-01

Both mild cognitive impairment and fatigue are common among people with HIV/AIDS. This study examined the efficacy of modafinil for HIV+ patients who sought treatment for fatigue in a placebo-controlled double-blind 4-week trial. A battery of standard neuropsychological tests was administered at study entry and Week 4, and change in performance was compared for 59 patients receiving modafinil versus 44 patients receiving placebo. A significant effect on fatigue was observed. In addition, cognitive performance, as measured by a global change score, improved more in the modafinil than in the placebo group although the effect was not specific to any cognitive domain.

Outpatient cervical ripening by nitric oxide donors for prolonged pregnancy: a randomized controlled trial.

PubMed

Schmitz, Thomas; Fuchs, Florent; Closset, Emmanuel; Rozenberg, Patrick; Winer, Norbert; Perrotin, Franck; Verspyck, Eric; Azria, Elie; Carbonne, Bruno; Lepercq, Jacques; Maillard, Françoise; Goffinet, François

2014-12-01

To assess whether outpatient cervical ripening at 41 0/7 weeks of gestation with the nitric oxide donor isosorbide mononitrate reduces cesarean delivery rates in nulliparous women with an unfavorable cervix. We recruited nulliparous pregnant women with a Bishop score less than 6 in a randomized, multicenter, double-blind, placebo-controlled trial. Women received 40 mg vaginal isosorbide mononitrate or a placebo at 41 0/7, 41 2/7, and 41 4/7 weeks of gestation. They returned home between visits. At 41 5/7 weeks of gestation, for women who had not yet given birth, labor was induced with oxytocin or prostaglandins, depending on cervical status. We needed 685 women per group to detect a 25% reduction in the cesarean delivery rate, the primary outcome measure, from 25% in the placebo group to 18.75% in the isosorbide mononitrate group (1-β=0.8, α=0.05, two-sided). The NOCETER (NO donors for reduction of CEsareans at TERm) trial was a negative study. The cesarean delivery rate was 27.3% (185/678) in the isosorbide mononitrate group and 27.2% (186/684) in the placebo group (relative risk 1.00, 95% confidence interval [CI] 0.84-1.19). None of the maternal secondary efficacy outcomes differed between groups. Side effects were more common among women receiving isosorbide mononitrate than in the placebo group (78.8% [534/678] compared with 27.9% [191/684], relative risk 2.82, 95% CI 2.49-3.20). Composite perinatal morbidity did not differ between groups. Outpatient cervical ripening with vaginal isosorbide mononitrate for prolonged pregnancy in nulliparous women does not reduce cesarean delivery rate. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00930618.

The effects of Lactobacillus reuteri probiotics combined with azithromycin on peri-implantitis: A randomized placebo-controlled study.

PubMed

Tada, Hiroaki; Masaki, Chihiro; Tsuka, Shintaro; Mukaibo, Taro; Kondo, Yusuke; Hosokawa, Ryuji

2018-01-01

The aim of this randomized placebo-controlled clinical study was to investigate the effects of a probiotic tablet containing Lactobacillus reuteri in peri-implantitis patients. Subjects comprised 30 patients with mild to moderate peri-implantitis. A baseline clinical examination and microbiological assessment were conducted, followed by an antibiotics treatment (azithromycin, 500mg, once a day for 3 days). Subjects were divided into probiotic and placebo groups. The clinical examination and bacterial sampling were performed 0, 4, 12 and 24 weeks after the intake of probiotics. The clinical examination included probing pocket depth (PPD), bleeding on probing (BOP), the modified plaque index (mPI), and modified bleeding index (mBI). The number of bacteria was assessed using the PCR-invader method. The Wilcoxon rank-sum test and Wilcoxon signed-rank test with Bonferroni corrections were used for data analyses. Although the number of bacteria decreased after the administration of azithromycin in both groups, they increased again thereafter. No significant difference was observed in bacterial numbers between the two groups. Although PPD in the probiotics group was significantly lower at 4 and 24 weeks than at 0 weeks (p<0.05), a significant decrease did not occur in the placebo group. The mBI score at 24 weeks was significantly lower in the probiotics group than in the placebo group (p<0.05). No significant difference was observed in BOP or mPI between the two groups. These results suggested that probiotics prevent inflammation by affecting host responses rather than improving microbial flora in peri-implant sulci in peri-implantitis patients. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Lactobacillus GG (LGG) and smectite versus LGG alone for acute gastroenteritis: a double-blind, randomized controlled trial.

PubMed

Pieścik-Lech, Małgorzata; Urbańska, Magdalena; Szajewska, Hania

2013-02-01

Diarrhea treatment with either Lactobacillus GG (LGG) or smectite as an adjuvant to standard rehydration therapy has proven efficacy. In countries where both LGG and smectite are available, concomitant use is frequently practiced. We investigated whether LGG plus smectite is superior to LGG alone in the management of children with acute gastroenteritis (AGE). A double-blind, placebo-controlled, randomized trial was performed. Children aged 4 to 60 months with AGE received LGG 6 × 10(9) colony forming units/day plus randomly either smectite (3 g) or placebo as an adjuvant to the standard rehydration therapy. Of the 88 children randomized, 81 (92 %) were available for intention-to-treat analysis. The duration of diarrhea in the LGG/smectite group (n = 44) compared with the LGG/placebo group (n = 37) was similar (P = 0.43). There were no significant differences between the study groups for the secondary outcomes, with three exceptions. On day 4, in the LGG/placebo group compared to the LGG/smectite group, there was significantly reduced stool frequency (P = 0.03). While there was a significant (P = 0.05) difference in stool consistency on the Bristol Stool Form Scale on day 4, it was not of clinical relevance. Finally, in the LGG/smectite group compared to the LGG/placebo group, there was a significantly shorter duration of intravenous therapy after randomization (P = 0.02). No adverse events were observed in the study groups. LGG plus smectite and LGG alone are equally effective for treating young children with AGE. Combined use of the two interventions is not justified.

Effectiveness of Riluzole as a pharmacotherapeutic treatment option for early cervical myelopathy: a double-blinded, placebo-controlled randomised controlled trial.

