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-masked, placebo-controlled study of fluoxetine for hypochondriasis.

PubMed

Fallon, Brian A; Petkova, Eva; Skritskaya, Natalia; Sanchez-Lacay, Arturo; Schneier, Franklin; Vermes, Donna; Cheng, Jianfeng; Liebowitz, Michael R

2008-12-01

This study assessed the efficacy, durability, and tolerability of fluoxetine for hypochondriasis, a disorder for which controlled pharmacological trials are scarce. Fifty-seven patients with hypochondriasis were enrolled: 12 discontinued during the placebo run-in, and 45 were randomized to either fluoxetine or placebo for 12 weeks (acute treatment). Responder status was defined as a Clinical Global Impression rating for hypochondriasis of much or very much improved. Secondary outcome measures included severity of hypochondriasis, somatization, anxiety, and depression. Responders to acute treatment entered a 12-week maintenance phase to week 24. Sustained responders at week 24 entered a 12-week double-masked discontinuation phase. Primary analysis used the intent-to-treat sample. More patients responded with improvement in hypochondriasis when given fluoxetine compared with placebo, starting at week 8 (50.0% vs 19.0%, P = 0.03) and continuing to week 12 (62.5% vs 33.3%, P = 0.05). Mean dose at week 12 dose was 51.4 mg (SD, +/-23 mg). The acute treatment response was maintained to week 24 with more responders in the fluoxetine compared with the placebo group (54.2% vs 23.8%, P = 0.04). Significant improvement was not noted on the continuous secondary outcomes measures of hypochondriasis, with the exception of the Clinical Global Impression hypochondriasis severity scale at week 24. Likelihood of response was not associated with severity of psychiatric comorbidity. Durability of response after controlled drug discontinuation could not be reasonably assessed, given the small sample size of patients who entered the discontinuation phase (n = 10). Fluoxetine was well tolerated, with no significant differences in discontinuation due to side effects between treatment groups. Fluoxetine is a moderately effective and well-tolerated treatment for hypochondriasis.

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.

[Placebo-controlled trials in schizophrenia].

PubMed

Melamed, Yuval; Davidson, Michael; Bleich, Avi

2004-03-01

Clinical trials involving human subjects give rise to ethical and medico-legal dilemmas. Essential research of new drugs may potentially expose patients to ineffective medications or to placebo. The complexity of the problem increases when dealing with mentally ill patients, for whom, on the one hand there is no known cure for their disease, and on the other hand, it is sometimes questionable whether or not they are able to provide informed consent to participate in clinical trials. The Israel Psychiatric Association decided to develop a position paper on the subject of placebo-controlled clinical trials in schizophrenia patients. Discussion groups were established, and the available material in the professional literature was examined, with an emphasis on recent developments. The Declaration of Helsinki and its amendments were analyzed, and experts in the field were consulted. Clinical drug trials for development of new medications are essential in all fields of medicine, especially in psychiatry. The requirement for a placebo arm in pharmaceutical trials presents ethical and clinical dilemmas that are especially complicated with regard to mentally ill persons whose free choice and ability to provide informed consent may be questionable. However, we do not believe that this predicament justifies unconditional rejection of placebo use in psychiatry, when it may provide substantial benefit for some patients. Simultaneously, it is our duty to provide stringent restrictions that will enable strict supervision over the scientific, clinical and ethical aspects of the trials. We propose the following criteria for approval of pharmaceutical trials that include a placebo arm: scientific justification; clinical and ethical justification; provision of informed consent; recruitment of patients hospitalized voluntarily; prevention of harm; administration of additional potential therapeutic interventions; benefit to patients participating in the study; control and follow

Double-blind, placebo-controlled study with alginate suspension for laryngopharyngeal reflux disease.

PubMed

Tseng, Wen-Hsuan; Tseng, Ping-Huei; Wu, Jia-Feng; Hsu, Ya-Chin; Lee, Ting-Yi; Ni, Yen-Hsuan; Wang, Hsiu-Po; Hsiao, Tzu-Yu; Hsu, Wei-Chung

2018-02-05

Treatment for laryngopharyngeal reflux disease (LPRD) is challenging because of delays in recognition and poor responsiveness to proton-pump inhibitor therapy. The aim of this study was to determine the efficacy and safety of liquid alginate suspension for treating LPRD. A double-blind, placebo-controlled, prospective study comparing 8 weeks of treatment with Alginos Oral Suspension (TTY Biopharm Co. Ltd., Taipei, Taiwan) (sodium alginate 1,000 mg three times daily) with a placebo was conducted on patients who fulfilled the criteria of at least one symptom consistent with LPRD, a total reflux symptom index (RSI) score of > 10, and a total reflux finding score (RFS) of > 5. Those with erosive gastroesophageal reflux disease, as evidenced through screened transnasal upper gastrointestinal endoscopy, were excluded. Efficacy was assessed by RSI, RFS, and ambulatory multichannel intraluminal impedance and pH (MII-pH) monitoring. A total of 80 patients aged 22 to 72 years were enrolled. Compared with baseline, both Alginos (TTY Biopharm Co. Ltd.) and the placebo significantly reduced the total RSI (P < 0.001) and the total number of reflux episodes shown by MII-pH monitoring (P < 0.05) after 8 weeks of treatment. However, liquid alginate suspension was unable to show superiority over the placebo. The incidence of various adverse events from Alginos (TTY Biopharm Co. Ltd.) was relatively low (7.7%) and mild. This study showed that liquid alginate suspension was well tolerated by LPRD patients. It effectively improved symptoms and reflux numbers but was unable to show superiority over placebo. As observed in previous studies, a great placebo effect was present. The importance of lifestyle modification could not be overlooked. 2. Laryngoscope, 00:000-000, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

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

Risperidone in children with autism: randomized, placebo-controlled, double-blind study.

PubMed

Nagaraj, Ravishankar; Singhi, Pratibha; Malhi, Prahbhjot

2006-06-01

Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism. We aimed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior (aggressiveness, hyperactivity, irritability), social and emotional responsiveness, and communication skills. We conducted a randomized, double-blind, placebo-controlled trial with 40 consecutive children with autism, whose ages ranged from 2 to 9 years, who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months. Autism symptoms were monitored periodically. The outcome variables were total scores on the Childhood Autism Rating Scale (CARS) and the Children's Global Assessment Scale (CGAS) after 6 months. Of the 40 children enrolled, 39 completed the trial over a period of 18 months; 19 received risperidone, and 20 received placebo. In the risperidone group, 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children's Global Assessment Scale score in the placebo group (P < .001 and P = .035, respectively). Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression. Risperidone was associated with increased appetite and a mild weight gain, mild sedation in 20%, and transient dyskinesias in three children. Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated.

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.

Effect of Intranasal Oxytocin Administration on Psychiatric Symptoms: A Meta-Analysis of Placebo-Controlled Studies

PubMed Central

Hofmann, Stefan G.; Fang, Angela; Brager, Daniel N.

2015-01-01

Clinical trials of intranasal administration of oxytocin for treating psychiatric problems have yielded mixed results. To conduct a quantitative review of placebo-controlled clinical trials of intranasally-administered oxytocin (OT) for psychiatric symptoms, manual and electronic searches using PubMed and PsycINFO were conducted. Of 1,828 entries, 16 placebo-controlled studies totaling 330 participants were included in the analysis. The overall placebo-controlled effect size was moderately strong (Hedges’ g = 0.67) and robust as suggested by the fail-safe N and funnel plot analysis. OT reduced symptoms of depression, anxiety, autism/repetitive behaviors, psychotic symptoms, and general psychopathology. In the combined sample, symptom reduction was moderated by frequency of administration. Publication year and diagnostic category did not moderate the effect of OT on the clinical outcome measures. We conclude that intranasal administration of OT is a potentially useful intervention for reducing psychiatric symptoms. However, more studies are needed to determine the best treatment target and to identify the mechanism of treatment change. PMID:26094200

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.

Twelve Months of Nightly Zolpidem Does Not Lead to Dose Escalation: A Prospective Placebo-Controlled Study

PubMed Central

Roehrs, Timothy A.; Randall, Surilla; Harris, Erica; Maan, Renee; Roth, Thomas

2011-01-01

Study Objectives: To assess hypnotic self-administration and likelihood of dose escalation over 12 months of nightly use of zolpidem versus placebo in primary insomniacs. Design: Randomized, double-blind, placebo-controlled, clinical trial. Setting: Outpatient with tri-monthly one-week, sleep laboratory assessments. Participants: Thirty-three primary insomniacs, without psychiatric disorders or drug and alcohol abuse, 32–64 yrs old, 14 men and 19 women. Interventions: Participants were randomized to take zolpidem 10 mg (n = 17) or placebo (n = 16) nightly for 12 months. In probes during month 1, 4, and 12, after sampling color-coded placebo or zolpidem capsules on 2 nights, color-coded zolpidem or placebo was chosen on 5 consecutive nights and 1, 2, or 3 of the chosen capsules (5 mg each) could be self-administered on a given choice night. Results: Zolpidem was chosen more nights than placebo (80% of nights) and number of nights zolpidem was chosen did not differ over the 12 months. More zolpidem than placebo capsules were self-administered, and the total number of placebo or zolpidem capsules self-administered did not differ as a function of duration of use. In contrast, the total number of placebo capsules self-administered by the placebo group increased across time. The nightly capsule self-administration on zolpidem nights did not differ from that on placebo nights and neither nightly self-administration rates increased over the 12 months. An average 9.3 mg nightly dose was self-administered. Conclusions: Zolpidem was preferred to placebo, but its self-administration did not increase with 12 months of use. Chronic hypnotic use by primary insomniacs does not lead to dose escalation. Clinical Trial Registration: Safety and Efficacy of Chronic Hypnotic Use; # NCT01006525; http://www.clinicaltrials.gov/ Citation: Roehrs TA; Randall S; Harris E; Maan R; Roth T. Twelve months of nightly zolpidem does not lead to dose escalation: a prospective placebo-controlled

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.

QUETIAPINE IMPROVES RESPONSE INHIBITION IN ALCOHOL DEPENDENT PATIENTS: A PLACEBO-CONTROLLED PILOT STUDY

PubMed Central

Moallem, Nathasha; Ray, Lara A.

2013-01-01

Rationale Quetiapine has been shown to be a promising medication for the treatment of alcoholism. As an atypical antipsychotic medication with antagonist activity at D1 and D2, 5-HT1A and 5-HT2A, H1 and α1 and α2 receptors, quetiapine has been found to decrease impulsivity in other psychiatric disorders but its effects on impulsivity have not been studied in alcohol dependent patients. Objective This study seeks to test the effects of quetiapine on a specific dimension of impulsivity, namely response inhibition. This pilot study seeks to further elucidate the mechanisms of action of quetiapine for alcohol use disorders. Method A total of 20 non-treatment seeking alcohol dependent individuals were randomized to one of the following conditions in a double-blind, placebo-controlled design: (1) quetiapine (400 mg/day); or (2) matched placebo. Participants completed two counterbalanced intravenous placebo-alcohol administration sessions as well as behavioral measure of response inhibition (i.e. stop signal task) pre and post placebo-alcohol administration sessions. Results Analyses revealed a significant effect of quetiapine in improving response inhibition as measured by the stop signal task. These results provide preliminary evidence suggesting that quetiapine improves response inhibition in alcohol dependent patients, as compared to placebo. Conclusion This pilot study contributes a novel putative mechanism of action of quetiapine in alcoholism, namely an improvement in response inhibition. PMID:22037407

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).

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.

Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia.

PubMed

Schabus, Manuel; Griessenberger, Hermann; Gnjezda, Maria-Teresa; Heib, Dominik P J; Wislowska, Malgorzata; Hoedlmoser, Kerstin

2017-04-01

See Thibault et al. (doi:10.1093/awx033) for a scientific commentary on this article.Neurofeedback training builds upon the simple concept of instrumental conditioning, i.e. behaviour that is rewarded is more likely to reoccur, an effect Thorndike referred to as the 'law of effect'. In the case of neurofeedback, information about specific electroencephalographic activity is fed back to the participant who is rewarded whenever the desired electroencephalography pattern is generated. If some kind of hyperarousal needs to be addressed, the neurofeedback community considers sensorimotor rhythm neurofeedback as the gold standard. Earlier treatment approaches using sensorimotor-rhythm neurofeedback indicated that training to increase 12-15 Hz sensorimotor rhythm over the sensorimotor cortex during wakefulness could reduce attention-deficit/hyperactivity disorder and epilepsy symptoms and even improve sleep quality by enhancing sleep spindle activity (lying in the same frequency range). In the present study we sought to critically test whether earlier findings on the positive effect of sensorimotor rhythm neurofeedback on sleep quality and memory could also be replicated in a double-blind placebo-controlled study on 25 patients with insomnia. Patients spent nine polysomnography nights and 12 sessions of neurofeedback and 12 sessions of placebo-feedback training (sham) in our laboratory. Crucially, we found both neurofeedback and placebo feedback to be equally effective as reflected in subjective measures of sleep complaints suggesting that the observed improvements were due to unspecific factors such as experiencing trust and receiving care and empathy from experimenters. In addition, these improvements were not reflected in objective electroencephalographic-derived measures of sleep quality. Furthermore, objective electroencephalographic measures that potentially reflected mechanisms underlying the efficacy of neurofeedback such as spectral electroencephalographic

Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia

PubMed Central

Griessenberger, Hermann; Gnjezda, Maria-Teresa; Heib, Dominik P. J.; Wislowska, Malgorzata; Hoedlmoser, Kerstin

2017-01-01

Abstract See Thibault et al. (doi:10.1093/awx033) for a scientific commentary on this article. Neurofeedback training builds upon the simple concept of instrumental conditioning, i.e. behaviour that is rewarded is more likely to reoccur, an effect Thorndike referred to as the ‘law of effect’. In the case of neurofeedback, information about specific electroencephalographic activity is fed back to the participant who is rewarded whenever the desired electroencephalography pattern is generated. If some kind of hyperarousal needs to be addressed, the neurofeedback community considers sensorimotor rhythm neurofeedback as the gold standard. Earlier treatment approaches using sensorimotor-rhythm neurofeedback indicated that training to increase 12–15 Hz sensorimotor rhythm over the sensorimotor cortex during wakefulness could reduce attention-deficit/hyperactivity disorder and epilepsy symptoms and even improve sleep quality by enhancing sleep spindle activity (lying in the same frequency range). In the present study we sought to critically test whether earlier findings on the positive effect of sensorimotor rhythm neurofeedback on sleep quality and memory could also be replicated in a double-blind placebo-controlled study on 25 patients with insomnia. Patients spent nine polysomnography nights and 12 sessions of neurofeedback and 12 sessions of placebo-feedback training (sham) in our laboratory. Crucially, we found both neurofeedback and placebo feedback to be equally effective as reflected in subjective measures of sleep complaints suggesting that the observed improvements were due to unspecific factors such as experiencing trust and receiving care and empathy from experimenters. In addition, these improvements were not reflected in objective electroencephalographic-derived measures of sleep quality. Furthermore, objective electroencephalographic measures that potentially reflected mechanisms underlying the efficacy of neurofeedback such as spectral

[The relationship between the placebo effect and spontaneous improvement in research on antidepressants. Are placebos powerless?].

PubMed

Hougaard, Esben

2005-08-08

Clinical trials of antidepressant medications have generally found large changes in groups given a placebo, which may be due to either spontaneous remission or a true placebo effect. This paper reviews the evidence for a true placebo effect in the treatment of unipolar depressed outpatients. Although there is no evidence from experimental studies, a rather substantial amount of circumstantial evidence indicates a true placebo effect. This article raises the question of whether it is meaningful to require experimental evidence for a loose and unspecified concept involving varying components such as placebo.

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 effect of vitamin-mineral supplementation on the intelligence of American schoolchildren: a randomized, double-blind placebo-controlled trial.

PubMed

Schoenthaler, S J; Bier, I D; Young, K; Nichols, D; Jansenns, S

2000-02-01

Many medical, nutrition, and education professionals have long suspected that poor diet impairs the academic performance of Western schoolchildren; academic performance often improves after improved diet. However, others have suggested that such academic gains may be due to psychologic effects rather than nutrition. To resolve this issue, two independent research teams conducted randomized trials in which children were given placebos or low-dose vitamin-mineral tablets designed to raise nutrient intake to the equivalent of a well-balanced diet. Both teams reported significantly greater gains in nonverbal intelligence among the supplemented groups. The findings were important because of the apparent inadequacy of diet they revealed and the magnitude of the potential for increased intelligence. However, none of the ten subsequent replications, or the two original trials, were without limitations leaving this issue in controversy. To determine if schoolchildren who consume low-dose vitamin-mineral tablets will have a significantly larger increase in nonverbal intelligence than children who consume placebos in a study that overcomes the primary criticisms directed at the previous 12 controlled trials. A double-blind, placebo-controlled trial using stratified randomization within each teacher's class based on preintervention nonverbal intelligence. Two "working class," primarily Hispanic, elementary schools in Phoenix, Arizona, participated in the study. Slightly more than half the teachers in each school distributed the tablets daily to 245 schoolchildren aged 6 to 12 years. Daily vitamin-mineral supplementation at 50% of the U.S. daily recommended allowance (RDA) for 3 months versus placebo. Post-test nonverbal IQ, as measured by the Wechsler Intelligence Scale for Children-Revised (WISC-R), while controlling for pretest nonverbal IQ as a covariate. FOUR MAIN RESULTS: First, a significant difference of 2.5 IQ points (95% CI: 1.85-3.15) was found between 125 children

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.

Randomised placebo-controlled trials of surgery: ethical analysis and guidelines.

PubMed

Savulescu, Julian; Wartolowska, Karolina; Carr, Andy

2016-12-01

Use of a placebo control in surgical trials is a divisive issue. We argue that, in principle, placebo controls for surgery are necessary in the same way as for medicine. However, there are important differences between these types of trial, which both increase justification and limit application of surgical studies. We propose that surgical randomised placebo-controlled trials are ethical if certain conditions are fulfilled: (1) the presence of equipoise, defined as a lack of unbiased evidence for efficacy of an intervention; (2) clinically important research question; (3) the risk to patients is minimised and reasonable; (4) there is uncertainty about treatment allocation rather than deception; (5) there is preliminary evidence for efficacy, which justifies a placebo-controlled design; and (6) ideally, the placebo procedure should have some direct benefit to the patient, for example, as a diagnostic tool. Placebo-controlled trials in surgery will most often be justified when surgery is performed to improve function or relieve symptoms and when objective outcomes are not available, while the risk of mortality or significant morbidity is low. In line with medical placebo-controlled trials, the surgical trial (1) should be sufficiently powered and (2) standardised so that its results are valid, (3) consent should be valid, (4) the standard treatment or rescue medication should be provided if possible, and (5) after the trial, the patients should be told which treatment they received and there should be provision for post-trial care if the study may result in long-term negative effects. We comment and contrast our guidelines with those of the American Medical Association. 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/.

Decline in placebo-controlled trial results suggests new directions for comparative effectiveness research.

PubMed

Olfson, Mark; Marcus, Steven C

2013-06-01

The Affordable Care Act offers strong support for comparative effectiveness research, which entails comparisons among active treatments, to provide the foundation for evidence-based practice. Traditionally, a key form of research into the effectiveness of therapeutic treatments has been placebo-controlled trials, in which a specified treatment is compared to placebo. These trials feature high-contrast comparisons between treatments. Historical trends in placebo-controlled trials have been evaluated to help guide the comparative effectiveness research agenda. We investigated placebo-controlled trials reported in four leading medical journals between 1966 and 2010. We found that there was a significant decline in average effect size or average difference in efficacy (the ability to produce a desired effect) between the active treatment and placebo. On average, recently studied treatments offered only small benefits in efficacy over placebo. A decline in effect sizes in conventional placebo-controlled trials supports an increased emphasis on other avenues of research, including comparative studies on the safety, tolerability, and cost of treatments with established efficacy.

Summary of anti-malarial prophylactic efficacy of tafenoquine from three placebo-controlled studies of residents of malaria-endemic countries.

PubMed

Dow, Geoffrey S; Liu, Jun; Lin, Gina; Hetzell, Brian; Thieling, Sarah; McCarthy, William F; Tang, Douglas; Smith, Bryan

2015-11-26

Tafenoquine is a long half-life primaquine analog being developed for malaria prophylaxis. The US Army recently performed a unified analysis of efficacy in preparation for a regulatory submission, utilizing legacy data from three placebo-controlled studies conducted in the late 1990s and early 2000s. The subjects were residents of Africa who were naturally exposed to Plasmodium falciparum for 12-26 weeks. The prophylactic efficacy of tafenoquine and mefloquine (included in some studies as a comparator) was calculated using incidence density among subjects who had completed the three-day loading doses of study drug, had at least one maintenance dose and had at least one blood smear assessed during the prophylactic period. The three placebo-controlled studies were analysed separately and then in two pooled analyses: one for tafenoquine versus placebo (three studies) and one for tafenoquine and mefloquine versus placebo (two studies). The pooled protective efficacy (PE) of a tafenoquine regimen with three daily loading doses plus weekly maintenance at 200-mg for 10 weeks or longer (referred to as 200-mg weekly hereafter) relative to placebo in three placebo-controlled studies was 93.1 % [95 % confidence interval (CI) 89.1-95.6 %; total N = 492]. The pooled PEs of regimens of tafenoquine 200-mg weekly and mefloquine 250-mg weekly relative to placebo in two placebo-controlled studies (total N = 519) were 93.5 % (95 % CI 88.6-96.2 %) and 94.5 % (95 % CI 88.7-97.3 %), respectively. Three daily loading plus weekly maintenance doses of 50- and 100-mg, but not 25-mg, exhibited similar PEs. The PEs of tafenoquine regimens of a three-day loading dose at 400-mg with and without follow-up weekly maintenance doses at 400-mg were 93.7 % (95 % CI 85.4-97.3 %) and 81.0 % (95 % CI 66.8-89.1 %), respectively. Tafenoquine provided the same level of prophylactic efficacy as mefloquine in residents of Africa. These data support the prophylactic efficacy of tafenoquine and mefloquine that

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

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.

Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans.

PubMed

Verhoef, Petra; Pasman, Wilrike J; Van Vliet, Trinette; Urgert, Rob; Katan, Martijn B

2002-12-01

A high plasma total homocysteine concentration is associated with increased risk of cardiovascular disease. Consumption of unfiltered or filtered coffee raises total homocysteine concentrations in healthy volunteers. The responsible compound, however, is unknown. The objective was to determine whether caffeine explains the homocysteine-raising effect of coffee. Forty-eight subjects aged 19-65 y completed this randomized crossover study with 3 treatments, each lasting 2 wk. Subjects consumed 6 capsules providing 870 mg caffeine/d (test treatment), 0.9 L paper-filtered coffee providing approximately 870 mg caffeine/d, or 6 placebo capsules. Blood samples were drawn fasting and 4 h after consumption of 0.45 L coffee or 3 capsules. The mean fasting plasma homocysteine concentration after the placebo treatment was 9.6 +/- 3.1 micro mol/L. The caffeine and coffee treatments increased fasting homocysteine by 0.4 micro mol/L (95% CI: 0.1, 0.7; P = 0.04), or 5%, and by 0.9 micro mol/L (95% CI: 0.6, 1.2; P = 0.0001), or 11%, respectively, compared with placebo. The increase in homocysteine concentrations 4 h after consumption of 0.45 L coffee relative to consumption of 3 placebo capsules was 19% (P = 0.0001). Caffeine treatment had a much weaker acute effect on homocysteine (4%; P = 0.09). Effects of caffeine were stronger in women than in men, but the effects of coffee did not differ significantly between men and women. Caffeine is partly responsible for the homocysteine-raising effect of coffee. Coffee, but not caffeine, affects homocysteine metabolism within hours after intake, although the effect is still substantial after an overnight fast.

Apremilast for Behçet's syndrome--a phase 2, placebo-controlled study.

PubMed

Hatemi, Gulen; Melikoglu, Melike; Tunc, Recep; Korkmaz, Cengiz; Turgut Ozturk, Banu; Mat, Cem; Merkel, Peter A; Calamia, Kenneth T; Liu, Ziqi; Pineda, Lilia; Stevens, Randall M; Yazici, Hasan; Yazici, Yusuf

2015-04-16

Oral ulcers, the hallmark of Behçet's syndrome, can be resistant to conventional treatment; therefore, alternative agents are needed. Apremilast is an oral phosphodiesterase-4 inhibitor that modulates several inflammatory pathways. We conducted a phase 2, multicenter, placebo-controlled study in which 111 patients with Behçet's syndrome who had two or more oral ulcers were randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12 weeks. This regimen was followed by a 12-week extension phase in which the placebo group was switched to apremilast and a 28-day post-treatment observational follow-up phase. The patients and clinicians were unaware of the study assignments throughout the trial. The primary end point was the number of oral ulcers at week 12. Secondary outcomes included pain from these ulcers (measured on a 100-mm visual-analogue scale, with higher scores indicating worse pain), the number of genital ulcers, overall disease activity, and quality of life. The mean (±SD) number of oral ulcers per patient at week 12 was significantly lower in the apremilast group than in the placebo group (0.5±1.0 vs. 2.1±2.6) (P<0.001). The mean decline in pain from oral ulcers from baseline to week 12 was greater with apremilast than with placebo (-44.7±24.3 mm vs. -16.0±32.5 mm) (P<0.001). Nausea, vomiting, and diarrhea were more common in the apremilast group (with 22, 9, and 12 incidents, respectively, among 55 patients) than in the placebo group (with 10, 1, and 2 incidents, respectively, among 56 patients), findings that were similar to those in previous studies of apremilast. There were two serious adverse events in patients receiving apremilast. Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet's syndrome. This preliminary study was neither large enough nor long enough to assess long-term efficacy, the effect on other manifestations of Behçet's syndrome, or the risk of uncommon serious

Fluoxetine and premature ejaculation: a double-blind, crossover, placebo-controlled study.

PubMed

Haensel, S M; Klem, T M; Hop, W C; Slob, A K

1998-02-01

The purpose of this study was to investigate the effect of fluoxetine on sexual function in men with premature ejaculation and/or erectile dysfunction and control subjects in a prospective, double-blind, placebo-controlled, crossover study. There were four groups: (1) premature ejaculation (PE, N = 9); (2) premature ejaculation and erectile dysfunction (PE/ED, N = 9); (3) erectile dysfunction (ED, N = 7); and (4) healthy, sexually functional control subjects (N = 15). The study consisted of three 4-week periods: fluoxetine, washout, and placebo (or vice versa). Fluoxetine began at 5 mg/day for 2 weeks, followed by 10 mg/day for 2 weeks. At weeks 0, 4, 8, and 12, subjects visited the laboratory for evaluation of sexual function and assessment of erectile response, ejaculation, and sexual arousal to visual erotic stimulation without and with concomitant vibrotactile stimulation to the penis. At home, daily logs for sexual activities and feelings of well-being were maintained, and nocturnal penile tumescence was measured. The latency to ejaculation increased significantly in the PE/ED group (p = 0.03) and in the PE and the PE/ED group taken together (p = 0.007) but not in the PE group alone. Fluoxetine stimulated objectively but not subjectively measured erectile response during laboratory assessment in all groups. No major side effects were reported. In conclusion, fluoxetine (5-10 mg/day) was effective in increasing latency to ejaculation in patients with PE (PE and PE/ED groups combined).

The efficacy of agomelatine in elderly patients with recurrent major depressive disorder: a placebo-controlled study.

PubMed

Heun, Reinhard; Ahokas, Antti; Boyer, Patrice; Giménez-Montesinos, Natalia; Pontes-Soares, Fernando; Olivier, Valérie

2013-06-01

The present placebo-controlled study evaluated the efficacy, tolerability, and safety of 8-week treatment with agomelatine (25-50 mg/d by mouth) in elderly patients with major depressive disorder (MDD). Elderly outpatients aged ≥ 65 years with a primary diagnosis of moderate to severe episode of recurrent MDD (DSM-IV-TR) were recruited in 27 clinical centers in Argentina, Finland, Mexico, Portugal, and Romania from November 2009 to October 2011. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS17) total score. A total of 222 elderly patients entered the study (151 in the agomelatine group, 71 in the placebo group), including 69 patients aged 75 years and older. Agomelatine improved depressive symptoms in the elderly population, as evaluated by the HDRS17 total score, in terms of last postbaseline value (agomelatine-placebo difference: mean estimate [standard error] = 2.67 [1.06] points; P = .013) and response to treatment (agomelatine, 59.5%; placebo, 38.6%; P = .004). The agomelatine-placebo difference according to the Clinical Global Impressions-Severity of Illness scale (CGI-S) score was 0.48 (0.19). The agomelatine-placebo difference (estimate [standard error]) for remission on the HDRS17 was 6.9% (4.7%) and did not achieve statistical significance (P = .179, post hoc analysis). Clinically relevant effects of agomelatine were confirmed on all end points in the subset of severely depressed patients (HDRS17 total score ≥ 25 and CGI-S score ≥ 5 at baseline). Agomelatine was well tolerated by patients, with only minimal distinctions from placebo. The present study provides the first evidence that an 8-week treatment with agomelatine 25-50 mg/d efficiently relieves depressive symptoms and is well tolerated in elderly depressed patients older than 65 years. Controlled-Trials.com identifier: ISRCTN57507360. © Copyright 2011 Physicians Postgraduate Press, Inc.

The ethics of placebo-controlled trials: a comparison of inert and active placebo controls.

PubMed

Edward, Sarah J L; Stevens, Andrew J; Braunholtz, David A; Lilford, Richard J; Swift, Teresa

2005-05-01

Because of the recent and controversial example of sham surgery for the evaluation of fetal tissue transplants for Parkinson's disease, there is renewed interest in the ethics of using "active" placebos in surgical trials, where otherwise there are no inert procedures available, and in pharmacological trials, where there are inert substances, but where patients may guess to which arm they have been allocated. This paper seeks to clarify the ethical arguments surrounding the use of active placebos in trials, and to set up a notation for assessing the ethics of trials more generally. We first establish an framework by which ethics committees can analyze such trials. We examine (1) the scientific value of the research; (2) the expected risks and benefits to individual patients, and (3) the voluntary nature of consent. We then contrast the implications of this framework for inert and active placebo-controlled trials, respectively. In particular, we analyze their relative expected utility using three main utility factors, namely, treatment effects, placebo effects, and altruism. We conclude that, when the intervention is already widely available, active placebo trials rely more heavily on altruism than do inert placebo trials and, when the intervention is restricted, this excess reliance may not be needed. What our analysis provides is the explicit justification for the apparent caution of Institutional Review Boards or ethics committees when reviewing sham operations, especially when the expected harm is not trivial and the risk of exploitation is high.

An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk.

PubMed

Rodgers, Anthony; Patel, Anushka; Berwanger, Otavio; Bots, Michiel; Grimm, Richard; Grobbee, Diederick E; Jackson, Rod; Neal, Bruce; Neaton, Jim; Poulter, Neil; Rafter, Natasha; Raju, P Krishnam; Reddy, Srinath; Thom, Simon; Vander Hoorn, Stephen; Webster, Ruth

2011-01-01

There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

Intravenous subhypnotic propofol in central pain: a double-blind, placebo-controlled, crossover study.

PubMed

Canavero, S; Bonicalzi, V

2004-01-01

To validate IV subhypnotic propofol, a gamma-aminobutyric acid A (GABA-A) agonist, as a diagnostic test for central pain. The efficacy of systemic propofol (0.2 mg/kg IV bolus) was evaluated in a double-blind, placebo-controlled and crossover fashion on both spontaneous ongoing pain and allodynia in 44 patients with chronic central pain of both brain and cord origin. Propofol was significantly superior to the placebo (Intralipid, Kabi Pharmacia) in reducing the intensity of spontaneous ongoing pain for up to 1 hour after the injection: 24 of 44 patients (55%) receiving propofol showed a significant reduction in spontaneous pain, whereas only 6 patients showed this after the placebo. Propofol also significantly reduced the intensity of both mechanical and cold allodynia. In a few cases, only the evoked components were abolished but not the spontaneous pain. In general, the side effects were minimal and consisted mainly of transitory burning upon injection of both propofol and placebo and slight lightheadedness in a few cases. Systemic propofol induces analgesic effects on all studied components of central pain and highlights the key role of GABA modulation in central pain.

Choto-san in the treatment of vascular dementia: a double-blind, placebo-controlled study.

PubMed

Terasawa, K; Shimada, Y; Kita, T; Yamamoto, T; Tosa, H; Tanaka, N; Saito, Y; Kanaki, E; Goto, S; Mizushima, N; Fujioka, M; Takase, S; Seki, H; Kimura, I; Ogawa, T; Nakamura, S; Araki, G; Maruyama, I; Maruyama, Y; Takaori, S

1997-03-01

In an earlier placebo-controlled study, we demonstrated that a kampo (Japanese herbal) medicine called Choto-san (Diao-Teng-San in Chinese) was effective in treating vascular dementia. To evaluate its efficacy using more objective criteria, we carried out a multi-center, double-blind study of Choto-san extract (7.5 g/day) and a placebo, each given three times a day for 12 weeks to patients suffering from this condition. The study enrolled and analyzed 139 patients, 50 males and 89 females, with a mean age of 76.6 years. Choto-san was statistically superior to the placebo in global improvement rating, utility rating, global improvement rating of subjective symptoms, global improvement rating of psychiatric symptoms and global improvement rating of disturbance in daily living activities. Such items as spontaneity of conversation, lack of facial expression, decline in simple mathematical ability, global intellectual ability, nocturnal delirium, sleep disturbance, hallucination or delusion, and putting on and taking off clothes were significantly improved at one or more evaluation points in those taking Choto-san compared to those taking the placebo. Furthermore, the change in revised version of Hasegawa's dementia scale from the beginning point in Choto-san group was tended to be higher than that in placebo group with no statistical significance. These results suggest that Choto-san is effective in the treatment of vascular dementia. Copyright © 1997 Gustav Fischer Verlag. Published by Elsevier GmbH.. All rights reserved.

Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy.

PubMed

Shang, Aijing; Huwiler-Müntener, Karin; Nartey, Linda; Jüni, Peter; Dörig, Stephan; Sterne, Jonathan A C; Pewsner, Daniel; Egger, Matthias

Homoeopathy is widely used, but specific effects of homoeopathic remedies seem implausible. Bias in the conduct and reporting of trials is a possible explanation for positive findings of trials of both homoeopathy and conventional medicine. We analysed trials of homoeopathy and conventional medicine and estimated treatment effects in trials least likely to be affected by bias. Placebo-controlled trials of homoeopathy were identified by a comprehensive literature search, which covered 19 electronic databases, reference lists of relevant papers, and contacts with experts. Trials in conventional medicine matched to homoeopathy trials for disorder and type of outcome were randomly selected from the Cochrane Controlled Trials Register (issue 1, 2003). Data were extracted in duplicate and outcomes coded so that odds ratios below 1 indicated benefit. Trials described as double-blind, with adequate randomisation, were assumed to be of higher methodological quality. Bias effects were examined in funnel plots and meta-regression models. 110 homoeopathy trials and 110 matched conventional-medicine trials were analysed. The median study size was 65 participants (range ten to 1573). 21 homoeopathy trials (19%) and nine (8%) conventional-medicine trials were of higher quality. In both groups, smaller trials and those of lower quality showed more beneficial treatment effects than larger and higher-quality trials. When the analysis was restricted to large trials of higher quality, the odds ratio was 0.88 (95% CI 0.65-1.19) for homoeopathy (eight trials) and 0.58 (0.39-0.85) for conventional medicine (six trials). Biases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of

Expectancies and memory for an emotional film fragment: a placebo study.

PubMed

Van Oorsouw, Kim; Merckelbach, Harald

2007-01-01

This study investigated whether positive ("memory-enhancing") and negative ("memory-impairing") placebos may enhance and undermine, respectively, memory of a film fragment. After watching an emotional film fragment, participants were assigned to a "memory-enhancing" placebo group (n = 30), control group (n = 30), or "memory-impairing" placebo group (n = 30). Only participants who believed in the placebo effect were included in the analyses. In the positive placebo group, memory for the film fragment was better than that of participants who received negative placebos or control participants. Participants in the negative placebo group made more distortion errors than participants in the positive placebo or control group. Our findings show that people's expectancies about their memory may affect their memory performance. These results may have implications for both clinical practice and the legal domain.

Oxcarbazepine in migraine headache: a double-blind, randomized, placebo-controlled study.

PubMed

Silberstein, S; Saper, J; Berenson, F; Somogyi, M; McCague, K; D'Souza, J

2008-02-12

To evaluate the efficacy, safety, and tolerability of oxcarbazepine (1,200 mg/day) vs placebo as prophylactic therapy for patients with migraine headaches. This multicenter, double-blind, randomized, placebo-controlled, parallel-group trial consisted of a 4-week single-blind baseline phase and a 15-week double-blind phase consisting of a 6-week titration period, an 8-week maintenance period, and a 1-week down-titration period, after which patients could enter a 13-week open-label extension phase. During the 6-week titration period, oxcarbazepine was initiated at 150 mg/day and increased by 150 mg/day every 5 days to a maximum tolerated dose of 1,200 mg/day. The primary outcome measure was change from baseline in the number of migraine attacks during the last 28-day period of the double-blind phase. Eighty-five patients were randomized to receive oxcarbazepine and 85 to receive placebo. There was no difference between the oxcarbazepine (-1.30) and placebo groups in mean change in number of migraine attacks from baseline during the last 28 days of double-blind phase (-1.74; p = 0.2274). Adverse events were reported for 68 oxcarbazepine-treated patients (80%) and 55 placebo-treated patients (65%). The majority of adverse events were mild or moderate in severity. The most common adverse events (>or=15% of patients) in the oxcarbazepine-treated group were fatigue (20.0%), dizziness (17.6%), and nausea (16.5%); no adverse event occurred in more than 15% of the placebo-treated patients. Overall, oxcarbazepine was safe and well tolerated; however, oxcarbazepine did not show efficacy in the prophylactic treatment of migraine headaches.

A preliminary double-blind, placebo-controlled randomized study of baclofen effects in alcoholic smokers

PubMed Central

Zywiak, William H.; Edwards, Steven M.; Tidey, Jennifer W.; Swift, Robert M.; Kenna, George A.

2014-01-01

Rationale There is presently no approved single treatment for dual alcohol and nicotine dependencies. Objective This pilot study investigated baclofen effects in alcoholic smokers. Methods This was a preliminary double-blind placebo-controlled randomized clinical study with 30 alcoholic smokers randomized to baclofen at 80 mg/day or placebo. A subgroup (n=18) participated in an alcohol cue-reactivity experiment. Results Baclofen, compared with placebo, significantly decreased the percent days of abstinence from alcohol-tobacco co-use (p=0.004). Alcohol dependence severity moderated baclofen effects, with the higher severity group having the greater baclofen response (p<0.001). Although the percent days of alcohol-tobacco co-use declined in both groups, this decline was greater after placebo than baclofen (p<0.001). Secondary analyses on alcohol or tobacco use alone suggested that the increase in percent days of co-abstinence was driven by the medication differences on heavy drinking days and on percent days smoking. In the cue-reactivity substudy, baclofen slightly decreased alcohol urge (p=0.058) and significantly reduced salivation (p=0.001), but these effects were not related to cue type. Conclusions This study provides preliminary evidence suggesting a possible role of baclofen in the treatment of alcoholic smokers. However, the mixed results and the small sample require larger confirmatory studies. PMID:24973894

EEG-tomographic studies with LORETA on vigilance differences between narcolepsy patients and controls and subsequent double-blind, placebo-controlled studies with modafinil.

PubMed

Saletu, M; Anderer, P; Saletu-Zyhlarz, G M; Mandl, M; Arnold, O; Zeitlhofer, J; Saletu, B

2004-11-01

The aim of the present study was to identify brain regions associated with vigilance in untreated and modafinil-treated narcoleptic patients by means of low-resolution brain electromagnetic tomography (LORETA). 16 drug-free narcoleptics and 16 normal controls were included in the baseline investigation. Subsequently patients participated in a double-blind, placebo-controlled crossover study receiving a three-week fixed titration of modafinil (200, 300, 400 mg) and placebo. Measurements comprised LORETA, the Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) obtained before and after three weeks' therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant inter-group differences in the resting (R-EEG), but not in the vigilance-controlled recordings (V-EEG). Subsequent univariate analysis revealed a decrease in alpha-2 and beta 1-3 power in prefrontal, temporal and parietal cortices, with the right hemisphere slightly more involved in this vigilance decrement. Modafinil 400 mg/d as compared with placebo induced changes opposite to the aforementioned baseline differences (key-lock principle) with a preponderance in the left hemisphere. This increase in vigilance resulted in an improvement in the MSLT and the ESS. LORETA provided evidence of a functional deterioration of the fronto-temporo-parietal network of the right-hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil on the left hemisphere, which is less affected by the disease.

Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Dalbeth, Nicola; Saag, Kenneth G; Palmer, William E; Choi, Hyon K; Hunt, Barbara; MacDonald, Patricia A; Thienel, Ulrich; Gunawardhana, Lhanoo

2017-12-01

To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline -0.43 versus -0.07; P <0.001), decreased the overall incidence of gout flares (29.3% versus 41.4%; P < 0.05), and improved serum UA control (62.8% versus 5.7%; P < 0.001). No major safety concerns were reported. Urate-lowering therapy with febuxostat improved magnetic resonance imaging-determined synovitis and reduced the incidence of gout flares in subjects with early gout. © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

[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.

Design of clinical trials of antidepressants: should a placebo control arm be included?

PubMed

Fritze, J; Möller, H J

2001-01-01

There is no doubt that available antidepressants are efficacious and effective. Nevertheless, more effective drugs with improved tolerability are needed. With this need in mind, some protagonists claim that future antidepressants should be proved superior to, or at least as effective as, established antidepressants, making placebo control methodologically dispensable in clinical trials. Moreover, the use of placebo control is criticised as unethical because it might result in effective treatment being withheld. There are, however, a number of methodological reasons why placebo control is indispensable for the proof of efficacy of antidepressants. Comparing investigational antidepressants only with standard antidepressants and not placebo yields ambiguous results that are difficult to interpret, be it in superiority or equivalence testing, and this method of assessment requires larger sample sizes than those required with the use of placebo control. Experimental methodology not adhering to the optimal study design is ethically questionable. Restricting the testing of investigational antidepressants only to superiority over standard antidepressants is an obstacle to therapeutic progress in terms of tolerability and the detection of innovative mechanisms of action from which certain subgroups of future patients might benefit. The use of a methodology that requires larger samples for testing of superiority or equivalence is also ethically questionable. In view of the high placebo response rates in trials of antidepressants, placebo treatment does not mean withholding effective treatment. Accepting the necessity of the clinical evaluation of new, potentially ineffective antidepressants implicitly means accepting placebo control as ethically justified. Three- or multi-arm comparisons including placebo and an active reference represent the optimal study design.

A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber.

PubMed

Horak, Friedrich; Zieglmayer, Petra; Zieglmayer, René; Lemell, Patrick; Yao, Ruji; Staudinger, Heribert; Danzig, Melvyn

2009-02-01

Studies on the efficacy of phenylephrine in the treatment of nasal congestion have yielded inconsistent results, notwithstanding its approval for this indication. To evaluate and compare the decongestant effect of a single dose of phenylephrine to placebo and pseudoephedrine in patients with seasonal allergic rhinitis. This randomized, placebo-controlled, 3-way crossover study evaluated patient-scored nasal congestion, peak nasal inspiratory flow, and rhinomanometry at more than 6 hours in 39 grass-sensitive patients exposed to grass pollen in the Vienna Challenge Chamber. Patients were dosed with immediate-release formulations of phenylephrine, 12 mg, pseudoephedrine, 60 mg, as a control, or placebo. Phenylephrine was not significantly different from placebo in the primary end point, mean change in nasal congestion score at more than 6 hours (P = .56), whereas pseudoephedrine was significantly more effective than both placebo (P < .01) and phenylephrine (P = .01). Phase 1 results showed a difference between phenylephrine and placebo that was 64% of the difference between pseudoephedrine and placebo, substantially greater than the 17% difference observed for all phases. Carryover bias due to patient recall of the pseudoephedrine effect may have influenced these results. Rhinomanometry and peak nasal inspiratory flow results were consistent with these data. Neither phenylephrine nor pseudoephedrine had an effect on the nonnasal symptoms. No adverse events were reported in this study. During a 6-hour observation period, a single dose of pseudoephedrine but not phenylephrine resulted in significant improvement in measures of nasal congestion. Neither phenylephrine nor pseudoephedrine had an effect on nonnasal symptoms.

Effect of Saccharomyces boulardii in dog with chronic enteropathies: double-blinded, placebo-controlled study.

PubMed

D'Angelo, Simona; Fracassi, Federico; Bresciani, Francesca; Galuppi, Roberta; Diana, Alessia; Linta, Nikolina; Bettini, Giuliano; Morini, Maria; Pietra, Marco

2018-03-03

Saccharomyces boulardii is used to treat acute and chronic enteropathies in humans, but to date, no studies have evaluated the use of this yeast in dogs. The current study, a prospective non-randomised, double-blinded, placebo-controlled study, evaluated the effects of S boulardii in healthy dogs and dogs with chronic enteropathies (CE). Four healthy dogs and 20 dogs with CE were included. In healthy dogs, S boulardii was administered for 10 days. Possible short-term adverse effects were recorded, and quantitative stool cultures for yeasts were performed. In dogs with CE, S boulardii or a placebo was administered in addition to standard treatment protocols. Canine Chronic Enteropathy Clinical Activity Index, abdominal ultrasonography, gastroenteroscopy and histology were performed at the time of diagnosis and after 60 days of treatment. In healthy dogs, S boulardii reached a steady state in five days and was completely eliminated on day 4 after administration. No short-term side effects were seen. Clinical activity index, stool frequency, stool consistency and body condition score improved significantly in dogs with CE receiving S boulardii versus the placebo. In conclusion, S boulardii can be safely used in dogs with CE and seems to achieve better control of clinical signs than standard therapy alone. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials.

PubMed

Viney, Nicholas J; van Capelleveen, Julian C; Geary, Richard S; Xia, Shuting; Tami, Joseph A; Yu, Rosie Z; Marcovina, Santica M; Hughes, Steven G; Graham, Mark J; Crooke, Rosanne M; Crooke, Stanley T; Witztum, Joseph L; Stroes, Erik S; Tsimikas, Sotirios

2016-11-05

Elevated lipoprotein(a) (Lp[a]) is a highly prevalent (around 20% of people) genetic risk factor for cardiovascular disease and calcific aortic valve stenosis, but no approved specific therapy exists to substantially lower Lp(a) concentrations. We aimed to assess the efficacy, safety, and tolerability of two unique antisense oligonucleotides designed to lower Lp(a) concentrations. We did two randomised, double-blind, placebo-controlled trials. In a phase 2 trial (done in 13 study centres in Canada, the Netherlands, Germany, Denmark, and the UK), we assessed the effect of IONIS-APO(a) Rx , an oligonucleotide targeting apolipoprotein(a). Participants with elevated Lp(a) concentrations (125-437 nmol/L in cohort A; ≥438 nmol/L in cohort B) were randomly assigned (in a 1:1 ratio in cohort A and in a 4:1 ratio in cohort B) with an interactive response system to escalating-dose subcutaneous IONIS-APO(a) Rx (100 mg, 200 mg, and then 300 mg, once a week for 4 weeks each) or injections of saline placebo, once a week, for 12 weeks. Primary endpoints were mean percentage change in fasting plasma Lp(a) concentration at day 85 or 99 in the per-protocol population (participants who received more than six doses of study drug) and safety and tolerability in the safety population. In a phase 1/2a first-in-man trial, we assessed the effect of IONIS-APO(a)-L Rx , a ligand-conjugated antisense oligonucleotide designed to be highly and selectively taken up by hepatocytes, at the BioPharma Services phase 1 unit (Toronto, ON, Canada). Healthy volunteers (Lp[a] ≥75 nmol/L) were randomly assigned to receive a single dose of 10-120 mg IONIS-APO(a)L Rx subcutaneously in an ascending-dose design or placebo (in a 3:1 ratio; single-ascending-dose phase), or multiple doses of 10 mg, 20 mg, or 40 mg IONIS-APO(a)L Rx subcutaneously in an ascending-dose design or placebo (in an 8:2 ratio) at day 1, 3, 5, 8, 15, and 22 (multiple-ascending-dose phase). Primary endpoints were mean percentage change

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.

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut.

PubMed

van der Valk, Johanna P M; Gerth van Wijk, Roy; Dubois, Anthony E J; de Groot, Hans; Reitsma, Marit; Vlieg-Boerstra, Berber; Savelkoul, Huub F J; Wichers, Harry J; de Jong, Nicolette W

2016-01-01

Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. A total of 179 children were included (median age 9.0 years; range 2-17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens. www.ncbi.nlm.nih.gov/pubmed NTR3572.

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.

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

Microcurrent transcutaneous electric nerve stimulation in painful diabetic neuropathy: a randomized placebo-controlled study.

PubMed

Gossrau, Gudrun; Wähner, Michael; Kuschke, Marion; Konrad, Birgit; Reichmann, Heinz; Wiedemann, Bärbel; Sabatowski, Rainer

2011-06-01

Diabetes is a common health care problem in western countries. Painful diabetic neuropathy (PDN) might be one of the consequences of long ongoing diabetes; it is estimated that approximately 20% of European diabetic patients suffer from PDN. Transcutaneous electrical nerve stimulation (TENS) is often used as additional pain treatment. However, recent studies show inconsistent results. We aimed to assess the effect of micro-TENS in reducing neuropathic pain in patients with PDN in a placebo-controlled, single-blinded, and randomized design. DESIGN/SETTING/PATIENTS/OUTCOME MEASURES: 22 diabetic patients have been treated with a micro-TENS therapy and 19 patients have been treated with a placebo therapy. Treatment duration was 4 weeks with three therapeutical settings per week. Standardized questionnaires (Pain Disability Index [PDI], neuropathic pain score [NPS], Center for Epidemiologic Studies Depression Scale [CES-D]) were used to assess pain intensity, pain disability, as well as quality of life at baseline at the end of the treatment period and 4 weeks after treatment termination. Patients with a minimum of 30% reduction in NPS were defined as therapy responders. After 4 weeks of treatment, 6/21 patients in the verum group vs 10/19 patients in the placebo group responded to therapy. The median PDI score after 4 weeks of treatment showed a reduction of 23% in the verum vs 25% in the placebo group. The differences did not reach statistical significance. The pain reduction with the applied transcutaneous electrotherapy regimen is not superior to a placebo treatment. Wiley Periodicals, Inc.

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

Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

PubMed

Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

2013-03-01

Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Impact of patient selection and study characteristics on signal detection in placebo-controlled trials with antidepressants.

PubMed

Mancini, Michele; Wade, Alan G; Perugi, Giulio; Lenox-Smith, Alan; Schacht, Alexander

2014-04-01

An increasing rate of antidepressant trials fail due to large placebo responses. This analysis aimed to identify variables influencing signal detection in clinical trials of major depressive disorder. Patient-level data of randomized patients with a duloxetine dose ≥ 60 mg/day were obtained from Lilly. Total scores of the Hamilton Depression Rating scale (HAM-D) were used as efficacy endpoints. In total, 4661 patients from 14 studies were included in the analysis. The overall effect size (ES), based on the HAM-D total score at endpoint, between duloxetine and placebo was -0.272. Although no statistically significant interactions were found, the following results for factors influencing ES were seen: a very low ES (-0.157) in patients in the lowest baseline HAM-D category and in patients recruited in the last category of the recruitment period (-0.122). A higher ES in patients recruited in centers with a site-size at but not more than 2.5 times the average site-size for the study (-0.345). Study characteristics that resulted in low signal detection in our database were: <80% study completers, a HAM-D placebo response >5 points, a high variability of placebo response (SD > 7 points HAM-D), >6 post baseline visits per study, and use of an active control drug. Simpler trial designs, more homogeneous and mid-sized study sites, a primary analysis based on a higher cutoff blinded to investigators to avoid the influence of score inflation in mild patients and, if possible, studies without an active control group could lead to a better signal detection of antidepressive efficacy. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study.

PubMed

Arnold, Lesley M; Arsenault, Pierre; Huffman, Cynthia; Patrick, Jeffrey L; Messig, Michael; Chew, Marci L; Sanin, Luis; Scavone, Joseph M; Pauer, Lynne; Clair, Andrew G

2014-10-01

Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as <30% pain reduction relative to single-blind baseline or discontinuation owing to lack of efficacy or adverse event (AE). Secondary endpoints included measures of pain severity, global assessment, functional status, tiredness/fatigue, and sleep. ClinicalTrials.gov NCT01271933. A total of 441 patients entered the single-blind phase, and 63 were randomized to pregabalin CR and 58 to placebo. The median time to LTR (Kaplan-Meier analysis) was significantly longer in the pregabalin CR group than placebo (58 vs. 22 days, p = 0.02). By trial end, 34/63 (54.0%) pregabalin CR and 41/58 (70.7%) placebo patients experienced LTR. Significantly more patients reported 'benefit from treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance

A double-blind, placebo-controlled study of the safety and efficacy of ipratropium bromide nasal spray versus placebo in patients with the common cold.

PubMed

Dockhorn, R; Grossman, J; Posner, M; Zinny, M; Tinkleman, D

1992-12-01

Ipratropium bromide (IB) has been found to reduce secretions in the upper respiratory tract; this is accomplished through competitive inhibition of acetylcholine at muscarinic receptors that control rhinorrhea production. This study compared the safety and efficacy of IB with placebo in the symptomatic relief of rhinorrhea in patients with the common cold. Human subjects with symptoms of a common cold, primarily rhinorrhea, were enrolled and treated with either IB (84 micrograms/nostril) or placebo; each was administered as two sprays per nostril, four times a day, for 4 days. Primary efficacy analyses were in-clinic measurements of nasal discharge weights over a 3-hour period after administration on days 1 and 2 and assessment of rhinorrhea symptoms by use of a subjective patient-completed visual analog rating scale. IB significantly reduced rhinorrhea an average of 18% over placebo for days 1 and 2 (p = 0.01). Visual analog scale scores showed an average improvement in rhinorrhea of 22% over placebo (p = 0.001). When patients with relatively minor rhinorrhea (baseline weight of nasal discharge < or = 1.0 gm) were excluded, IB produced an average reduction in nasal discharge of 23% over placebo for days 1 and 2 (p = 0.003).

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).

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.

Randomized, Placebo-Controlled, Double-Blind Pilot Study of D-Cycloserine in Chronic Stroke

PubMed Central

Kallos, Justiss; Housley, Stephen N.; LaPlaca, Michelle C.; Traynelis, Stephen F.; Wolf, Steven L.

2015-01-01

Stroke is a leading cause of death and disability in the USA. Up to 60% of patients do not fully recover despite intensive physical therapy treatment. N-Methyl-D-aspartate receptors (NMDA-R) have been shown to play a role in synaptic plasticity when activated. D-Cycloserine promotes NMDA receptor function by binding to receptors with unoccupied glycine sites. These receptors are involved in learning and memory. We hypothesized that D-cycloserine, when combined with robotic-assisted physiotherapy (RAP), would result in greater gains compared with placebo + RAP in stroke survivors. Participants (n = 14) were randomized to D-cycloserine plus RAP or placebo plus RAP. Functional, cognitive, and quality-of-life measures were used to assess recovery. There was significant improvement in grip strength of the affected hand within both groups from baseline to 3 weeks (95% confidence interval for mean change, 3.95 ± 2.96 to 4.90 ± 3.56 N for D-cycloserine and 5.72 ± 3.98 to 8.44 ± 4.90 N for control). SIS mood domain showed improvement for both groups (95% confidence interval for mean change, 72.6 ± 16.3 to 82.9 ± 10.9 for D-cycloserine and 82.9 ± 13.5 to 90.3 ± 9.9 for control). This preliminary study does not provide evidence that D-cycloserine can provide greater gains in learning compared with placebo for stroke survivors. PMID:26587287

Rotigotine transdermal patch in Chinese patients with advanced Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study.

PubMed

Zhang, Zhen-Xin; Liu, Chun-Feng; Tao, En-Xiang; Shao, Ming; Liu, Yi-Ming; Wang, Jian; Asgharnejad, Mahnaz; Xue, Hai-Bo; Surmann, Erwin; Bauer, Lars

2017-11-01

Rotigotine was demonstrated to be efficacious and well-tolerated in three placebo-controlled studies (CLEOPATRA-PD/PREFER/SP921) of patients with advanced-stage Parkinson's disease (PD), most of whom were Caucasian. This multicenter phase 3 study (SP1037; NCT01646255) was the first to investigate the efficacy and safety of rotigotine in Chinese patients with advanced-stage PD. Chinese patients with PD, inadequately controlled on levodopa (stable dose ≥200 mg/day), with ≥2.5 h/day "off" time, and Hoehn & Yahr stage 2-4, were randomized 1:1 to receive transdermal rotigotine or placebo, titrated over ≤7 weeks, maintained at optimal/maximum dose (4-16 mg/24 h) for 12 weeks. Primary efficacy variable: mean change in absolute "off" time (according to patient diaries) from baseline to end of maintenance. Safety variables included adverse events (AEs) and discontinuations due to AEs. 346 patients were randomized and 89.9% completed the study (87.8% placebo; 92.0% rotigotine). All were Chinese (58.7% male; mean ± SD age: 62.2 ± 8.9 years; mean ± SD time since PD diagnosis: 6.62 ± 3.70 years). Rotigotine significantly reduced "off" time vs placebo (LS mean [95% CI] treatment difference: -1.20 h/day [-1.83, -0.57]; p = 0.0002), and resulted in more responders (≥30% decrease in "off" time: 36.9% placebo; 48.8% rotigotine; p = 0.0269). AEs were reported for 86 (50.0%) placebo- and 103 (59.2%) rotigotine-treated patients; 15 discontinued due to AEs (placebo 7; rotigotine 8). The most common AEs (≥5%) were dizziness, nausea, pruritus, and dyskinesia. Rotigotine was efficacious in Chinese patients with advanced-stage PD as add-on therapy to levodopa, significantly reducing "off" time vs placebo; the treatment difference was similar to that observed in previous studies of mainly Caucasian patients. Rotigotine was generally well-tolerated and had a similar AE profile to those observed in previous studies. Copyright © 2017 Elsevier Ltd. All rights

Does EEG-Neurofeedback Improve Neurocognitive Functioning in Children with Attention-Deficit/Hyperactivity Disorder? A Systematic Review and a Double-Blind Placebo-Controlled Study

ERIC Educational Resources Information Center

Vollebregt, Madelon A.; van Dongen-Boomsma, Martine; Buitelaar, Jan K.; Slaats-Willemse, Dorine

2014-01-01

Background: The number of placebo-controlled randomized studies relating to EEG-neurofeedback and its effect on neurocognition in attention-deficient/hyperactivity disorder (ADHD) is limited. For this reason, a double blind, randomized, placebo-controlled study was designed to assess the effects of EEG-neurofeedback on neurocognitive functioning…

An adaptogenic role for omega-3 fatty acids in stress; a randomised placebo controlled double blind intervention study (pilot) [ISRCTN22569553

PubMed Central

Bradbury, Joanne; Myers, Stephen P; Oliver, Chris

2004-01-01

Background There is evidence for an adaptive role of the omega -3 fatty acid, docosahexaenoic acid (DHA) during stress. Mechanisms of action may involve regulation of stress mediators, such as the catecholamines and proinflammatory cytokines. Prevention of stress-induced aggression and hostility were demonstrated in a series of clinical trials. This study investigates whether perceived stress is ameliorated by DHA in stressed university staff. Methods Subjects that scored ≥ 17 on the Perceived Stress Scale were randomised into a 6-week pilot intervention study. The diet reactive group was supplemented with 6 g of fish oil containing 1.5 g per day DHA, while the placebo group was supplemented with 6 g a day of olive oil. The groups were compared with each other and a wider cross sectional study population that did not receive either active or placebo intervention. Results There was a significant reduction in perceived stress in both the fish oil and the placebo group from baseline. There was also a significant between-group difference between the fish oil group and the no-treatment controls in the rate of stress reduction (p < 0.05). However, there was not a significant between-group difference between the fish oil and the placebo group, nor the placebo group and the control group. These results are discussed in the context of several methodological limitations. The significant stress reductions in both the fish oil and the placebo group are considered in view of statistical regression, an effect likely to have been exaggerated by the time course of the study, a large placebo effect and the possibility of an active effect from the placebo. Conclusion There were significant differences (p < 0.05) in the fish oil group compared with no-treatment controls. This effect was not demonstrated in the placebo group. As a pilot study, it was not sufficiently powered to find the difference between the fish oil group and the placebo group significant. Further work needs to be

Placebo-controlled pilot study of ramelteon for adiposity and lipids in patients with schizophrenia

PubMed Central

Borba, Christina P.C.; Fan, Xiaoduo; Copeland, Paul M.; Paiva, Alexander; Freudenreich, Oliver; Henderson, David C.

2013-01-01

Objective Few interventions have been successful to prevent or reverse the medical complications associated with antipsychotic agents in the schizophrenia population. In particular, no single agent can correct multiple metabolic abnormalities such as insulin resistance, hyperlipidemia, inflammation, obesity and fat distribution. We now report a randomized placebo-controlled pilot study to examine the effects of ramelteon on obesity and metabolic disturbances among subjects with schizophrenia. Methods A double-blind, placebo-controlled, 8-week pilot trial was conducted, adding ramelteon 8 mg/day to stable outpatients with schizophrenia. Vital signs, anthropometric measurements, including height, weight, waist circumference, and body fat were assessed and laboratory assays were tracked to monitor changes in metabolic markers. Results Twenty-five subjects were randomly assigned to treatment with study drug or placebo and twenty subjects were included in the final analysis. Ramelteon did not improve anthropometric measurements, glucose metabolism and inflammatory markers. There was, however, a significant decrease in total cholesterol and cholesterol to HDL ratio in the ramelteon group. While the standard anthropometric measures did not show significant change, the DEXA scan showed a trend toward reduction in fat in the abdominal and trunk areas with a moderate effect size. Conclusions While ramelteon decreased cholesterol, treatment may have to be longer than 8 weeks and with a higher dose for maximal effect of ramelteon for body fat and lipid changes. Future studies are needed for patients with schizophrenia with a larger sample size to fully understand ramelteon’s effects on abdominal adiposity and lipids. PMID:21869685

Placebo-controlled pilot study of ramelteon for adiposity and lipids in patients with schizophrenia.

PubMed

Borba, Christina P C; Fan, Xiaoduo; Copeland, Paul M; Paiva, Alexander; Freudenreich, Oliver; Henderson, David C

2011-10-01

Few interventions have been successful to prevent or reverse the medical complications associated with antipsychotic agents in the schizophrenia population. In particular, no single agent can correct multiple metabolic abnormalities such as insulin resistance, hyperlipidemia, inflammation, obesity, and fat distribution. We now report a randomized placebo-controlled pilot study to examine the effects of ramelteon on obesity and metabolic disturbances among subjects with schizophrenia. A double-blind, placebo-controlled, 8-week pilot trial was conducted, adding ramelteon 8 mg/d to stable outpatients with schizophrenia. Vital signs and anthropometric measurements, including height, weight, waist circumference, and body fat were assessed, and laboratory assays were tracked to monitor changes in metabolic markers. Twenty-five subjects were randomly assigned to treatment with study drug or placebo, and 20 subjects were included in the final analysis. Ramelteon did not improve anthropometric measurements, glucose metabolism, and inflammatory markers. There was, however, a significant decrease in total cholesterol and ratio of cholesterol to high-density lipoprotein in the ramelteon group. Although the standard anthropometric measures did not show significant change, the dual-energy x-ray absorptiometry scan showed a trend toward reduction in fat in the abdominal and trunk areas with a moderate effect size. Although ramelteon decreased cholesterol, treatment may have to be longer than 8 weeks and with a higher dose for maximal effect of ramelteon for body fat and lipid changes. Future studies are needed for patients with schizophrenia with a larger sample size to fully understand ramelteon's effects on abdominal adiposity and lipids.

Exposure of eyes to perfume: a double-blind, placebo-controlled experiment.

PubMed

Elberling, J; Duus Johansen, J; Dirksen, A; Mosbech, H

2006-08-01

Environmental perfume exposure can elicit bothersome respiratory symptoms. Symptoms are induced at exposure levels which most people find tolerable, and the mechanisms are unclear. The aim of the study was to investigate patients with eye and respiratory symptoms related to environmental perfume, by exposing the eyes to perfume in a double-blind, placebo-controlled study.Twenty-one eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case-control study. The participants completed a symptom questionnaire, and underwent a double-blind, placebo-controlled exposure to perfume. Of the 42 individuals tested, 10 had more eye symptoms (irritation, itching, and tears) during perfume exposure than during placebo exposures, and eight of these individuals (P = 0.07, Fisher's exact test) belonged to the patient group. A true positive eye reaction to perfume was significantly associated with identification of perfume as an active exposure (P < 0.05). In this study, vapor of perfume elicited irritation in the eyes independently of olfaction, but the relative importance of ocular chemoperception in relation to elicitation of respiratory symptoms from common environmental exposures to perfume remains unclear. We investigated the hypothesis of an association between respiratory symptoms related to perfume and ocular perfume sensitivity by exposing the eyes to perfume in a double blind, placebo-controlled experiment. Vapors of perfume provoked symptoms in the relevant eye in some patients and healthy control persons, but under our exposure conditions, ocular chemesthesis failed to elicit respiratory symptoms.

Efficacy of desvenlafaxine 50 mg compared with placebo in patients with moderate or severe major depressive disorder: a pooled analysis of six randomized, double-blind, placebo-controlled studies.

PubMed

Papakostas, George I; Culpepper, Larry; Fayyad, Rana S; Musgnung, Jeff; Guico-Pabia, Christine J

2013-11-01

This study assessed the efficacy of desvenlafaxine 50 mg/day compared with placebo for treating moderate or severe major depressive disorder (MDD). Data were pooled from six double-blind, placebo-controlled, desvenlafaxine 50 mg/day fixed-dose studies in adults with MDD. The primary endpoint was improvement in 17-item Hamilton Rating Scale for Depression (HAM-D17) scores from baseline at week 8. HAM-D17 changes were evaluated in patients with moderate (18study, and baseline in the model. The pooled analysis included 2189 patients (desvenlafaxine 50 mg, n=1150; placebo, n=1039). Of those, 694 (32%) patients had severe depression at baseline. Desvenlafaxine improved HAM-D17 scores versus placebo in patients with either moderate [desvenlafaxine, adjusted mean (±SE), -10.26±0.24; placebo, -8.87±0.26; P<0.001] or severe MDD (desvenlafaxine, -11.91±0.40; placebo, -9.85±0.42; P<0.001). Both moderately and severely depressed patients had significantly higher rates of response and remission with desvenlafaxine treatment compared with placebo (all P's≤0.029). Results were similar when baseline severity was defined by Montgomery-Åsberg Depression Rating Scale or Sheehan Disability Scale scores. Desvenlafaxine 50 mg/day significantly improved depressive symptoms regardless of severity at baseline and was effective in treating both moderate and severe MDD.

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

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.

A randomized, double-blind, placebo-controlled study of escitalopram in patients with social anxiety disorder in Japan.

PubMed

Asakura, Satoshi; Hayano, Taiji; Hagino, Atsushi; Koyama, Tsukasa

2016-01-01

This randomized, double-blind placebo-controlled study compared the efficacy and tolerability of escitalopram (10 and 20 mg/day) in Japanese patients with social anxiety disorder (SAD). Patients aged 18-64 years with a primary diagnosis of DSM-IV-TR defined SAD, a Liebowitz Social Anxiety Scale Japanese version (LSAS-J) total score ≥60 and a Clinical Global Impression-Severity (CGI-S) score ≥4 at baseline were randomly assigned (1:1:1) to placebo, escitalopram 10 mg or escitalopram 20 mg. The primary endpoint was change from baseline to Week 12 in the LSAS-J total score for both escitalopram 10 mg and 20 mg versus placebo (ANCOVA, FAS, LOCF), using a hierarchical testing procedure. Pre-specified secondary endpoints included LSAS-J sensitivity analyses. This study has the www.japic.or.jp identifier: JapicCTI-121842. For the primary efficacy endpoint, the difference from placebo in the LSAS-J was -3.9 (p = 0.089) for escitalopram 10 mg. Since the superiority of escitalopram 10 mg over placebo was not confirmed, an analysis without multiplicity adjustment was made, which showed a difference for escitalopram 20 mg versus placebo of -9.8 (p < 0.001). In pre-specified sensitivity analyses, the difference versus placebo was -4.9 (p = 0.035) (ANCOVA, FAS, OC) and -5.0 (p = 0.028) (MMRM, FAS) (escitalopram 10 mg) and -10.1 (p < 0.001) (ANCOVA, FAS, OC) and -10.6 (p < 0.001) (MMRM, FAS) (escitalopram 20 mg). Common adverse events (incidence ≥5% and significantly different from placebo) were somnolence, nausea and ejaculation disorder. Escitalopram was efficacious, safe and well tolerated by patients with SAD in Japan. Study limitations are discussed including patient characteristics.

Effect of aromatherapy massage on menopausal symptoms: a randomized placebo-controlled clinical trial.

PubMed

Darsareh, Fatemeh; Taavoni, Simin; Joolaee, Soodabeh; Haghani, Hamid

2012-09-01

Menopause is a significant event in most women's lives because it marks the end of a woman's natural reproductive life. The purpose of this study was to determine the effect of aromatherapy massage on menopausal symptoms. A randomized placebo-controlled clinical trial was conducted at a menopausal clinic at a gynecology hospital in Tehran. The study population comprised 90 women who were assigned to an aromatherapy massage group, a placebo massage group, or a control group. Each participant in the aromatherapy massage group received 30-minute aromatherapy treatment sessions twice a week for 4 weeks with aroma oil, whereas participants in the placebo massage group received the same treatment with plain oil. No treatment was provided to participants in the control group. The outcome measures in this study were menopausal symptoms, as obtained through the Menopause Rating Scale. The mean baseline level of the menopausal score did not differ among all groups. However, after eight sessions of intervention, the Menopause Rating Scale score differed significantly among the three groups (P < 0.001). Post hoc analysis revealed that women in both the aromatherapy massage group and the placebo massage group had a lower menopausal score than the control group (P < 0.001). When the aromatherapy massage and the placebo massage groups were compared, the menopausal score for the aromatherapy massage group was found to be significantly lower (P < 0.001) than for the placebo group. The results of the study demonstrate that both massage and aromatherapy massage were effective in reducing menopausal symptoms. However, aromatherapy massage was more effective than only massage.

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut

PubMed Central

van der Valk, Johanna P. M.; Gerth van Wijk, Roy; Dubois, Anthony E. J.; de Groot, Hans; Reitsma, Marit; Vlieg-Boerstra, Berber; Savelkoul, Huub F. J.; Wichers, Harry J.; de Jong, Nicolette W.

2016-01-01

Background Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. Methods and Findings A total of 179 children were included (median age 9.0 years; range 2–17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. Conclusion This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens

Escitalopram treatment of depression in human immunodeficiency virus/acquired immunodeficiency syndrome: a randomized, double-blind, placebo-controlled study.

PubMed

Hoare, Jacqueline; Carey, Paul; Joska, John A; Carrara, Henri; Sorsdahl, Katherine; Stein, Dan J

2014-02-01

Depression can be a chronic and impairing illness in people with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Large randomized studies of newer selective serotonin reuptake inhibitors such as escitalopram in the treatment of depression in HIV, examining comparative treatment efficacy and safety, have yet to be done in HIV-positive patients. This was a fixed-dose, placebo-controlled, randomized, double-blind study to investigate the efficacy of escitalopram in HIV-seropositive subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive disorder. One hundred two participants were randomly assigned to either 10 mg of escitalopram or placebo for 6 weeks. An analysis of covariance of the completers found that there was no advantage for escitalopram over placebo on the Montgomery-Asberg Depression Rating Scale (p = 0.93). Sixty-two percent responded to escitalopram and 59% responded to placebo on the Clinical Global Impression Scale. Given the relatively high placebo response, future trials in this area need to be selective in participant recruitment and to be adequately powered.

Pentoxifylline for the treatment of nonalcoholic fatty liver disease: a meta-analysis of randomized double-blind, placebo-controlled studies.

PubMed

Zeng, Tao; Zhang, Cui-Li; Zhao, Xiu-Lan; Xie, Ke-Qin

2014-06-01

Pentoxifylline has been used to treat nonalcoholic fatty liver diseases (NAFLDs) due to its anti-tumor necrosis factor-α effects. We conducted a meta-analysis of randomized, double-blinded, placebo-controlled trials to investigate the effect of pentoxifylline on the biochemical and histological parameters of NAFLD patients. A comprehensive literature search was conducted in the database including PubMed, Embase, ISI web of knowledge, the Cochrane Library, and Google Scholar to identify randomized, double-blind, placebo-controlled clinical trials about the effects of pentoxifylline on NAFLD. The pooled weighted mean difference (WMD) with 95% confidence interval (CI) was calculated to compare the effects of pentoxifylline and placebo. Five well-designed studies were retrieved. Pooled results showed that pentoxifylline significantly reduced the serum alanine transaminase activity (WMD=-27.97; 95% CI: -42.59, -13.34) and aspartate transaminase activity (WMD=-13.97; 95% CI: -23.31, -4.63) in NAFLD patients compared with placebo. In addition, pentoxifylline significantly improved steatosis (WMD=-0.68; 95% CI: -1.01, -0.34), lobular inflammation (WMD=-0.49; 95% CI: -0.86, -0.12), and fibrosis (WMD=-0.60; 95% CI: -0.99, -0.21). Furthermore, pentoxifylline also led to significant reduction in BMI (WMD=-0.51; 95% CI: -0.96, -0.06) and fasting glucose (WMD=-8.97; 95% CI: -14.52, -3.42), but did not significantly affect the serum tumor necrosis factor α and adiponectin levels when compared with placebo. Pentoxifylline could reduce the aminotransferase activities and improve the histological parameters in NAFLD patients. Large well-designed, randomized, placebo-controlled studies are needed to confirm these results.