PubMed

Rajasekaran, S; Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi Mugesh; Maheswaran, Anupama; Shetty, Janardhan Yerram

2016-06-01

To evaluate the effectiveness of Riluzole as a pharmacotherapeutic treatment option for early cervical myelopathy using clinical parameters and DTI analysis. Early cervical myelopathy cases with MJOA scores ≥13, were recruited for the double-blinded, placebo-controlled randomised control trial. Thirty cases with fifteen cases each in the test and placebo group were studied. Analysis was done using diffusion tensor imaging (DTI) and clinical evaluation, pre- and post-institution of sodium channel blocker Riluzole for a period of 1 month (50 mg twice daily). Placebo group was treated with Vitamin B complex tablets. Diffusion co-efficient fractional anisotrophy (FA), apparent diffusion co-efficient (ADC), volume ratio (VR), relative anisotrophy (RA) and Eigen vectors were calculated. Outcomes analysis was based on clinical scores of MJOA, Nurick grading, SF-12, NDI, and statistical analysis of DTI datametrics. The mean MJOA score was 15.6 (13-17) with no significant change in the test and control groups. The mean ADC, FA values were 1533.36 (1238-1779) and 494.36 (364-628) and changed to 1531.57 (1312-2091) and 484.86 (294-597), respectively, in the Riluzole group. However, the changes in the values of ADC, FA, and other co-efficients including VR, RA and eigenvectors in the two groups were not statistically significant. The functional scores in the SF-12 and NDI questionnaires did not change significantly. Our study did not show a significant change in the clinical outcome and DTI Indices with the use of Riluzole as a standalone pharmacotherapeutic agent for early cervical myelopathy. More studies may be needed to confirm the usefulness of Riluzole as a treatment option for cervical myelopathy.

EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: The factorial group results of the Trial to Assess Chelation Therapy.

PubMed

Lamas, Gervasio A; Boineau, Robin; Goertz, Christine; Mark, Daniel B; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L; Terry Chappell, L; Lindblad, Lauren; Lewis, Eldrin F; Drisko, Jeanne; Lee, Kerry L

2014-07-01

Disodium ethylenediaminetetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes. This was a double-blind, placebo-controlled, 2 × 2 factorial multicenter randomized trial of 1,708 post-myocardial infarction (MI) patients ≥50 years of age and with creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitamin-multimineral mixture or placebo. The primary end point was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina. Median age was 65 years, 18% were female, 94% were Caucasian, 37% were diabetic, 83% had prior coronary revascularization, and 73% were on statins. Five-year Kaplan-Meier estimates for the primary end point was 31.9% in the chelation + high-dose vitamin group, 33.7% in the chelation + placebo vitamin group, 36.6% in the placebo infusion + active vitamin group, and 40.2% in the placebo infusions + placebo vitamin group. The reduction in primary end point by double active treatment compared with double placebo was significant (hazard ratio 0.74, 95% CI 0.57-0.95, P = .016). In patients with diabetes, the primary end point reduction of double active compared with double placebo was more pronounced (hazard ratio 0.49, 95% CI 0.33-0.75, P < .001). In stable post-MI patients on evidence-based medical therapy, the combination of oral high-dose vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Trazodone improves sleep parameters in Alzheimer disease patients: a randomized, double-blind, and placebo-controlled study.

PubMed

Camargos, Einstein F; Louzada, Luciana L; Quintas, Juliana L; Naves, Janeth O S; Louzada, Fernando M; Nóbrega, Otávio T

2014-12-01

There are no randomized clinical trials regarding efficacy of trazodone in the treatment of sleep disturbances (SD) in patients with Alzheimer disease (AD). We tested the efficacy and safety of trazodone to treat SD in patients with AD. We conducted a double-blind, randomized and controlled trial during periods of 7-9 days at baseline and 2 weeks of treatment. Geriatric medical center of the university's general hospital. Individuals with probable AD and SD. The complete analysis comprised 30 patients assigned to either the active treatment group (N = 15) or the placebo group (N = 15). Patients received 50 mg of trazodone once daily at 10:00 P.M. or placebo in a 1:1 ratio for 2 weeks. Patients were evaluated using actigraphy and structured scales before and after intervention. Compared with the placebo group, trazodone users slept 42.5 more minutes per night and had their nighttime percent sleep increased 8.5 percentage points according to actigraphic data post-treatment. Neither trazodone nor placebo induced significant daytime sleepiness or naps. The treatments with trazodone or placebo did not show any effects either on cognition (Mini-Mental State Examination, forward/backward digit span task, letter-number sequencing, arithmetic, digit symbol-coding, and symbol search) or functionality (Katz index). There were no differences in frequency or severity rating of adverse events between the groups. This study shows significant therapeutic effects of trazodone 50 mg in community-dwelling AD patients with SD. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Parecoxib Provides Analgesic and Opioid-Sparing Effects Following Major Orthopedic Surgery: A Subset Analysis of a Randomized, Placebo-Controlled Clinical Trial.

PubMed

Diaz-Borjon, Efrain; Torres-Gomez, Armando; Essex, Margaret Noyes; Salomon, Patricia; Li, Chunming; Cheung, Raymond; Parsons, Bruce

2017-06-01

Orthopedic surgeries are among the most common and most painful surgeries performed. A multimodal analgesic approach is recommended to reduce opioid consumption, provide effective pain relief, and improve outcomes following surgery. This study examined the efficacy and opioid-sparing effects of parecoxib following major orthopedic surgery. This subset analysis of a large, multicenter, randomized, double-blind, placebo-controlled study of parecoxib examined treatment effects on postoperative pain severity, pain interference with function, opioid consumption, occurrence of opioid-related symptoms, safety, and patient satisfaction following major orthopedic surgery. Pain scores were significantly lower in the parecoxib group (n = 142) compared with placebo (n = 139) on day 2 (-22%; p < 0.001) and day 3 (-17%; p = 0.004). Pain interference with function scores were also significantly lower in the parecoxib group on day 2 (-32%; p < 0.001) and day 3 (-27%; p = 0.003) relative to placebo. Additionally, significantly less supplemental morphine was required in the parecoxib group relative to placebo through 24 h (-28%; p = 0.008) and 48 h (-33%; p < 0.001). Patients in the parecoxib group had a reduced risk of experiencing opioid-related symptoms including fatigue, drowsiness, inability to concentrate, confusion, nausea, constipation, and confusion on day 2 and/or day 3. Finally, more patients receiving parecoxib (42%) rated treatment as "excellent" compared to those receiving placebo (21%). These findings support the use of parecoxib for the management of pain following major orthopedic surgery.

Immunomodulatory Effects of ResistAid™: A Randomized, Double-Blind, Placebo-Controlled, Multidose Study

PubMed Central

Udani, Jay K.

2013-01-01

Objective To evaluate the ability of a proprietary arabinogalactan extract from the larch tree (ResistAid, Lonza Ltd., Basel, Switzerland) to change the immune response in healthy adults to a standardized antigenic challenge (tetanus and influenza vaccines) in a dose-dependent manner compared to placebo. Methods This randomized, double-blind, placebo-controlled trial included 75 healthy adults (18–61 years old). Subjects were randomized to receive either 1.5 or 4.5 g/day of ResistAid or placebo for 60 days. At day 30, subjects were administered both tetanus and influenza vaccines. Serum antigenic response (tetanus immunoglobulin G [IgG], influenza A and B IgG and immunoglobulin M [IgM]) was measured at days 45 (15 days after vaccination) and 60 (30 days after vaccination) of the study and compared to baseline antibody levels. Frequency and intensity of adverse events were monitored throughout the study. Results As expected, all 3 groups demonstrated an expected rise in tetanus IgG levels 15 and 30 days following the vaccine. There was a strongly significant difference in the rise in IgG levels at day 60 in the 1.5 g/day group compared to placebo (p = 0.008). In the 4.5 g/day group, there was significant rise in tetanus IgG at days 45 and 60 compared to baseline (p < 0.01) but these values were not significant compared to placebo. Neither group demonstrated any significant elevations in IgM or IgG antibodies compared to placebo following the influenza vaccine. There were no clinically or statistically significant or serious adverse events. Conclusions ResistAid at a dose of 1.5 g/day significantly increased the IgG antibody response to tetanus vaccine compared to placebo. In conjunction with earlier studies, this validates the effect of ResistAid on the augmentation of the response to bacterial antigens (in the form of vaccine). PMID:24219376

Immunomodulatory effects of ResistAid™: A randomized, double-blind, placebo-controlled, multidose study.

PubMed

Udani, Jay K

2013-01-01

To evaluate the ability of a proprietary arabinogalactan extract from the larch tree (ResistAid, Lonza Ltd., Basel, Switzerland) to change the immune response in healthy adults to a standardized antigenic challenge (tetanus and influenza vaccines) in a dose-dependent manner compared to placebo. This randomized, double-blind, placebo-controlled trial included 75 healthy adults (18-61 years old). Subjects were randomized to receive either 1.5 or 4.5 g/day of ResistAid or placebo for 60 days. At day 30, subjects were administered both tetanus and influenza vaccines. Serum antigenic response (tetanus immunoglobulin G [IgG], influenza A and B IgG and immunoglobulin M [IgM]) was measured at days 45 (15 days after vaccination) and 60 (30 days after vaccination) of the study and compared to baseline antibody levels. Frequency and intensity of adverse events were monitored throughout the study. As expected, all 3 groups demonstrated an expected rise in tetanus IgG levels 15 and 30 days following the vaccine. There was a strongly significant difference in the rise in IgG levels at day 60 in the 1.5 g/day group compared to placebo (p = 0.008). In the 4.5 g/day group, there was significant rise in tetanus IgG at days 45 and 60 compared to baseline (p < 0.01) but these values were not significant compared to placebo. Neither group demonstrated any significant elevations in IgM or IgG antibodies compared to placebo following the influenza vaccine. There were no clinically or statistically significant or serious adverse events. ResistAid at a dose of 1.5 g/day significantly increased the IgG antibody response to tetanus vaccine compared to placebo. In conjunction with earlier studies, this validates the effect of ResistAid on the augmentation of the response to bacterial antigens (in the form of vaccine).

Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine

NASA Technical Reports Server (NTRS)

Jankovic, J.; Gilden, J. L.; Hiner, B. C.; Kaufmann, H.; Brown, D. C.; Coghlan, C. H.; Rubin, M.; Fouad-Tarazi, F. M.

1993-01-01

PURPOSE: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure. PATIENTS: Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years). METHODS: After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level). RESULTS: Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%). CONCLUSION: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

Randomized, Double-Blind, Placebo-Controlled Trial of Asenapine Maintenance Therapy in Adults With an Acute Manic or Mixed Episode Associated With Bipolar I Disorder.

PubMed

Szegedi, Armin; Durgam, Suresh; Mackle, Mary; Yu, Sung Yun; Wu, Xiao; Mathews, Maju; Landbloom, Ronald P

2018-01-01

The authors determined the efficacy and safety of asenapine in preventing recurrence of any mood episode in adults with bipolar I disorder. Adults with an acute manic or mixed episode per DSM-IV-TR criteria were enrolled in this randomized, placebo-controlled trial consisting of an initial 12- to 16-week open-label period and a 26-week double-blind randomized withdrawal period. The target asenapine dosage was 10 mg b.i.d. in the open-label period but could be titrated down to 5 mg b.i.d. After completing the open-label period, subjects meeting stabilization/stable-responder criteria were randomized to asenapine or placebo treatment in the double-blind period. The primary efficacy endpoint was time to recurrence of any mood event during the double-blind period. Kaplan-Meier estimation was performed, and 95% confidence intervals were determined. Safety was assessed throughout. A total of 549 subjects entered the open-label period, of whom 253 enrolled in the double-blind randomized withdrawal period (127 in the placebo group; 126 in the asenapine group). Time to recurrence of any mood episode was statistically significantly longer for asenapine- than placebo-treated subjects. In post hoc analyses, significant differences in favor of asenapine over placebo were seen in time to recurrence of manic and depressive episodes. The most common treatment-emergent adverse events were somnolence (10.0%), akathisia (7.7%), and sedation (7.7%) in the open-label period and mania (11.9% of the placebo group compared with 4.0% of the asenapine group) and bipolar I disorder (6.3% compared with 1.6%) in the double-blind period. Long-term treatment with asenapine was more effective than placebo in preventing recurrence of mood events in adults with bipolar I disorder and was generally well-tolerated.

Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study123

PubMed Central

Velmurugan, Shanti; Gan, Jasmine Ming; Rathod, Krishnaraj S; Khambata, Rayomand S; Ghosh, Suborno M; Hartley, Amy; Van Eijl, Sven; Sagi-Kiss, Virag; Chowdhury, Tahseen A; Curtis, Mike; Kuhnle, Gunter GC; Wade, William G; Ahluwalia, Amrita

2016-01-01

Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: −0.4, −0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo treatment. Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts. This trial was registered at clinicaltrials.gov as NCT01493752. PMID:26607938

Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial.

PubMed

Raal, Frederick J; Santos, Raul D; Blom, Dirk J; Marais, A David; Charng, Min-Ji; Cromwell, William C; Lachmann, Robin H; Gaudet, Daniel; Tan, Ju L; Chasan-Taber, Scott; Tribble, Diane L; Flaim, Joann D; Crooke, Stanley T