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.

Placebo Devices as Effective Control Methods in Acupuncture Clinical Trials: A Systematic Review

PubMed Central

Zhang, Claire Shuiqing; Tan, Hsiewe Ying; Zhang, George Shengxi; Zhang, Anthony Lin; Xue, Charlie Changli; Xie, Yi Min

2015-01-01

While the use of acupuncture has been recognised by the World Health Organisation, its efficacy for many of the common clinical conditions is still undergoing validation through randomised controlled trials (RCTs). A credible placebo control for such RCTs to enable meaningful evaluation of its efficacy is to be established. While several non-penetrating acupuncture placebo devices, namely the Streitberger, the Park and the Takakura Devices, have been developed and used in RCTs, their suitability as inert placebo controls needs to be rigorously determined. This article systematically reviews these devices as placebo interventions. Electronic searches were conducted on four English and two Chinese databases from their inceptions to July 2014; hand searches of relevant references were also conducted. RCTs, in English or Chinese language, comparing acupuncture with one of the aforementioned devices as the control intervention on human participants with any clinical condition and evaluating clinically related outcomes were included. Thirty-six studies were included for qualitative analysis while 14 were in the meta-analysis. The meta-analysis does not support the notion of either the Streitberger or the Park Device being inert control interventions while none of the studies involving the Takakura Device was included in the meta-analysis. Sixteen studies reported the occurrence of adverse events, with no significant difference between verum and placebo acupuncture. Author-reported blinding credibility showed that participant blinding was successful in most cases; however, when blinding index was calculated, only one study, which utilised the Park Device, seemed to have an ideal blinding scenario. Although the blinding index could not be calculated for the Takakura Device, it was the only device reported to enable practitioner blinding. There are limitations with each of the placebo devices and more rigorous studies are needed to further evaluate their effects and

[A Multi-arm Placebo-controlled Study with Glutamic Acid Conducted in Rostock in 1953/1954].

PubMed

Häßler, Frank; Weirich, Steffen

2017-09-01

A Multi-arm Placebo-controlled Study with Glutamic Acid Conducted in Rostock in 1953/1954 Glutamic acid was commonly used in the treatment of intellectually disabled children in the 50s. Koch reported first results of an observation of 140 children treated with glutamic acid in 1952. In this line is the multi-arm placebo-controlled study reported here. The original study protocols were available. 58 children with speech problems who attending a school of special needs received glutamic acid, or vitamin B, or St.-John's-wort. The effect of glutamic acid was in few cases an improvement of attention. On the other hand restlessness and stutter increased. The majority of all reported a weight loss. The treatment with vitamin B showed a positive effect concerning concentration. The treatment with St.-John's wort was stopped caused by headache and vomiting in eight of nine cases. The results of the study reported here are unpublished. The reason may be that until the 60s the effects of glutamic acid in the treatment of intellectually disabled children were in generally overestimated.

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.

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.

Rotigotine may improve sleep architecture in Parkinson's disease: a double-blind, randomized, placebo-controlled polysomnographic study.

PubMed

Pierantozzi, Mariangela; Placidi, Fabio; Liguori, Claudio; Albanese, Maria; Imbriani, Paola; Marciani, Maria Grazia; Mercuri, Nicola Biagio; Stanzione, Paolo; Stefani, Alessandro

2016-05-01

Growing evidence demonstrates that in Parkinson's Disease (PD) sleep disturbances are frequent and difficult to treat. Since the efficacy of rotigotine on sleep is corroborated by studies lacking polysomnography (PSG), this study explores the possible rotigotine-mediated impact on PSG parameters in PD patients. This is a randomized, double-blind, placebo-controlled, parallel-group study to determine the efficacy of rotigotine vs placebo on PSG parameters in moderately advanced PD patients. An unusual protocol was utilized, since patches were maintained from 18:00 h to awakening, minimizing the possible diurnal impact on motor symptoms. All participants underwent sleep PSG recordings, subjective sleep questionnaires (Parkinson Disease Sleep Scale [PDSS], Pittsburgh Sleep Quality Index [PSQI]), and the assessment of early-morning motor disability. We evaluated 42 PD patients (Hoehn & Yahr stages 2 and 3) with sleep impairment randomly assigned to active branch (N =21) or placebo (N = 21). Rotigotine significantly increased sleep efficiency and reduced both wakefulness after sleep onset and sleep latency compared to placebo. Moreover, the mean change in REM sleep quantity was significantly higher in the rotigotine than placebo group. The improvement of PSG parameters corresponded to the amelioration of PDSS and PSQI scores together with the improvement of patient morning motor symptoms. This study demonstrated the significant effect of rotigotine on sleep quality and continuity in PD patients by promoting sleep stability and increasing REM. The effectiveness of rotigotine on sleep may be ascribed to its pharmacokinetic/pharmacodynamic profile directly on both D1 and D2 receptors. Copyright © 2016 Elsevier B.V. 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

Treatment with L-citrulline in patients with post-polio syndrome: study protocol for a single-center, randomised, placebo-controlled, double-blind trial.

PubMed

Schmidt, Simone; Gocheva, Vanya; Zumbrunn, Thomas; Rubino-Nacht, Daniela; Bonati, Ulrike; Fischer, Dirk; Hafner, Patricia

2017-03-09

Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute infection by the Poliomyelitis virus. Most often, patients who suffered from polio start to experience gradual new weakening in muscles, a gradual decrease in the size of muscles (muscle atrophy) and fatigue years after the acute illness. L-citrulline is known to change muscular metabolism synthesis by raising nitric oxide (NO) levels and increasing protein synthesis. This investigator-initiated, randomised, placebo-controlled, double-blind, trial aims to demonstrate that L-citrulline positively influences muscle function and increases muscular energy production in patients with PPS. Thirty ambulant PPS patients will be recruited in Switzerland. Patients will be randomly allocated to one of the two arms of the study (placebo:verum 1:1). After a 24-week run-in phase to observe natural disease history and progression, participants will be treated either with L-citrulline or placebo for 24 weeks. The primary endpoint is change in the 6-min Walking Distance Test. Secondary endpoints will include motor function measure, quantitative muscle force, quantitative muscle magnetic resonance imaging and magnetic resonance spectroscopy and serum biomarker laboratory analysis DISCUSSION: The aim of this phase IIa trial is to determine if treatment with L-citrulline shows a positive effect on clinical function and paraclinical biomarkers in PPS. If treatment with L-citrulline shows positive effects, this might represent a cost-efficient symptomatic therapy for PPS patients. ClinicalTrial.gov, ID: NCT02801071 . Registered on 6 June 2016.

Treatment with L-citrulline and metformin in Duchenne muscular dystrophy: study protocol for a single-centre, randomised, placebo-controlled trial.

PubMed

Hafner, Patricia; Bonati, Ulrike; Rubino, Daniela; Gocheva, Vanya; Zumbrunn, Thomas; Gueven, Nuri; Fischer, Dirk

2016-08-03

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease that affects 1 in 3500-6000 male births. Despite broad research aiming to improve muscle function as well as heart and brain function, sufficient therapeutic efficacy has not yet been achieved and current therapeutic management is still supportive. In a recent pilot trial, oral treatment with L-arginine and metformin showed consistent changes of muscular metabolism both in vitro and in vivo by raising NO levels and expression of mitochondrial proteins in the skeletal muscle tissue of patients with DMD. This randomised, double-blind, placebo-controlled trial aims to demonstrate the superiority of L-citrulline and metformin therapy over placebo in DMD patients with regard to the Motor Function Measure (MFM) D1 subscore (primary endpoint) as well as additional clinical and subclinical tests. A total of 40-50 ambulant patients with DMD will be recruited at the outpatient department of the University of Basel Children's Hospital (Switzerland), as well as from the DMD patient registries of Switzerland, Germany and Austria. Patients will be randomly allocated to one of the two arms of the study and will receive either a combination of L-citrulline and metformin or placebo for 26 weeks. Co-medication with glucocorticoids is allowed. The primary endpoint is the change of the MFM D1 subscore from baseline to week 26 under L-citrulline and metformin therapy. Secondary endpoints will include the motor function measure (MFM) and its items and subscores, the 6-minute walking test, timed function tests and quantitative muscle testing. Furthermore, quantitative muscle MRI assessment to evaluate the muscle fat fraction as well as safety and biomarker laboratory analyses from blood will be included. For comparison, muscle metabolism and mitochondrial function will be analysed in 10-20 healthy age-matched male children. The aim of this study is to test if a 6-month treatment of a combination of L-citrulline and

Homeopathy for Depression: A Randomized, Partially Double-Blind, Placebo-Controlled, Four-Armed Study (DEP-HOM)

PubMed Central

Adler, Ubiratan C.; Krüger, Stephanie; Teut, Michael; Lüdtke, Rainer; Schützler, Lena; Martins, Friederike; Willich, Stefan N.; Linde, Klaus; Witt, Claudia M.

2013-01-01

Background The specific clinical benefit of the homeopathic consultation and of homeopathic remedies in patients with depression has not yet been investigated. Aims To investigate the 1) specific effect of individualized homeopathic Q-potencies compared to placebo and 2) the effect of an extensive homeopathic case taking (case history I) compared to a shorter, rather conventional one (case history II) in the treatment of acute major depression (moderate episode) after six weeks. Methods A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2×2 factorial design with a six-week study duration per patient was performed. Results A total of 44 from 228 planned patients were randomized (2∶1∶2∶1 randomization: 16 homeopathic Q-potencies/case history I, 7 placebo/case history I, 14 homeopathic Q-potencies/case history II, 7 placebo/case history II). Because of recruitment problems, the study was terminated prior to full recruitment, and was underpowered for the preplanned confirmatory hypothesis testing. Exploratory data analyses showed heterogeneous and inconclusive results with large variance in the sample. The mean difference for the Hamilton-D after 6 weeks was 2.0 (95%CI −1.2;5.2) for Q-potencies vs. placebo and −3.1 (−5.9;−0.2) for case history I vs. case history II. Overall, no consistent or clinically relevant results across all outcomes between homeopathic Q-potencies versus placebo and homeopathic versus conventional case taking were observed. The frequency of adverse events was comparable for all groups. Conclusions Although our results are inconclusive, given that recruitment into this trial was very difficult and we had to terminate early, we cannot recommend undertaking a further trial addressing this question in a similar setting. Prof. Dr. Claudia Witt had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Trial registration

Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study

PubMed Central

Jenkins, Tim M; Smart, Trevor S; Hackman, Frances; Cooke, Carol; Tan, Keith KC

2012-01-01

Background: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population. Methods: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP) to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study. Results: Twenty-five adults (20–70 years of age) with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1) pregabalin followed by placebo or (2) placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5–15). In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint) were significantly reduced for pregabalin versus placebo, with a mean treatment difference of −0.81 (95% confidence interval: −1.45 to −0.17; P = 0.015). Conclusion: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain. PMID:22888270

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

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.

Lafutidine prevents low-dose aspirin and loxoprofen induced gastric injury: a randomized, double-blinded, placebo controlled study.

PubMed

Kato, Mototsugu; Kamada, Go; Yamamoto, Keiko; Nishida, Urara; Imai, Aki; Yoshida, Takeshi; Ono, Shouko; Nakagawa, Manabu; Nakagawa, Soichi; Shimizu, Yuichi; Asaka, Masahiro

2010-10-01

The concomitant use of non-steroidal anti-inflammatory drugs is a risk factor for low-dose aspirin (LDA)-associated upper gastrointestinal toxicity. Lafutidine is an H2-receptor antagonist with gastroprotective activity, produced by acting on capsaicin-sensitive afferent neurons. To evaluate the preventive effect of lafutidine on gastric damage caused by LDA alone and by the combination of both LDA and loxoprofen, we conducted a clinical study using healthy volunteers. A randomized, double-blinded, placebo-controlled, crossover study was carried out. Sixteen healthy volunteers without Helicobacter pylori infection were randomly assigned to two groups. Both groups received 81 mg of aspirin once daily for 14 days (on days 1 to 14) and 60 mg of loxoprofen three times daily for the last 7 days (on days 8 to 14). Placebo or 10 mg of lafutidine was administered twice daily for 14 days in each group. After a 2-week washout period, placebo and lafutidine were crossed over. Endoscopic findings of gastric mucosal damage were evaluated according to the modified Lanza score. The mean modified Lanza score was 2.19 ± 1.06 (SD) for aspirin plus placebo as compared with 0.50 ± 0.77 for aspirin plus lafutidine (P < 0.001), and 3.00 ± 1.56 for aspirin plus loxoprofen and placebo as compared with 1.25 ± 1.37 for aspirin plus loxoprofen and lafutidine (P < 0.01). The addition of loxoprofen to LDA increases gastric mucosal damage. Standard-dose lafutidine significantly prevents gastric mucosal damage induced by LDA alone or LDA plus loxoprofen in H. pylori-negative volunteers. Larger controlled studies are needed to strengthen these findings. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

On Suggestibility and Placebo: A Follow-Up Study.

PubMed

Lifshitz, Michael; Sheiner, Eli O; Olson, Jay A; Thériault, Rémi; Raz, Amir

2017-04-01

Identifying what makes some people respond well to placebos remains a major challenge. Here, we attempt to replicate an earlier study in which we found a relationship between hypnotic suggestibility and subjective ratings of relaxation following the ingestion of a placebo sedative (Sheiner, Lifshitz, & Raz, 2016). To assess the reliability of this effect, we tested 34 participants using a similar design. Participants ingested a placebo capsule in one of two conditions: (1) relaxation, wherein we described the capsule as a herbal sedative, or (2) control, wherein we described the capsule as inert. To index placebo response, we collected measures of blood pressure and heart rate, as well as self-report ratings of relaxation and drowsiness. Despite using a similar experimental design as in our earlier study, we were unable to replicate the correlation between hypnotic suggestibility and placebo response. Furthermore, whereas in our former experiment we observed a change in subjective ratings of relaxation but no change in physiological measures, here we found that heart rate dropped in the relaxation condition while subjective ratings remained unchanged. Even within a consistent context of relaxation, therefore, our present results indicate that placebos may induce effects that are fickle, tenuous, and unreliable. Although we had low statistical power, our findings tentatively accord with the notion that placebo response likely involves a complex, multifaceted interaction between traits, expectancies, and contexts.

Randomised, placebo-controlled, double-blind, split-face study on the clinical efficacy of Tricutan on skin firmness.

PubMed

Sommerfeld, B

2007-11-01

Tricutan is a combination product of herbal extracts traditionally used for treatment of skin conditions, together with dimethylaminoethanol. The effectiveness of Tricutan in improving skin firmness and elasticity in photoaged facial skin was examined in a randomised, placebo-controlled, double-blind, split-face study in 28 women, 34-67 years old. Treatment with Tricutan and placebo was given for 4 weeks. Skin firmness and elasticity was evaluated using the speed of propagation of ultrasound shear waves in the skin as end point (Reviscometer RVM 600). The study was completed by 25 women. The Tricutan treatment resulted in a significantly reduced propagation speed indicating increased firmness. There was no immediate effect by Tricutan application on propagation speed. At self evaluation the women evaluated the treatment effect of Tricutan to be significantly better than the treatment effect of placebo. The clinical evaluation also showed Tricutan to give a significantly better treatment result than placebo. Tolerance to Tricutan was generally good. However, three women did not complete the study because of mild irritative contact dermatitis. The results show that Tricutan can increase skin firmness both objectively and subjectively. Further studies are warranted, especially to investigate if Tricutan can delay the need for surgical face-lift procedures.

Inorganic Nitrate in Angina Study: A Randomized Double-Blind Placebo-Controlled Trial.

PubMed

Schwarz, Konstantin; Singh, Satnam; Parasuraman, Satish K; Rudd, Amelia; Shepstone, Lee; Feelisch, Martin; Minnion, Magdalena; Ahmad, Shakil; Madhani, Melanie; Horowitz, John; Dawson, Dana K; Frenneaux, Michael P

2017-09-08

In this double-blind randomized placebo-controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina. Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2-week washout period before crossing over to the other treatment (n=34 placebo-nitrate, n=36 nitrate-placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P =0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P =0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] μmol/L, P <0.0001) and almost doubled circulating nitrite concentrations (346 [285, 405] versus 552 [398, 706] nmol/L, P =0.003; placebo versus nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation. Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012-000196-17. �

Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.

PubMed

Corey-Bloom, Jody; Wolfson, Tanya; Gamst, Anthony; Jin, Shelia; Marcotte, Thomas D; Bentley, Heather; Gouaux, Ben

2012-07-10

Spasticity is a common and poorly controlled symptom of multiple sclerosis. Our objective was to determine the short-term effect of smoked cannabis on this symptom. We conducted a placebo-controlled, crossover trial involving adult patients with multiple sclerosis and spasticity. We recruited participants from a regional clinic or by referral from specialists. We randomly assigned participants to either the intervention (smoked cannabis, once daily for three days) or control (identical placebo cigarettes, once daily for three days). Each participant was assessed daily before and after treatment. After a washout interval of 11 days, participants crossed over to the opposite group. Our primary outcome was change in spasticity as measured by patient score on the modified Ashworth scale. Our secondary outcomes included patients' perception of pain (as measured using a visual analogue scale), a timed walk and changes in cognitive function (as measured by patient performance on the Paced Auditory Serial Addition Test), in addition to ratings of fatigue. Thirty-seven participants were randomized at the start of the study, 30 of whom completed the trial. Treatment with smoked cannabis resulted in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo (p < 0.0001). In addition, treatment reduced pain scores on a visual analogue scale by an average of 5.28 points more than placebo (p = 0.008). Scores for the timed walk did not differ significantly between treatment and placebo (p = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo (p = 0.003). No serious adverse events occurred during the trial. Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact.

RETRACTED: Acarbose on insulin resistance after an oral fat load: a double-blind, placebo controlled study.

PubMed

Derosa, Giuseppe; Maffioli, Pamela; D'Angelo, Angela; Fogari, Elena; Bianchi, Lucio; Cicero, Arrigo F G

2011-01-01

We evaluated the effects of acarbose on insulin resistance parameters in diabetic patients before and after a standardized oral fat load (OFL). Patients were assigned to take acarbose 50 mg three times a day or placebo; after the first month, acarbose was titrated to 100 mg three times a day. We evaluated body mass index, glycemic control, fasting plasma insulin (FPI), post-prandial plasma insulin (PPI), homeostasis model assessment insulin resistance index (HOMA-IR), blood pressure, lipid profile, retinol binding protein-4 (RBP-4), adiponectin (ADN), tumor necrosis factor-α and resistin (r). Furthermore, at the baseline and at the end of the study, all patients underwent an OFL and an euglycemic hyperinsulinemic clamp. We observed that acarbose was better than placebo in improving glycemic control and HOMA-IR and that it was also more effective in improving lipid profile, RBP-4 and ADN. Regarding FPI, PPI and r, we did not obtain any significant differences between the two groups. During the second OFL, performed after 7 months of therapy with acarbose, we observed a significant decrease of blood glucose, lipid profile and all insulin resistance parameters peaks compared with the OFL administered at baseline with acarbose, but not with placebo. Acarbose was more effective than placebo in improving glycemic and lipid profile and in reducing the post-OFL peaks of the various parameters including the insulin resistance biomarkers. Copyright © 2011 Elsevier Inc. All rights reserved.

Radon balneotherapy and physical activity for osteoporosis prevention: a randomized, placebo-controlled intervention study.

PubMed

Winklmayr, Martina; Kluge, Christian; Winklmayr, Wolfgang; Küchenhoff, Helmut; Steiner, Martina; Ritter, Markus; Hartl, Arnulf

2015-03-01

Low-dose radon hyperthermia balneo treatment (LDRnHBT) is applied as a traditional measure in the non-pharmacological treatment of rheumatic diseases in Europe. During the last decades, the main approach of LDRnHBT was focused on the treatment of musculoskeletal disorders, but scientific evidence for the biological background of LDRnHBT is weak. Recently, evidence emerged that LDRnHBT influences bone metabolism. We investigated, whether combined LDRnHBT and exercise treatment has an impact on bone metabolism and quality of life in a study population in an age group at risk for developing osteoporosis. This randomized, double-blind, placebo-controlled trial comprised guided hiking tours and hyperthermia treatment in either radon thermal water (LDRnHBT) or radon-free thermal water (PlaceboHBT). Markers of bone metabolism, quality of life and somatic complaints were evaluated. Statistics was performed by linear regression and a linear mixed model analysis. Significant changes over time were observed for most analytes investigated as well as an improvement in self-assessed health in both groups. No significant impact from the LDRnHBT could be observed. After 6 months, the LDRnHBT group showed a slightly stronger reduction of the osteoclast stimulating protein receptor activator of nuclear kB-ligand compared to the PlaceboHBT group, indicating a possible trend. A combined hyperthermia balneo and exercise treatment has significant immediate and long-term effects on regulators of bone metabolism as well as somatic complaints. LDRnHBT and placeboHBT yielded statistically equal outcomes.

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. ACTRN

Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study.

PubMed

Michopoulos, Vasiliki; Norrholm, Seth D; Stevens, Jennifer S; Glover, Ebony M; Rothbaum, Barbara O; Gillespie, Charles F; Schwartz, Ann C; Ressler, Kerry J; Jovanovic, Tanja

2017-09-01

Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n=62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD- (n=37) and PTSD+ (n=25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all p<0.05). However, only PTSD- control participants showed decreases in fear-potentiated startle across extinction blocks during both conditions (p's≤0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone

Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome--a pilot study.

PubMed

Tuteja, Ashok K; Fang, John C; Al-Suqi, Manal; Stoddard, Gregory J; Hale, Devon C

2012-10-01

Post-infective irritable bowel syndrome (PI-IBS) is characterized by continuing symptoms of irritable bowel syndrome, typically diarrhea-predominant, following an episode of acute gastroenteritis. There is often an increase in sub-epithelial inflammatory and neuroendocrine cells on colonic mucosal biopsy. Mesalamine is an anti-inflammatory agent, effective in the treatment of inflammatory bowel disease. The goal of this study was to compare mesalamine to placebo on symptoms and quality-of-life (QOL) in PI-IBS. Twenty patients who developed diarrhea-predominant IBS after gastroenteritis were randomized to receive mesalamine (Asacol®) 1.6 gm b.i.d. or placebo for 12 weeks in a double-blind placebo-controlled study. QOL was assessed using the IBS-QOL questionnaire. Stool frequency, stool consistency, urgency, severity of abdominal pain, severity of bloating, and global-improvement scale were recorded in daily diaries for 7 days at baseline and every 4 weeks. Data were analyzed by comparing the change from baseline to last follow-up. One patient withdrew after randomization; data were incomplete in two patients. Thus, data were analyzed from 17 patients (11 men and 6 women, median age: 27 years, range 22-45 years). Mesalamine was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all p ≥ 0.11) or QOL (p ≥ 0.16). There was no significant improvement in global symptoms or overall QOL with mesalamine in patients with PI-IBS.

How Placebo Needles Differ From Placebo Pills?

PubMed Central

Chae, Younbyoung; Lee, Ye-Seul; Enck, Paul

2018-01-01

Because acupuncture treatment is defined by the process of needles penetrating the body, placebo needles were originally developed with non-penetrating mechanisms. However, whether placebo needles are valid controls in acupuncture research is subject of an ongoing debate. The present review provides an overview of the characteristics of placebo needles and how they differ from placebo pills in two aspects: (1) physiological response and (2) blinding efficacy. We argue that placebo needles elicit physiological responses similar to real acupuncture and therefore provide similar clinical efficacy. We also demonstrate that this efficacy is further supported by ineffective blinding (even in acupuncture-naïve patients) which may lead to opposite guesses that will further enhances efficacy, as compared to no-treatment, e.g., with waiting list controls. Additionally, the manner in which placebo needles can exhibit therapeutic effects relative to placebo pills include enhanced touch sensations, direct stimulation of the somatosensory system and activation of multiple brain systems. We finally discuss alternative control strategies for the placebo effects in acupuncture therapy.

A Randomized Placebo-Controlled Trial of a School-Based Depression Prevention Program.

ERIC Educational Resources Information Center

Merry, Sally; McDowell, Heather; Wild, Chris J.; Bir, Julliet; Cunliffe, Rachel

2004-01-01

Objective: To conduct a placebo-controlled study of the effectiveness of a universal school-based depression prevention program. Method: Three hundred ninety-two students age 13 to 15 from two schools were randomized to intervention (RAP-Kiwi) and placebo programs run by teachers. RAP-Kiwi was an 11-session manual-based program derived from…

Dose dependent sun protective effect of topical melatonin: A randomized, placebo-controlled, double-blind study.

PubMed

Scheuer, Cecilie; Pommergaard, Hans-Christian; Rosenberg, Jacob; Gögenur, Ismail

2016-11-01

Ultraviolet radiation (UVR) by sunlight results in an increasing number of skin conditions. Earlier studies have suggested a protective effect of topical treatment with the pineal hormone melatonin. However, this protective effect has never been evaluated in natural sunlight, and the optimal dosing has not been clarified. The aim of this study was to investigate the sun protective effect of topical treatment with three different doses of melatonin (0.5%, 2.5%, 12.5%) against erythema induced by natural sunlight. The study was a randomized, placebo-controlled, double-blind study in healthy volunteers. Twenty-three healthy volunteers, 8 male and 15 female, were enrolled. The protective effect of three different doses of melatonin cream (0.5%, 2.5%, 12.5%) against erythema induced by natural sunlight was tested. All participants had their backs exposed to sun from 1:22 PM to 2:02 PM local time and UV-index was 9. Primary outcome was reduction in erythema evaluated by chromatography after sun exposure, when treated with topical melatonin cream (0.5%, 2.5%, 12.5%) versus placebo and no treatment. The erythema reaction was evaluated with chromatography and visual scoring at baseline, one, four, eight and 24h after exposure. Significant difference in erythema formation was found between areas treated with melatonin cream 12.5% and areas receiving placebo or no treatment (repeated measures ANOVA p=0.001). No differences were found between placebo and the 0.5% and 2.5% concentrations. Application of melatonin cream 12.5% protects against natural sunlight induced erythema. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Comparison of Intravenous Morphine Versus Paracetamol in Sciatica: A Randomized Placebo Controlled Trial.

PubMed

Serinken, Mustafa; Eken, Cenker; Gungor, Faruk; Emet, Mucahit; Al, Behcet

2016-06-01

The objective was to compare intravenous morphine and intravenous acetaminophen (paracetamol) for pain treatment in patients presenting to the emergency department with sciatica. Patients, between the ages of 21 and 65 years, suffering from pain in the sciatic nerve distribution and a positive straight leg-raise test composed the study population. Study patients were assigned to one of three intravenous interventions: morphine (0.1 mg/kg), acetaminophen (1 g), or placebo. Physicians, nurses, and patients were blinded to the study drug. Changes in pain intensity were measured at 15 and 30 minutes using a visual analog scale. Rescue drug (fentanyl) use and adverse effects were also recorded. Three-hundred patients were randomized. The median change in pain intensity between treatment arms at 30 minutes were as follows: morphine versus acetaminophen 25 mm (95% confidence interval [CI] = 20 to 29 mm), morphine versus placebo 41 mm (95% CI = 37 to 45 mm), and acetaminophen versus placebo 16 mm (95% CI = 12 to 20 mm). Eighty percent of the patients in the placebo group (95% CI = 63.0% to 99%), 18% of the patients in the acetaminophen group (95% CI = 10.7% to 28.5%), and 6% of those in the morphine group (95% CI = 2.0% to 13.2%) required a rescue drug. Adverse effects were similar between the morphine and acetaminophen groups. Morphine and acetaminophen are both effective for treating sciatica at 30 minutes. However, morphine is superior to acetaminophen. © 2016 by the Society for Academic Emergency Medicine.

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

Oxytocin Effect on Collective Decision Making: A Randomized Placebo Controlled Study.

PubMed

Hertz, Uri; Kelly, Maria; Rutledge, Robb B; Winston, Joel; Wright, Nicholas; Dolan, Raymond J; Bahrami, Bahador

2016-01-01

Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants' (unwarranted) reliance on their partners' opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other's performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration.

Modafinil treatment for fatigue in HIV/AIDS: a randomized placebo-controlled study.

PubMed

Rabkin, Judith G; McElhiney, Martin C; Rabkin, Richard; McGrath, Patrick J

2010-06-01

To evaluate the efficacy and safety of modafinil in the treatment of fatigue in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and to assess effect on depressive symptoms. Patients who were HIV+ and had clinically significant fatigue (according to the Fatigue Severity Scale [FSS]) were included in a 4-week randomized, placebo-controlled, double-blind trial. This was followed by an additional 8 weeks of open-label treatment for modafinil responders and 12 weeks for placebo nonresponders. The primary outcome measure for fatigue and depression was the Clinical Global Impressions-Improvement scale, supplemented by the FSS, Hamilton Depression Rating Scale, and Beck Depression Inventory. Safety was assessed with assays of CD4 cell count and HIV ribonucleic acid (RNA) viral load. Visits were weekly for 4 weeks, then biweekly, with a follow-up visit at 6 months. Maximum trial dose of modafinil was 200 mg/d. Data for this study were collected between December 2004 and December 2008. 115 patients were randomly assigned. In intention-to-treat analyses, fatigue response rate to modafinil was 73% and to placebo, 28%. Attrition was 9%. Modafinil did not have an effect on mood alone in the absence of improved energy. At week 4, CD4 cell counts did not change significantly; HIV RNA viral load showed a trend decline for patients taking modafinil but not for those taking placebo. At 6 months, those still taking modafinil had more energy and fewer depressive symptoms than patients who were not taking modafinil, and only those still taking modafinil showed a significant decline from baseline in their HIV RNA viral load. Modafinil appears to be effective and well tolerated in treating fatigue in HIV+ patients. Consideration of its use is warranted considering the high prevalence of fatigue in the HIV community, its minimal side effects, and overall patient acceptance. clinicaltrials.gov Identifier: NCT00118378. 2010 Physicians Postgraduate

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.

Effect of homeopathy on analgesic intake following knee ligament reconstruction: a phase III monocentre randomized placebo controlled study

PubMed Central

Paris, A; Gonnet, N; Chaussard, C; Belon, P; Rocourt, F; Saragaglia, D; Cracowski, J L

2008-01-01

Aims The efficacy of homeopathy is still under debate. The objective of this study was to assess the efficacy of homeopathic treatment (Arnica montana 5 CH, Bryonia alba 5 CH, Hypericum perforatum 5 CH and Ruta graveolens 3 DH) on cumulated morphine intake delivered by PCA over 24 h after knee ligament reconstruction. Methods This was an add-on randomized controlled study with three parallel groups: a double-blind homeopathic or placebo arm and an open-label noninterventional control arm. Eligible patients were 18–60 years old candidates for surgery of the anterior cruciate ligament. Treatment was administered the evening before surgery and continued for 3 days. The primary end-point was cumulated morphine intake delivered by PCA during the first 24 h inferior or superior/equal to 10 mg day−1. Results One hundred and fifty-eight patients were randomized (66 in the placebo arm, 67 in the homeopathic arm and 25 in the noninterventional group). There was no difference between the treated and the placebo group for primary end-point (mean (95% CI) 48% (35.8, 56.3), and 56% (43.7, 68.3), required less than 10 mg day−1 of morphine in each group, respectively). The homeopathy treatment had no effect on morphine intake between 24 and 72 h or on the visual analogue pain scale, or on quality of life assessed by the SF-36 questionnaire. In addition, these parameters were not different in patients enrolled in the open-label noninterventional control arm. Conclusions The complex of homeopathy tested in this study was not superior to placebo in reducing 24 h morphine consumption after knee ligament reconstruction. What is already known about this subject The efficacy of homeopathy is still under debate and a recent meta-analysis recommended further randomized double-blind clinical trials to identify any clinical situation in which homeopathy might be effective. What this study adds The complex of homeopathy tested in this study (Arnica montana 5 CH, Bryonia alba 5 CH

Relapse Prevention in Pediatric Patients with ADHD Treated with Atomoxetine: A Randomized, Double-Blind, Placebo-Controlled Study

ERIC Educational Resources Information Center

Michelson, David; Buitelaar, Jan K.; Danckaerts, Marina; Gillberg, Christopher; Spencer, Thomas J.; Zuddas, Alessandro; Faries, Douglas E.; Zhang, Shuyu; Biederman, Joseph

2004-01-01

Objective: Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; however, few placebo-controlled, long-term studies of efficacy have been reported. Method: In a global multicenter study, children and adolescents who responded to an initial 12-week, open-label period of treatment with atomoxetine, a…

Saccharomyces boulardii in acute childhood diarrhoea: a randomized, placebo-controlled study.

PubMed

Villarruel, Gladys; Rubio, Daniel Martinez; Lopez, Fani; Cintioni, Julio; Gurevech, Rubén; Romero, Gladis; Vandenplas, Yvan

2007-04-01

To evaluate the efficacy of the probiotic yeast Saccharomyces boulardii (S. boulardii) as an adjuvant to oral rehydration solution (ORS) in shortening the duration of acute infectious gastroenteritis in children less than 2 years old in ambulatory care. In a period of 1 year, 100 outpatients between 3 and 24 months old presenting with acute mild to moderate diarrhoea of less than 7 days duration, were included in a double-blind, randomized, placebo-controlled trial evaluating the efficacy of S. boulardii administered for 6 days. Twelve children were lost in follow-up; the data of 88 children could be analysed (44 in the placebo and 44 in the S. boulardii group). Seventy-two patients were followed for one month (37 in the placebo and 35 in the S. boulardii group) allowing the calculation of the duration of diarrhoea. The mean duration of diarrhoea was 6.16 days (range 2-13 days) in the placebo group and 4.70 days (range 2-10 days) in the S. boulardii group (p<0.05). On the 4th day, the patients in the S. boulardii group passed 2.5+/-1.4 stools/day versus 3.5+/-1.8 in the placebo group (p<0.001). The risk of having diarrhoea lasting more than 7 days was lower in the S. boulardii group (3/44 versus 12/44; RR 0.25; 95% CI 0.1-0.8). In no patient diarrhoea persisted longer than 14 days. A statistically significant difference was observed in the number of stools on the 4th and 7th day favouring the subgroup that received early treatment (within the first 48 h of the onset of diarrhoea). The administration of antibiotics before inclusion did not make any difference. S. boulardii as an adjuvant to ORS in ambulatory care in children less than 2 years old with mild or moderate acute diarrhoea decreased the duration of diarrhoea, accelerated recovery and reduced the risk of prolonged diarrhoea. The data also indicate increased efficacy if S. boulardii is administered within the first 48 h of the onset of diarrhoea.

L-carnitine supplementation in patients with HIV/AIDS and fatigue: a double-blind, placebo-controlled pilot study.

PubMed

Cruciani, Ricardo A; Revuelta, Manuel; Dvorkin, Ella; Homel, Peter; Lesage, Pauline; Esteban-Cruciani, Nora

2015-01-01

The purpose of this study was to determine the effect of L-carnitine supplementation on fatigue in patients with terminal human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). In this randomized, double-blind, placebo-controlled, parallel-group study, patients who had end-stage HIV/AIDS with carnitine deficiency and fatigue received 3 g of oral L-carnitine or placebo for 2 weeks, followed by a 2-week, open-label phase with the same amount of L-carnitine for all patients. The primary outcome was the degree of fatigue according to the Brief Fatigue Inventory. Secondary outcomes included serum carnitine and lactate levels, physical, emotional, social, and functional well-being, performance status, mood, and CD4 count. Eighteen patients in the treatment arm and 17 in the placebo arm completed the trial. At the end of the double-blind phase, total and free carnitine levels in the treatment arm rose from 28±9 to 48±17 nM/L (P<0.001) and from 24±8 to 40±13 nM/L (P<0.001) respectively, with no changes in the placebo arm. The primary outcome, ie, fatigue measured at the end of the blinded phase, did not improve. Secondary outcomes of function, quality of life, and mood did not show improvement either. The secondary outcome of serum lactate decreased from baseline in the treatment group (1.45±0.76 to 1.28±0.52 mmol/L) and increased in the placebo group (1.38±0.62 to 1.84±0.74 mmol/L; P<0.005). Our study suggests that 3 g of oral L-carnitine supplementation for 2 weeks in terminally ill HIV/AIDS patients does not improve fatigue. This study might help to determine the dose and duration of treatment used in future clinical trials, as higher doses and/or longer periods of supplementation might be needed in order to detect an improvement. The reduction in serum lactate levels suggests a potential role for L-carnitine supplementation in patients undergoing certain types of antiretroviral therapy. This study contributes evidence-based data to the

Intrathecal Baclofen in Children with Spastic Cerebral Palsy: A Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study

ERIC Educational Resources Information Center

Hoving, Marjanke A.; van Raak, Elisabeth P. M.; Spincemaille, Geert H. J. J.; Palmans, Liesbeth J.; Sleypen, Frans A. M.; Vles, Johan S. H.