2010-03-20

Homozygous familial hypercholesterolaemia is a rare genetic disorder in which both LDL-receptor alleles are defective, resulting in very high concentrations of LDL cholesterol in plasma and premature coronary artery disease. This study investigated whether an antisense inhibitor of apolipoprotein B synthesis, mipomersen, is effective and safe as an adjunctive agent to lower LDL cholesterol concentrations in patients with this disease. This randomised, double-blind, placebo-controlled, phase 3 study was undertaken in nine lipid clinics in seven countries. Patients aged 12 years and older with clinical diagnosis or genetic confirmation of homozygous familial hypercholesterolaemia, who were already receiving the maximum tolerated dose of a lipid-lowering drug, were randomly assigned to mipomersen 200 mg subcutaneously every week or placebo for 26 weeks. Randomisation was computer generated and stratified by weight (<50 kg vs >/=50 kg) in a centralised blocked randomisation, implemented with a computerised interactive voice response system. All clinical, medical, and pharmacy personnel, and patients were masked to treatment allocation. The primary endpoint was percentage change in LDL cholesterol concentration from baseline. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00607373. 34 patients were assigned to mipomersen and 17 to placebo; data for all patients were analysed. 45 patients completed the 26-week treatment period (28 mipomersen, 17 placebo). Mean concentrations of LDL cholesterol at baseline were 11.4 mmol/L (SD 3.6) in the mipomersen group and 10.4 mmol/L (3.7) in the placebo group. The mean percentage change in LDL cholesterol concentration was significantly greater with mipomersen (-24.7%, 95% CI -31.6 to -17.7) than with placebo (-3.3%, -12.1 to 5.5; p=0.0003). The most common adverse events were injection-site reactions (26 [76%] patients in mipomersen group vs four [24%] in placebo group). Four (12%) patients in the mipomersen group but none in the placebo group had increases in concentrations of alanine aminotransferase of three times or more the upper limit of normal. Inhibition of apolipoprotein B synthesis by mipomersen represents a novel, effective therapy to reduce LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia who are already receiving lipid-lowering drugs, including high-dose statins. ISIS Pharmaceuticals and Genzyme Corporation. Copyright 2010 Elsevier Ltd. All rights reserved.

A randomized controlled study of finerenone versus placebo in Japanese patients with type 2 diabetes mellitus and diabetic nephropathy.

PubMed

Katayama, Shigehiro; Yamada, Daishiro; Nakayama, Mikihiro; Yamada, Takashi; Myoishi, Masafumi; Kato, Masaharu; Nowack, Christina; Kolkhof, Peter; Yamasaki, Yoshimitsu

2017-04-01

Finerenone (BAY 94-8862) is a novel non-steroidal mineralocorticoid receptor antagonist. The aim of this study was to compare the efficacy and safety of seven once-daily oral doses of finerenone (1.25-20mg) and placebo in 96 patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) receiving a RAS blocker. ARTS-DN Japan was a multicenter, randomized, double-blind, placebo-controlled, phase 2b study. Analysis of the urinary albumin-to-creatinine ratio (UACR) at day 90 relative to baseline indicated a nominally significant effect of finerenone. The UACR at day 90 relative to baseline for each finerenone treatment group was numerically reduced compared with placebo. No serious adverse events (AEs) or deaths were reported and no patients experienced treatment-emergent AEs resulting in discontinuation of study drug. Small mean increases in serum potassium level were observed in the finerenone treatment groups (0.025-0.167mmol/L) compared with the placebo group (-0.075mmol/L); no patients developed hyperkalemia. When given in addition to a RAS inhibitor, finerenone reduced albuminuria without adverse effects on serum potassium levels or renal function in Japanese patients with T2DM and DN. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The effects of paracetamol (acetaminophen) on hepatic tests in patients who chronically abuse alcohol - a randomized study.

PubMed

Dart, R C; Green, J L; Kuffner, E K; Heard, K; Sproule, B; Brands, B

2010-08-01

Retrospective accounts suggest that therapeutic doses of paracetamol can produce severe hepatic injury in patients with putative high-risk conditions, including alcoholism and infectious hepatitis. Metabolism of paracetamol to its hepatotoxic metabolite is enhanced in patients who abuse alcohol, who also have compromised liver defences from depressed hepatic glutathione. To determine the effect of paracetamol on serum liver tests of newly abstinent subjects who abuse alcohol, including subjects with hepatitis C infection. A randomized, double-blind, placebo-controlled study. Adult alcohol abusers with a current drinking episode longer than 7 days received either placebo or paracetamol 4 g/day for 5 days. Of 142 subjects enrolled, 74 received paracetamol and 68 received placebo. Mean ALT activity during treatment increased from 48 to 62 IU/L in the paracetamol group and from 47 to 49 IU/L in the placebo group. Maximum ALT was 238 and 249 IU/L in the paracetamol and control groups respectively. The INR remained unchanged and serum bilirubin decreased in both groups. Subgroup analyses for subjects with alcoholic hepatitis, hepatitis C virus antibody and other subgroups showed no statistical difference between groups. Administration of paracetamol 4 g/day appears safe in newly abstinent patients who abuse alcohol.

Zinc-rich oysters as well as zinc-yeast- and astaxanthin-enriched food improved sleep efficiency and sleep onset in a randomized controlled trial of healthy individuals.

PubMed

Saito, Hitomi; Cherasse, Yoan; Suzuki, Rina; Mitarai, Makoto; Ueda, Fumitaka; Urade, Yoshihiro

2017-05-01

Zinc is an essential mineral that plays an important role in the body. We previously reported that orally feeding zinc-enriched yeast to mice induces nonrapid-eye-movement sleep. In addition, astaxanthin, an antioxidant abundant in seafood such as salmon and krill, is able to chelate minerals and may promote zinc absorption, which in return may also improve sleep. The purpose of our study was to examine the effect of zinc-rich and astaxanthin-containing food on sleep in humans. We conducted a randomized, double-blinded, placebo-controlled parallel group trial of 120 healthy subjects and recorded their night activity by actigraphy for 12 weeks. These subjects were divided into four groups: placebo, zinc-rich food, zinc-, and astaxanthin-rich food, and placebo supplemented with zinc-enriched yeast and astaxanthin oil. Compared with the placebo group, the zinc-rich food group efficiently decreased the time necessary to fall asleep and improved sleep efficiency, whereas the group that ingested zinc-enriched yeast and astaxanthin oil significantly improved the sleep onset latency. Actigraphic sleep monitoring demonstrated that eating zinc-rich food improved sleep onset latency as well as improved the sleep efficiency in healthy individuals. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Penicillin to prevent recurrent leg cellulitis.

PubMed

Thomas, Kim S; Crook, Angela M; Nunn, Andrew J; Foster, Katharine A; Mason, James M; Chalmers, Joanne R; Nasr, Ibrahim S; Brindle, Richard J; English, John; Meredith, Sarah K; Reynolds, Nicholas J; de Berker, David; Mortimer, Peter S; Williams, Hywel C

2013-05-02

Cellulitis of the leg is a common bacterial infection of the skin and underlying tissue. We compared prophylactic low-dose penicillin with placebo for the prevention of recurrent cellulitis. We conducted a double-blind, randomized, controlled trial involving patients with two or more episodes of cellulitis of the leg who were recruited in 28 hospitals in the United Kingdom and Ireland. Randomization was performed according to a computer-generated code, and study medications (penicillin [250 mg twice a day] or placebo for 12 months) were dispensed by a central pharmacy. The primary outcome was the time to a first recurrence. Participants were followed for up to 3 years. Because the risk of recurrence was not constant over the 3-year period, the primary hypothesis was tested during prophylaxis only. A total of 274 patients were recruited. Baseline characteristics were similar in the two groups. The median time to a first recurrence of cellulitis was 626 days in the penicillin group and 532 days in the placebo group. During the prophylaxis phase, 30 of 136 participants in the penicillin group (22%) had a recurrence, as compared with 51 of 138 participants in the placebo group (37%) (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P=0.01), yielding a number needed to treat to prevent one recurrent cellulitis episode of 5 (95% CI, 4 to 9). During the no-intervention follow-up period, there was no difference between groups in the rate of a first recurrence (27% in both groups). Overall, participants in the penicillin group had fewer repeat episodes than those in the placebo group (119 vs. 164, P=0.02 for trend). There was no significant between-group difference in the number of participants with adverse events (37 in the penicillin group and 48 in the placebo group, P=0.50). In patients with recurrent cellulitis of the leg, penicillin was effective in preventing subsequent attacks during prophylaxis, but the protective effect diminished progressively once drug therapy was stopped. (Funded by Action Medical Research; PATCH I Controlled-Trials.com number, ISRCTN34716921.).

Dronabinol for the Treatment of Cannabis Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Levin, Frances R.; Mariani, John J.; Brooks, Daniel J.; Pavlicova, Martina; Cheng, Wendy; Nunes, Edward

2011-01-01

Cannabis dependence is a substantial public health problem. Behavioral treatments have shown promise, but there are no effective medications for cannabis dependence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, in treating cannabis dependence. 156 cannabis-dependent adults were enrolled in a randomized, double-blind, placebo-controlled, 12-week trial. After a 1-week placebo lead-in phase, participants were randomized to receive dronabinol 20 mg twice a day or placebo. Doses were maintained until the end of week 8 and then tapered off over 2 weeks. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline followback method. There was no significant difference between treatment groups in the proportion of participants who achieved 2 weeks of abstinence at the end of the maintenance phase (dronabinol: 17.7%; placebo: 15.6%). Although both groups showed a reduction in marijuana use over time, there were no differences between the groups. Treatment retention was significantly higher at the end of the maintenance phase on dronabinol (77%), compared to placebo (61%) (P = .02), and withdrawal symptoms were significantly lower on dronabinol than placebo (P= .02). This is the first trial using an agonist substitution strategy for treatment of cannabis dependence. Dronabinol showed promise, it was well-tolerated, and improved treatment retention and withdrawal symptoms. Future trials might test higher doses, combinations of dronabinol with other medications with complementary mechanisms, or with more potent behavioral interventions. PMID:21310551

Propranolol as an adjunct therapy for hyperthyroid tremor.

PubMed

Henderson, J M; Portmann, L; Van Melle, G; Haller, E; Ghika, J A

1997-01-01

We evaluated the use of propranolol as an adjunct to carbimazole in the treatment of hyperthyroid tremor and tachycardia in a double-blind, cross-over and placebo-controlled study. Seven patients were given carbimazole plus either placebo or propranolol (40 mg) for 1 month and then switched to the alternative adjunct treatment for a further month. All patients showed significant improvements (p < 0.001) of heart rate and tremor amplitude after 1 or 2 months from baseline. One month after the baseline, the mean improvements of heart rate were 23% for the carbimazole + placebo group and 38% for carbimazole + propranolol group. Tremor also improved during the 1st month of the study by 31% in the carbimazole + placebo group versus 59% in the carbimazole + propranolol group. Whereas further improvements were observed in both variables in those receiving propranolol as the second adjunct treatment, this was not the case in those who received placebo during the same period. These findings confirm that the beta-blocker propranolol is a useful adjunct in the early treatment of both the tremor and tachycardia of hyperthyroidism.

Antipsychotic treatment of very late-onset schizophrenia-like psychosis (ATLAS): a randomised, controlled, double-blind trial.

PubMed

Howard, Robert; Cort, Elizabeth; Bradley, Rosie; Harper, Emma; Kelly, Linda; Bentham, Peter; Ritchie, Craig; Reeves, Suzanne; Fawzi, Waleed; Livingston, Gill; Sommerlad, Andrew; Oomman, Sabu; Nazir, Ejaz; Nilforooshan, Ramin; Barber, Robert; Fox, Chris; Macharouthu, Ajay Verma; Ramachandra, Pranathi; Pattan, Vivek; Sykes, John; Curran, Val; Katona, Cornelius; Dening, Tom; Knapp, Martin; Gray, Richard

2018-07-01

Very late (aged ≥60 years) onset schizophrenia-like psychosis occurs frequently but no placebo-controlled, randomised trials have assessed the efficacy and risks of antipsychotic treatment. We investigated whether low-dose amisulpride (100 mg daily) is superior to placebo in reducing psychosis symptoms over 12 weeks and whether any benefit is maintained by continuing treatment after 12 weeks. The ATLAS double-blind controlled trial enrolled participants from 25 old age psychiatry services in the UK. Eligible participants (ie, those with a diagnosis of very late-onset schizophrenia-like psychosis and a Brief Psychiatric Rating Scale [BPRS] score of ≥30, without cognitive impairment) were randomly assigned (1:1:1) to one of three groups in a two-stage trial: amisulpride in stage 1 and 2 (group A), amisulpride then placebo (group B), or placebo then amisulpride (group C). Treatment (100 mg oral amisulpride daily vs placebo) was given for 12 weeks in stage 1 and, initially, 24 weeks then reduced to 12 weeks in stage 2. Participants, investigators, and outcome assessors were masked to treatment allocation. Primary outcomes were psychosis symptoms assessed by the BPRS at 4, 12, and 24, or 36 weeks, and trial treatment discontinuation for non-efficacy. The primary, secondary, and safety endpoints were all analysed in participants given at least one dose of study treatment in modified intention-to-treat analyses. This study is registered with EudraCT, number 2010-022184-35, and ISRCTN, number ISRCTN45593573. Between Sept 27, 2012, and June 28, 2016, we recruited 101 participants. 92 (91%) of 101 participants took trial medication, of whom 59 (64%) completed stage 1 and 34 (58%) of these 59 participants completed stage 2 treatment. Despite suboptimal compliance, improvements in BPRS scores at 12 weeks were 7·7 points (95% CI 3·8-11·5, p=0·0002) greater with amisulpride (mean 11·9 points [SE 1·3]) than with placebo (4·2 points [1·0]). In stage 2, BPRS scores improved by a mean of 1·1 points (1·6) from 12 weeks to the final assessment in those who continued amisulpride but deteriorated by 5·2 points (2·0) in those who switched from amisulpride to placebo (difference 6·3 points [95% CI 0·9-11·7], p=0·024). Fewer participants who were allocated amisulpride than placebo stopped treatment because of non-efficacy in stage 1 (p=0·010) and stage 2 (p=0·031). Serious adverse events were reported more frequently in the amisulpride group than in the placebo group in stage 1 (p=0·057) and stage 2 (p=0·19). The most common serious adverse events were infection (five patients in the amisulpride group, three in the placebo group) and extrapyramidal side-effects (three patients in the amisulpride group, none in the placebo group). Five patients died during the study, one from a gastric ulcer bleed before treatment started (group B), two while taking stage 2 treatment (one in group A and one in group C), and two who stopped trial treatment in stage 1 and died many weeks later (one in group B and one in group C). No deaths were related to treatment. Low-dose amisulpride is effective and well tolerated as a treatment for very late-onset schizophrenia-like psychosis, with benefits maintained by prolonging treatment. UK National Institute for Health Research. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Neuroprotective effects of agmatine in experimental peripheral nerve injury in rats: a prospective randomized and placebo-controlled trial.