2007-01-01

Intrathecal baclofen (ITB) therapy can be very effective in the treatment of intractable spasticity, but its effectiveness and safety have not yet been thoroughly studied in children with cerebral palsy (CP). The aims of this double-blind, randomized, placebo-controlled, dose-finding study were to select children eligible for continuous ITB…

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.

Efficacy and safety of acarbose in the treatment of Type 1 diabetes mellitus: a placebo-controlled, double-blind, multicentre study.

PubMed

Riccardi, G; Giacco, R; Parillo, M; Turco, S; Rivellese, A A; Ventura, M R; Contadini, S; Marra, G; Monteduro, M; Santeusanio, F; Brunetti, P; Librenti, M C; Pontiroli, A E; Vedani, P; Pozza, G; Bergamini, L; Bianchi, C

1999-03-01

The aim of the study was to evaluate the efficacy and safety of acarbose in patients with Type 1 diabetes mellitus (DM). A multicentre double-blind, randomized, placebo-controlled study was performed. After a 6-week run-in, 121 patients were randomized to acarbose or placebo and to high- or low-fibre diet for 24 weeks. Acarbose dose was 50 mg t.d.s. for the first 2 weeks and 100 mg t.d.s. for the subsequent weeks. At the end of 24 weeks of treatment the intention to treat analysis showed that acarbose compared with placebo decreased 2 h postprandial plasma glucose levels (12.23 +/- 0.83 vs. 14.93 +/- 0.87 mmol/l; F = 6.1, P < 0.02) (least square means +/- SEM). No significant effect of acarbose was recorded on HbA1c or on the number of hypoglycaemic episodes. The effect of acarbose on blood glucose control was not influenced by the amount of carbohydrate and/or fibre intake. The incidence of adverse events were 75% and 39% in acarbose and placebo groups, respectively; they were mild and confined to the gastrointestinal tract. The use of acarbose in combination with insulin reduces postprandial plasma glucose levels in Type 1 diabetic patients who are not satisfactorily controlled with insulin alone but without significant effect on HbA1c.

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.

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.

Testing Public Anxiety Treatments against a Credible Placebo Control

ERIC Educational Resources Information Center

Duff, Desiree C.; Levine, Timothy R.; Beatty, Michael J.; Woolbright, Jessica; Park, Hee Sun

2007-01-01

Research investigating public speaking anxiety treatments is subject to demand effects. This study tests the relative effectiveness of systematic desensitization (SD) and multiple treatment method (MT) containing visualization therapy against no-treatment and credible placebo controls. Data (N = 238) were collected at six points in a public…

A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients.

PubMed Central

McKee, P J; Blacklaw, J; Forrest, G; Gillham, R A; Walker, S M; Connelly, D; Brodie, M J

1994-01-01

1. The effect of carbamazepine (CBZ), sodium valproate (VPA) and phenytoin (PHT) on the pharmacokinetics of oxcarbazepine (OXC) was explored in three groups of 12 epileptic patients taking one of these drug as monotherapy. 2. Each patient took a single 600 mg dose of OXC followed 7 days later by 3 weeks' treatment with OXC 300 mg thrice daily and matched placebo in random order. 3. Seven untreated patients, acting as controls, were prescribed the single OXC dose and 3 weeks' active treatment only. 4. In those patients completing the study, the area under the concentration-time curve (AUC) at steady-state for hydroxycarbazepine (OHCZ), the active metabolite of OXC, was significantly lower in the CBZ-treated group than in controls (P < 0.05). 5. No other differences in AUCs or elimination half-lives for OHCZ were found between treated and untreated patients following single or multiple OXC dosing. 6. Median AUCs of CBZ, VPA and PHT during a dosage interval did not differ significantly after treatment with OXC and placebo. 7. Ten patients completing the study complained of side-effects during treatment with OXC compared with one taking placebo (P < 0.01). 8. There were no important changes in cognitive function testing during administration of OXC compared with placebo. 9. Standard doses of OXC can be given as add-on therapy in epileptic patients receiving CBZ, VPA or PHT without producing a clinically relevant pharmacokinetic interaction. PMID:8148215

Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study.

PubMed

Hauge, Anne W; Asghar, Mohammed S; Schytz, Henrik W; Christensen, Karl; Olesen, Jes

2009-08-01

Migraine with aura is thought likely to be caused by cortical spreading depression (CSD). Tonabersat inhibits CSD, and we therefore investigated whether tonabersat has a preventive effect in migraine with aura. In this randomised, double-blind, placebo-controlled crossover trial, 40 mg tonabersat once daily was compared with matched placebo in patients who had at least one aura attack per month during the past 3 months. Randomisation was by computer-generated list. Patients kept a detailed diary to enable objective diagnosis of each attack as migraine with aura, migraine without aura, or other type of headache. Primary endpoints were a reduction in aura attacks with or without headache and a reduction in migraine headache days with or without an aura. Analysis was per protocol. This trial is registered, number NCT00332007. 39 patients were included in the study, of whom 31 were included in the statistical analysis of efficacy. Median (IQR) attacks of aura were reduced from 3.2 (1.0-5.0) per 12 weeks on placebo to 1.0 (0-3.0) on tonabersat (p=0.01), whereas the other primary outcome measure, median migraine headache days with or without aura, was not significantly different between placebo and tonabersat groups (3.0 days in each group; p=0.09). Tonabersat was well tolerated but overall had more side-effects than placebo. Tonabersat showed a preventive effect on attacks of migraine aura but no efficacy on non-aura attacks, in keeping with its known inhibitory effect on CSD. The results support the theory that auras are caused by CSD and that this phenomenon is not involved in attacks without aura. Minster Pharmaceuticals; Lundbeck Foundation.

Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis.

PubMed

Dorkin, Henry L; Staab, Doris; Operschall, Elisabeth; Alder, Jeff; Criollo, Margarita

2015-01-01

Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population. Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group. The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115). Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF. Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40.

Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis

PubMed Central

Dorkin, Henry L; Staab, Doris; Operschall, Elisabeth; Alder, Jeff; Criollo, Margarita

2015-01-01

Background Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population. Methods Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group. Results The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115). Conclusions Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF. Trial registration number Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40. PMID:26688732

Adverse Events of Atomoxetine in a Double-Blind Placebo-Controlled Study in Children with Autism.

PubMed

Tumuluru, Rameshwari V; Corbett-Dick, Patricia; Aman, Michael G; Smith, Tristram; Arnold, L Eugene; Pan, Xueliang; Buchan-Page, Kristin A; Brown, Nicole V; Ryan, Melissa M; Hyman, Susan L; Hellings, Jessica; Williams, Craig; Hollway, Jill A; Lecavalier, Luc; Rice, Robert R; McAuliffe-Bellin, Sarah; Handen, Benjamin L

2017-10-01

Attention-deficit/hyperactivity disorder (ADHD) symptoms, including inattention and over activity, occur in approximately one-third of children with autism spectrum disorder (ASD). We describe the rate and duration of adverse events in a randomized controlled trial of atomoxetine (ATX) and parent training (PT) for ADHD symptoms and noncompliance in children with ASD. We conducted a 10-week, double-blind, 2 × 2 trial of ATX and PT with 128 children (ages 5-14) randomized to ATX alone, ATX+PT, placebo+PT, or placebo alone. For 6 weeks, ATX (or placebo) doses were clinically adjusted to a maximum of 1.8 mg/(kg·day) and maintained for an additional 4 weeks. An average of seven PT sessions were conducted in the two PT arms. Adverse events (AEs) were assessed through parent ratings of common symptoms on a seven-point Likert severity scale and through direct interviews with study medical staff. ATX was associated with decreased appetite and fatigue, but was otherwise well tolerated. Most reported AEs lasted 4 weeks or less. Unlike reports with typically developing (TD) children, there were no concerns with QTc changes or suicidal ideation. This study extends the findings of previous studies of ATX in ASD by documenting that the type of AEs was similar to that of TD children, with no significant safety concerns.

Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer's disease psychosis: a phase 2, randomised, placebo-controlled, double-blind study.

PubMed

Ballard, Clive; Banister, Carol; Khan, Zunera; Cummings, Jeffrey; Demos, George; Coate, Bruce; Youakim, James M; Owen, Randall; Stankovic, Srdjan

2018-03-01

Pimavanserin is a selective 5-HT 2A receptor inverse agonist and antagonist approved in the USA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. No safe or effective pharmacological treatment is approved for psychosis in patients with Alzheimer's disease. Therefore, we aimed to evaluate the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer's disease psychosis. We did a phase 2, randomised, double-blind, placebo-controlled, single-centre (with multiple affiliated nursing home sites across the UK) study. We included participants of either sex who were aged 50 years or older with possible or probable Alzheimer's disease and psychotic symptoms including visual or auditory hallucinations, delusions, or both. Participants were randomly assigned (1:1) to 12 weeks of oral treatment with either pimavanserin (two 17 mg tablets daily) or placebo, with use of permuted block sizes of four and stratified by baseline Mini-Mental State Examination (MMSE) total score (<6 or ≥6) and Neuropsychiatric Inventory-Nursing Home version (NPI-NH) psychosis score (<12 or ≥12). Participants, caregivers, the study sponsor, and study personnel at the clinic site were masked to treatment assignment. The primary endpoint was mean change from baseline to week 6 in the NPI-NH psychosis score for pimavanserin versus placebo in the modified intention-to-treat population. Sustained benefit and safety of pimavanserin were assessed through week 12. This study is registered at ClinicalTrials.gov, number NCT02035553. Between Jan 16, 2014, and Oct 27, 2016, 345 participants across 133 nursing homes were screened, of whom 181 were randomly assigned treatment (n=90 pimavanserin and n=91 placebo). 178 participants were included in the modified intention-to-treat population. Mean total baseline NPI-NH psychosis scores were 9·5 (SD 4·8) for the pimavanserin group and 10·0 (5·6) for the placebo group. Mean change

Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial

PubMed Central

Corey-Bloom, Jody; Wolfson, Tanya; Gamst, Anthony; Jin, Shelia; Marcotte, Thomas D.; Bentley, Heather; Gouaux, Ben

2012-01-01

Background: Spasticity is a common and poorly controlled symptom of multiple sclerosis. Our objective was to determine the short-term effect of smoked cannabis on this symptom. Methods: We conducted a placebo-controlled, crossover trial involving adult patients with multiple sclerosis and spasticity. We recruited participants from a regional clinic or by referral from specialists. We randomly assigned participants to either the intervention (smoked cannabis, once daily for three days) or control (identical placebo cigarettes, once daily for three days). Each participant was assessed daily before and after treatment. After a washout interval of 11 days, participants crossed over to the opposite group. Our primary outcome was change in spasticity as measured by patient score on the modified Ashworth scale. Our secondary outcomes included patients’ perception of pain (as measured using a visual analogue scale), a timed walk and changes in cognitive function (as measured by patient performance on the Paced Auditory Serial Addition Test), in addition to ratings of fatigue. Results: Thirty-seven participants were randomized at the start of the study, 30 of whom completed the trial. Treatment with smoked cannabis resulted in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo (p < 0.0001). In addition, treatment reduced pain scores on a visual analogue scale by an average of 5.28 points more than placebo (p = 0.008). Scores for the timed walk did not differ significantly between treatment and placebo (p = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo (p = 0.003). No serious adverse events occurred during the trial. Interpretation: Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial

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

Family physicians believe the placebo effect is therapeutic but often use real drugs as placebos.

PubMed

Kermen, Rachel; Hickner, John; Brody, Howard; Hasham, Irma

2010-10-01

Few national data exist on physicians' use of and beliefs about placebos in routine health care. We mailed a 22-question, confidential survey about placebo use and beliefs to a random sample of 1,000 members of the American Academy of Family Physicians. A total of 412 of 970 (43%) eligible physicians responded, and 56% of respondents said they had used a placebo in clinical practice. Forty percent of respondents had used an antibiotic as a placebo, and 11% had used inert substances. The most common reason for prescribing placebos was "after unjustified demand for medication." Eighty-five percent of respondents believed placebos can have both psychological and physical benefits. The majority (61%) recommended a placebo over offering no treatment, while 8% said clinical placebo use should be categorically prohibited. Nearly all respondents believed a number of routine clinical practices promote the placebo effect. Many US family physicians use placebos and generally believe the placebo effect has both psychological and physical benefits. Physicians recognize the broader application of the placebo effect but they commonly use active medication as placebos. The responses to this survey raise important questions about the appropriate use of placebos and the therapeutic value of the placebo effect in clinical practice.

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%).

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

A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders.

PubMed

McDougle, C J; Holmes, J P; Carlson, D C; Pelton, G H; Cohen, D J; Price, L H

1998-07-01

Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism. Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone. For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (P<.002). Risperidone was superior to placebo in reducing repetitive behavior (P<.001), aggression (P<.001), anxiety or nervousness (P<.02), depression (P<.03), irritability (P<.01), and the overall behavioral symptoms of autism (P<.02). Objective, measurable change in social behavior and language did not occur. Nine (60%) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded. Other than mild, transient sedation, risperidone was well tolerated, with no evidence of extrapyramidal effects, cardiac events, or seizures. Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults.

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.

Treatment of Aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study.

PubMed

Aaron, Shawn D; Vandemheen, Katherine L; Freitag, Andreas; Pedder, Linda; Cameron, William; Lavoie, Annick; Paterson, Nigel; Wilcox, Pearce; Rabin, Harvey; Tullis, Elizabeth; Morrison, Nancy; Ratjen, Felix

2012-01-01

Many patients with cystic fibrosis develop persistent airway infection/colonization with Aspergillus fumigatus, however the impact of A. fumigatus on clinical outcomes remains unclear. The objective of this study was to determine whether treatment directed against Aspergillus fumigatus improves pulmonary function and clinical outcomes in patients with cystic fibrosis (CF). We performed a double-blind randomized placebo-controlled pilot clinical trial involving 35 patients with CF whose sputum cultures were chronically positive for A. fumigatus. Participants were centrally randomized to receive either oral itraconazole 5 mg/kg/d (N = 18) or placebo (N = 17) for 24 weeks. The primary outcome was the proportion of patients who experienced a respiratory exacerbation requiring intravenous antibiotics over the 24 week treatment period. Secondary outcomes included changes in FEV(1) and quality of life. Over the 24 week treatment period, 4 of 18 (22%) patients randomized to itraconazole experienced a respiratory exacerbation requiring intravenous antibiotics, compared to 5 of 16 (31%) placebo treated patients, P = 0.70. FEV(1) declined by 4.62% over 24 weeks in the patients randomized to itraconazole, compared to a 0.32% improvement in the placebo group (between group difference = -4.94%, 95% CI: -15.33 to 5.45, P = 0.34). Quality of life did not differ between the 2 treatment groups throughout the study. Therapeutic itraconazole blood levels were not achieved in 43% of patients randomized to itraconazole. We did not identify clinical benefit from itraconazole treatment for CF patients whose sputum was chronically colonized with A. fumigatus. Limitations of this pilot study were its small sample size, and failure to achieve therapeutic levels of itraconazole in many patients. ClinicalTrials.gov NCT00528190.

Early botulinum toxin treatment for spastic pes equinovarus--a randomized double-blind placebo-controlled study.

PubMed

Fietzek, U M; Kossmehl, P; Schelosky, L; Ebersbach, G; Wissel, J

2014-08-01

Spastic pes equinovarus is a frequent pathological posture of the lower extremity. Botulinum toxin (BoNT/A) has been successfully applied to treat lower limb spasticity. However, the best time to initiate treatment remains unclear. A beneficial effect of an early treatment has been suggested in previous studies. A single-centre double-blind randomized placebo-controlled trial was performed to investigate the efficacy of BoNT/A to reduce muscle hypertonicity at the ankle. Fifty-two patients with unilateral or bilateral spastic pes equinovarus with a modified Ashworth score (mAS) of at least 1+ after stroke, traumatic brain injury or hypoxic encephalopathy were allocated to receive either BoNT/A or placebo treatment. A second, open injection was optional at week 12. Patients received unilateral or bilateral injections with 230 or 460 U onabotulinumtoxinA, respectively. The course of the mAS was explored during the open study phase. Patients who had received BoNT/A treatment had lower mAS compared with placebo at week 12 (P < 0.01). During the open label phase, patients from the placebo group showed further deterioration of muscle tone despite starting from a similar baseline and receiving BoNT treatment. Spastic feet that had received BoNT/A in the first cycle had comparatively lower mAS scores over all follow-up data and at week 24 (P < 0.01). The study demonstrates a reduction of muscular hypertonicity in spastic pes equines with BoNT/A treatment given during the first 3 months after the lesion. Exploratory analyses of the course of muscular hypertonicity during the open phase favour earlier to later treatment. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

Evaluation of homeopathic Arnica montana for ecchymosis after upper blepharoplasty: a placebo-controlled, randomized, double-blind study.

PubMed

Kotlus, Brett S; Heringer, Dustin M; Dryden, Robert M

2010-01-01

Ecchymosis is commonly encountered after upper eyelid blepharoplasty. The use of homeopathic preparations of Arnica montana, a flowering herb, has been advocated by physicians, patients, and manufacturers for reduction of postsurgical ecchymosis. The authors evaluate its efficacy after upper eyelid blepharoplasty. A prospective, placebo-controlled, double-blind study was performed in which patients were randomly assigned to the administration of homeopathic A. montana or placebo concurrent with unilateral upper eyelid blepharoplasty followed by contralateral treatment at least 1 month later. Ecchymosis was evaluated at days 3 and 7 by rank order of severity and measurement of surface area of observable ecchymosis. There was no statistically significant difference in area of ecchymosis or rank order of ecchymosis severity for days 3 and 7 after treatment with A. montana versus placebo. Additionally, there was no difference in ease of recovery per patient report, and there was no difference in the rate of ecchymosis resolution. The authors find no evidence that homeopathic A. montana, as used in this study, is beneficial in the reduction or the resolution of ecchymosis after upper eyelid blepharoplasty.

Reducing depressive symptomatology with a smartphone app: study protocol for a randomized, placebo-controlled trial.

PubMed

Giosan, Cezar; Cobeanu, Oana; Mogoaşe, Cristina; Szentagotai, Aurora; Mureşan, Vlad; Boian, Rareș

2017-05-12

�weeks. A short therapist check-in via phone will take place every week. Participants in the delayed-intervention condition will be given access to the app after 6 weeks from randomization. The primary outcome is the level of depressive symptomatology. The intervention delivered through the app to the active condition includes psychoeducational materials and exercises based on CBT for depression, while the placebo intervention uses a sham version of the app (i.e., similar structure of courses and exercises). To our knowledge, this study protocol is the first to test the efficacy of a smartphone app for depressive symptomatology in the form of a randomized controlled trial (RCT) that includes an active placebo condition. As such, this can substantially add to the body of evidence supporting the use of apps designed to decrease depression. ClinicalTrials.gov, identifier: NCT03060200 . Registered on 1 February 2017. The first participant was enrolled on 17 February 2017.

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

Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder.

PubMed

Spencer, Thomas; Heiligenstein, John H; Biederman, Joseph; Faries, Douglas E; Kratochvil, Christopher J; Conners, C Keith; Potter, William Z

2002-12-01

Atomoxetine is a nonstimulant drug being studied for the treatment of attention-deficit/hyperactivity disorder (ADHD). Atomoxetine is a highly specific inhibitor of the presynaptic norepinephrine transporter with minimal affinity for other noradrenergic receptors or other neurotransmitter transporters or receptors. Results of 2 proof-of-concept studies are reported that tested the hypothesis that a selective inhibitor of presynaptic norepinephrine uptake would be effective for the treatment of ADHD in school-aged children. Two identical 12-week, stratified, randomized, double-blind, placebo-controlled trials were conducted in children who met DSM-IV criteria for ADHD. The primary efficacy outcome measure was the mean change from baseline to endpoint in the Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD RS) total score. Secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and the Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S). A total of 291 patients were randomized in the 2 trials combined (Study 1, N = 147; Study 2, N = 144). Stimulant-naive patients were randomized to atomoxetine, placebo, or methylphenidate. Patients with prior stimulant exposure were randomized to atomoxetine or placebo. Atomoxetine significantly reduced ADHD RS total scores compared with placebo in each study (p <.001). Changes in the CGI-ADHD-S (Study 1: p =.003; Study 2: p =.001) and CPRS-ADHD Index (Study 1: p =.023; Study 2: p <.001) also showed atomoxetine to be statistically significantly superior to placebo in reducing ADHD symptoms. Atomoxetine was found to be well tolerated in this population of pediatric patients. Two studies of atomoxetine early in its development confirmed that atomoxetine, a specific and selective inhibitor of noradrenergic uptake, was effective for the treatment of children with ADHD. In addition, atomoxetine was found to be well tolerated.

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.

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

Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind placebo-controlled trial

PubMed Central

Rangaka, Molebogeng X; Wilkinson, Robert J; Boulle, Andrew; Glynn, Judith R; Fielding, Katherine; van Cutsem, Gilles; Wilkinson, Katalin A; Goliath, Rene; Mathee, Shaheed; Goemaere, Eric; Maartens, Gary

2014-01-01

Background Antiretroviral therapy (ART) reduces the risk of tuberculosis, but the incidence still exceeds that in HIV-uninfected people. Isoniazid preventive therapy (IPT), which decreases the risk of tuberculosis in people not on ART, may offer additional protection. Methods Pragmatic randomized double-blind placebo-controlled trial to evaluate the effect of 12 months IPT among participants established on or newly starting ART, in Khayelitsha, South Africa (NCT00463086, Lancet D-09-02885). Tuberculosis was excluded at screening by sputum culture. Incident tuberculosis was the primary endpoint. Findings 1,329 participants contributed 3,227 person-years (PY) of follow up in the modified intention-to-treat analysis; 662 on IPT and 667 on placebo. There were 95 incident tuberculosis cases: 2.3 (95%CI 1.6-3.1) versus 3.6 (95%CI 2.8-4.7) per 100 PY in the IPT and placebo arms respectively (hazard ratio 0.63, 95%CI 0.41-0.94). Study drug was discontinued due to grade 3 or 4 raised ALT in 19/662 in the IPT and 10/667 in the placebo arm, risk ratio=1.9 (95%CI 0.90-4.09). In secondary analyses, there was no evidence that the effect of IPT was restricted to those who were positive on tuberculin skin test (TST) or interferon gamma release assay (IGRA): adjusted hazard ratio for those with negative tests 0.43 (95%CI 0.21-0.86) and 0.43 (95%CI 0.20-0.96); for positive tests 0.86 (95%CI 0.37-2.00) and 0.55 (95%CI 0.26-1.24) respectively. No all cause mortality benefit of IPT was demonstrated Interpretation IPT reduced the incidence of tuberculosis in HIV-infected individuals on ART. In this high incidence setting, individuals on ART who have TST or IGRA negative results may also benefit from IPT. IPT can easily be implemented in ART clinics. PMID:24835842

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.

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

Efficacy and tolerability of Hairgain in individuals with hair loss: a placebo-controlled, double-blind study.

PubMed

Thom, E

2001-01-01

This randomized, placebo-controlled, double-blind study was designed to investigate the efficacy and tolerability of a new agent for the treatment of hair loss, based on a marine protein, minerals and vitamins. Sixty subjects with hair loss of different aetiologies participated in the 6-month blinded phase of the study. Objective assessments indicated that the treatment was effective and subjective assessments showed a statistically significant positive effect of treatment. Exposure to the active preparation for a further 6 months in an open phase indicated a further improvement in hair growth. Exposure of the patients previously treated with placebo to the active preparation for 12 months gave similar results. Tolerability was good and no side-effects were reported. The product investigated may provide an alternative to pharmacotherapy for the treatment of hair-loss problems in individuals with androgenic alopecia.

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.

The influence of short-chain essential fatty acids on children with attention-deficit/hyperactivity disorder: a double-blind placebo-controlled study.

PubMed

Raz, Raanan; Carasso, Rafael L; Yehuda, Shlomo

2009-04-01

Essential fatty acids (EFA) are needed for normal sensory, cognitive, and motor function. The EFA blood profile seems to be different in children with attention-deficit/hyperactivity disorder (ADHD) as compared to matched controls. Previous open EFA supplementation trials were successful in demonstrating significant therapeutic effects in this population, whereas most of the randomized controlled trials failed to show any benefit over placebo. The current randomized, double-blind, placebo-controlled trial tested the influence of short-chain EFA supplementation on ADHD children, using parent and teacher questionnaires and a computerized continuous performance test. A total of 73 unmedicated children aged 7-13 years with a diagnosis of ADHD participated in the study; 63 children completed the study. The EFA supplement contained 480 mg of linoleic acid and 120 mg of alpha-linolenic acid, and the placebo contained 1000 mg of vitamin C (daily amounts); both were given for a 7-week supplementation period. Analysis of variance for repeated measures revealed that both treatments ameliorated some of the symptoms, but no significant differences were found between the groups in any of the treatment effects.

New validated recipes for double-blind placebo-controlled low-dose food challenges.

PubMed

Winberg, Anna; Nordström, Lisbeth; Strinnholm, Åsa; Nylander, Annica; Jonsäll, Anette; Rönmark, Eva; West, Christina E

2013-05-01

Double-blind placebo-controlled food challenges are considered the most reliable method to diagnose or rule out food allergy. Despite this, there are few validated challenge recipes available. The present study aimed to validate new recipes for low-dose double-blind placebo-controlled food challenges in school children, by investigating whether there were any sensory differences between the active materials containing cow's milk, hen's egg, soy, wheat or cod, and the placebo materials. The challenge materials contained the same hypoallergenic amino acid-based product, with or without added food allergens. The test panels consisted of 275 school children, aged 8-10 and 14-15 yr, respectively, from five Swedish schools. Each participant tested at least one recipe. Standardized blinded triangle tests were performed to investigate whether any sensory differences could be detected between the active and placebo materials. In our final recipes, no significant differences could be detected between the active and placebo materials for any challenge food (p > 0.05). These results remained after stratification for age and gender. The taste of challenge materials was acceptable, and no unfavourable side effects related to test materials were observed. In summary, these new validated recipes for low-dose double-blinded food challenges contain common allergenic foods in childhood; cow's milk, hen's egg, soy, wheat and cod. All test materials contain the same liquid vehicle, which facilitates preparation and dosing. Our validated recipes increase the range of available recipes, and as they are easily prepared and dosed, they may facilitate the use of double-blind placebo-controlled food challenges in daily clinical practice. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study

PubMed Central

Lortholary, Olivier; Chandesris, Marie Olivia; Livideanu, Cristina Bulai; Paul, Carle; Guillet, Gérard; Jassem, Ewa; Niedoszytko, Marek; Barete, Stéphane; Verstovsek, Srdan; Grattan, Clive; Damaj, Gandhi; Canioni, Danielle; Fraitag, Sylvie; Lhermitte, Ludovic; Lavialle, Sophie Georgin; Frenzel, Laurent; Afrin, Lawrence B; Hanssens, Katia; Agopian, Julie; Gaillard, Raphael; Kinet, Jean-Pierre; Auclair, Christian; Mansfield, Colin; Moussy, Alain; Dubreuil, Patrice; Hermine, Olivier

2018-01-01

Summary Background Indolent systemic mastocytosis, including the subvariant of smouldering systemic mastocytosis, is a lifelong condition associated with reduced quality of life. Masitinib inhibits KIT and LYN kinases that are involved in indolent systemic mastocytosis pathogenesis. We aimed to assess safety and efficacy of masitinib versus placebo in severely symptomatic patients who were unresponsive to optimal symptomatic treatments. Methods In this randomised, double-blind, placebo-controlled, phase 3 study, we enrolled adults (aged 18–75 years) with indolent or smouldering systemic mastocytosis, according to WHO classification or documented mastocytosis based on histological criteria, at 50 centres in 15 countries. We excluded patients with cutaneous or non-severe systemic mastocytosis after a protocol amendment. Patients were centrally randomised (1:1) to receive either oral masitinib (6 mg/kg per day over 24 weeks with possible extension) or matched placebo with minimisation according to severe symptoms. The primary endpoint was cumulative response (≥75% improvement from baseline within weeks 8–24) in at least one severe baseline symptom from the following: pruritus score of 9 or more, eight or more flushes per week, Hamilton Rating Scale for Depression of 19 or more, or Fatigue Impact Scale of 75 or more. We assessed treatment effiect using repeated measures methodology for rare diseases via the generalised estimating equation model in a modified intention-to-treat population, including all participants assigned to treatment minus those who withdrew due to a non-treatment-related cause. We assessed safety in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00814073. Findings Between Feb 19, 2009, and July 15, 2015, 135 patients were randomly assigned to masitinib (n=71) or placebo (n=64). By 24 weeks, masitinib was associated with a cumulative response of 18·7% in the primary

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

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

Effects of SuperUlam on Supporting Concentration and Mood: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

PubMed

Udani, Jay K

2013-01-01

Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35-65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS) survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P < 0.05). When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P < 0.05). There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood.

Effects of SuperUlam on Supporting Concentration and Mood: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

PubMed Central

Udani, Jay K

2013-01-01

Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35–65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS) survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P < 0.05). When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P < 0.05). There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood. PMID:24371452

Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo - controlled study.

PubMed

Akhtari, Elham; Raisi, Firoozeh; Keshavarz, Mansoor; Hosseini, Hamed; Sohrabvand, Farnaz; Bioos, Soodabeh; Kamalinejad, Mohammad; Ghobadi, Ali

2014-04-28

Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p < 0.001), desire (p < 0.001), arousal (p = 0.037), lubrication (p < 0.001), satisfaction (p < 0.001) and pain (p = 0.041) domains of FSFI. Frequency of side effects was similar between the two groups. Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted.

Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo - controlled study

PubMed Central

2014-01-01

Background Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Results Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p < 0.001), desire (p < 0.001), arousal (p = 0.037), lubrication (p < 0.001), satisfaction (p < 0.001) and pain (p = 0.041) domains of FSFI. Frequency of side effects was similar between the two groups. Conclusions Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted. PMID:24773615

L-carnitine supplementation in patients with HIV/AIDS and fatigue: a double-blind, placebo-controlled pilot study

PubMed Central

Cruciani, Ricardo A; Revuelta, Manuel; Dvorkin, Ella; Homel, Peter; Lesage, Pauline; Esteban-Cruciani, Nora

2015-01-01

Background The purpose of this study was to determine the effect of L-carnitine supplementation on fatigue in patients with terminal human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Methods In this randomized, double-blind, placebo-controlled, parallel-group study, patients who had end-stage HIV/AIDS with carnitine deficiency and fatigue received 3 g of oral L-carnitine or placebo for 2 weeks, followed by a 2-week, open-label phase with the same amount of L-carnitine for all patients. The primary outcome was the degree of fatigue according to the Brief Fatigue Inventory. Secondary outcomes included serum carnitine and lactate levels, physical, emotional, social, and functional well-being, performance status, mood, and CD4 count. Results Eighteen patients in the treatment arm and 17 in the placebo arm completed the trial. At the end of the double-blind phase, total and free carnitine levels in the treatment arm rose from 28±9 to 48±17 nM/L (P<0.001) and from 24±8 to 40±13 nM/L (P<0.001) respectively, with no changes in the placebo arm. The primary outcome, ie, fatigue measured at the end of the blinded phase, did not improve. Secondary outcomes of function, quality of life, and mood did not show improvement either. The secondary outcome of serum lactate decreased from baseline in the treatment group (1.45±0.76 to 1.28±0.52 mmol/L) and increased in the placebo group (1.38±0.62 to 1.84±0.74 mmol/L; P<0.005). Conclusion Our study suggests that 3 g of oral L-carnitine supplementation for 2 weeks in terminally ill HIV/AIDS patients does not improve fatigue. This study might help to determine the dose and duration of treatment used in future clinical trials, as higher doses and/or longer periods of supplementation might be needed in order to detect an improvement. The reduction in serum lactate levels suggests a potential role for L-carnitine supplementation in patients undergoing certain types of antiretroviral therapy. This study

A double-blind randomized placebo-controlled feasibility study evaluating individualized homeopathy in managing pain of knee osteoarthritis.

PubMed

Koley, Munmun; Saha, Subhranil; Ghosh, Shubhamoy

2015-07-01

Few homeopathic complexes seemed to produce significant effects in osteoarthritis; still, individualized homeopathy remained untested. We evaluated the feasibility of conducting an efficacy trial of individualized homeopathy in osteoarthritis. A prospective, parallel-arm, double-blind, randomized, placebo-controlled pilot study was conducted from January to October 2014 involving 60 patients (homeopathy, n = 30; placebo, n = 30) who were suffering from acute painful episodes of knee osteoarthritis and visiting the outpatient clinic of Mahesh Bhattacharyya Homeopathic Medical College and Hospital, West Bengal, India. Statistically significant reduction was achieved in 3 visual analog scales (measuring pain, stiffness, and loss of function) and Osteoarthritis Research Society International scores in both groups over 2 weeks (P < .05); however, group differences were not significant (P > .05). Overall, homeopathy did not appear to be superior to placebo; still, further rigorous evaluation in this design involving a larger sample size seems feasible in future. Clinical Trials Registry, India (CTRI/2014/05/004589). © The Author(s) 2015.

A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, FIXED-DOSE PHASE III STUDY OF VILAZODONE IN PATIENTS WITH GENERALIZED ANXIETY DISORDER

PubMed Central

Gommoll, Carl; Durgam, Suresh; Mathews, Maju; Forero, Giovanna; Nunez, Rene; Tang, Xiongwen; Thase, Michael E

2015-01-01

Background Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist, is approved for treating major depressive disorder in adults. This study (NCT01629966 ClinicalTrials.gov) evaluated the efficacy and safety of vilazodone in adults with generalized anxiety disorder (GAD). Methods A multicenter, double-blind, parallel-group, placebo-controlled, fixed-dose study in patients with GAD randomized (1:1:1) to placebo (n = 223), or vilazodone 20 mg/day (n = 230) or 40 mg/day (n = 227). Primary and secondary efficacy parameters were total score change from baseline to week 8 on the Hamilton Rating Scale for Anxiety (HAMA) and Sheehan Disability Scale (SDS), respectively, analyzed using a predefined mixed-effect model for repeated measures (MMRM). Safety outcomes were presented by descriptive statistics. Results The least squares mean difference (95% confidence interval) in HAMA total score change from baseline (MMRM) was statistically significant for vilazodone 40 mg/day versus placebo (–1.80 [–3.26, –0.34]; P = .0312 [adjusted for multiple comparisons]), but not for vilazodone 20 mg/day versus placebo. Mean change from baseline in SDS total score was not significantly different for either dose of vilazodone versus placebo when adjusted for multiplicity; significant improvement versus placebo was noted for vilazodone 40 mg/day without adjustment for multiplicity (P = .0349). The incidence of adverse events was similar for vilazodone 20 and 40 mg/day (∼71%) and slightly lower for placebo (62%). Nausea, diarrhea, dizziness, vomiting, and fatigue were reported in ≥5% of patients in either vilazodone group and at least twice the rate of placebo. Conclusions Vilazodone was effective in treating anxiety symptoms of GAD. No new safety concerns were identified. PMID:25891440

A double-blind, randomized, placebo-controlled, fixed-dose phase III study of vilazodone in patients with generalized anxiety disorder.

PubMed

Gommoll, Carl; Durgam, Suresh; Mathews, Maju; Forero, Giovanna; Nunez, Rene; Tang, Xiongwen; Thase, Michael E

2015-06-01

Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist, is approved for treating major depressive disorder in adults. This study (NCT01629966 ClinicalTrials.gov) evaluated the efficacy and safety of vilazodone in adults with generalized anxiety disorder (GAD). A multicenter, double-blind, parallel-group, placebo-controlled, fixed-dose study in patients with GAD randomized (1:1:1) to placebo (n = 223), or vilazodone 20 mg/day (n = 230) or 40 mg/day (n = 227). Primary and secondary efficacy parameters were total score change from baseline to week 8 on the Hamilton Rating Scale for Anxiety (HAMA) and Sheehan Disability Scale (SDS), respectively, analyzed using a predefined mixed-effect model for repeated measures (MMRM). Safety outcomes were presented by descriptive statistics. The least squares mean difference (95% confidence interval) in HAMA total score change from baseline (MMRM) was statistically significant for vilazodone 40 mg/day versus placebo (-1.80 [-3.26, -0.34]; P = .0312 [adjusted for multiple comparisons]), but not for vilazodone 20 mg/day versus placebo. Mean change from baseline in SDS total score was not significantly different for either dose of vilazodone versus placebo when adjusted for multiplicity; significant improvement versus placebo was noted for vilazodone 40 mg/day without adjustment for multiplicity (P = .0349). The incidence of adverse events was similar for vilazodone 20 and 40 mg/day (∼71%) and slightly lower for placebo (62%). Nausea, diarrhea, dizziness, vomiting, and fatigue were reported in ≥5% of patients in either vilazodone group and at least twice the rate of placebo. Vilazodone was effective in treating anxiety symptoms of GAD. No new safety concerns were identified. © 2015 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

Trial of early noninvasive ventilation for ALS: A pilot placebo-controlled study.