PubMed

Sezer, Aykut; Guclu, Bulent; Kazanci, Burak; Cakir, Murteza; Coban, Mustafa Kemal

2014-01-01

The purpose of this study was to demonstrate the activity of agmatine, an inducible nitric oxide synthase (iNOS) inhibitor and selective N-methyl-D-aspartate receptor (NMDAR) antagonist, on reducing tissue damage in distal part of traumatic nerve in an experimental rat peripheral nerve injury model. Sciatic nerves of 30 Sprague Dawley male rats were used. Rats were divided into 5 groups; group 1 (n=6), control group; group 2 (n=6), axonotmesis + placebo group; group 3 (n=6), axonotmesis + 50 mg/kg agmatine treatment group; group 4 (n=6), neurotmesis + placebo group; group 5 (n=6), neurotmesis + 50 mg/kg agmatine treatment group. Axonolysis, axon degeneration, edema, hemorrhage, and inflammation were evaluated in histopathologic examinations of all the groups. When group 2 was compared with group 3 in histopathologic sections, axonolysis was less in group 3 (p=0.007), as was axon degeneration (p=0.022) and edema (p=0.018). When group 4 was compared with group 5, axonolysis was less in group 5 (p=0.009), as was axon degeneration (p=0.006) and edema (p=0.021). This study demonstrated agmatine to have antioxidant and antineurotoxic effects in an experimental rat peripheral nerve injury model.

Microbiological and clinical effects of probiotics and antibiotics on nonsurgical treatment of chronic periodontitis: a randomized placebo- controlled trial with 9-month follow-up

PubMed Central

Morales, Alicia; Gandolfo, Alessandro; Bravo, Joel; Carvajal, Paola; Silva, Nora; Godoy, Claudia; Garcia-Sesnich, Jocelyn; Hoare, Anilei; Diaz, Patricia; Gamonal, Jorge

2018-01-01

ABSTRACT Objective The aim of this double-blind, placebo-controlled and parallel- arm randomized clinical trial was to evaluate the effects of Lactobacillus rhamnosus SP1-containing probiotic sachet and azithromycin tablets as an adjunct to nonsurgical therapy in clinical parameters and in presence and levels of Tannerella forsythia, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Material and Methods Forty-seven systemically healthy volunteers with chronic periodontitis were recruited and monitored clinically and microbiologically at baseline for 3, 6 and 9 months after therapy. Subgingival plaque samples were collected from four periodontal sites with clinical attachment level ≥1 mm, probing pocket depth ≥4 mm and bleeding on probing, one site in each quadrant. Samples were cultivated and processed using the PCR technique. Patients received nonsurgical therapy including scaling and root planing (SRP) and were randomly assigned to a probiotic (n=16), antibiotic (n = 16) or placebo (n = 15) group. L. rhamnosus SP1 was taken once a day for 3 months. Azithromycin 500mg was taken once a day for 5 days. Results All groups showed improvements in clinical and microbiological parameters at all time points evaluated. Probiotic and antibiotic groups showed greater reductions in cultivable microbiota compared with baseline. The placebo group showed greater reduction in number of subjects with P. gingivalis compared with baseline. However, there were no significant differences between groups. Conclusions The adjunctive use of L. rhamnosus SP1 sachets and azithromycin during initial therapy resulted in similar clinical and microbiological improvements compared with the placebo group. PMID:29364340

Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine

PubMed Central

Powers, Scott W.; Coffey, Christopher S.; Chamberlin, Leigh A.; Ecklund, Dixie J.; Klingner, Elizabeth A.; Yankey, Jon W.; Korbee, Leslie L.; Porter, Linda L.; Hershey, Andrew D.

2016-01-01

BACKGROUND Which, medication, if any, to use to prevent the headache of pediatric migraine has not been established. METHODS We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment. RESULTS A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P = 0.26; topiramate vs. placebo, P = 0.48; amitriptyline vs. topiramate, P = 0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group had a suicide attempt. CONCLUSIONS There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events. (Funded by the National Institutes of Health; CHAMP ClinicalTrials.gov number, NCT01581281). PMID:27788026

A study on the efficacy of rebamipide for patients with proton pump inhibitor-refractory non-erosive reflux disease.

PubMed

Adachi, Kyoichi; Furuta, Kenji; Miwa, Hiroto; Oshima, Tadayuki; Miki, Masaharu; Komazawa, Yoshinori; Iwakiri, Katsuhiko; Furuta, Takahisa; Koike, Tomoyuki; Shimatani, Tomohiko; Kinoshita, Yoshikazu

2012-06-01

Reflux symptoms in patients with non-erosive reflux disease (NERD) cannot be easily controlled by treatment with proton pump inhibitors (PPI). The anti-inflammatory function of rebamipide may be effective for protecting the esophageal mucosa. This prospective randomized multicenter placebo-controlled study was performed to clarify the efficacy of rebamipide for NERD patients whose reflux symptoms were refractory to PPI treatment. One hundred forty-nine patients were enrolled on the basis of a QUEST score of over 6 and absence of endoscopically proven esophageal mucosal breaks. All the patients were initially administered 15 mg of lansoprazole for 4 weeks, and the symptoms were then assessed using QUEST and GSRS. PPI-refractory patients were randomly assigned to administration of rebamipide or placebo t.i.d. for 4 weeks. Three of the 149 patients were lost to follow-up, and 60 among the remaining 146 patients were found to be PPI-refractory. Among these PPI-refractory patients, 31 were randomly assigned to a rebamipide group and 29 to a placebo group. At the end of drug administration, the QUEST and GSRS scores did not differ between the rebamipide and placebo groups, although a significantly higher proportion of patients in the rebamipide group showed amelioration of abdominal pain and diarrhea. Administration of rebamipide cannot effectively control reflux symptoms in NERD patients whose symptoms are refractory to PPI therapy.

Expectation-induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial.

PubMed

Vits, Sabine; Dissemond, Joachim; Schadendorf, Dirk; Kriegler, Lisa; Körber, Andreas; Schedlowski, Manfred; Cesko, Elvir

2015-12-01

Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation-induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative 'wound gel' was applied on one of the two wounds, whereas a 'non-active gel' was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non-active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation-induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Transcutaneous Nerve Stimulation for Pain Relief During Office Hysteroscopy: A Randomized Controlled Trial.

PubMed

Lisón, Juan F; Amer-Cuenca, Juan J; Piquer-Martí, Silvia; Benavent-Caballer, Vicente; Biviá-Roig, Gemma; Marín-Buck, Alejandro

2017-02-01

To evaluate the pain-relieving effect of transcutaneous electrical nerve stimulation (TENS) during office-based hysteroscopy without sedation. We conducted a randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to the active TENS, placebo TENS, or control group. The active TENS intervention consisted of a varying high-frequency (80-100 Hz), 400-microseconds, individually adjusted, high-intensity TENS application with two self-adhesive electrodes placed parallel to the spinal cord at the T10-L1 and S2-S4 levels. In the placebo group, participants were connected to the TENS unit but delivering no electrical stimulation. The primary outcome was self-reported pain intensity (0-100 mm) measured on a visual analog scale at several stages (entry, contact, biopsy, and residual). The minimum clinically relevant difference for the visual analog scale has been previously reported as 10 mm. Sample size was calculated to provide 80% power to show a 10-mm difference (α=0.0125) in the primary outcome. Secondary outcomes included duration of the procedure, vital parameters, vasovagal symptoms, and participant satisfaction index (0-10 rating scale). A total of 138 women (46 per group) participated in the study between January 2016 and April 2016. No differences were found between groups regarding age, weight, body mass index, parity status, menopausal status, or previous hysteroscopy status. Visual analog scale scores highlighted a decrease in pain in the active TENS group compared with the placebo group (entry: -11 mm, 95% confidence interval [CI] -17 to -5; contact: -21.9 mm, 95% CI -30 to -13.9; biopsy: -30.5 mm, 95% CI -47.1 to -13.8, P<.001). Moreover, the reduction in pain reached the minimum clinically relevant difference. Regarding satisfaction, results also revealed differences between active TENS and placebo groups (1.3, 95% CI 0.5-2.2, P=.001). Transcutaneous electrical nerve stimulation reduces pain and increases patient satisfaction during office hysteroscopy without sedation. ClinicalTrials.gov, www.clinicaltrials.gov, NCT02647008.

Prolonged Follow-Up of Patients in the U.S. Multicenter Trial of Ursodeoxycholic Acid for Primary Biliary Cirrhosis

PubMed Central

Combes, Burton; Luketic, Velimir A.; Peters, Marion G.; Zetterman, Rowen K.; Garcia-Tsao, Guadalupe; Munoz, Santiago J.; Lin, Danyu; Flye, Nancy; Carithers, Robert L.

2013-01-01

OBJECTIVE Randomized, double-blind, placebo-controlled trials of ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) have not demonstrated improvement in survival during the placebo-controlled phases of these trials. Analyses purporting to demonstrate a survival advantage of UDCA are largely dependent on data obtained after the placebo phases were terminated, and placebo-treated patients were offered open-label UDCA. After completion of our 2-yr placebo-controlled trial of UDCA in which we observed no survival benefit for UDCA, we provided the patients with open-label UDCA to see if delay in providing UDCA for 2 yr had any effect on subsequent liver transplantation or death without liver transplantation. METHODS In our previously reported 2-yr placebo-controlled trial, 151 patients with PBC were randomized to receive either UDCA (n = 77) or placebo (n = 74). The number of patients who progressed to liver transplantation or death without transplantation were similar in both the groups, 12 (16%) in the UDCA-treated and 11 (15%) in placebo-treated patients. All the patients were then offered open-label UDCA, with 61 original UDCA and 56 original placebo-treated patients now taking UDCA in an extended open-label phase of the trial. RESULTS No significant differences were observed in the number of patients who underwent liver transplantation or died without liver transplantation in the open-label phase of the trial. Moreover, no difference in the time to these endpoints was seen over the period of observation of as long as 6 yr from the time of initial randomization. CONCLUSIONS Results of open-label extensions of previous conducted placebo-controlled trials of UDCA in PBC leave uncertain whether UDCA impacts significantly on liver transplantation and death without liver transplantation in patients with PBC. PMID:15046215

Better sexual acceptability of agomelatine (25 and 50 mg) compared to escitalopram (20 mg) in healthy volunteers. A 9-week, placebo-controlled study using the PRSexDQ scale.

PubMed

Montejo, Angel L; Deakin, J F W; Gaillard, Raphael; Harmer, Catherine; Meyniel, Florent; Jabourian, Artin; Gabriel, Cecilia; Gruget, Celine; Klinge, Corinna; MacFayden, Christine; Milligan, Holly; Mullings, Emma; Goodwin, Guy

2015-10-01

The present double-blind, placebo-controlled study evaluates the effects of agomelatine and the selective serotonin reuptake inhibitor escitalopram on sexual dysfunction in healthy men and women. A total of 133 healthy volunteers (67 men, 66 women) were randomly assigned to agomelatine (25 or 50 mg) or escitalopram (20 mg) or placebo for nine weeks. Sexual acceptability was evaluated by using the psychotropic-related sexual dysfunction questionnaire 5-items total score and sexual dysfunction relative to each sub-score (in 110 volunteers with sexual activity). Sexual dysfunction was evaluated at baseline and after two, five and eight weeks of treatment and one week after drug discontinuation. The psychotropic-related sexual dysfunction questionnaire 5-items total score was significantly lower in both agomelatine groups versus escitalopram at all visits (p < 0.01 to p < 0.0001) with no difference between agomelatine and placebo nor between both agomelatine doses. Similar results were observed after drug discontinuation. The total score was significantly higher in the escitalopram group than in the placebo group at each post-baseline visit (p < 0.01 to p < 0.001). Similar results were observed regardless of volunteers' gender. Compared to placebo, only escitalopram significantly impaired dysfunction relative to "delayed orgasm or ejaculation" (p < 0.01) and "absence of orgasm or ejaculation" (p < 0.05 to p < 0.01). The percentage of participants with a sexual dysfunction was higher in the escitalopram group than in agomelatine groups (p < 0.01 to p < 0.05) and placebo (p < 0.01). The study confirms the better sexual acceptability profile of agomelatine (25 or 50 mg) in healthy men and women, compared to escitalopram. Evaluation of the effect of agomelatine and escitalopram on emotions and motivation in healthy male and female volunteers. ISRCTN75872983. © The Author(s) 2015.