PubMed

Jacobs, Teresa L; Brown, Devin L; Baek, Jonggyu; Migda, Erin M; Funckes, Timothy; Gruis, Kirsten L

2016-11-01

To evaluate the use and tolerability of noninvasive positive pressure ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS) early in their disease by comparing active NIV and sham NIV in patients not yet eligible for NIV use as recommended by practice guidelines. This was a single-center, prospective, double-blind, randomized, placebo (sham)-controlled pilot trial. Patients with ALS were randomized to receive either sham NIV or active NIV and underwent active surveillance approximately every 3 months until they reached a forced vital capacity (FVC) <50% or required NIV for clinical symptom management. In total, 54 participants were randomized. The mean NIV use was 2.0 hours (95% confidence interval [CI] 1.1-3.0) per day in the sham NIV treatment group and 3.3 hours (CI 2.0-4.6) per day in the active NIV group, which did not differ by treatment group (p = 0.347). The majority of sham NIV participants (88%) and active NIV participants (73%) reported only mild or no problem with NIV use. Difference of change in FVC through the treatment period by group (0.44 per month) favored active NIV (p = 0.049). Survival and changes in maximal inspiratory or expiratory pressure did not differ between treatment groups. The efficacy of early NIV in ALS should be tested in randomized, placebo-controlled trials. The trial is registered on clinicaltrials.gov (NCT00580593). This study provides Class II evidence that for patients with ALS, adherence with NIV and sham NIV are similar. © 2016 American Academy of Neurology.

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

Glutamine supplementation in cystic fibrosis: A randomized placebo-controlled trial.

PubMed

Forrester, Doug L; Knox, Alan J; Smyth, Alan R; Barr, Helen L; Simms, Rebecca; Pacey, Sarah J; Pavord, Ian D; Honeybourne, David; Dewar, Jane; Clayton, Andy; Fogarty, Andrew W

2016-03-01

Pulmonary infection and malnutrition in cystic fibrosis are associated with decreased survival. Glutamine has a possible anti-microbial effect, with a specific impact against Pseudomonas aeruginosa. We aimed to test the hypothesis that oral glutamine supplementation (21 g/day) for 8 weeks in adults with cystic fibrosis would decrease pulmonary inflammation and improve clinical status. The study design was a randomized double-blind placebo-controlled study design with an iso-nitrogenous placebo. The primary analysis was intention to treat, and the primary outcome was change in induced sputum neutrophils. Thirty-nine individuals were recruited and thirty-six completed the study. Glutamine supplementation had no impact on any of the outcome measures in the intention-to-treat analysis. In the per protocol analysis, glutamine supplementation was associated with an increase in induced sputum neutrophils (P = 0.046), total cells (P = 0.03), and in Pseudomonas isolation agar colony forming units (P = 0.04) compared to placebo. There was no effect of glutamine supplementation on markers of pulmonary inflammation in the intention-to-treat analysis. © 2015 Wiley Periodicals, Inc.

Noncultured keratinocyte/melanocyte cosuspension: effect on reepithelialization and repigmentation--a randomized, placebo-controlled study.

PubMed

Back, Christopher; Dearman, Bronwyn; Li, Amy; Neild, Tim; Greenwood, John E

2009-01-01

Randomized controlled trials in the literature investigating the efficacy of noncultured keratinocyte/melanocyte suspensions are scarce; however, the advocates of such techniques press the value of their application based largely on case studies and anecdote. Caucasian patients with burn hypopigmentation seldom request cosmetic revision making worthwhile clinical trials difficult so that informal case treatments with new therapies generate anecdotal results. A randomized, placebo-controlled trial was carried out to evaluate whether cosuspensions of noncultured skin cells are capable of (1) decreasing the time to reepithelialization and (2) reestablishing pigmentation in vitiligo leukoderma following epidermal/superficial dermal ablation (in the knowledge that a positive result would make the technique likely to be successful in burn hypopigmentation). Vitiligo is common and is socially more debilitating such that suitable trial subjects for new therapies from this pool are more forthcoming. This study demonstrated that suspensions of noncultured keratinocytes and melanocytes do not decrease the time to epithelialization of superficial partial thickness wounds compared with controls. It also suggested that the achievement, quality, and duration of any pigmentation were unpredictable and largely disappointing. Some pigmentation was recorded in placebo-treated areas indicating an effect of the method of epidermal ablation in these patients. These findings have mandated a complete review of the use of these techniques in burn care at the Royal Adelaide Hospital; they have been omitted from surgical protocols where the aim of use was to speed reepithelialization. Their infrequent use in burns hypopigmentation will continue contingent on the successful repigmentation of a test patch.

A placebo-controlled investigation of synaesthesia-like experiences under LSD.

PubMed

Terhune, Devin B; Luke, David P; Kaelen, Mendel; Bolstridge, Mark; Feilding, Amanda; Nutt, David; Carhart-Harris, Robin; Ward, Jamie

2016-07-29

The induction of synaesthesia in non-synaesthetes has the potential to illuminate the mechanisms that contribute to the development of this condition and the shaping of its phenomenology. Previous research suggests that lysergic acid diethylamide (LSD) reliably induces synaesthesia-like experiences in non-synaesthetes. However, these studies suffer from a number of methodological limitations including lack of a placebo control and the absence of rigorous measures used to test established criteria for genuine synaesthesia. Here we report a pilot study that aimed to circumvent these limitations. We conducted a within-groups placebo-controlled investigation of the impact of LSD on colour experiences in response to standardized graphemes and sounds and the consistency and specificity of grapheme- and sound-colour associations. Participants reported more spontaneous synaesthesia-like experiences under LSD, relative to placebo, but did not differ across conditions in colour experiences in response to inducers, consistency of stimulus-colour associations, or in inducer specificity. Further analyses suggest that individual differences in a number of these effects were associated with the propensity to experience states of absorption in one's daily life. Although preliminary, the present study suggests that LSD-induced synaesthesia-like experiences do not exhibit consistency or inducer-specificity and thus do not meet two widely established criteria for genuine synaesthesia. Copyright © 2016 Elsevier Ltd. All rights reserved.

[The concept of placebo and the effect of placebo].

PubMed

Göka, Erol

2002-01-01

The discussions about what placebo means and how its effect occurs go far back in the history of medicine. In general medicinal understanding, placebo means the subjective feeling of a positive effect in response to something that is used for curative intentions. In spite of difficulties in its definition and unknown content, its existence is generally accepted. What is discussed is its level of effectiveness in any disorder and medication. The placebo effect varies not only among diseases but also among regions and countries. Even the physicians' belief in a placebo increases its effect. Another interesting point about the placebo is its side effects. In many placebo controlled studies, the side effects of the placebo are found to be greater than those of real drugs. Different from other diseases, psychiatric disorders have strong connections with the placebo effect. The results of many studies support this idea. The increasing importance of placebos in psychiatry is really an interesting subject. For some people, the reason for this is hidden in the nature of psychiatric diseases. However, nonpharmacologic placebos such as "inspiration", "convincing", "confidence", and "belief" are believed to play a central role in psychiatry. In this article, placebo (the placebo effect) is defined, the implications of placebo in general medicine or psychiatry are discussed, and specific or nonspecific treatment methods are explained. The effects of a placebo on both the patient and the physician are emphasized. The significance of the placebo effect in psychiatry is also mentioned; and a new point of view, based upon the importance of symbolization and satisfaction is introduced in treatment and related action mechanisms.

A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder.

PubMed

Marcus, Ronald N; Owen, Randall; Kamen, Lisa; Manos, George; McQuade, Robert D; Carson, William H; Aman, Michael G

2009-11-01

To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Two hundred eighteen children and adolescents (aged 6-17 years) with a diagnosis of autistic disorder, and with behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these symptoms, were randomized 1:1:1:1 to aripiprazole (5, 10, or 15 mg/day) or placebo in this 8-week double-blind, randomized, placebo-controlled, parallel-group study. Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale (primary efficacy measure) and the clinician-rated Clinical Global Impressions-Improvement score. Safety and tolerability were also assessed. At week 8, all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores (5 mg/day, -12.4; 10 mg/day, -13.2; 15 mg/day, -14.4; versus placebo, -8.4; all p < .05). All aripiprazole doses demonstrated significantly greater improvements in mean Clinical Global Impressions-Improvement score than placebo at week 8. Discontinuation rates due to adverse events were as follows: placebo 7.7%, aripiprazole 5 mg/day 9.4%, 10 mg/day 13.6%, and 15 mg/day 7.4%. The most common adverse event leading to discontinuation was sedation. There were two serious adverse events: presyncope (5 mg/day) and aggression (10 mg/day). At week 8, mean weight change (last observation carried forward) was as follows: placebo +0.3 kg, aripiprazole 5 mg/day +1.3 kg, 10 mg/day +1.3 kg, and 15 mg/day +1.5 kg; all p < .05 versus placebo. Aripiprazole was efficacious and generally safe and well tolerated in the treatment of children and adolescents with irritability associated with autistic disorder.

A dietary cholesterol challenge study to assess Chlorella supplementation in maintaining healthy lipid levels in adults: a double-blinded, randomized, placebo-controlled study.

PubMed

Kim, Sangmi; Kim, Joohee; Lim, Yeni; Kim, You Jin; Kim, Ji Yeon; Kwon, Oran

2016-05-13

Previous animal studies suggested that Chlorella, a unicellular green alga, has a preventive role in maintaining serum cholesterol levels against excess dietary cholesterol intake. This study aimed to conduct a pioneering investigation to clarify this issue in healthy subjects by adopting a dietary cholesterol challenge, which has not been used previously in similar studies of Chlorella in hypercholesterolemia. In this double blind, randomized, placebo-controlled study, 34 participants ingested 510 mg of dietary cholesterol from three eggs concomitantly with a usual dose of Chlorella (5 g/d) or a matched placebo for 4 weeks. The dietary cholesterol challenge induced consistently higher concentrations of serum total cholesterol (TC, P < 0.001), LDL-C (P = 0.004), and HDL-C (P = 0.010) compared with baseline values, suggesting that the challenge was reliable. Thus, we observed a preventive action of Chlorella in maintaining serum TC versus placebo levels (3.5 % versus 9.8 %, respectively; P = 0.037) and LDL-C versus placebo levels (1.7 % versus 14.3 %, respectively; P = 0.012) against excessive dietary cholesterol intake and in augmenting HDL-C versus placebo levels (8.3 % versus 3.8 %, respectively). Furthermore, serum α-carotene showed the best separation between the placebo and Chlorella groups (R(2)X and R(2)Y > 0.5; Q(2) > 0.4). The results suggest that a fully replicated dietary cholesterol challenge may be useful in assessing the effectiveness of dietary supplements in maintaining the serum lipid profiles of adults whose habitual diets are high in cholesterol. WHO International Clinical Trials Registry Platform ( KCT0000258 ).

Nifedipine vs Placebo for Treatment of Chronic Chilblains: A Randomized Controlled Trial

PubMed Central

Souwer, Ibo H.; Bor, Jacobus H. J.; Smits, Paul; Lagro-Janssen, Antoine L. M.

2016-01-01

PURPOSE Nifedipine is commonly prescribed for the treatment of chilblains (pernio, perniosis) on the basis of observational studies and a single small, older clinical trial. We aimed to confirm the proposed superiority of oral nifedipine 60 mg per day over placebo for treatment of chronic chilblains in primary care. METHODS We performed a randomized, placebo-controlled, double-blind, crossover trial, closely following the design of the older trial. A total of 32 patients with chronic chilblains were randomly assigned to nifedipine (30 mg controlled release twice a day) or placebo. The primary outcome was patient-reported complaints; the secondary outcome was patient-reported disability. Both were assessed from daily ratings on 100-mm visual analogue scales recorded in a diary. We took ambient temperatures into account and checked for a carry-over effect, and monitored for adverse effects. RESULTS After 6 weeks of treatment, mean scores on the visual analogue scale on complaints showed a nonsignificant difference of 1.84 mm (95% CI, −6.67 to 2.99 mm) in favor of nifedipine (P = .44). Mean scores on the visual analogue scale on disability showed a nonsignificant difference of 0.56 mm (95% CI, −2.97 to 4.09 mm) in favor of placebo (P = .75). There was no carry-over effect of prior study treatment. Nifedipine was associated with significantly lower systolic blood pressure and a significantly higher incidence of edema. CONCLUSIONS In our study, nifedipine was not superior to placebo for treating chronic chilblains. These findings contrast with those of the older study and do not support routine use of nifedipine for this condition. PMID:27621162

Effects of testosterone and nandrolone on cardiac function: a randomized, placebo-controlled study.

PubMed

Chung, T; Kelleher, S; Liu, P Y; Conway, A J; Kritharides, L; Handelsman, D J

2007-02-01

Androgens have striking effects on skeletal muscle, but the effects on human cardiac muscle function are not well defined, neither has the role of metabolic activation (aromatization, 5alpha reduction) of testosterone on cardiac muscle been directly studied. To assess the effects of testosterone and nandrolone, a non-amplifiable and non-aromatizable pure androgen, on cardiac muscle function in healthy young men. Double-blind, randomized, placebo-controlled, three-arm parallel group clinical trial. Ambulatory care research centre. Healthy young men randomized into three groups of 10 men. Weekly intramuscular injections of testosterone (200 mg mixed esters), nandrolone (200 mg nandrolone decanoate) or matching (2 ml arachis oil vehicle) placebo for 4 weeks. Comprehensive measures of cardiac muscle function involving transthoracic cardiac echocardiography measuring myocardial tissue velocity, peak systolic strain and strain rates, and bioimpedance measurement of cardiac output and systematic vascular resistance. Left ventricular (LV) function (LV ejection fraction, LV modified TEI index), right ventricular (RV) function (ejection area, tricuspid annular systolic planar motion, RV modified TEI index) as well as cardiac afterload (mean arterial pressure, systemic vascular resistance) and overall cardiac contractility (stroke volume, cardiac output) were within age- and gender-specific reference ranges and were not significantly (P < 0.05) altered by either androgen or placebo over 4 weeks of treatment. Minor changes remaining within normal range were observed solely within the testosterone group for: increased LV end-systolic diameter (30 +/- 7 vs. 33 +/- 5 mm, P = 0.04) and RV end-systolic area (12.8 +/- 1.3 vs. 14.6 +/- 3.3 cm(2), P = 0.04), reduced LV diastolic septal velocity (Em, 9.5 +/- 2.6 vs. 8.7 +/- 2.0 cm/s, P = 0.006), increased LV filling pressure (E/Em ratio, 7.1 +/- 1.6 vs. 8.3 +/- 1.8, P = 0.02) and shortened PR interval on the electrocardiogram (167

The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies

PubMed Central

Baldwin, David S; Chrones, Lambros; Florea, Ioana; Nielsen, Rebecca; Nomikos, George G; Palo, William; Reines, Elin

2016-01-01

The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5–20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5–20mg/day) was 4.5–7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5–20mg/day) were nausea (20.9–31.2%) and vomiting (2.9–6.5%). For vortioxetine (5–20mg/day), the incidence of TEAEs associated with insomnia was 2.0–5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6–1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7–0.8kg. Thus, vortioxetine (5–20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder. PMID:26864543

The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies.

PubMed

Baldwin, David S; Chrones, Lambros; Florea, Ioana; Nielsen, Rebecca; Nomikos, George G; Palo, William; Reines, Elin

2016-03-01

The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5-20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5-20mg/day) was 4.5-7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5-20mg/day) were nausea (20.9-31.2%) and vomiting (2.9-6.5%). For vortioxetine (5-20mg/day), the incidence of TEAEs associated with insomnia was 2.0-5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6-1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7-0.8kg. Thus, vortioxetine (5-20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder. © The Author(s) 2016.

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

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.

Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study

PubMed Central

Predel, H; Koll, R; Pabst, H; Dieter, R; Gallacchi, G; Giannetti, B; Bulitta, M; Heidecker, J; Mueller, E

2004-01-01

Objectives: To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries. Methods: This was a randomised, placebo controlled, double blind, multicentre study in 120 patients with traumatic blunt soft tissue injury. Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days. Patients were randomised (1:1) to two parallel groups. Tenderness produced by pressure was measured twice daily during the first 3 days after enrolment as well as at day 7. Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient. Results: The primary efficacy variable was the area under the curve for tenderness over the first 3 days. The diclofenac patch was significantly more effective than placebo (p<0.0001). The treatment effect was 64.7 kp h/cm2 (95% confidence interval 48.7 to 80.9) between diclofenac and placebo patches. These results were supported by all secondary efficacy variables. The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo (p<0.0001). The diclofenac patch was well tolerated. The most frequently observed adverse events were local cutaneous adverse reactions (pruritus, rash) of minor severity occurring with the same frequency as in the placebo group. Conclusions: A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries. PMID:15155436

Arnica Ointment 10% Does Not Improve Upper Blepharoplasty Outcome: A Randomized, Placebo-Controlled Trial.

PubMed

van Exsel, Denise C E; Pool, Shariselle M W; van Uchelen, Jeroen H; Edens, Mireille A; van der Lei, Berend; Melenhorst, Wynand B W H

2016-07-01

It has been suggested that arnica can reduce postoperative edema and ecchymosis associated with cosmetic surgical procedures and improve outcome. Despite a high incidence of arnica use among upper blepharoplasty patients, evidence to support its treatment effect is lacking. The authors performed a randomized, double-blind, placebo-controlled trial to investigate the efficacy of arnica ointment after upper blepharoplasty. One hundred thirty-six bilateral upper blepharoplasty patients were randomized between arnica ointment 10% and placebo ointment. In both study arms, one periorbital area was designated as the treatment side (either arnica or placebo ointment), and the contralateral side served as an untreated (no ointment) internal control. As the primary endpoint, the overall periorbital appearance as based on light photography and judged by a medical and nonmedical panel, was assessed after 3 days, 7 days, and 6 weeks. Secondary endpoints were swelling, ecchymosis, erythema, pain, and patient satisfaction with recovery and outcome. There was no significant difference between arnica and placebo in overall judgment of periorbital appearance 3 days, 7 days, and 6 weeks after surgery. Furthermore, swelling, ecchymosis, erythema, pain, and patient satisfaction with recovery and outcome did not differ between arnica and placebo. Postoperative outcome in untreated eyelids was not different from eyelids treated with either arnica or placebo on any of the studied outcome measures. The authors' study demonstrates that topical arnica ointment after upper blepharoplasty does not improve postoperative outcome. Therapeutic, II.

Effects of timolol and atenolol on benign essential tremor: placebo-controlled studies based on quantitative tremor recording.

PubMed

Dietrichson, P; Espen, E

1981-08-01

Two different beta-adrenoreceptor antagonists, atenolol and timolol, were separately compared with a placebo in the suppression of essential tremor. In two-week single-blind placebo-controlled studies with cross-over, timolol (5 mg twice daily) and atenolol (100 mg once daily) produced an equal reduction in sitting heart rate and sitting blood pressure. Timolol was effective in reducing tremor while atenolol failed to reduce tremor amplitude. These results indicate that essential tremor can be reduced but not blocked, by the adrenergic blocker timolol with both beta 1 and beta 2 blocking properties; but not by the relatively selective beta 1 blocking drug atenolol. Possibly, the tremor reduction is medicated by a peripheral effect on beta 2 adrenoreceptors.

A Prospective, Randomized, Masked, Placebo-Controlled Clinical Study of Capromorelin in Dogs with Reduced Appetite.

PubMed

Zollers, B; Wofford, J A; Heinen, E; Huebner, M; Rhodes, L

2016-11-01

Reduced appetite is a common clinical sign in dogs. This study evaluated the effectiveness and safety of capromorelin oral solution, (ENTYCE ® , Aratana Therapeutics, Leawood, KS) a new drug that is a ghrelin receptor agonist, for stimulation of appetite in dogs with reduced appetite. Capromorelin will increase appetite, as measured by the owner's evaluation, over 4 days. An additional objective was to evaluate the safety of capromorelin at the labeled dose. A total of 244 client-owned dogs reported by owners to be inappetent for at least 2 days were enrolled, with 177 cases in the effectiveness analysis. In this prospective, randomized, masked, placebo-controlled study, dogs were treated daily with capromorelin (3 mg/kg) oral solution (n = 121) or placebo oral solution (n = 56). Owners completed an evaluation of appetite at days 0 and 3 ± 1. Success was defined as improvement in appetite at day 3. Safety was evaluated by physical examination, clinical pathology, and monitoring adverse events and owner observations. Capromorelin treatment improved appetite compared to placebo (68.6% and 44.6% treatment successes with 95% CI 59.7, 76.3 and 32.2, 57.8, respectively, P = .008). Mean body weight in capromorelin-treated dogs increased compared to placebo-treated dogs (1.8% with 95% CI 1.3, 2.3, and 0.1% with 95% CI 0.9, 1.1, respectively, P < .001). Adverse reactions occurring in >5% of either group were diarrhea and vomiting. Capromorelin oral solution is an effective treatment for stimulation of appetite in dogs and represents the first ghrelin receptor agonist shown to be effective for this indication. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Oxytocin treatment in children with Prader-Willi syndrome: A double-blind, placebo-controlled, crossover study.

PubMed

Miller, Jennifer L; Tamura, Roy; Butler, Merlin G; Kimonis, Virginia; Sulsona, Carlos; Gold, June-Anne; Driscoll, Daniel J

2017-05-01

Prader-Willi syndrome (PWS) is a rare, complex multisystem genetic disorder which includes hypothalamic dysfunction, hyperphagia, cognitive and behavioral problems, increased anxiety, and compulsive behaviors. Individuals with PWS have a deficit of oxytocin producing neurons in the paraventricular nucleus of the hypothalamus. Oxytocin plays a role in regulation of feeding behaviors, social interactions, and emotional reactivity, which are all issues that significantly affect the quality of life for individuals with this syndrome. We performed a double-blind, placebo-controlled, crossover study in 24 children with PWS at three academic institutions using 5 days of intranasal oxytocin (IN-OT) or 5 days of intranasal placebo spray, followed by a 4 week washout period, and then patients returned for 5 days of treatment with the alternate source. Questionnaires, including the Aberrant Behavior Checklist, Social Responsiveness Scale, Repetitive Behavior Scale - Revised, and the Hyperphagia Questionnaire, as well as Clinical Global Impression scales were administered. Blood testing for sodium, potassium, and glucose levels on days 2, 4, and 6, and a 24 hr diet recall. All scales factor improvement from Day 3 to Day 6 favored oxytocin over placebo. No single factor showed a statistically significant difference (P < 0.05) between groups at Day 6. The drug effect appeared to be diminished at Day 14. There was no evidence of a difference between oxytocin and placebo in safety lab parameters, 60 min post dose vital signs, weight, or diet parameters. The results from this study suggest that low dose intranasal oxytocin is safe for individuals with PWS and may result in reduction in appetite drive, and improvements in socialization, anxiety, and repetitive behaviors. Further, long-term studies with a larger population of participants are necessary to confirm these findings. The results of this study are encouraging that oxytocin may be a safe and effective treatment for

Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients.

PubMed

Glue, Paul; Cape, Gavin; Tunnicliff, Donna; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, C Tak; Harland, Sarah; Devane, Jane; Crockett, R S; Howes, John; Darpo, Borje; Zhou, Meijian; Weis, Holger; Friedhoff, Lawrence

2016-11-01

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and C max and was slowly eliminated (mean t 1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues. © 2016, The American College of Clinical Pharmacology.

MODAFINIL TREATMENT FOR FATIGUE IN PATIENTS WITH HIV/AIDS: A PLACEBO CONTROLLED STUDY

PubMed Central

Rabkin, Judith G.; McElhiney, Martin C.; Rabkin, Richard; McGrath, Patrick

2009-01-01

Objective To evaluate the efficacy and safety of modafinil in the treatment of fatigue in patients with HIV/AIDS, and to assess effect on depressive symptoms. Method A 4-week randomized placebo-controlled double-blind trial followed by an additional 8 weeks of open-label treatment for modafinil responders and 12 weeks for placebo non-responders. Primary outcome measure for fatigue and depression was CGI Improvement, supplemented by the Fatigue Severity Scale, Hamilton Depression Scale and Beck Depression Inventory. Safety was assessed with assays of CD4 cell count and HIV RNA viral load. Visits were weekly for 4 weeks, then biweekly, with a follow-up visit at 6 months. Maximum trial dose of modafinil was 200 mg/day. Results 115 patients were randomized. In intention to treat analyses, fatigue response rate to modafinil was 73% and to placebo, 28%. Attrition was 9%. Modafinil did not have an effect on mood alone in the absence of improved energy. At Week 4, CD4 cell counts did not change; HIV RNA viral load declined significantly for patients on modafinil but not placebo. At 6 months, those still taking modafinil had more energy and fewer depressive symptoms than patients who were not taking modafinil and only those still taking modafinil showed a significant decline from baseline in their HIV RNA viral load. Conclusion Modafinil appears to be effective and well tolerated in treating fatigue in HIV+ patients. Consideration of its use is warranted considering the high prevalence of fatigue in the HIV community, its minimal side effects, and overall patient acceptance. NCT00614926 PMID:20492840

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

[Efficacy of Arnica in varicose vein surgery: results of a randomized, double-blind, placebo-controlled pilot study].

PubMed

Wolf, M; Tamaschke, C; Mayer, W; Heger, M

2003-10-01

In homeopathy ARNICA is widely used as a woundhealing medication and for the treatment of hematomas. In this pilot study the efficacy and safety of ARNICA D12 in patients following varicose vein surgery were investigated. Prospective, randomized, double-blind, placebo-controlled pilot trial according to ICH GCP guidelines. The study was conducted by a surgeon at the Angiosurgical Clinic, Berlin- Buch. After randomized allocation, 60 patients received either ARNICA D12 or placebo. Start of medication occurred the evening before operation with 5 globules. On the operation day one preoperative and hourly postoperative dosages after awakening were given. On days 2-14 of the study 5 globules 3 times a day were given. OUTCOME CRITERIA: Surface (in cm(2) and using a three-point verbal rating scale) and intensity of hematomas induced by operation, complications of wound healing, and intensity of pain (five-point verbal rating scale) as well as efficacy and safety of the study medication were assessed. Hematoma surface was reduced (from day 7 to day 14) under ARNICA by 75.5% and under placebo by 71.5% (p = 0.4726). The comparison of hematoma surface (small, medium, large) using the verbal rating scale yielded a value of p = 0.1260. Pain score decreased by 1.0 +/- 2.2 points under ARNICA and 0.3 +/- 0.8 points under placebo (p = 0.1977). Remission or improvement of pain was observed in 43.3% of patients in the ARNICA group and in 27.6% of patients in the placebo group. Tolerability was rated as very good in all cases. The results of this pilot study showed a trend towards a beneficial effect of ARNICA D12 with regard to reduction of hematoma and pain during the postoperative course. For a statistically significant proof of efficacy of ARNICA D12 in patients following varicose vein surgery a larger sample size is necessary. Copyright 2003 S. Karger GmbH, Freiburg

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.

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.

The placebo effect.

PubMed

Margo, C E

1999-01-01

Placebos have been traditionally regarded as deceptive therapies and have not been understood in the broader context of social symbols and of interpersonal factors that surround the healing process itself. Although the power of inert substances to heal is well recognized, the placebo effect also influences the outcome of conventional therapies. The role of the placebo in modern medicine is poorly defined because of a lack of a common understanding of what the placebo effect is and because of the negative connotions associated with its use. The response rate to placebo varies by illness. The natural course of disease and patient or physician bias can be misinterpreted as a placebo response. In research, the placebo effect is therapeutic noise to be removed by placebo-controlled trials. Few studies are designed to measure the placebo response rate directly. Placebos are a reminder of how little is known about mind-body interaction. The placebo effect may be one of the most versatile and underused therapeutic tools at the disposal of physicians.

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.

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

PubMed Central

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

2014-01-01

Objective 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. Methods 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. Results 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. Conclusion The results of this study suggest that methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and rapidly acting analgesic. Trial registration number: NCT01420159. PMID:24743584

A randomized placebo-controlled clinical trial of five smoking cessation pharmacotherapies

PubMed Central

Piper, Megan E.; Smith, Stevens S.; Schlam, Tanya R.; Fiore, Michael C.; Jorenby, Douglas E.; Fraser, David; Baker, Timothy B.

2010-01-01

Context Little direct evidence exists on the relative efficacies of different smoking cessation pharmacotherapies, yet such evidence is needed to make informed decisions about their clinical use. Objective The primary objective of this research was to assess the relative efficacies of five smoking cessation pharmacotherapy interventions using placebo-controlled, head-to-head comparisons. Design This was a randomized double-blind, placebo-controlled clinical trial. Setting Smokers were recruited from the community at two urban research sites. Patients Participants were 1504 adult smokers who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking. Participants were excluded if they reported: using any form of tobacco other than cigarettes; current use of bupropion; having a current psychosis or schizophrenia diagnosis; or having medical contraindications for any of the study medications. Interventions Participants were randomized to one of six treatment conditions: nicotine lozenge, nicotine patch, bupropion SR, nicotine patch + nicotine lozenge, bupropion + nicotine lozenge or placebo. In addition, all participants received six individual counseling sessions. Main Outcome Measures The main outcome measures were biochemically-confirmed 7-day point-prevalence abstinence assessed at 1 week post-quit, end of treatment (8 weeks post-quit) and 6 months post-quit. Other outcomes were initial cessation, number of days to lapse, number of days to relapse, and latency to relapse after the first lapse. Results All pharmacotherapies differed from placebo when examined without protection for multiple comparisons (OR’s = 1.63–2.34). With such protection, only the nicotine patch + nicotine lozenge (OR = 2.34, p < .001) produced significantly higher abstinence rates at 6-months post-quit than did placebo. Conclusions While the nicotine lozenge, bupropion, and bupropion + lozenge produced effects that were comparable to those

Placebo-controlled trial of lubiprostone for constipation associated with Parkinson disease.

PubMed

Ondo, W G; Kenney, C; Sullivan, K; Davidson, A; Hunter, C; Jahan, I; McCombs, A; Miller, A; Zesiewicz, T A

2012-05-22

To evaluate the efficacy and tolerability of lubiprostone (Amitiza) for constipation in Parkinson disease (PD) in a double-blind, randomized, controlled study. Patients with PD and clinically meaningful constipation (constipation rating scale score > 10 [range: 0-28]) were recruited from 2 academic movement disorder centers to participate in the study. After enrollment, patients were initially followed for 2 weeks and then were randomly assigned 1:1 to lubiprostone, and the dose was titrated up to 48 μg/day. They returned 4 weeks later for a final assessment. Data included stool diaries and global impressions (co-primary endpoints), demographics, Unified Parkinson's Disease Rating Scale scores, constipation scale scores, visual analog scale (VAS) scores, a stool diary, and adverse events. Fifty-four subjects (39 male, mean age 67.0 ± 10.1 years, and mean duration of PD 8.3 ± 5.4 years) were randomly assigned to lubiprostone or placebo. One patient in the drug group discontinued the study because of logistics, and one patient in the placebo group discontinued the study because of lack of efficacy. A marked or very marked clinical global improvement was reported by 16 of 25 (64.0%) subjects receiving drug vs 5 of 27 (18.5%) subjects receiving placebo (p = 0.001). The constipation rating scale (p < 0.05), VAS (p = 0.001), and stools per day in the diary (p < 0.001) all improved with drug compared with placebo. Adverse events with drug were mild, most commonly intermittent loose stools. In this randomized controlled trial, lubiprostone seemed to be well tolerated and effective for the short-term treatment of constipation in PD.

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

Erlotinib, erlotinib-sulindac versus placebo: a randomized, double-blind, placebo-controlled window trial in operable head and neck cancer.

PubMed

Gross, Neil D; Bauman, Julie E; Gooding, William E; Denq, William; Thomas, Sufi M; Wang, Lin; Chiosea, Simion; Hood, Brian L; Flint, Melanie S; Sun, Mai; Conrads, Thomas P; Ferris, Robert L; Johnson, Jonas T; Kim, Seungwon; Argiris, Athanassios; Wirth, Lori; Nikiforova, Marina N; Siegfried, Jill M; Grandis, Jennifer R

2014-06-15

The EGF receptor (EGFR) and COX2 pathways are upregulated in head and neck squamous cell carcinoma (HNSCC). Preclinical models indicate synergistic antitumor activity from dual blockade. We conducted a randomized, double-blind, placebo-controlled window trial of erlotinib, an EGFR inhibitor; erlotinib plus sulindac, a nonselective COX inhibitor; versus placebo. Patients with untreated, operable stage II-IVb HNSCC were randomized 5:5:3 to erlotinib, erlotinib-sulindac, or placebo. Tumor specimens were collected before and after seven to 14 days of treatment. The primary endpoint was change in Ki67 proliferation index. We hypothesized an ordering effect in Ki67 reduction: erlotinib-sulindac > erlotinib > placebo. We evaluated tissue microarrays by immunohistochemistry for pharmacodynamic modulation of EGFR and COX2 signaling intermediates. From 2005-2009, 47 patients were randomized for the target 39 evaluable patients. Thirty-four tumor pairs were of sufficient quality to assess biomarker modulation. Ki67 was significantly decreased by erlotinib or erlotinib-sulindac (omnibus comparison, two-sided Kruskal-Wallis, P = 0.04). Wilcoxon pairwise contrasts confirmed greater Ki67 effect in both erlotinib groups (erlotinib-sulindac vs. placebo, P = 0.043; erlotinib vs. placebo, P = 0.027). There was a significant trend in ordering of Ki67 reduction: erlotinib-sulindac > erlotinib > placebo (two-sided exact Jonckheere-Terpstra, P = 0.0185). Low baseline pSrc correlated with greater Ki67 reduction (R(2) = 0.312, P = 0.024). Brief treatment with erlotinib significantly decreased proliferation in HNSCC, with additive effect from sulindac. Efficacy studies of dual EGFR-COX inhibition are justified. pSrc is a potential resistance biomarker for anti-EGFR therapy, and warrants investigation as a molecular target. ©2014 American Association for Cancer Research.

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.

A randomized, placebo-controlled study of zonisamide to prevent olanzapine-associated weight gain.

PubMed

McElroy, Susan L; Winstanley, Erin; Mori, Nicole; Martens, Brian; McCoy, Jessica; Moeller, Dianna; Guerdjikova, Anna I; Keck, Paul E

2012-04-01

Weight gain is commonly observed with olanzapine treatment. Zonisamide is an antiepileptic drug associated with weight loss. This study examined the effectiveness of zonisamide in preventing weight gain in 42 patients beginning olanzapine for bipolar disorder or schizophrenia. Each patient had a body mass index of 22 mg/kg or greater and was randomized to taking olanzapine with either zonisamide (n = 20) or placebo (n = 22) for 16 weeks. The primary outcome measure was change in body weight in kilograms from baseline. In the primary analysis using longitudinal regression, patients who received zonisamide had a significantly slower rate of weight gain and increase in body mass index than those who received placebo. The patients treated with zonisamide gained a mean (SD) of 0.9 (3.3) kg, whereas those treated with placebo gained a mean (SD) of 5.0 (5.5) kg; P = 0.01. None of the patients in the zonisamide group, compared with 7 patients (33%) in the placebo group, gained 7% of body weight or greater from baseline (Fisher exact test, P = 0.009). The zonisamide group, however, reported significantly more cognitive impairment as an adverse event than the placebo group (25% vs 0, respectively; P = 0.02). Zonisamide was effective for mitigating weight gain in patients with bipolar disorder or schizophrenia initiating treatment with olanzapine but was associated with cognitive impairment as an adverse event.

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.

Headache: the placebo effects in the control groups in randomized clinical trials; an analysis of systematic reviews.

PubMed

de Groot, Femke M; Voogt-Bode, Annieke; Passchier, Jan; Berger, Marjolein Y; Koes, Bart W; Verhagen, Arianne P

2011-06-01

The purpose of this study is to describe the effects in the placebo and "no treatment" arms in trials with headache patients. This is a secondary analysis of randomized controlled trials from 8 systematic reviews and selected trials with a "no treatment" or placebo control group. The different types of "no treatment" and placebo interventions were assessed and classified into 6 subgroups. The analyses were carried out according to type of outcome variable. In total, 119 studies were included (7119 participants). The mean recovery rate in all control groups was 35.7%. Significantly more participants recovered in control groups of pharmacological studies than in nonpharmacological studies: 38.5% vs 15.0%, respectively. Adults were more likely to recover in nonpharmacological studies and children in pharmacological studies. The mean recovery rate in the control groups was 36%. The recovery rate varied substantially between type of intervention and patients. Copyright © 2011 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

Curcuma decreases serum hepcidin levels in healthy volunteers: a placebo-controlled, randomized, double-blind, cross-over study.

PubMed

Lainé, Fabrice; Laviolle, Bruno; Bardou-Jacquet, Edouard; Fatih, Nadia; Jezequel, Caroline; Collet, Nicolas; Ropert, Martine; Morcet, Jeff; Hamon, Catherine; Reymann, Jean-Michel; Loréal, Olivier

2017-10-01

Hepcidin, secreted by hepatocytes, controls iron metabolism by limiting iron egress in plasma. Hepcidin is upregulated during inflammation through the activation of the signal transducer and activator of transcription 3 (STAT3) transduction pathway, which decreases iron bioavailability and may explain the anemia of chronic inflammatory disease. In vitro, it has been shown that curcumin can decrease hepcidin synthesis by decreasing STAT3 activity. We conducted a proof-of-concept study to assess the effect of curcuma on hepcidin synthesis in human. This was a placebo-controlled, randomized, double-blind, cross-over, two-period study performed in 18 healthy male volunteers. Subjects received a single oral dose of 6 g curcuma containing 2% of curcumin or placebo. Serum hepcidin and iron parameters were assessed repeatedly until 48 h after dosing. When compared with a placebo curcuma decreased hepcidin levels significantly at 6 h (-19%, P = 0.004), 8 h (-17%, P = 0.009), and 12 h (-17%, P = 0.007) and tended to decrease hepcidin at 24 h (-15%, P = 0.076). Curcuma also significantly increased serum ferritin levels at 6 and 8 h (+7% for both times, P = 0.018, 0.030, respectively) and had no effects on serum iron, transferrin, and transferrin saturation. This pilot study showed that curcuma decreases serum hepcidin levels in human and supports the idea that curcuma could be useful in treating hepcidin overproduction during inflammatory processes. Confirmatory studies in patients with chronic inflammation are now required to determine the optimal dose and therapeutic scheme of curcuma. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial

PubMed Central

2012-01-01

Introduction To evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed. Methods Thirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety. Results There was a significant (P = 0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50 ± 27 to 108 ± 73 mL/minute (mean ± SEM) for the AP group; and from 40 ± 37 to 65 ± 30 mL/minute for placebo; P = 0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring

Therapeutic Benefit of Smoked Cannabis in Randomized Placebo-Controlled Studies.

PubMed

Bowen, Lynneice L; McRae-Clark, Aimee L

2018-01-01

The medicinal use of marijuana has been legalized in 28 states, with a wide range of specificity for approved medical conditions. Even with the emergence of non-combustion-based delivery systems, 90% of marijuana users in 2014 used smoked marijuana. This review summarizes the data available on the use of smoked marijuana for medical purposes. A literature search was performed to retrieve randomized controlled trials exploring the efficacy of smoked cannabis for treatment of a medical condition. Studies with the primary end point listed as the effect of smoked cannabis on a disease-specific characteristic were included. Open-label studies and studies using other administration methods were excluded. Seven studies met these criteria and were included in this review. Cannabis did not outperform placebo on experimentally evoked pain or the timed walk test. Clear evidence indicates that smoked cannabis reduces intraocular pressure, but the effect is too brief (less than 4 hrs) to be of therapeutic benefit for this chronic disorder. Consistent evidence also showed that smoked marijuana, even at lower concentrations of tetrahydrocannabinol, increased total daily calorie intake and number of eating occasions. Neither of the studies with quality of life as secondary outcome measures revealed statistically significantly improved outcomes with cannabis use. © 2017 Pharmacotherapy Publications, Inc.

Topiramate and motivational enhancement therapy for cannabis use among youth: a randomized placebo-controlled pilot study.

PubMed

Miranda, Robert; Treloar, Hayley; Blanchard, Alexander; Justus, Alicia; Monti, Peter M; Chun, Thomas; Swift, Robert; Tidey, Jennifer W; Gwaltney, Chad J

2017-05-01

Cannabis misuse accounts for nearly all of the substance abuse treatment admissions among youth in the United States. Most youth do not experience sustained benefit from existing psychosocial treatments; however, medication development research for treating adolescent cannabis misuse is almost nonexistent. We conducted a double-blind, placebo-controlled, pilot study to test the potential efficacy of topiramate plus motivational enhancement therapy (MET) for treating cannabis use among adolescents. Sixty-six heavy cannabis users, ages 15 to 24 years, were randomized to one of two 6-week treatment conditions: topiramate plus MET or placebo plus MET. Topiramate was titrated over 4 weeks then stabilized at 200 mg/day for 2 weeks. MET was delivered biweekly for a total of three sessions. Only 48 percent of youths randomized to topiramate completed the 6-week trial (n = 19), compared with 77 percent of youths in the placebo condition (n = 20). Adverse medication side effects were the most common reason for withdrawal among participants in the topiramate group. Latent growth models showed that topiramate was superior to placebo for reducing the number of grams smoked per use day, but it did not improve abstinence rates. The same pattern of results was found when values for missing outcomes were imputed. We show that topiramate combined with MET demonstrated efficacy for reducing how much cannabis adolescents smoked when they used but did not affect abstinence rates. The magnitude of this effect was modest, however, and topiramate was poorly tolerated by youths, which calls into question the clinical importance of these findings. © 2016 Society for the Study of Addiction.

A randomized, placebo-controlled pilot study of patients with spontaneous intraventricular haemorrhage treated with intraventricular thrombolysis.

PubMed

King, Nicolas K K; Lai, Jin Li; Tan, Li Bing; Lee, Kah Keow; Pang, Boon Chuan; Ng, Ivan; Wang, Ernest

2012-07-01

Intraventricular hemorrhage (IVH) occurring after spontaneous intracerebral hemorrhage (ICH) is an independent risk factor for mortality. The use of intraventricular urokinase (Uk) to reduce intraventricular blood clot volume and improve outcome was investigated. Patients with IVH requiring external ventricular drainage were recruited and randomized into a double-blind placebo controlled study. Assessments of collected cerebrospinal fluid (CSF) haemoglobin (Hb) and serial CT scans were performed. The study outcomes were: infection rates, length of stay in the intensive care unit, survival, National Institutes of Health Stroke Scale score; and modified Rankin Scale scores. Our results showed an increase in both the drained CSF Hb concentration in patients treated with Uk compared to placebo and in the rate of resolution clot volume. No differences were found in the other outcome measures but there was a trend towards lowered mortality in the group treated with Uk. Therefore, intraventricular Uk resulted in faster resolution of IVH with no adverse events. Copyright © 2011 Elsevier Ltd. All rights reserved.

Randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitis.

PubMed

de Bièvre, M A; Vrij, A A; Schoon, E J; Dijkstra, G; de Jong, A E; Oberndorff-Klein Woolthuis, A H; Hemker, H C; Stockbrügger, R W

2007-06-01

In several open and 1 controlled trial, unfractionated heparin was effective in the treatment of active ulcerative colitis (UC). Low molecular weight heparin (LMWH) had a similar effect in several open studies. We studied the efficacy, safety, and tolerability of LMWH in mild to moderately active UC in a randomized, double-blind, placebo-controlled trial. In all, 29 patients with a mild or moderate recurrence of UC during salicylate treatment were randomized to receive either reviparin 3,436 IU (n = 15) subcutaneously twice daily or placebo (n = 14). The study period was 8 weeks. Treatment was discontinued if there was no improvement at 4 weeks or at any disease progression. Primary outcome measure was clinical improvement at 8 weeks measured by the Colitis Activity Index (CAI) and the Clinical Symptoms Grading (CSG, based on the CAI). Endoscopic and histologic grading and quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) were secondary outcome measures. Patients were closely monitored for adverse events. Twenty of 29 patients finished the 8-week treatment period (reviparin versus placebo: 11 versus 9; P = 0.70). There was no difference in CSG, CAI, endoscopic and histologic grading, or IBDQ. Treatment was well tolerated and no serious adverse events occurred. In this study, treatment with LMWH showed no significant clinical advantage compared to placebo in mild to moderately active UC.

Effects of timolol and atenolol on benign essential tremor: placebo-controlled studies based on quantitative tremor recording.

PubMed Central

Dietrichson, P; Espen, E

1981-01-01

Two different beta-adrenoreceptor antagonists, atenolol and timolol, were separately compared with a placebo in the suppression of essential tremor. In two-week single-blind placebo-controlled studies with cross-over, timolol (5 mg twice daily) and atenolol (100 mg once daily) produced an equal reduction in sitting heart rate and sitting blood pressure. Timolol was effective in reducing tremor while atenolol failed to reduce tremor amplitude. These results indicate that essential tremor can be reduced but not blocked, by the adrenergic blocker timolol with both beta 1 and beta 2 blocking properties; but not by the relatively selective beta 1 blocking drug atenolol. Possibly, the tremor reduction is medicated by a peripheral effect on beta 2 adrenoreceptors. Images PMID:7028921

Oxygen therapy for cluster headache. A mask comparison trial. A single-blinded, placebo-controlled, crossover study.

PubMed

Petersen, Anja S; Barloese, Mads Cj; Lund, Nunu Lt; Jensen, Rigmor H

2017-03-01

Purpose The purpose of this article is to investigate possible differences in effect between three types of masks in the acute treatment of cluster headache (CH). Patients and methods Fifty-seven CH patients according to ICHD-II-criteria participated in a single-blinded, semi-randomized, placebo-controlled, crossover inpatient study, and 102 CH attacks were treated with 100% oxygen delivered by demand valve oxygen (DVO), O 2 ptimask or simple mask (15 liters/min) or placebo delivered by DVO for 15 minutes. Primary endpoint: Two-point decrease of pain on a five-point rating scale within 15 minutes. Results Only 10 CH patients had multiple attacks and reached the point of placebo. There were no significant differences between masks in the primary endpoints ( p = 0.412). After 15 minutes 48% had a two-point decrease using the DVO compared to 45% with placebo ( p = 0.867). After 30 minutes 68% were pain free or had pain relief using DVO and 45% by placebo ( p = 0.061). The DVO was preferred by 62% compared to 5% and 33% for simple mask ( p < 0.0001) and O 2 ptimask ( p = 0.061). In the first attack the DVO was significantly better at achieving pain relief at 15 minutes ( p = 0.018). Treatment with DVO or O 2 ptimask reduced the need for rescue medication compared to the simple mask (23%, 19%, 50%, respectively). No treatment-related adverse events were observed. Conclusion The primary endpoint with pain relief at 15 minutes was non-significant; however, a post hoc analysis of the first attack significantly favored DVO. Further, therapy by O 2 ptimask and DVO resulted in a decreased need for rescue medication. We recommend that CH patients be offered DVO or O 2 ptimask before oxygen therapy is abandoned.

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.

Erotic Stimulus Processing under Amisulpride and Reboxetine: A Placebo-Controlled fMRI Study in Healthy Subjects

PubMed Central

Wiegers, Maike; Metzger, Coraline D.; Walter, Martin; Grön, Georg; Abler, Birgit

2015-01-01

Background: Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects. Methods: Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire. Results: Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged. Conclusions: In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents. PMID:25612894

Zinc supplementation for improving glucose handling in pre-diabetes: A double blind randomized placebo controlled pilot study.

PubMed

Islam, Md Rafiqul; Attia, John; Ali, Liaquat; McEvoy, Mark; Selim, Shahjada; Sibbritt, David; Akhter, Ayesha; Akter, Shahnaz; Peel, Roseanne; Faruque, Omar; Mona, Tazreen; Lona, Hafiza; Milton, Abul Hasnat

2016-05-01

There are a number of studies showing that zinc supplementation may improve glucose handling in people with established diabetes. We sought to investigate whether this zinc-dependent improvement in glucose handling could potentially be harnessed to prevent the progression of pre-diabetes to diabetes. In this double-blind randomized placebo-controlled trial, we determined participants' fasting blood glucose levels, (FBG) and Homeostasis Model Assessment (HOMA) parameters (beta cell function, insulin sensitivity and insulin resistance) at baseline and after 6 months of zinc supplementation. The Bangladesh Institute of Health Sciences Hospital (BIHS) (Mirpur, Dhaka, Bangladesh) database was used to identify 224 patients with prediabetes, of whom 55 met the inclusion criteria and agreed to participate. The participants were randomized either to the intervention or control group using block randomization. The groups received either 30mg zinc sulphate dispersible tablet or placebo, once daily for six months. After six months, the intervention group significantly improved their FBG concentration compared to the placebo group (5.37±0.20mmol/L vs 5.69±0.26, p<0.001) as well as compared to their own baseline (5.37±0.20mmol/L vs 5.8±0.09, p<0.001). Beta cell function, insulin sensitivity and insulin resistance all showed a statistically significant improvement as well. To our knowledge this is the first trial to show an improvement in glucose handling using HOMA parameters in participants with prediabetes. Larger randomized controlled trials are warranted to confirm these findings and to explore clinical endpoints. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Oral Aripiprazole as Maintenance Treatment in Adolescent Schizophrenia: Results From a 52-Week, Randomized, Placebo-Controlled Withdrawal Study.

PubMed

Correll, Christoph U; Kohegyi, Eva; Zhao, Cathy; Baker, Ross A; McQuade, Robert; Salzman, Phyllis M; Sanchez, Raymond; Nyilas, Margaretta; Carson, William

2017-09-01

To evaluate the efficacy, safety, and tolerability of aripiprazole, a dopamine D 2 receptor partial agonist, as maintenance treatment in adolescent outpatients with schizophrenia. This was a multicenter, double-blind, placebo-controlled, randomized withdrawal design trial. Participants 13 to 17 years of age with a diagnosis of schizophrenia (DSM-IV-TR) were first cross-titrated from their other oral antipsychotic(s) (4-6 weeks), then stabilized (7-21 weeks) on oral aripiprazole 10 to 30 mg/d, and finally randomized 2:1 to continuation of oral aripiprazole or to placebo in a double-blind maintenance phase (≤52 weeks). The primary endpoint was time from randomization to exacerbation of psychotic symptoms/impending relapse. Safety and tolerability were assessed. Of 201 enrolled participants, 146 were randomized to aripiprazole (n = 98) or placebo (n = 48) in the double-blind maintenance phase. Treatment with aripiprazole was associated with a significantly longer time to exacerbation of psychotic symptoms/impending relapse compared with placebo (hazard ratio, 0.46 [95% CI = 0.24-0.88]; p = .016). Aripiprazole was associated with lower rates of serious treatment-emergent adverse events (TEAEs) versus placebo (3.1% versus 12.5%; p = .059) and severe TEAEs (2.0% versus 10.4%; p = .039). The rate of discontinuation due to TEAEs was lower with aripiprazole versus placebo (20.4% versus 39.6%, p = .014; number-needed-to-harm = 5.1). The incidences of extrapyramidal symptoms, weight gain, and somnolence were similar or lower with aripiprazole than with placebo, and no TEAEs related to elevated serum prolactin were reported. Based on Tanner staging, 27.6% of participants treated with aripiprazole and 16.7% of those who received placebo progressed one or two stages from baseline. Aripiprazole was observed to be safe and effective for the maintenance treatment of adolescents with schizophrenia. Efficacy and Safety Study of Oral Aripiprazole in Adolescents With

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

PubMed

Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

2016-11-01

Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

PubMed Central

Ray, Lara A; Bujarski, Spencer; Courtney, Kelly E; Moallem, Nathasha R; Lunny, Katy; Roche, Daniel; Leventhal, Adam M; Shoptaw, Steve; Heinzerling, Keith; London, Edythe D; Miotto, Karen

2015-01-01

Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatment-seeking individuals meeting DSM-IV criteria for MA abuse or dependence (n=30) completed two separate 5-day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared with placebo. NTX decreased overall subjective ratings of ‘crave drug,' ‘stimulated,' and ‘would like drug access,' decreased the the post-MA administration timecourse of ‘anxious' and increased ratings of ‘bad drug effects,' as compared with placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence, as well as ongoing clinical trials for MA. PMID:25801501

Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study.

PubMed

O'Neil, Patrick M; Smith, Steven R; Weissman, Neil J; Fidler, Meredith C; Sanchez, Matilde; Zhang, Jinkun; Raether, Brian; Anderson, Christen M; Shanahan, William R

2012-07-01

The BLOOM-DM (Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus) study evaluated efficacy and safety of lorcaserin for weight loss in patients with type 2 diabetes. Secondary objectives included evaluations of glycemic control, lipids, blood pressure, and quality of life. This 1-year, randomized, placebo-controlled trial enrolled 604 patients 1:1:1 to placebo, lorcaserin 10 mg once daily (QD) or lorcaserin 10 mg twice daily (BID). Patients were treated with metformin, a sulfonylurea (SFU) or both; had glycated hemoglobin (HbA(1c)) 7-10%; were 18-65 years old; and had BMI 27-45 kg/m(2). Patients received diet and exercise counseling. Safety monitoring included serial echocardiograms. Mean (± SD) age was 52.7 ± 8.7; 54.2% were women; 60.5% were white, 20.9% were African American, and 13.8% were Hispanic. Mean (± SD) weight was 103.6 ± 17.8 kg; BMI was 36.0 ± 4.5 kg/m(2). Most patients (91.7%) took metformin; 50.2% took a SFU. More patients lost ≥5% body weight with lorcaserin BID (37.5%; P < 0.001) or lorcaserin QD (44.7%; P < 0.001) vs. placebo (16.1%; modified intent to treat (MITT)/last observation carried forward (LOCF)). Least square mean (± SEM) weight change was -4.5 ± 0.35% with lorcaserin BID and -5.0 ± 0.5% with lorcaserin QD vs. -1.5 ± 0.36% with placebo (P < 0.001 for each). HbA(1c) decreased 0.9 ± 0.06 with lorcaserin BID, 1.0 ± 0.09 with lorcaserin QD, and 0.4 ± 0.06 with placebo (P < 0.001 for each); fasting glucose decreased 27.4 ± 2.5 mg/dl, -28.4 ± 3.8 mg/dl, and 11.9 ± 2.5 mg/dl, respectively (P < 0.001 for each). Symptomatic hypoglycemia occurred in 7.4% of patients on lorcaserin BID, 10.5% on lorcaserin QD, and 6.3% on placebo. Common adverse events were headache, back pain, nasopharyngitis, and nausea. Lorcaserin was associated with significant weight loss and improvement in glycemic control in patients with type 2 diabetes.

Olanzapine versus Placebo in Adolescents with Schizophrenia; a 6-Week, Randomized Double-Blind, Placebo-Controlled Trial

ERIC Educational Resources Information Center

Kryzhanovskaya, Ludmila; Schulz, Charles; McDougle, Christopher; Frazier, Jean; Dittman, Ralf; Robertson-Plouch, Carol; Bauer, Theresa; Xu, Wen; Wang, Wei; Carlson, Janice; Tohen, Mauricio

2009-01-01

The efficacy of olanzapine in treating schizophrenia was tested through a placebo-controlled trial involving one hundred seven inpatient and outpatients adolescents. Patients who took olanzapine experienced significant symptom improvement.

Treating intermittent allergic rhinitis: a prospective, randomized, placebo and antihistamine-controlled study of Butterbur extract Ze 339.

PubMed

Schapowal, Andreas

2005-06-01

Intermittent allergic rhinitis (IAR) causes patients distress and impairs their work performance and quality of life. A variety of medicines are used by sufferers whose anguish frequently leads to trying new treatments, increasingly from herbal sources. Prospective, randomized, double-blind, parallel group comparison study of Butterbur extract (Ze 339; 8 mg total petasine; one tablet thrice-daily), fexofenadine (Telfast 180, one tablet once-daily) and placebo in 330 patients. Protocol and analysis were according to the latest guidelines on new treatments for allergic rhinitis. The primary efficacy variable was a change in symptoms from baseline to endpoint during daytime. The secondary efficacy variables were: (a) as per primary variable (evening/night); (b) Physician's global assessment; (c) Responder rates. Safety was closely monitored. Both active treatments were individually significantly superior to placebo (p<0.001) in improving symptoms of IAR, while there were no differences between the two active treatments (p=0.37). Superiority to placebo was similarly shown during the evening/night (p<0.001), by physicians' own assessment and by responder rates. Both treatments were well tolerated. Butterbur Ze 339 and Fexofenadine are comparably efficacious relative to placebo. Despite being a herbal drug, Butterbur Ze 339 has now been subject to a series of well controlled trials and should be considered as an alternative treatment for IAR. Copyright (c) 2005 John Wiley & Sons, Ltd.

BounceBack capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study.

PubMed

Udani, Jay K; Singh, Betsy B; Singh, Vijay J; Sandoval, Elizabeth

2009-06-05

Delayed onset muscle soreness (DOMS) is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack, to alleviate the severity of DOMS after standardized eccentric exercise. The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18-45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. In this controlled pilot study, intake of BounceBack capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein) and muscle damage (creatine phosphokinase and myoglobin). BounceBack capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results.

BounceBack™ capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study

PubMed Central

Udani, Jay K; Singh, Betsy B; Singh, Vijay J; Sandoval, Elizabeth

2009-01-01

Background Delayed onset muscle soreness (DOMS) is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack™, to alleviate the severity of DOMS after standardized eccentric exercise. Methods The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18–45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. Results In this controlled pilot study, intake of BounceBack™ capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein) and muscle damage (creatine phosphokinase and myoglobin). Conclusion BounceBack™ capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results. PMID:19500355

The role of thalidomide and placebo for the treatment of cancer-related anorexia-cachexia symptoms: results of a double-blind placebo-controlled randomized study.

PubMed

Yennurajalingam, Sriram; Willey, Jie S; Palmer, J Lynn; Allo, Julio; Del Fabbro, Egidio; Cohen, Evan N; Tin, Sanda; Reuben, James M; Bruera, Eduardo

2012-10-01

To determine the effects of thalidomide and placebo on anorexia-cachexia and its related symptoms, body composition, resting metabolic rate, and serum cytokines and their receptors in patients with advanced cancer. Included in the study were patients with advanced cancer with weight loss greater than 5% in 6 months and who reported anorexia, fatigue, and one of the following: anxiety, depression, or sleep disturbances. Patients on chemotherapy within 2 weeks prior or during the study were excluded from the study. Patients were randomly assigned to either 100 mg thalidomide or placebo once a day for 14 days. The Edmonton Symptom Assessment Scale (ESAS), Functional Assessment of Anorexia/Cachexia Therapy (FAACT), Functional Assessment of Cancer Illness Therapy (FACIT-F), Hospital Anxiety Depression Scale (HADS) Pittsburgh Sleep Quality Index (PSQI) were utilized, and in addition body composition, Resting Energy Expenditure (REE), and serum cytokine levels were assessed. Of the 31 patients entered in the study, 15 were assigned to the thalidomide group and 16 to the placebo group. However only 21/31 patients were able to complete the study. Compared with their baseline values, both the thalidomide and the placebo groups showed significant reduction in cytokines. Tumor necrosis factor (TNF)-α (p=0.04) and its receptors TNFR1 (p=0.04), TNFR2 (p=0.04), and interleukin (IL)-8 (p=0.04) were statistically significant in the thalidomide group. In the placebo group, TNF-α (p=0.008), TNFR1 (p=0.005), TNFR2 (p=0.005), IL-RA (p=0.005), IL-6 (p=0.005), and IL-8 (p=0.005) were statistically significant. However, improvement in these symptoms and cytokine levels were not significantly different in the thalidomide group compared with the placebo group. None of the patients withdrew from the study because of toxicity of either thalidomide or placebo. Based on the poor accrual rate and attrition observed in this study, it is important that future research on thalidomide as a

Erlotinib, erlotinib-sulindac vs. placebo: a randomized, double-blind, placebo-controlled window trial in operable head and neck cancer

PubMed Central

Gross, Neil D.; Bauman, Julie E.; Gooding, William E.; Denq, William; Thomas, Sufi M.; Wang, Lin; Chiosea, Simion; Hood, Brian L.; Flint, Melanie S.; Sun, Mai; Conrads, Thomas P.; Ferris, Robert L.; Johnson, Jonas T.; Kim, Seungwon; Argiris, Athanassios; Wirth, Lori; Nikiforova, Marina N.; Siegfried, Jill M.; Grandis, Jennifer R.

2014-01-01

Purpose The epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) pathways are upregulated in head and neck squamous cell carcinoma (HNSCC). Preclinical models indicate synergistic anti-tumor activity from dual blockade. We conducted a randomized, double-blind, placebo-controlled window trial of erlotinib, an EGFR inhibitor; erlotinib plus sulindac, a non-selective COX inhibitor, vs. placebo. Experimental Design Patients with untreated, operable Stage II-IVb HNSCC were randomized 5:5:3 to erlotinib, erlotinib-sulindac, or placebo. Tumor specimens were collected before and after 7-14 days of treatment. The primary endpoint was change in Ki-67 proliferation index. We hypothesized an ordering effect in Ki-67 reduction: erlotinib-sulindac > erlotinib > placebo. We evaluated tissue microarrays by immunohistochemistry for pharmacodynamic modulation of EGFR and COX-2 signaling intermediates. Results From 2005-2009, 47 patients were randomized for the target 39 evaluable patients. Thirty-four tumor pairs were of sufficient quality to assess biomarker modulation. Ki-67 was significantly decreased by erlotinib or erlotinib-sulindac (omnibus comparison, two-sided Kruskal-Wallis, p=0.04). Wilcoxon pairwise contrasts confirmed greater Ki-67 effect in both erlotinib groups (erlotinib-sulindac vs. placebo p=0.043; erlobinib vs. placebo, p=0.027). There was a significant trend in ordering of Ki-67 reduction: erlotinib-sulindac > erlotinib > placebo (two-sided exact Jonckheere-Terpstra, p =0.0185). Low baseline pSrc correlated with greater Ki-67 reduction (R2 = .312, p = 0.024). Conclusions Brief treatment with erlotinib significantly decreased proliferation in HNSCC, with additive effect from sulindac. Efficacy studies of dual EGFR-COX inhibition are justified. pSrc is a potential resistance biomarker for anti-EGFR therapy, and warrants investigation as a molecular target. PMID:24727329

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.

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

Is Skin-Touch Sham Needle Not Placebo? A Double-Blind Crossover Study on Pain Alleviation

PubMed Central

Homma, Ikuo; Izumizaki, Masahiko

2015-01-01

It remains an open question whether placebo/sham acupuncture, in which the needle tip presses the skin, can be used as a placebo device for research on pain. We compare the analgesic effect of the skin-touch placebo needle with that of the no-touch placebo needle, in which the needle tip does not touch the skin, in a double-blind crossover manner including no-treatment control in 23 healthy volunteers. The subjects received painful electrical stimulation in the forearm before and during needle retention to the LI 4 acupoint and after the removal of the needle and rated pain intensity using a visual analogue scale. We found no significant difference in analgesic effects among the skin-touch placebo needle, no-touch placebo needle, and no-treatment control at every point before, during, and after the treatments (p > 0.05). The results indicate that the skin-touch placebo needle can be used as a placebo device in clinical studies on pain. PMID:26064153

Minoxidil 2% lotion for eyebrow enhancement: a randomized, double-blind, placebo-controlled, spilt-face comparative study.

PubMed

Lee, Saridpong; Tanglertsampan, Chuchai; Tanchotikul, Mingkwan; Worapunpong, Nigun

2014-02-01

Topical minoxidil has been successfully used to treat androgenetic alopecia. It can also be applied to enhance eyebrows. However, there is no study comparing minoxidil lotion with placebo for eyebrow enhancement. In this trial, we determined the efficacy and safety of minoxidil 2% lotion for eyebrow enhancement compared with placebo. Forty patients were randomized for minoxidil on the eyebrow on one side of the face and placebo on the other. Efficacy was evaluated by global photographic assessment, eyebrow diameter, eyebrow count and subject's satisfaction. Side-effects were also evaluated. Thirty-nine patients (97.5%) completed the study. After 16 weeks, the minoxidil group achieved significantly better results in all measured outcomes compared to the placebo group. Side-effects were minor and did not preclude patients from continuing the study. Our study suggests that minoxidil 2% lotion is a safe and effective treatment for eyebrow hypotrichosis. © 2014 Japanese Dermatological Association.

How informative are open-label studies for youth with bipolar disorder? A meta-analysis comparing open-label versus randomized, placebo-controlled clinical trials.

PubMed

Biederman, Joseph; Petty, Carter R; Woodworth, K Yvonne; Lomedico, Alexandra; O'Connor, Katherine B; Wozniak, Janet; Faraone, Stephen V

2012-03-01

To examine the informativeness of open-label trials toward predicting results in subsequent randomized, placebo-controlled clinical trials of psychopharmacologic treatments for pediatric bipolar disorder. We searched journal articles through PubMed at the National Library of Medicine using bipolar disorder, mania, pharmacotherapy, treatment and clinical trial as keywords. This search was supplemented with scientific presentations at national and international scientific meetings and submitted manuscripts from our group. Selection criteria included (1) enrollment of children diagnosed with DSM-IV bipolar disorder; (2) prospective assessment of at least 3 weeks; (3) monotherapy of a pharmacologic treatment for bipolar disorder; (4) use of a randomized placebo-controlled design or an open-label design for the same therapeutic compound; and (5) repeated use of the Young Mania Rating Scale (YMRS) as an outcome. The following information and data were extracted from 14 studies: study design, name of medication, class of medication, dose of medication, sample size, age, sex, trial length, and YMRS mean and standard deviation baseline and follow-up scores. For both study designs, the pooled effect size was statistically significant (open-label studies, z = 8.88, P < .001; randomized placebo-controlled studies, z = 13.75, P < .001), indicating a reduction in the YMRS from baseline to endpoint in both study designs. In a meta-analysis regression, study design was not a significant predictor of mean change in the YMRS. We found similarities in the treatment effects between open-label and randomized placebo-controlled studies in youth with bipolar disorder indicating that open-label studies are useful predictors of the potential safety and efficacy of a given compound in the treatment of pediatric bipolar disorder. © Copyright 2012 Physicians Postgraduate Press, Inc.

Lack of efficacy for fluoxetine in PTSD: a placebo controlled trial in combat veterans.

PubMed

Hertzberg, M A; Feldman, M E; Beckham, J C; Kudler, H S; Davidson, J R

2000-06-01

Fluoxetine and placebo were studied in a population of combat veterans with severe, chronic PTSD. Twelve male veterans with PTSD were enrolled in a 12 week double-blind evaluation of fluoxetine and placebo. Mean fluoxetine dose at endpoint (week 12) was 48 mg/day with a range of 10 mg to 60 mg. One fluoxetine patient responded (17%) and two of the six placebo patients responded (33%). Fluoxetine patients did not show a greater response than placebo patients in this small sample of male combat veterans with severe, chronic PTSD. Fluoxetine has displayed an efficacious response in controlled studies of patients with PTSD who were predominantly female, suffered civilian (noncombat) traumas, and were overall experiencing less severe PTSD. The reasons for the low response rate to fluoxetine in our study is unknown and will await further study examining variables other than symptoms that might influence outcome, such as gender, comorbidity, prior treatment history, trauma type, severity and chronicity.

Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial.

PubMed

Taylor, Jerome H; Landeros-Weisenberger, Angeli; Coughlin, Catherine; Mulqueen, Jilian; Johnson, Jessica A; Gabriel, Daniel; Reed, Margot O; Jakubovski, Ewgeni; Bloch, Michael H

2018-01-01

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F 9,115 =2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F 10,141 =0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.

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.

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.

Creatine supplementation and physical training in patients with COPD: A double blind, placebo-controlled study

PubMed Central

Faager, Gun; Söderlund, Karin; Sköld, Carl Magnus; Rundgren, Siw; Tollbäck, Anna; Jakobsson, Per

2006-01-01

Study objectives Patients with chronic obstructive pulmonary disease (COPD) have low exercise capacity and low content of high energetic phosphates in their skeletal muscles. The aim of the present study was to investigate whether creatine supplementation together with exercise training may increase physical performance compared with exercise training in patients with COPD. Design In a randomized, double-blind, placebo-controlled study, 23 patients with COPD (forced expiratory volume in one second [FEV1] < 70% of predicted) were randomized to oral creatine (n = 13) or placebo (n = 10) supplementation during an 8-week rehabilitation programme including exercise training. Physical performance was assessed by Endurance Shuttle Walking Test (ESWT), dyspnea and leg fatigue with Borg CR-10, quality of life with St George’s Respiratory Questionnaire (SGRQ). In addition, lung function test, artery blood gases, grip strength test, muscle strength and fatigue in knee extensors were measured. Results COPD patients receiving creatine supplementation increased their average walking time by 61% (ESWT) (p < 0.05) after the training period compared with 48% (p = 0.07) in the placebo group. Rated dyspnea directly after the ESWT decreased significantly from 7 to 5 (p < 0.05) in the creatine group. However, the difference between the groups was not statistically significant neither in walking time nor in rated dyspnea. Creatine supplementation did not increase the health related quality of life, lung function, artery blood gases, grip strength and knee extensor strength/fatigue. Conclusions Oral creatine supplementation in combination with exercise training showed no significant improvement in physical performance, measured as ESWT, in patients with COPD compared with exercise training alone. PMID:18044100

The Effect of the Type and Colour of Placebo Stimuli on Placebo Effects Induced by Observational Learning.

PubMed

Świder, Karolina; Bąbel, Przemysław

2016-01-01

Research shows that placebo analgesia and nocebo hyperalgesia can be induced through observational learning. Our aim was to replicate and extend these results by studying the influence of the type and colour of stimuli used as placebos on the placebo effects induced by observational learning. Three experimental and two control groups were tested. All participants received pain stimuli of the same intensity preceded by colour lights (green and red) or geometric shapes (circles and squares). Before receiving pain stimuli, participants in the experimental groups, but not in the control groups, observed a model who rated pain stimuli that were preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than those preceded by either red lights (green placebo group), green lights (red placebo group), or squares (circle placebo group). As a result participants in the experimental groups rated pain stimuli preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than the participants in the control groups did, indicating that placebo effect was induced. No statistically significant differences were found in the magnitudes of the placebo effects between the three experimental groups (green placebo, red placebo, and circle placebo groups), indicating that neither the type nor the colour of placebo stimuli affected the placebo effects induced by observational learning. The placebo effects induced by observational learning were found to be unrelated to the individual differences in pain anxiety, fear of pain, and empathy.

The Effect of the Type and Colour of Placebo Stimuli on Placebo Effects Induced by Observational Learning

PubMed Central

Świder, Karolina; Bąbel, Przemysław

2016-01-01

Research shows that placebo analgesia and nocebo hyperalgesia can be induced through observational learning. Our aim was to replicate and extend these results by studying the influence of the type and colour of stimuli used as placebos on the placebo effects induced by observational learning. Three experimental and two control groups were tested. All participants received pain stimuli of the same intensity preceded by colour lights (green and red) or geometric shapes (circles and squares). Before receiving pain stimuli, participants in the experimental groups, but not in the control groups, observed a model who rated pain stimuli that were preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than those preceded by either red lights (green placebo group), green lights (red placebo group), or squares (circle placebo group). As a result participants in the experimental groups rated pain stimuli preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than the participants in the control groups did, indicating that placebo effect was induced. No statistically significant differences were found in the magnitudes of the placebo effects between the three experimental groups (green placebo, red placebo, and circle placebo groups), indicating that neither the type nor the colour of placebo stimuli affected the placebo effects induced by observational learning. The placebo effects induced by observational learning were found to be unrelated to the individual differences in pain anxiety, fear of pain, and empathy. PMID:27362552

Short-term effects of highly-bioavailable curcumin for treating knee osteoarthritis: a randomized, double-blind, placebo-controlled prospective study.