Pharmacological and Expectancy Effects of a Low Amount of Alcohol Drinking on Outcome Valuation and Risk Perception in Males and Females

PubMed Central

Tsurugizawa, Tomokazu; Tokuda, Shinsuke; Harada, Tokiko; Takahashi, Taiki; Sadato, Norihiro

2016-01-01

The high-dose, alcohol-induced influences on risk perception and loss aversion depend on sex. On the other hand, low-dose alcohol has less effect on risky behavior. However, the effect of low-dose alcohol on subjective valuation of gain or loss and also the effect of placebo (expectancy of alcohol) on risk perception have not been fully investigated. We investigated the effects of low-dose alcohol (0.02 g/100 ml blood alcohol concentration) and placebo effects on subjective risk perception and subjective valuation of uncertain gain and loss in females and males. Participants in the control group and the placebo group were served alcohol-free, wine-flavored beverage and participants of alcohol group were served wine (14% alcohol). The placebo group was not informed that the drink was not alcohol but the control group was informed. Then paper–pencil tasks for subjective risk perception and valuation of gain or loss were performed 45 min after drinking the beverage. The participants were asked to draw the line on a 180 mm scale for each question. The placebo effects as well as the low-dose alcohol effects were observed in subjective valuations of gain or loss. Except for effect of beverages, a gender difference was also observed for subjective likelihood. The females estimated a low-probability loss as more likely and estimated a high-probability gain as less likely than did the males. From the Stevens’ law fitting analysis, the placebo, not alcohol, significantly induced the psychophysical effect of the subjective valuation of gain or loss. These results indicate that the psychological effects of expectancy of alcohol (placebo) could be a major factor in changing the subjective valuation of gain or loss over the pharmacological effects of a small amount of alcohol (like a glass of wine). Furthermore, these results also indicate that gender differences should be taken into account when investigating pharmacological or psychological effect on decision-making. PMID:27100898

A randomized, double-blind, placebo-controlled trial of a traditional herbal formula, Yukmijihwang-tang in elderly subjects with xerostomia.

PubMed

Han, Gajin; Ko, Seok-Jae; Kim, Juyeon; Oh, Ja-Young; Park, Jae-Woo; Kim, Jinsung

2016-04-22

Yukmijihwang-tang (YMJ) is a typical herbal formula to treat Yin-deficiency (YD) syndrome by enriching the fluid-humor of the body. YMJ has been used to treat dry mouth symptoms for hundreds of years in traditional East Asian medicine. Xerostomia, a subjective oral dryness, is common in the elderly and results in impaired quality of life. Many conventional treatments for xerostomia provide only temporary symptom relief, and have side effects. The aim of this study is to investigate the efficacy and safety of YMJ for the treatment of xerostomia in the elderly. This study was designed as a randomized, placebo-controlled, double-blinded, two center trial. Ninety-six subjects aged 60-80 years who had experienced xerostomia for at least 3 months and presented with score>40 on the visual analog scale (VAS) for subjective oral dryness were recruited and randomly allocated to YMJ and placebo groups. YMJ or placebo was administered to each group for 8 weeks (3g of YMJ or placebo, three times per day). The primary outcome was change of VAS for xerostomia from 0 to 8 weeks. VAS for xerostomia was decreased by 22.04±22.76 in the YMJ group and 23.58±23.04 in the placebo group. YMJ had no effect on xerostomia. However, participants with BMIs lower than 29.37kg/m(2) showed improvement of xerostomia after 8 weeks of treatment with YMJ compared to placebo. In addition, YMJ improved oral moisture, which is associated with subjective oral dryness in the YMJ group, and the relationship between VAS for xerostomia and YD was significant. A trend was observed in which YMJ improved oral moisture status and subjective oral dryness in elderly subjects with lower BMI and greater tendency toward YD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial.

PubMed

McGraw, Thomas

2016-01-01

To evaluate the safety and tolerability of aqueous solution concentrate (ASC) of polyethylene glycol (PEG) 3350 in patients with functional constipation. The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g) ASC or placebo solution for 14 days. The study comprised a screening period (visit 1), endoscopy procedure (visits 2 and 3), and followup telephone calls 30 days post-treatment. Safety end points included adverse events (AEs), clinical laboratory evaluations, vital signs, and others. The primary end points were the proportion of patients with abnormalities of the oral and esophageal mucosa, detected by visual and endoscopic examination of the oral cavity and esophagus, respectively, compared with placebo. A secondary objective was to compare the safety and tolerability of ASC by evaluating AEs or adverse drug reactions. A total of 65 patients were enrolled in this study, 31 were randomized to PEG 3350 ASC and 34 were randomized to placebo, of which 62 patients completed the study. No patients in either group showed abnormalities in inflammation of the oral mucosa during visit 2 (before treatment) or visit 3 (after treatment). Fewer abnormalities of the esophageal mucosa were observed in the PEG 3350 ASC group than in the placebo group on visit 3, with no significant difference in the proportion of abnormalities between the treatment groups. Overall, 40 treatment-emergent AEs were observed in 48.4% of patients treated with PEG 3350 ASC, and 41 treatment-emergent AEs were observed in 55.9% of patients treated with placebo - nonsignificant difference of -7.5% (95% CI: -21.3, 6.3) between treatment groups. No serious AEs or deaths were reported, and no patient discontinued because of an AE. PEG 3350 ASC is safe and well tolerated in patients with functional constipation (NCT01885104).

Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial

PubMed Central

McGraw, Thomas

2016-01-01

Purpose To evaluate the safety and tolerability of aqueous solution concentrate (ASC) of polyethylene glycol (PEG) 3350 in patients with functional constipation. Patients and methods The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g) ASC or placebo solution for 14 days. The study comprised a screening period (visit 1), endoscopy procedure (visits 2 and 3), and followup telephone calls 30 days post-treatment. Safety end points included adverse events (AEs), clinical laboratory evaluations, vital signs, and others. The primary end points were the proportion of patients with abnormalities of the oral and esophageal mucosa, detected by visual and endoscopic examination of the oral cavity and esophagus, respectively, compared with placebo. A secondary objective was to compare the safety and tolerability of ASC by evaluating AEs or adverse drug reactions. Results A total of 65 patients were enrolled in this study, 31 were randomized to PEG 3350 ASC and 34 were randomized to placebo, of which 62 patients completed the study. No patients in either group showed abnormalities in inflammation of the oral mucosa during visit 2 (before treatment) or visit 3 (after treatment). Fewer abnormalities of the esophageal mucosa were observed in the PEG 3350 ASC group than in the placebo group on visit 3, with no significant difference in the proportion of abnormalities between the treatment groups. Overall, 40 treatment-emergent AEs were observed in 48.4% of patients treated with PEG 3350 ASC, and 41 treatment-emergent AEs were observed in 55.9% of patients treated with placebo – nonsignificant difference of −7.5% (95% CI: −21.3, 6.3) between treatment groups. No serious AEs or deaths were reported, and no patient discontinued because of an AE. Conclusion PEG 3350 ASC is safe and well tolerated in patients with functional constipation (NCT01885104). PMID:27486340