PubMed

Nakagawa, Yasuaki; Mukai, Shogo; Yamada, Shigeru; Matsuoka, Masayuki; Tarumi, Eri; Hashimoto, Tadashi; Tamura, Chieko; Imaizumi, Atsushi; Nishihira, Jun; Nakamura, Takashi

2014-11-01

We previously developed a surface-controlled water-dispersible form of curcumin and named it Theracurmin(®) (Theracurmin; Theravalues, Tokyo, Japan). The area under the blood concentration-time curve of Theracurmin in humans was 27-fold higher than that of curcumin powder. We determined the clinical effects of orally administered Theracurmin in patients with knee osteoarthritis during 8 weeks of treatment. Fifty patients with knee osteoarthritis of Kellgren-Lawrence grade II or III and who were aged more than 40 years were enrolled in this randomized, double-blind, placebo-controlled, prospective clinical study. Placebo or Theracurmin containing 180 mg/day of curcumin was administered orally every day for 8 weeks. To monitor adverse events, blood biochemistry analyses were performed before and after 8 weeks of each intervention. The patients' knee symptoms were evaluated at 0, 2, 4, 6, and 8 weeks by the Japanese Knee Osteoarthritis Measure, the knee pain visual analog scale (VAS), the knee scoring system of the Japanese Orthopedic Association, and the need for nonsteroidal anti-inflammatory drugs. At 8 weeks after treatment initiation, knee pain VAS scores were significantly lower in the Theracurmin group than in the placebo group, except in the patients with initial VAS scores of 0.15 or less. Theracurmin lowered the celecoxib dependence significantly more than placebo. No major side effects were observed with Theracurmin treatment. Theracurmin shows modest potential for the treatment of human knee osteoarthritis.

Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study.

PubMed

Bone, Henry G; Lindsay, Robert; McClung, Michael R; Perez, Alfonso T; Raanan, Marsha G; Spanheimer, Robert G

2013-12-01

Meta-analyses of clinical studies have suggested an increased incidence of peripheral fractures in postmenopausal women with type 2 diabetes mellitus taking pioglitazone. The mechanism behind this apparent increase is unknown. The objective of the study was to examine the effects of pioglitazone on bone mineral density (BMD) and turnover. Twenty-five sites (in the United States) enrolled participants in this randomized, double-blind, placebo-controlled study. Postmenopausal women (n = 156) with impaired fasting glucose or impaired glucose tolerance participated in the study. The intervention consisted of pioglitazone 30 mg/d (n = 78) or placebo (n = 78), increased to 45 mg/d after 1 month, for 12 months of treatment total, followed by 6 months of washout/follow-up. Percentage changes from baseline to month 12 and from month 12 to month18 in BMD in total proximal femur (primary end point), total body, femoral neck, lumbar spine, and radius were measured. Least squares mean changes from baseline to month 12 in total proximal femur BMD were -0.69% for pioglitazone and -0.14% for placebo (P = .170). No statistically significant between-group differences were observed for any BMD or bone remodeling marker end point. We observed improved glycemic control and insulin sensitivity with pioglitazone treatment. In addition, pioglitazone appeared to increase body fat, which may affect bone density measurements, especially in the lumbar spine. One pioglitazone-treated and three placebo-treated women experienced confirmed fractures. Over 18 months, one pioglitazone-treated (1.3%) and eight placebo-treated women (10.3%) developed overt type 2 diabetes mellitus. The pattern and incidence of adverse events with pioglitazone were consistent with clinical experience with thiazolidinediones. Maximal-dose pioglitazone had no effects on BMD or bone turnover, while improving glycemic control as expected, in postmenopausal women with impaired fasting glucose or impaired glucose tolerance.

N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study.

PubMed

Grant, Jon E; Odlaug, Brian L; Kim, Suck Won

2009-07-01

Trichotillomania is characterized by repetitive hair pulling that causes noticeable hair loss. Data on the pharmacologic treatment of trichotillomania are limited to conflicting studies of serotonergic medications. N-acetylcysteine, an amino acid, seems to restore the extracellular glutamate concentration in the nucleus accumbens and, therefore, offers promise in the reduction of compulsive behavior. To determine the efficacy and tolerability of N-acetylcysteine in adults with trichotillomania. Twelve-week, double-blind, placebo-controlled trial. Ambulatory care center. Fifty individuals with trichotillomania (45 women and 5 men; mean [SD] age, 34.3 [12.1] years). N-acetylcysteine (dosing range, 1200-2400 mg/d) or placebo was administered for 12 weeks. Patients were assessed using the Massachusetts General Hospital Hair Pulling Scale, the Clinical Global Impression scale, the Psychiatric Institute Trichotillomania Scale, and measures of depression, anxiety, and psychosocial functioning. Outcomes were examined using analysis of variance modeling analyses and linear regression in an intention-to-treat population. Patients assigned to receive N-acetylcysteine had significantly greater reductions in hair-pulling symptoms as measured using the Massachusetts General Hospital Hair Pulling Scale (P < .001) and the Psychiatric Institute Trichotillomania Scale (P = .001). Fifty-six percent of patients "much or very much improved" with N-acetylcysteine use compared with 16% taking placebo (P = .003). Significant improvement was initially noted after 9 weeks of treatment. This study, the first to our knowledge that examines the efficacy of a glutamatergic agent in the treatment of trichotillomania, found that N-acetylcysteine demonstrated statistically significant reductions in trichotillomania symptoms. No adverse events occurred in the N-acetylcysteine group, and N-acetylcysteine was well tolerated. Pharmacologic modulation of the glutamate system may prove to be useful in

Neurophysiological effects of modafinil on cue-exposure in cocaine dependence: a randomized placebo-controlled cross-over study using pharmacological fMRI.

PubMed

Goudriaan, Anna E; Veltman, Dick J; van den Brink, Wim; Dom, Geert; Schmaal, Lianne

2013-02-01

Enhanced reactivity to substance related cues is a central characteristic of addiction and has been associated with increased activity in motivation, attention, and memory related brain circuits and with a higher probability of relapse. Modafinil was promising in the first clinical trials in cocaine dependence, and was able to reduce craving in addictive disorders. However, its mechanism of action remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study therefore, cue reactivity in cocaine dependent patients was compared to cue reactivity in healthy controls (HCs) under modafinil and placebo conditions. An fMRI cue reactivity study, with a double-blind, placebo-controlled cross-over challenge with a single dose of modafinil (200mg) was employed in 13 treatment seeking cocaine dependent patients and 16 HCs. In the placebo condition, watching cocaine-related pictures (versus neutral pictures) resulted in higher brain activation in the medial frontal cortex, anterior cingulate cortex, angular gyrus, left orbitofrontal cortex, and ventral tegmental area (VTA) in the cocaine dependent group compared to HCs. However, in the modafinil condition, no differences in brain activation patterns were found between cocaine dependent patients and HCs. Group interactions revealed decreased activity in the VTA and increased activity in the right ACC and putamen in the modafinil condition relative to the placebo condition in cocaine dependent patients, whereas such changes were not present in healthy controls. Decreases in self-reported craving when watching cocaine-related cues after modafinil administration compared to the placebo condition were associated with modafinil-induced increases in ACC and putamen activation. Enhanced cue reactivity in the cocaine dependent group compared to healthy controls was found in brain circuitries related to reward, motivation, and autobiographical memory processes. In cocaine dependent patients, these enhanced brain

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

Bright light therapy and melatonin in motor restless behaviour in dementia: a placebo-controlled study.

PubMed

Haffmans, P M; Sival, R C; Lucius, S A; Cats, Q; van Gelder, L

2001-01-01

The purpose of this study was to evaluate the effects of bright light therapy combined with melatonin on motor restless behaviour in dementia. Double-blind, placebo-controlled, cross-over trial consisting of four periods. One week wash-out was followed by a 2-week period of light therapy in combination with placebo or melatonin. The second wash-out period of 1 week was followed by 2 weeks of treatment (cross-over). Twenty-four bed medium-stay psychogeriatric ward at a Dutch psychiatric teaching hospital. Ten patients, who met the criteria for dementia (DSM-IV) and motor restless behaviour (subscale 10 of the GIP), were included. Informed consent was obtained by proxy. All subjects were exposed during 2x5 consecutive days for 30 minutes to 10,000 lux bright light and randomly administered 2.5 mg melatonin or placebo at 22.00 h. Clinical Global Impression (CGI), Dutch version of the geriatric behavioural observation scale (GIP), Social Dysfunction and Aggression Scale (SDAS) were assessed after each wash-out and treatment period. Outcome criteria were CGI, assessing motor restless behaviour, the SDAS, measuring extrovert aggression and the GIP, assessing social, psychomotor and emotional behaviour. Six demented inpatients completed the trial. Positive effects were found for the treatment combined with placebo. Patients were less restless and more co-operative. The condition with melatonin showed no additional positive effects, additionally, patients became more aggressive and showed the same or more disturbed behaviour. Bright light therapy has a positive effect on motor restless behaviour. Light therapy in combination with melatonin has no positive effects. The results might be explained by a possible overshoot of chronobiological synchronisation or the timing of the melatonin intake. Copyright 2001 John Wiley & Sons, Ltd.

A randomized placebo-controlled study of noninvasive cortical electrostimulation in the treatment of fibromyalgia patients.

PubMed

Hargrove, Jeffrey B; Bennett, Robert M; Simons, David G; Smith, Susan J; Nagpal, Sunil; Deering, Donald E

2012-01-01

The aim of this multicenter study was to evaluate the efficacy, safety, and tolerability of noninvasive cortical electrostimulation in the management of fibromyalgia (FM). A prospective, randomized, double-blind, placebo-controlled design was used. Setting.  Subjects received therapy at two different outpatient clinical locations. There were 77 subjects meeting the American College of Rheumatology 1990 classification criteria for FM. Intervention.  Thirty-nine (39) active treatment (AT) FM patients and 38 placebo controls received 22 applications of either noninvasive cortical electrostimulation or a sham therapy over an 11-week period. The primary outcome measures were the number of tender points (TePs) and pressure pain threshold (PPT). Secondary outcome measures were responses to the Fibromyalgia Impact Questionnaire (FIQ), Symptom Checklist-90 (SCL-90), Beck Depression Inventory-II, and a novel sleep questionnaire, all evaluated at baseline and at the end of treatment. Intervention provided significant improvements in TeP measures: compared with placebo, the AT patients improved in the number of positive TePs (-7.4 vs -0.2, P<0.001) and the PPT (19.6 vs -3.2, P<0.001). Most secondary outcomes also improved more in the AT group: total FIQ score (-15.5 vs -5.6, P=0.03), FIQ pain (-2.0 vs -0.6, P=0.03), FIQ fatigue (-2.0 vs -0.4, P=0.02), and FIQ refreshing sleep (-2.1 vs -0.7, P=0.02); and while FIQ function improved (-1.0 vs -0.2), the between-group change had a 14% likelihood of occurring due to chance (P=0.14). There were no significant side effects observed. Noninvasive cortical electrostimulation in FM patients provided modest improvements in pain, TeP measures, fatigue, and sleep; and the treatment was well tolerated. This form of therapy could potentially provide worthwhile adjunctive symptom relief for FM patients. Wiley Periodicals, Inc.

Residual effects of zopiclone 7.5 mg on highway driving performance in insomnia patients and healthy controls: a placebo controlled crossover study.

PubMed

Leufkens, T R M; Ramaekers, J G; de Weerd, A W; Riedel, W J; Vermeeren, A

2014-07-01

Residual effects of hypnotics on driving performance have been mainly determined in studies using a standardized driving test with healthy good sleepers. Responses to effects may differ, however, between insomniacs and healthy volunteers due to the underlying sleep disorder. In addition, a majority of insomniacs uses hypnotics chronically resulting in the development of tolerance to impairing effects. Impaired driving performance in healthy volunteers may then be an overestimation of the actual effects in insomniacs. The present study aims to compare the residual effects of zopiclone 7.5 mg on on-the-road driving performance of 16 middle-aged insomniacs chronically using hypnotics (chronic users), 16 middle-aged insomniacs not or infrequently using hypnotics (infrequent users), and 16 healthy, age matched, good sleepers (controls). The study was conducted according to a 3 × 2 double-blind, placebo controlled crossover design, with three groups and two treatment conditions. Treatments were single oral doses of zopiclone 7.5 mg and placebo administered at bedtime (2330 hours). Between 10 and 11 h after administration subjects performed a standardized highway driving test. Zopiclone 7.5 mg significantly impaired on-the-road driving performance in both insomnia groups and healthy controls. The magnitude of impairment was significantly less in the chronic users group as compared with the controls. The smaller magnitude of effects suggests that investigating residual effects of hypnotics in healthy volunteers may yield a minor overestimation of the actual effects in insomnia patients.

Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study.

PubMed

Ringman, John M; Frautschy, Sally A; Teng, Edmond; Begum, Aynun N; Bardens, Jenny; Beigi, Maryam; Gylys, Karen H; Badmaev, Vladimir; Heath, Dennis D; Apostolova, Liana G; Porter, Verna; Vanek, Zeba; Marshall, Gad A; Hellemann, Gerhard; Sugar, Catherine; Masterman, Donna L; Montine, Thomas J; Cummings, Jeffrey L; Cole, Greg M

2012-01-01

Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD. We performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex(®) with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured. Mean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex(®) was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between

Efficacy of antidepressants for dysthymia: a meta-analysis of placebo-controlled randomized trials.

PubMed

Levkovitz, Yeciel; Tedeschini, Enrico; Papakostas, George I

2011-04-01

The authors sought to determine the efficacy of antidepressants in dysthymic disorder and to compare antidepressant and placebo response rates between major depressive disorder (MDD) and dysthymic disorder. PubMed/MEDLINE databases were searched for double-blind, randomized, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD or dysthymic disorder. We defined antidepressants as those with a letter of approval by the US, Canadian, or European Union drug regulatory agencies for treatment of MDD or dysthymic disorder, which included the following: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, ritanserin, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. Eligible studies were identified by cross-referencing the search term placebo with each of the above-mentioned agents. The search was limited to articles published between January 1, 1980, and November 20, 2009 (inclusive). To expand our database, we also reviewed the reference lists of the identified studies. We selected randomized, double-blind, placebo-controlled trials of antidepressants for either MDD or dysthymic disorder according to preset criteria relating to comorbidities, patient age, drug formulation, study duration, diagnostic criteria, choice of assessment scales, and whether or not the study reported original data. Final selection of articles was determined by consensus among the authors. A total of 194 studies were found that were eligible for inclusion in our analysis. Of these, 177 focused on the treatment of MDD and 17 on the treatment of dysthymic disorder. We found that

Reducing placebo exposure in trials: Considerations from the Research Roundtable in Epilepsy.

PubMed

Fureman, Brandy E; Friedman, Daniel; Baulac, Michel; Glauser, Tracy; Moreno, Jonathan; Dixon-Salazar, Tracy; Bagiella, Emilia; Connor, Jason; Ferry, Jim; Farrell, Kathleen; Fountain, Nathan B; French, Jacqueline A

2017-10-03

The randomized controlled trial is the unequivocal gold standard for demonstrating clinical efficacy and safety of investigational therapies. Recently there have been concerns raised about prolonged exposure to placebo and ineffective therapy during the course of an add-on regulatory trial for new antiepileptic drug approval (typically ∼6 months in duration), due to the potential risks of continued uncontrolled epilepsy for that period. The first meeting of the Research Roundtable in Epilepsy on May 19-20, 2016, focused on "Reducing placebo exposure in epilepsy clinical trials," with a goal of considering new designs for epilepsy regulatory trials that may be added to the overall development plan to make it, as a whole, safer for participants while still providing rigorous evidence of effect. This topic was motivated in part by data from a meta-analysis showing a 3- to 5-fold increased rate of sudden unexpected death in epilepsy in participants randomized to placebo or ineffective doses of new antiepileptic drugs. The meeting agenda included rationale and discussion of different trial designs, including active-control add-on trials, placebo add-on to background therapy with adjustment, time to event designs, adaptive designs, platform trials with pooled placebo control, a pharmacokinetic/pharmacodynamic approach to reducing placebo exposure, and shorter trials when drug tolerance has been ruled out. The merits and limitations of each design were discussed and are reviewed here. © 2017 American Academy of Neurology.

Adjunctive α-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study.

PubMed

Kim, Nam Wook; Song, Yul-Mai; Kim, Eosu; Cho, Hyun-Sang; Cheon, Keun-Ah; Kim, Su Jin; Park, Jin Young

2016-09-01

α-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600-1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics.

Effects of rotigotine on daytime symptoms in patients with primary restless legs syndrome: a randomized, placebo-controlled study.

PubMed

Garcia-Borreguero, Diego; Allen, Richard; Hudson, John; Dohin, Elisabeth; Grieger, Frank; Moran, Kimberly; Schollmayer, Erwin; Smit, René; Winkelman, John

2016-01-01

This 12 week double-blind, placebo-controlled study (ClinicalTrials.gov: NCT01569464) was conducted to evaluate the effects of rotigotine transdermal patch on daytime symptoms in patients with idiopathic restless legs syndrome (RLS). Adult patients with moderate-to-severe RLS were randomized to rotigotine (optimal dose: 1-3 mg/24 h) or placebo. A modified four-assessment version (4:00 pm, 6:00 pm, 8:00 pm, and 10:00 pm) of the Multiple Suggested Immobilization Test (m-SIT) was performed at baseline and end of 4 week maintenance (EoM). Primary study outcomes were change from baseline to EoM in International Restless Legs Syndrome Rating Scale (IRLS) and in average of means for the m-SIT Discomfort Scale (m-SIT-DS) (combined average of mean values from each of the individual assessments). Secondary outcomes included average of means of Periodic Limb Movement during Wakefulness Index (PLMWI; PLM/hour) for the combination of m-SIT. A total of 150 patients were randomized and 137 (rotigotine: 92/101 [91.1%]; placebo: 45/49 [91.8%]) completed maintenance. All 150 randomized patients were assessed for efficacy. At EoM, mean change in IRLS was -14.9 ± 9.3 with rotigotine vs. -12.7 ± 7.6 with placebo (ANCOVA, LS mean treatment difference [95% CI]: -0.27 [-2.96, 2.42]; p = 0.8451). Changes in average of means of m-SIT-DS values of each individual SIT were comparable with rotigotine (-2.68 ± 2.31) vs. placebo (-2.62 ± 2.61) (ANCOVA, LS mean treatment difference [95% CI]: 0.07 [-0.61, 0.75]; p = 0.8336) and comparable reductions in PLMWI were observed in both treatment groups (8.34 [-8.50, 25.17]; p = 0.3290). Rotigotine was generally well tolerated. Application site reactions (rotigotine: 20 patients [19.8%]; placebo: 4 [8.2%]) and nausea (16 [15.8%]; 3 [6.1%]) were the most common AEs. Rotigotine was beneficial in improving overall RLS symptom severity (assessed by IRLS) and RLS symptom severity at various times of the day (m

A Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Adolescents and Young Adults with Anorexia Nervosa: A Pilot Study

ERIC Educational Resources Information Center

Hagman, Jennifer; Gralla, Jane; Sigel, Eric; Ellert, Swan; Dodge, Mindy; Gardner, Rick; O'Lonergan, Teri; Frank, Guido; Wamboldt, Marianne Z.

2011-01-01

Objective: The purpose of this double-blind, placebo-controlled exploratory pilot study was to evaluate the safety and efficacy of risperidone for the treatment of anorexia nervosa. Method: Forty female subjects 12 to 21 years of age (mean, 16 years) with primary anorexia nervosa in an eating disorders program were randomized to receive…

Vitamin B-12-fortified toothpaste improves vitamin status in vegans: a 12-wk randomized placebo-controlled study.

PubMed

Siebert, Anne-Kathrin; Obeid, Rima; Weder, Stine; Awwad, Hussain M; Sputtek, Andreas; Geisel, Juergen; Keller, Markus

2017-03-01

Background: The oral application of vitamin B-12 may prevent its deficiency if the vitamin is absorbed via the mucosal barrier. Objectives: We studied the effect of the use of a vitamin B-12-fortified toothpaste on vitamin-status markers in vegans and assessed the efficiency of markers in the identification of vitamin-augmentation status. Design: In this 12-wk, double-blinded, randomized, placebo-controlled study, 76 vegans received either a placebo ( n = 34) or vitamin B-12 ( n = 42) toothpaste. Sixty-six subjects ( n = 30 in the placebo arm; n = 36 in the vitamin B-12 arm) completed the intervention. Serum and plasma concentrations of vitamin B-12, holotranscobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA) were measured before and after the intervention. Results: Both postintervention concentrations of vitamin B-12 and holotranscobalamin and their changes over 12 wk were higher in the vitamin B-12 group (mean ± SD change: 81 ± 135 pmol/L for vitamin B-12 and 26 ± 34 pmol/L for holotranscobalamin) than in the placebo group (-27 ± 64 and -5 ± 17 pmol/L, respectively) after adjustment for baseline concentrations. Postintervention concentrations of MMA and their changes differed significantly between groups (MMA changes: -0.169 ± 0.340 compared with -0.036 ± 0.544 μmol/L in vitamin B-12 and placebo groups, respectively; P < 0.001). After adjustment for baseline tHcy, postintervention concentrations of tHcy tended to be lower ( P = 0.051), and the changes in tHcy (-0.7 ± 4.4 compared with 2.0 ± 5.6 μmol/L, respectively) were greater in the vitamin B-12 group than in the placebo group. Changes in vitamin B-12 markers were more prominent in vegans who reported that they had not taken vitamin B-12 supplements. Conclusion: Vitamin B-12 that is applied to the oral cavity via toothpaste enters the circulation and corrects the vitamin B-12 markers in the blood of vegans who are at higher risk of vitamin B-12 deficiency. This trial was registered

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.

Memantine Enhances the Effect of Olanzapine in Patients With Schizophrenia: A Randomized, Placebo-Controlled Study.

PubMed

Fakhri, Ahmad; Pakseresht, Sirous; Haghdoost, Mohammad Reza; Hekmatkhah, Nasihat; Torkashvand, Maria; Ghorbanzadeh, Behnam

2016-11-01

Glutamate dysregulation may be involved in the neuropathology of schizophrenia. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease, acts as a partial uncompetitive NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to olanzapine in patients with schizophrenia. In this double-blind, placebo-controlled studies, patients with schizophrenia according to DSM-IV clinical criteria were selected. Patients were randomly assigned to receive either memantine (week 1:10 mg/day; weeks 2-6:20 mg/day) plus olanzapine (15-20 mg/day) or olanzapine plus placebo. At baseline, no statistically significant difference regarding the mean total PANSS scores between treatment groups was found. Results showed that memantine significantly improved the positive and negative PANSS score in patients maintained on olanzapine after six weeks compared to olanzapine alone (P<0.001). Furthermore, female patients showed significantly better response than males, especially in positive PANSS score. No significant changes in extrapyramidal symptoms were observed.These findings indicate that olanzapine efficacy might be augmented with memantine. Furthermore, this effect is more remarkable in female patients with schizophrenia.

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

Erotic stimulus processing under amisulpride and reboxetine: a placebo-controlled fMRI study in healthy subjects.

PubMed

Graf, Heiko; Wiegers, Maike; Metzger, Coraline D; Walter, Martin; Grön, Georg; Abler, Birgit

2014-10-31

Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects. Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4 mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire. Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged. In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents. © The Author 2015. Published by Oxford University Press on behalf of CINP.

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.

Weight Maintenance with Litramine (IQP-G-002AS): A 24-Week Double-Blind, Randomized, Placebo-Controlled Study

PubMed Central

Grube, Barbara; Alt, Felix; Uebelhack, Ralf

2015-01-01

Background. Litramine (IQP-G-002AS) was shown to be effective and safe for weight loss in overweight and obese subjects. However, long-term effectiveness on maintenance of body weight loss has yet to be ascertained. Objective. To assess effect of Litramine on maintenance of body weight loss. Methods. A double-blind, randomised, placebo-controlled trial on overweight and obese patients was conducted over two sites in Germany for 24 weeks. Subjects with documented previous weight loss of 3% over the last 3–6 months were randomised to groups given either Litramine (3 g/day) or a matching placebo. Primary endpoints were difference of mean body weight (kg) between baseline and end of study and maintenance of initially lost body weight in verum group, where maintenance is defined as ≤1% weight gain. Results. Subjects who were taking Litramine lost significantly more body weight compared to the subjects taking placebo who gained weight instead (−0.62 ± 1.55 kg versus 1.62 ± 1.48 kg, p < 0.001). More importantly, 92% of subjects in Litramine group were able to maintain their body weight after initial weight loss, versus 25% in placebo group. No serious adverse events were reported throughout. Conclusion. Litramine is effective and safe for long-term body weight maintenance. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT01505387. PMID:26435849

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

Soy germ extract alleviates menopausal hot flushes: placebo-controlled double-blind trial.

PubMed

Imhof, Martin; Gocan, Anca; Imhof, Marianne; Schmidt, Mathias

2018-05-30

A double-blind, placebo-controlled study was performed to assess the potency of a soy germ preparation for the alleviation of menopausal hot flushes. Caucasian women with at least seven hot flushes daily were treated with soy germ extract (100 mg isoflavone glycosides) daily or with placebo for 12 weeks, followed by 12 weeks of open treatment with soy. Outcome parameters were the number of hot flushes and the evaluation of the Greene Climacteric Scale. A total of 192 women were included. As the hot flush diaries from one study centre were lost, the assessment of hot flushes was based on 136 participants (soy: 54 women; placebo: 82 women). After 12 weeks, 180 women were available for the analysis of Greene Scale and safety (soy and placebo: each 90 women). Hot flushes were reduced by 43.3% (-3.5 hot flushes) with soy and by 30.8% with placebo (-2.6; p < 0.001). After the open treatment phase with soy, both original groups showed a reduction of 68% of hot flushes. A subgroup analysis showed better effects for soy when symptoms were classified as "severe" at baseline. After 12 weeks of double-blind treatment, there was an improvement from baseline values of 71 and 78% with soy with the items "hot flushes" and "sweating", compared with 24% for both items with placebo. Hormonal safety parameters remained uninfluenced. Soy germ extract with 100 mg of isoflavone glycosides was shown to modestly, but significantly reduce menopausal hot flushes.

The effect of vitamin-mineral supplementation on juvenile delinquency among American schoolchildren: a randomized, double-blind placebo-controlled trial.

PubMed

Schoenthaler, S J; Bier, I D

2000-02-01

Numerous studies conducted in juvenile correctional institutions have reported that violence and serious antisocial behavior have been cut almost in half after implementing nutrient-dense diets that are consistent with the World Health Organization's guidelines for fats, sugar, starches, and protein ratios. Two controlled trials tested whether the cause of the behavioral improvements was psychological or biological in nature by comparing the behavior of offenders who either received placebos or vitamin-mineral supplements designed to provide the micronutrient equivalent of a well-balanced diet. These randomized trials reported that institutionalized offenders, aged 13 to 17 years or 18 to 26 years, when given active tablets produced about 40% less violent and other antisocial behavior than the placebo controls. However, generalization could not be made to typical schoolchildren without a controlled trial examining violence and antisocial behavior in public schools. To determine if schoolchildren, aged 6 to 12 years, who are given low dose vitamin-mineral tablets will produce significantly less violence and antisocial behavior in school than classmates who are given placebos. A stratified randomized, double-blind, placebo-controlled trial with pretest and post-test measures of antisocial behavior on school property. Two "working class," primarily Hispanic elementary schools in Phoenix, Arizona. Approximately half of the potential schoolchildren participated, i.e., 468 students aged 6 to 12 years. Daily vitamin-mineral supplementation at 50% of the U.S. recommended daily allowance (RDA) for 4 months versus placebo. The supplement was designed to raise vitamin-mineral intake up to the levels currently recommended by the National Academy of Sciences for children aged 6 to 11 years. Violent and nonviolent delinquency as measured by official school disciplinary records. Of the 468 students randomly assigned to active or placebo tablets, the 80 who were disciplined at

Effects of lacosamide and carbamazepine on human motor cortex excitability: a double-blind, placebo-controlled transcranial magnetic stimulation study.

PubMed

Lang, Nicolas; Rothkegel, Holger; Peckolt, Hannes; Deuschl, Günther

2013-11-01

Lacosamide (LCM) and carbamazepine (CBZ) are antiepileptic drugs both acting on neuronal voltage-gated sodium channels. Patch-clamp studies demonstrated significant differences in how LCM and CBZ affect neuronal membrane excitability. Despite valuable information patch-clamp studies provide, they also comprise some constraints. For example, little is known about effects of LCM on intracortical synaptic excitability. In contrast, transcranial magnetic stimulation (TMS) can describe drug-induced changes at the system level of the human cerebral cortex. The present study was designed to explore dose-depended effects of LCM and effects of CBZ on motor cortex excitability with TMS in a randomized, double-blind, placebo-controlled crossover trial in healthy human subjects. Subjects received 600 mg CBZ, 200 mg LCM, 400 mg LCM or placebo preceding TMS measurements. Compared to placebo, TMS motor thresholds were significantly increased after carbamazepine and lacosamide, with a trend for a dose dependent effect of lacosamide. Both, carbamazepine and lacosamide did not affect TMS parameters of intracortical synaptic excitability. TMS measurements suggest that lacosamide and carbamazepine predominantly act on neuronal membrane excitability. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study.

PubMed

Guttman-Yassky, Emma; Silverberg, Jonathan I; Nemoto, Osamu; Forman, Seth B; Wilke, August; Prescilla, Randy; de la Peña, Amparo; Nunes, Fabio P; Janes, Jonathan; Gamalo, Margaret; Donley, David; Paik, Jim; DeLozier, Amy M; Nickoloff, Brian J; Simpson, Eric L

2018-02-01

Baricitinib, an oral selective inhibitor of Janus kinase (JAK)1 and JAK2, modulates pro-inflammatory cytokine signaling. The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD). In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCS) for 4 weeks before randomization to once daily placebo, baricitinib 2 mg, or baricitinib 4 mg for 16 weeks. Use of TCS was permitted during the study. Primary outcome was the proportion of patients achieving ≥50% reduction in the Eczema Area and Severity Index (EASI-50) compared to placebo. Significantly more baricitinib 4-mg patients achieved EASI-50 compared to placebo (61% vs 37%; P=0.027) at 16 weeks. The proportion of baricitinib 2- and 4-mg patients achieving EASI-50 compared to placebo was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 (49%) placebo, 17 (46%) baricitinib 2-mg, and 27 (71%) baricitinib 4-mg patients. A TCS standardization period prior to randomization reduced disease severity, limiting the ability to compare results to baricitinib monotherapy. Longer studies are required to confirm baricitinib efficacy and safety in AD patients. Baricitinib used with TCS reduced inflammation and pruritus in patients with moderate-to-severe atopic dermatitis (AD). Copyright © 2018. Published by Elsevier Inc.

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study

PubMed Central

Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

2016-01-01

Kale (Brassica oleracea var. acephala), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21–64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140–187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30–120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (Cmax; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0–2 h (AUC0–2 h) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe. PMID:27882216

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study.

PubMed

Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

2016-11-01

Kale ( Brassica oleracea var. acephala ), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21-64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140-187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30-120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (C max ; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0-2 h (AUC 0-2 h ) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe.

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

Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study.

PubMed

Halaska, M; Beles, P; Gorkow, C; Sieder, C

1999-08-01

In a placebo-controlled, randomized, double-blind study the efficacy of a Vitex agnus castus extract-containing solution (VACS) was investigated in patients suffering from cyclical mastalgia. Patients had mastalgia on at least 5 days in the pre-treatment cycle. During this cycle and during treatment (3 cycles; 2 x 30 drops/day), the intensity of mastalgia was recorded once per cycle using a visual analogue scale (VAS). After one/two treatment cycles, the mean decrease in pain intensity (mm, VAS) was 21.4 mm /33.7 mm in women taking VACS (n=48) and 10.6 mm/20.3 mm with placebo (n=49). The differences of the VAS-values for VACS were significantly greater than those with placebo (p=0.018; p=0.006). After three cycles, the mean VAS-score reduction for women taking VACS was 34.3 mm, a reduction of 'borderline significance' (p=0.064) on statistical testing compared with placebo (25.7 mm). There was no difference in the frequency of adverse events between both groups (VACS: n=5; placebo : n=4). VACS appears effective and was well tolerated and further evaluation of this agent in the treatment of cyclical mastalgia is warranted.

High-dose baclofen for the treatment of alcohol dependence (BACLAD study): a randomized, placebo-controlled trial.

PubMed

Müller, Christian A; Geisel, Olga; Pelz, Patricia; Higl, Verena; Krüger, Josephine; Stickel, Anna; Beck, Anne; Wernecke, Klaus-Dieter; Hellweg, Rainer; Heinz, Andreas

2015-08-01

Previous randomized, placebo-controlled trials (RCTs) assessing the efficacy of the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen in the treatment of alcohol dependence have reported divergent results, possibly related to the low to medium dosages of baclofen used in these studies (30-80mg/d). Based on preclinical observations of a dose-dependent effect and positive case reports in alcohol-dependent patients, the present RCT aimed to assess the efficacy and safety of individually titrated high-dose baclofen for the treatment of alcohol dependence. Out of 93 alcohol-dependent patients initially screened, 56 were randomly assigned to a double-blind treatment with individually titrated baclofen or placebo using dosages of 30-270mg/d. The multiple primary outcome measures were (1) total abstinence and (2) cumulative abstinence duration during a 12-week high-dose phase. More patients of the baclofen group maintained total abstinence during the high-dose phase than those receiving placebo (15/22, 68.2% vs. 5/21, 23.8%, p=0.014). Cumulative abstinence duration was significantly higher in patients given baclofen compared to patients of the placebo group (mean 67.8 (SD 30) vs. 51.8 (SD 29.6) days, p=0.047). No drug-related serious adverse events were observed during the trial. Individually titrated high-dose baclofen effectively supported alcohol-dependent patients in maintaining alcohol abstinence and showed a high tolerability, even in the event of relapse. These results provide further evidence for the potential of baclofen, thereby possibly extending the current pharmacological treatment options in alcohol dependence. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

The effects of intranasal esketamine (84 mg) and oral mirtazapine (30 mg) on on-road driving performance: a double-blind, placebo-controlled study.

PubMed

van de Loo, Aurora J A E; Bervoets, Adriana C; Mooren, Loes; Bouwmeester, Noor H; Garssen, Johan; Zuiker, Rob; van Amerongen, Guido; van Gerven, Joop; Singh, Jaskaran; der Ark, Peter Van; Fedgchin, Maggie; Morrison, Randall; Wajs, Ewa; Verster, Joris C

2017-11-01

The purpose of this study is to evaluate the single dose effect of intranasal esketamine (84 mg) compared to placebo on on-road driving performance. Mirtazapine (oral, 30 mg) was used as a positive control, as this antidepressant drug is known to negatively affect driving performance. Twenty-six healthy volunteers aged 21 to 60 years were enrolled in this study. In the evening, 8 h after treatment administration, participants conducted the standardized 100-km on-road driving test. Primary outcome measure was the standard deviation of lateral position (SDLP), i.e., the weaving of the car. Mean lateral position, mean speed, and standard deviation of speed were secondary outcome measures. For SDLP, non-inferiority analyses were conducted, using +2.4 cm (relative to placebo) as a predefined non-inferiority margin for clinical relevant impairment. Twenty-four participants completed the study. No significant SDLP difference was found between esketamine and placebo (p = 0.7638), whereas the SDLP after mirtazapine was significantly higher when compared to placebo (p = 0.0001). The upper limit of the two-sided 95% confidence interval (CI) of the mean difference between esketamine and placebo was +0.86 cm, i.e., <+2.4 cm, thus demonstrating that esketamine was non-inferior to placebo. Non-inferiority could not be concluded for mirtazapine (+3.15 cm SDLP relative to placebo). No significant differences in mean speed, standard deviation of speed, and mean lateral position were observed between the active treatments and placebo. No significant difference in driving performance was observed 8 h after administering intranasal esketamine (84 mg) or placebo. In contrast, oral mirtazapine (30 mg) significantly impaired on road driving performance.

Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial.

PubMed

Barnes, Thomas R E; Leeson, Verity C; Paton, Carol; Costelloe, Céire; Simon, Judit; Kiss, Noemi; Osborn, David; Killaspy, Helen; Craig, Tom K J; Lewis, Shôn; Keown, Patrick; Ismail, Shajahan; Crawford, Mike; Baldwin, David; Lewis, Glyn; Geddes, John; Kumar, Manoj; Pathak, Rudresh; Taylor, Simon

2016-04-01

follow-up in either the health economics outcomes or costs, and no differences in the frequency or severity of adverse effects, including corrected QT interval prolongation. The trial under-recruited, partly because cardiac safety concerns about citalopram were raised, with the 62 participants recruited falling well short of the target recruitment of 358. Although this was the largest sample randomised to citalopram in a randomised controlled trial of antidepressant augmentation for negative symptoms of schizophrenia and had the longest follow-up, the power of statistical analysis to detect significant differences between the active and placebo groups was limited. Although adjunctive citalopram did not improve negative symptoms overall, there was evidence of some positive effect on avolition/amotivation, recognised as a critical barrier to psychosocial rehabilitation and achieving better social and community functional outcomes. Comprehensive assessment of side-effect burden did not identify any serious safety or tolerability issues. The addition of citalopram as a long-term prescribing strategy for the treatment of negative symptoms may merit further investigation in larger studies. Further studies of the viability of adjunctive antidepressant treatment for negative symptoms in schizophrenia should include appropriate safety monitoring and use rating scales that allow for evaluation of avolition/amotivation as a discrete negative symptom domain. Overcoming the barriers to recruiting an adequate sample size will remain a challenge. European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2009-009235-30 and Current Controlled Trials ISRCTN42305247. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 29. See the NIHR Journals Library website for further project information.

Human chorionic gonadotrophin and weight loss. A double-blind, placebo-controlled trial.

PubMed

Bosch, B; Venter, I; Stewart, R I; Bertram, S R

1990-02-17

Low-dose human chorionic gonadotrophin (HCG) combined with a severe diet remains a popular treatment for obesity, despite equivocal evidence of its effectiveness. In a double-blind, placebo-controlled study, the effects of HCG on weight loss were compared with placebo injections. Forty obese women (body mass index greater than 30 kg/m2) were placed on the same diet supplying 5,000 kJ per day and received daily intramuscular injections of saline or HCG, 6 days a week for 6 weeks. A psychological profile, hunger level, body circumferences, a fasting blood sample and food records were obtained at the start and end of the study, while body weight was measured weekly. Subjects receiving HCG injections showed no advantages over those on placebo in respect of any of the variables recorded. Furthermore, weight loss on our diet was similar to that on severely restricted intake. We conclude that there is no rationale for the use of HCG injections in the treatment of obesity.

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

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

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

Escitalopram in the treatment of adolescent depression: a randomized, double-blind, placebo-controlled extension trial.

PubMed

Findling, Robert L; Robb, Adelaide; Bose, Anjana

2013-09-01

The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Adolescents (12-17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10-20 mg versus placebo could enroll in a 16-24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥ 40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤ 2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤ 28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥ 5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were mild/moderate and not related to the study

Effects of daily treatment with citicoline: A double-blind, placebo-controlled study in cocaine-dependent volunteers

PubMed Central

Licata, S.C.; Penetar, D. M.; Ravichandran, C.; Rodolico, J.; Palmer, C.; Berko, J.; Geaghan, T.; Looby, A.; Peters, E.; Ryan, E.; Renshaw, P.F.; Lukas, S.E.

2011-01-01

Many pharmacotherapies for treating cocaine dependence are aimed at reducing drug effects, alleviating craving, and/or preventing relapse. We demonstrated previously that citicoline, a compound used to repair neuronal damage in stroke and brain injury, is safe in cocaine-abusing volunteers. Objectives This study assessed the effectiveness of an eight-week citicoline treatment period and four-week follow-up in cocaine-dependent individuals. Methods Twenty-nine healthy non-treatment-seeking cocaine-dependent male and female volunteers were randomized in this double-blind, placebo-controlled study, eighteen of whom completed the treatment period of the study. Participants took citicoline (500 mg b.i.d) or matched placebo each day, and recorded measures of craving and drug use. Participants visited the laboratory twice a week for urine screens, as well as to attend weekly group therapy sessions. Results Citicoline had no effect on cocaine craving or total use. Conclusions While the current preliminary results from this small trial suggest that citicoline is not an effective treatment for heavy cocaine users, further investigation of citicoline’s efficacy as a treatment for substance dependence in other settings may be warranted. PMID:21769048

Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study.

PubMed

Ditscheid, B; Fünfstück, R; Busch, M; Schubert, R; Gerth, J; Jahreis, G

2005-06-01

The essential amino acid L-methionine is a potential compound in the prophylaxis of recurrent or relapsing urinary tract infection due to acidification of urine. As an intermediate of L-methionine metabolism, homocysteine is formed. The objective was to study the metabolism of L-methionine and homocysteine, and to assess whether there are differences between patients with chronic urinary tract infection and healthy control subjects. A randomized placebo-controlled double-blind intervention study with cross-over design. Department of Nutritional Physiology, Institute of Nutrition in cooperation with the Department of Internal Medicine III, Friedrich Schiller University of Jena, Germany. Eight female patients with chronic urinary tract infection and 12 healthy women (controls). After a methionine-loading test, the volunteers received 500 mg L-methionine or a placebo three times daily for 4 weeks. Serum and urinary concentrations of methionine, homocysteine, cystathionine, cystine, serine, glycine and serum concentrations of vitamin B12, B6 and the state of folate. Homocysteine plasma concentrations increased from 9.4+/-2.7 micromol/l (patients) and 8.9+/-1.8 micromol/l (controls) in the placebo period to 11.2+/-4.1 micromol/l (P=0.031) and 11.0+/-2.3 micromol/l (P=0.000), respectively, during L-methionine supplementation. There were significant increases in serum methionine (53.6+/-22.0 micromol/l; P=0.003; n=20) and cystathionine (0.62+/-0.30 micromol/l; P=0.000; n=20) concentrations compared with the placebo period (33.0+/-12.0 and 0.30+/-0.10 micromol/l; n=20). Simultaneously, renal excretion of methionine and homocysteine was significantly higher during L-methionine intake. Despite an adequate vitamin status, the supplementation of 1500 mg of L-methionine daily significantly increases homocysteine plasma concentrations by an average of 2.0 micromol/l in patients and in control subjects. An optimal vitamin supplementation, especially with folate, might prevent

A renewed, ethical defense of placebo-controlled trials of new treatments for major depression and anxiety disorders.

PubMed

Dunlop, B W; Banja, J

2009-06-01

The use of placebo as a control condition in clinical trials of major depressive disorder and anxiety disorders continues to be an area of ethical concern. Typically, opponents of placebo controls argue that they violate the beneficent-based, "best proven diagnostic and therapeutic method" that the original Helsinki Declaration of 1964 famously asserted participants are owed. A more consequentialist, oppositional argument is that participants receiving placebo might suffer enormously by being deprived of their usual medication(s). Nevertheless, recent findings of potential for suicidality in young people treated with antidepressants, along with meta-analyses suggesting that antidepressants add no significant clinical benefit over placebos, warrant a re-evaluation of the arguments against placebo. Furthermore, the nature of placebo treatment in short-term clinical trials is often not well understood, and lack of understanding can foster opposition to it. This paper will show how scientific justifications for placebo use are morally relevant. The fundamental ethical importance of placebo controls is discussed in relation to several aspects of clinical trials, including detection of adverse events, accurate assessment of clinical benefit, advancing understanding of the heterogeneity of depression and anxiety disorders and respecting informed consent requirements. Prohibiting the use of placebo controls is morally concerning in that such prohibitions allow for the possibility of serious adverse public health consequences. Moral worries that research participants receiving placebo are being unduly jeopardised will be shown to be exaggerated, especially in relation to the net benefits for end-users to be gained from the quality of data resulting from using placebo controls.

Long-Term Nightly Treatment with Indiplon in Adults with Primary Insomnia: Results of a Double-Blind, Placebo-Controlled, 3-Month Study

PubMed Central

Scharf, Martin B.; Black, Jed; Hull, Steven; Landin, Rick; Farber, Robert

2007-01-01

Objectives: To evaluate the efficacy and safety of indiplon in primary insomnia. Design: Randomized, double-blind, placebo-controlled, 3-month study. Setting: Multi-center outpatient setting. Patients: N=702 (61% female; mean age 46 years) who met DSM-IV criteria for primary insomnia of at least 3 months' duration. Interventions: Indiplon 10 mg (n=236), indiplon 20 mg (n=233), or placebo (n=233). Measurements: Subjective assessment of each of the following: latency to sleep onset (sLSO), total sleep time (sTST), number of awakenings after sleep onset (sNAASO), wake time after sleep onset (sWASO), sleep quality, Insomnia Severity Index (ISI), and global improvement. Results: Treatment with indiplon resulted in significant improvement relative to placebo at all time points for the primary endpoint, sLSO. Mean sLSO at Month 1 for each treatment group was: 10 mg (34.0 ± 1.3 mins), 20 mg (33.0 ± 1.3 mins), and placebo (48.7 ± 1.9 mins; P <0.0001 for both comparisons); efficacy was sustained through Month 3. Both doses of indiplon resulted in significant improvement in sleep maintenance and duration endpoints, sTST and sWASO, as well as sleep quality, ISI, and global improvement at all assessment time points. Conclusions: In patients with chronic insomnia, long-term nightly treatment with 10 mg and 20 mg doses of indiplon resulted in significant and sustained efficacy in sleep onset, maintenance, and duration, and significant associated improvement in both daytime functioning and quality of life. Citation: Scharf MB; Black J; Hull S et al. Long-term nightly treatment with indiplon in adults with primary insomnia: Results of a double-blind, placebo-controlled, 3-month study. SLEEP 2007;30(6):743-752. PMID:17580596

Rotigotine transdermal patch in Chinese patients with early Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study.

PubMed

Zhang, Zhen-Xin; Shang, Hui-Fang; Hu, Xingyue; Chen, Shengdi; Zhao, Zhongxin; Du, Xinlu; Surmann, Erwin; Bauer, Lars; Asgharnejad, Mahnaz

2016-07-01

Two phase3 studies (SP512; SP513) involving mostly Caucasian patients showed that rotigotine (≤8 mg/24 h) was efficacious and welltolerated in early-stage Parkinson's disease (PD). We report results from a phase 3 study (SP0914/NCT01646268) investigating rotigotine in Chinese patients with early-stage PD. Patients were randomized 1:1 to rotigotine or placebo, titrated over 1-4 weeks, maintained at optimal/maximum dose (≤8 mg/24 h) for 24 weeks. Primary efficacy variable: change in Unified Parkinson's Disease Rating Scale (UPDRS) II + III total score from Baseline to End-of-Maintenance. Secondary variables: UPDRS II + III responders (≥20% decrease in UPDRS II + III) and changes in UPDRS II (activities of daily living [ADL]) and III (motor examination) subscores. Of 247 patients randomized, 113/124 (91.1%) rotigotine- and 107/123 (87.0%) placebo-treated patients completed the study. mean (SD) age: 59.4 (10.2) years; time since PD diagnosis: 1.01 (1.22) years, 60.7% male. Rotigotine significantly improved UPDRS II + III total score (change from Baseline LSmean [95%CI] treatment difference, -4.82 [-7.18 to -2.45]; P < 0.0001). UPDRS II + III responder rates were higher with rotigotine (42.3% vs 22.3%; P = 0.0006). UPDRS II and III subscores improved with rotigotine (both subscores: P < 0.0005 vs. placebo). Most frequent adverse events (AEs): nausea (8.9% rotigotine, 3.3% placebo), dizziness (8.1%, 5.7%), pruritus (8.1%, 4.1%), somnolence (8.1%, 3.3%), erythema (6.5%, 1.6%), and vomiting (5.6%, 1.6%). Thirteen (5.3%) patients discontinued due to AEs (6 rotigotine, 7 placebo). Rotigotine was efficacious in Chinese patients with early-stage PD, providing benefits to control of ADL and motor function. Rotigotine was generally welltolerated, with similar AEs to those observed in Caucasian patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Systematic review of quality of life and functional outcomes in randomized placebo-controlled studies of medications for attention-deficit/hyperactivity disorder.

PubMed

Coghill, David R; Banaschewski, Tobias; Soutullo, César; Cottingham, Matthew G; Zuddas, Alessandro

2017-11-01

Children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) experience functional impairment and poor health-related quality of life (HRQoL) in addition to symptoms of inattention/hyperactivity-impulsivity. To synthesize qualitatively the published evidence from randomized, double-blind, placebo-controlled trials of the effectiveness of pharmacotherapy on functional impairment or HRQoL in patients with ADHD, a systematic PubMed searching and screening strategy was designed to identify journal articles meeting pre-specified criteria. Post hoc analyses and meta-analyses were excluded. HRQoL outcomes, functional outcomes and the principal ADHD symptom-based outcome were extracted from included studies. An effect size of 0.5 versus placebo was used as a threshold for potential clinical relevance (unreported effect sizes were calculated when possible). Of 291 records screened, 35 articles describing 34 studies were included. HRQoL/functioning was usually self-rated in adults and proxy-rated in children/adolescents. Baseline data indicated substantial HRQoL deficits in children/adolescents. Placebo-adjusted effects of medication on ADHD symptoms, HRQoL and functioning, respectively, were statistically or nominally significant in 18/18, 10/12 and 7/9 studies in children/adolescents and 14/16, 9/11 and 9/10 studies in adults. Effect sizes were ≥0.5 versus placebo for symptoms, HRQoL and functioning, respectively, in 14/16, 7/9 and 4/8 studies in children/adolescents; and 6/12, 1/6 and 1/8 studies in adults. Effect sizes were typically larger for stimulants than for non-stimulants, for symptoms than for HRQoL/functioning, and for children/adolescents than for adults. The efficacy of ADHD medication extends beyond symptom control and may help reduce the related but distinct functional impairments and HRQoL deficits in patients with ADHD.

Suspected Nonceliac Gluten Sensitivity Confirmed in Few Patients After Gluten Challenge in Double-Blind, Placebo-Controlled Trials.

PubMed

Molina-Infante, Javier; Carroccio, Antonio

2017-03-01

A double-blind, placebo-controlled, gluten challenge has been proposed to confirm a diagnosis of nonceliac gluten sensitivity (NCGS) in patients without celiac disease who respond to a gluten-free diet. To determine the accuracy of this approach, we analyzed data from 10 double-blind, placebo-controlled, gluten-challenge trials, comprising 1312 adults. The studies varied in the duration of the challenge (range, 1 d to 6 wk), daily doses for the gluten challenge (range, 2-52 g; 3 studies administered <8 g/d), and composition of the placebo (gluten-free products, xylose, whey protein, rice, or corn starch containing fermentable carbohydrates). Most of the studies found gluten challenge to significantly increase symptom scores compared with placebo. However, only 38 of 231 NCGS patients (16%) showed gluten-specific symptoms. Furthermore, 40% of these subjects had a nocebo response (similar or increased symptoms in response to placebo). These findings reveal heterogeneity and potential methodology flaws among studies of gluten challenge, cast doubt on gluten as the culprit food component in most patients with presumptive NCGS, and highlight the importance of the nocebo effect in these types of studies. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Placebo effects in psychiatry: mediators and moderators

PubMed Central

Weimer, Katja; Colloca, Luana; Enck, Paul

2015-01-01

A strong placebo response in psychiatric disorders has been noted for the past 50 years and various attempts have been made to identify predictors of it, by use of meta-analyses of randomised controlled trials and laboratory studies. We reviewed 31 meta-analyses and systematic reviews of more than 500 randomised placebo-controlled trials across psychiatry (depression, schizophrenia, mania, attention-deficit hyperactivity disorder, autism, psychosis, binge-eating disorder, and addiction) for factors identified to be associated with increased placebo response. Of 20 factors discussed, only three were often linked to high placebo responses: low baseline severity of symptoms, more recent trials, and unbalanced randomisation (more patients randomly assigned to drug than placebo). Randomised controlled trials in non-drug therapy have not added further predictors, and laboratory studies with psychological, brain, and genetic approaches have not been successful in identifying predictors of placebo responses. This comprehensive Review suggests that predictors of the placebo response are still to be discovered, the response probably has more than one mediator, and that different and distinct moderators are probably what cause the placebo response within psychiatry and beyond. PMID:25815249

Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study.

PubMed

Libov, Igor; Miodownik, Chanoch; Bersudsky, Yuly; Dwolatzky, Tzvi; Lerner, Vladimir

2007-07-01

Piracetam is a potent antioxidant, a cerebral neuroprotector, a neuronal metabolic enhancer, and a brain integrative agent. More than 20 years ago, an intravenous preparation of piracetam demonstrated an improvement in the symptoms of tardive dyskinesia. The aim of our study was to reexamine the efficacy of piracetam in the treatment of tardive dyskinesia using an oral preparation. The study was conducted at the Be'er Sheva Mental Health Center from May 2003 to December 2004 and involved a 9-week, double-blind, crossover, placebo-controlled trial assessing 40 DSM-IV schizophrenic and schizo-affective patients with DSM-IV-TR tardive dyskinesia. All study subjects received their usual antipsychotic treatment. Initially, subjects were randomly assigned to receive 4 weeks of treatment with either piracetam (4800 mg/day) or placebo. Thereafter, following a washout period of 1 week, they entered the crossover phase of the study for a further 4 weeks. The change in score of the Extrapyramidal Symptom Rating Scale from baseline to the study endpoint was the primary outcome measure. The mean decrease in score from baseline to endpoint in the clinical global impression subscale in patients treated with piracetam was 1.1 points compared to 0.1 points in the placebo group (p = .004). The mean decrease in the tardive parkinsonism subscale was 8.7 points in patients treated with piracetam and 0.6 points in those on placebo (p = .001). The mean decrease in the tardive dyskinesia subscale was 3.0 points in the piracetam group in contrast to deterioration of condition in the placebo group by -0.2 points (p = .003). Piracetam appears to be effective in reducing symptoms of tardive dyskinesia. The specific mechanism by which piracetam may attenuate symptoms of tardive dyskinesia needs to be further evaluated. ClinicalTrials.gov identifier NCT00190008.

Rhodiola rosea therapy for major depressive disorder: a study protocol for a randomized, double-blind, placebo- controlled trial

PubMed Central

Mao, Jun J; Li, Qing S.; Soeller, Irene; Xie, Sharon X; Amsterdam, Jay D.

2014-01-01

Background Rhodiola rosea (R. rosea), a botanical of both western and traditional Chinese medicine, has been used as a folk remedy for improving stamina and reducing stress. However, few controlled clinical trials have examined the safety and efficacy of R. rosea for the treatment of major depressive disorder (MDD). This study seeks to evaluate the safety and efficacy of R. rosea in a 12-week, randomized, double-blind, placebo-controlled, parallel group study design. Methods / Design Subjects with MDD not receiving antidepressant therapy will be randomized to either R. rosea extract 340–1,360 mg daily; sertraline 50–200 mg daily, or placebo for 12 weeks. The primary outcome measure will be change over time in the mean 17-item Hamilton Depression Rating score. Secondary outcome measures will include safety and quality of life ratings. Statistical procedures will include mixed-effects models to assess efficacy for primary and secondary outcomes. Discussion This study will provide valuable preliminary information on the safety and efficacy data of R. rosea versus conventional antidepressant therapy of MDD. It will also inform additional hypotheses and study design of future, fully powered, phase III clinical trials with R. rosea to determine its safety and efficacy in MDD. PMID:25610752

Importance of placebo effect in cough clinical trials.

PubMed

Eccles, Ron

2010-01-01

Cough is a unique symptom because, unlike sneeze and other symptoms, it can be under voluntary control and this complicates clinical trials on cough medicines. All over-the-counter cough medicines (OTC) are very effective treatments because of their placebo effect. The placebo effect is enhanced by expectancy related to advertising, brand, packaging, and formulation. This placebo effect creates a problem for the conduct of clinical trials on OTC cough medicines that attempt to demonstrate the efficacy of a pharmacological agent above that of any placebo effect. Up to 85% of the efficacy of some cough medicines can be attributed to a placebo effect. The placebo effect apparent in clinical trials consists of several components: natural recovery, regression of cough response toward mean, demulcent effect, effect of sweetness, voluntary control, and effects related to expectancy and meaning of the treatment. The placebo effect has been studied most in the pain model, and placebo analgesia is reported to depend on the activation of endogenous opioid systems in the brain; this model may be applicable to cough. A balanced placebo design may help to control for the placebo effect, but this trial design may not be acceptable due to deception of patients. The placebo effect in clinical trials may be controlled by use of a crossover design, where feasible, and the changes in the magnitude of the placebo effect in this study design are discussed.

Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study*

PubMed Central

Rzany, B; Griffiths, T; Walker, P; Lippert, S; McDiarmid, J; Havlickova, B

2014-01-01

Summary Background Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation. Objectives To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF. Methods In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm−2) or placebo injections into their SMF at up to four treatment sessions ∽28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored. Results Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm−2, respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS;P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS;P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area. Conclusions ATX-101 was effective and well tolerated for nonsurgical SMF reduction. What's already known about this topic? Unwanted submental fat (SMF) is considered aesthetically unappealing. Liposuction and face-lift are effective treatments for SMF reduction but are

Efficacy and safety of diclofenac diethylamine 1.16% gel in acute neck pain: a randomized, double-blind, placebo-controlled study.

PubMed

Predel, Hans-Georg; Giannetti, Bruno; Pabst, Helmut; Schaefer, Axel; Hug, Agnes M; Burnett, Ian

2013-08-21

Neck pain (NP) is a common musculoskeletal disorder in primary care that frequently causes discomfort. Non-steroidal anti-inflammatory drugs (NSAIDs) may be used to reduce neck pain and associated inflammation and facilitate earlier recovery. Topical diclofenac diethylamine (DDEA) 1.16% gel is clinically proven to be effective and well tolerated in acute and chronic musculoskeletal conditions, but until now no clinical data existed for its use in acute NP. The aim of this study was to assess the efficacy and safety of DDEA 1.16% gel compared with placebo gel in acute NP. In a randomized, double-blind, placebo-controlled study, patients with acute NP (n = 72) were treated with DDEA 1.16% gel (2 g, 4x/day, for 5 days) or placebo. Efficacy assessments included pain-on-movement (POM), pain-at-rest (PAR), functional neck disability index (NDI) and response to treatment (decrease in POM by 50% after 48 h). Adverse events (AEs) were recorded throughout the study. The primary outcome, POM at 48 h, was statistically significantly lower with DDEA gel (19.5 mm) vs. placebo (56.9 mm) (p < 0.0001), representing a clinically relevant decrease from baseline (75% vs. 23%, respectively). All POM scores were significantly lower with DDEA gel vs. placebo from 1 h, as were PAR and NDI scores from first assessment (24 h) onwards (all p < 0.0001). Response to treatment was significantly higher with DDEA gel (94.4%) vs. placebo (8.3%) (p < 0.0001). There were no AEs with DDEA gel. DDEA 1.16% gel, which is available over-the-counter, was effective and well tolerated in the treatment of acute neck pain. The tools used to assess efficacy suggest that it quickly reduced neck pain and improved neck function. However, questions remain regarding the comparability and validity of such tools. Further studies will help ascertain whether DDEA 1.16% gel offers an alternative treatment option in this common, often debilitating condition. ClinicalTrials.gov identifier: NCT

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.

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

Randomized placebo-controlled study of baclofen in the treatment of muscle cramps in patients with liver cirrhosis.

PubMed

Elfert, Asem A; Abo Ali, Lobna; Soliman, Samah; Zakaria, Sherin; Shehab El-Din, Ibrahim; Elkhalawany, Walaa; Abd-Elsalam, Sherief

2016-11-01

Muscle cramps adversely influence the quality of life of patients with liver cirrhosis. Indeed, to date, a well-established therapy for this complication is still lacking. This is the first randomized placebo-controlled trial of baclofen in the treatment of muscle cramps in patients with liver cirrhosis. A total of 100 patients with liver cirrhosis and muscle cramps signed an informed consent to participate in this study. They were recruited from the Department of Tropical Medicine-Tanta University Hospital. They were randomized to receive either baclofen or placebo for 3 months. Patients were followed monthly and 1 month after withdrawal. At each visit, the clinicoepidemiological data were recorded, the muscle cramp questionnaire was filled, and any drug-related side effects were reported. In the baclofen group, the frequency of muscle cramps decreased significantly after 1 and 3 months of treatment (P<0.005), with a significant relapse after withdrawal (P<0.001). Patients receiving baclofen showed a significant decrease in the severity and duration of muscle cramps (P<0.001). After 3 months of baclofen therapy at a dose of 30 mg/day, muscle cramps disappeared completely in 72%, reduced in 20%, and led to no change in 8% of patients. No significant changes in the frequency, severity, and duration of muscle cramps were noted in the placebo group. There were few but nonsignificant side effects in the baclofen group compared with the placebo group. Baclofen was well tolerated, safe, and effective in the treatment of muscle cramps in patients with liver cirrhosis.

[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.

Randomized study of placebo and framing information in direct-to-consumer print advertisements for prescription drugs.

PubMed

O'Donoghue, Amie C; Sullivan, Helen W; Aikin, Kathryn J

2014-12-01

Research suggests that quantitative information in direct-to-consumer (DTC) prescription drug ads may be helpful for consumers. The objective was to examine the effect of adding placebo rates and framing to DTC ads. In study 1, 2,000 Internet panel members with chronic pain participated in a randomized controlled experiment of DTC ads varying in placebo rate and framing. In study 2, 596 physicians ranked DTC ads varying in placebo rate and framing by how well they conveyed scientific information and their usefulness for patients. In study 1, participants who viewed placebo rates were able to recall them and use them to form certain perceptions. A mixed frame led to lower placebo rate recall and perceived efficacy. In study 2, overall, physicians preferred a placebo/single frame ad. Adding placebo rates to DTC ads may be useful for consumers. The evidence does not support using a mixed frame.

Nicergoline in mild to moderate dementia. A multicenter, double-blind, placebo-controlled study.

PubMed

Battaglia, A; Bruni, G; Ardia, A; Sacchetti, G

1989-04-01

In view of some controversies still existing about the real efficacy of ergot derivatives in the management of dementia, a double-blind, randomized, parallel group trial extending up to 6 months was carried out to compare the effects of nicergoline, 60 mg daily, and placebo in 315 patients suffering from mild to moderate dementia. Clinical evaluation was performed by the SCAG scale. The trial, which included a 1-month placebo run-in period, showed that both placebo and nicergoline were associated with some degree of improvement. The effect of nicergoline, however, was significantly greater and more sustained, steadily increasing with time. In particular, the difference between nicergoline and placebo in mean total SCAG score was 5.5 at 3 months (95% confidence interval: 3.6-7.4) and increased to 9.8 at 6 months (95% confidence interval: 7.8-11.8). A comparison of nicergoline versus placebo in the frequencies of changes in each item of the SCAG showed also a significant difference at 6 months, the percent of patients displaying an improvement by at least 2 points ranging from 13.5 (bothersome) to 30.2 (disorientation) in nicergoline group, against 4.1 (self-care) to 14.3 (fatigue) in placebo group. The safety of nicergoline, as judged by hemodynamic changes and drug-related adverse reactions, was quite satisfactory.

Placebo Trends across the Border: US versus Canada.

PubMed

Harris, Cory S; Campbell, Natasha K J; Raz, Amir

2015-01-01

Physicians around the world report to using placebos in a variety of situations and with varying degrees of frequency. Inconsistent methodologies, however, complicate interpretation and prevent direct comparisons across studies. While US- and Canada-based physicians share similar professional standards, Canada harbours a less-litigious universal healthcare model with no formal placebo-related policy-factors that may impact how physicians view and use placebos. To compare American and Canadian data, we circulated an online survey to academic physicians practicing in Canada, collected anonymous responses, and extracted those of internists and rheumatologists for comparison to US data obtained through parallel methodologies. Whereas our data show overall concordance across the border-from definitions to ethical limitations and therapeutic potential-differences between American- and Canadian-based placebo practices merit acknowledgement. For example, compared to 45%-80% among US-based respondents, only 23±7% of Canada-based respondents reported using placebos in clinical practice. However, 79±7% of Canada-respondents-a figure comparable to US data-professed to prescribing at least one form of treatment without proven or expected efficacy. Placebo interventions including unwarranted vitamins and herbal supplements (impure placebos) as well as sugar pills and saline injections (pure placebos) appear more common in Canada, where more doctors described placebos as "placebos" (rather than "medications") and used them as a "diagnostic" tool (rather than a means of placating patient demands for treatment). Cross-border variation in the use of clinical placebos appears minor despite substantial differences in health care delivery system, malpractice climate, and placebo-related policy. The prevalence of impure placebos in both Canadian and US clinics raises ethical and practical questions currently unaddressed by policy and warranting investigation.

Testosterone and estrogen impact social evaluations and vicarious emotions: A double-blind placebo-controlled study.

PubMed

Olsson, Andreas; Kopsida, Eleni; Sorjonen, Kimmo; Savic, Ivanka

2016-06-01

The abilities to "read" other peoples' intentions and emotions, and to learn from their experiences, are critical to survival. Previous studies have highlighted the role of sex hormones, notably testosterone and estrogen, in these processes. Yet it is unclear how these hormones affect social cognition and emotion using acute hormonal administration. In the present double-blind placebo-controlled study, we administered an acute exogenous dose of testosterone or estrogen to healthy female and male volunteers, respectively, with the aim of investigating the effects of these steroids on social-cognitive and emotional processes. Following hormonal and placebo treatment, participants made (a) facial dominance judgments, (b) mental state inferences (Reading the Mind in the Eyes Test), and (c) learned aversive associations through watching others' emotional responses (observational fear learning [OFL]). Our results showed that testosterone administration to females enhanced ratings of facial dominance but diminished their accuracy in inferring mental states. In men, estrogen administration resulted in an increase in emotional (vicarious) reactivity when watching a distressed other during the OFL task. Taken together, these results suggest that sex hormones affect social-cognitive and emotional functions at several levels, linking our results to neuropsychiatric disorders in which these functions are impaired. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers.

PubMed

Udani, Jay K; Singh, Betsy B; Barrett, Marilyn L; Singh, Vijay J

2010-08-26

Arabinogalactan from Larch tree (Larix spp.) bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia) vaccine in healthy adults. This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against Streptococcus pneumoniae. The volunteers began taking the study product or placebo (daily dosage 4.5 g) at the screening visit (V1-Day 0) and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2). They were monitored the following day (V3-Day 31), as well as 21 days (V4-Day 51) and 42 days (V5-Day 72) after vaccination. Responses by the adaptive immune system (antigen specific) were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and salivary IgA levels. Responses by the innate immune system (non-specific) were measured via white blood cell counts, inflammatory cytokines and the complement system. Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F) at both Day 51 (p = 0.006 and p = 0.002) and at Day 72 (p = 0.008 and p = 0.041). These same subtypes (18C and 23F) also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001) and at Day 72 (p = 0.012 and p = 0.003). Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There was no effect from the vaccine or

Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers

PubMed Central

2010-01-01

Background Arabinogalactan from Larch tree (Larix spp.) bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia) vaccine in healthy adults. Methods This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against Streptococcus pneumoniae. The volunteers began taking the study product or placebo (daily dosage 4.5 g) at the screening visit (V1-Day 0) and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2). They were monitored the following day (V3-Day 31), as well as 21 days (V4-Day 51) and 42 days (V5-Day 72) after vaccination. Responses by the adaptive immune system (antigen specific) were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and salivary IgA levels. Responses by the innate immune system (non-specific) were measured via white blood cell counts, inflammatory cytokines and the complement system. Results Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F) at both Day 51 (p = 0.006 and p = 0.002) and at Day 72 (p = 0.008 and p = 0.041). These same subtypes (18C and 23F) also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001) and at Day 72 (p = 0.012 and p = 0.003). Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There was no

[Crataegus Special Extract WS 1442 in NYHA II heart failure. A placebo controlled randomized double-blind study].

PubMed

Leuchtgens, H

1993-07-20

In 30 patients with stage NYHA II cardiac insufficiency, a placebo-controlled randomized double-blind study was carried out to determine the efficacy of the Crataegus special extract WS 1442. Treatment duration was 8 weeks, and the substance was administered at a dose of 1 capsule taken twice a day. The main target parameters were alteration in the pressure-x-rate product (PRP) under standardised loading on a bicycle ergometer, and a score of subjective improvement of complaints elicited by a questionnaire. Secondary parameters were exercise tolerance and the change in heart rate and arterial blood pressure. The active substance group showed a statistically significant advantage over placebo in terms of changes in PRP (at a load of 50 W) and the score, but also in the secondary parameter heart rate. In both groups, systolic and diastolic blood pressure was mildly reduced. No adverse reactions occurred.

Phase I, randomized, double-blind, placebo-controlled, multiple intravenous, dose-ascending study of sirukumab in cutaneous or systemic lupus erythematosus.

PubMed

Szepietowski, Jacek C; Nilganuwong, Surasak; Wozniacka, Anna; Kuhn, Annegret; Nyberg, Filippa; van Vollenhoven, Ronald F; Bengtsson, Anders A; Reich, Adam; de Vries, Dick E; van Hartingsveldt, Bart; Robinson, Donald W; Gordon, Robert; Hsu, Benjamin

2013-10-01

We undertook a 2-part, phase I, double-blind, placebo-controlled study to evaluate the safety and pharmacokinetics of multiple intravenous infusions of sirukumab, a human anti-interleukin-6 monoclonal antibody, in patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE). In part A, patients with histologically confirmed CLE were randomized to 4 infusions of placebo or 1, 4, or 10 mg/kg sirukumab every 2 weeks. In part B, SLE patients diagnosed according to American College of Rheumatology criteria with a score of 5-12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index were randomized to 4 infusions of placebo or 10 mg/kg sirukumab every 2 weeks. We treated 31 CLE patients (23 with sirukumab, 8 with placebo) and 15 SLE patients (10 with sirukumab, 5 with placebo). Adverse events (AEs) occurred more often with sirukumab than placebo in CLE patients (91% versus 63%) and in SLE patients (90% versus 80%). Sirukumab led to sustained, dose-independent decreases in white blood cell counts, absolute neutrophil counts (neutropenia), and platelet counts (thrombocytopenia) and to minor elevations in total cholesterol levels. The majority of infections were mild respiratory infections. which were reported similarly across CLE cohorts but more often in sirukumab-treated than in placebo-treated SLE patients. Two serious AEs of infection occurred (pneumonia in the 10 mg/kg-treated group and iatrogenic wound infection in the 4 mg/kg-treated group). Sirukumab showed linear pharmacokinetics in CLE patients. Systemic exposure and half-life were comparable between CLE and SLE patients. No patient developed antibodies to sirukumab through 22 weeks. C-reactive protein and serum amyloid A mean concentrations were suppressed with sirukumab from week 1 to week 14. Treatment with intravenous sirukumab infusions was generally well tolerated in both CLE and SLE patients with mild, stable, active disease

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.

HT1001, a proprietary North American ginseng extract, improves working memory in schizophrenia: a double-blind, placebo-controlled study.

PubMed

Chen, Eric Y H; Hui, Christy L M

2012-08-01

Evidence suggests that HT1001™, a proprietary North American ginseng extract containing known levels of active ginsenosides, may improve cognitive function. Importantly, individuals with schizophrenia show marked deficits in working memory, which are believed to be predictive of functional outcome in this population. The present study aimed to characterize the effect of HT1001 on working memory in a group of stable individuals with schizophrenia. In a double-blind, placebo-controlled study design, a total of 64 individuals satisfying DSM-IV criteria for schizophrenia were randomly assigned to receive either HT100 or placebo for 4 weeks. Verbal working memory and visual working memory were assessed at baseline and again at the end of the treatment phase using the Letter-Number Span Test and Visual Pattern Test, respectively. Symptoms and medication side effects were also measured at baseline and post-treatment. Visual working memory was significantly improved in the HT1001 group, but not in the placebo group. Furthermore, extrapyramidal symptoms were significantly reduced after 4 weeks treatment with HT1001, whereas no difference in extrapyramidal effects was observed in the placebo group. These results provide a solid foundation for the further investigation of HT1001 as an adjunct therapy in schizophrenia, as an improvement in working memory and a reduction in medication-related side effects has considerable potential to improve functional outcome in this population. Copyright © 2011 John Wiley & Sons, Ltd.

Pharmacologic Modulation of Hand Pain in Osteoarthritis: A Double-Blind Placebo-Controlled Functional Magnetic Resonance Imaging Study Using Naproxen

PubMed Central

Sanders, Duncan; Krause, Kristina; O'Muircheartaigh, Jonathan; Thacker, Michael A; Huggins, John P; Vennart, William; Massat, Nathalie J; Choy, Ernest; Williams, Steven C R; Howard, Matthew A

2015-01-01

Objective In an attempt to shed light on management of chronic pain conditions, there has long been a desire to complement behavioral measures of pain perception with measures of underlying brain mechanisms. Using functional magnetic resonance imaging (fMRI), we undertook this study to investigate changes in brain activity following the administration of naproxen or placebo in patients with pain related to osteoarthritis (OA) of the carpometacarpal (CMC) joint. Methods A placebo-controlled, double-blind, 2-period crossover study was performed in 19 individuals with painful OA of the CMC joint of the right hand. Following placebo or naproxen treatment periods, a functionally relevant task was performed, and behavioral measures of the pain experience were collected in identical fMRI examinations. Voxelwise and a priori region of interest analyses were performed to detect between-period differences in brain activity. Results Significant reductions in brain activity following treatment with naproxen, compared to placebo, were observed in brain regions commonly associated with pain perception, including the bilateral primary somatosensory cortex, thalamus, and amygdala. Significant relationships between changes in perceived pain intensity and changes in brain activity were also observed in brain regions previously associated with pain intensity. Conclusion This study demonstrates the sensitivity of fMRI to detect the mechanisms underlying treatments of known efficacy. The data illustrate the enticing potential of fMRI as an adjunct to self-report for detecting early signals of efficacy of novel therapies, both pharmacologic and nonpharmacologic, in small numbers of individuals with persistent pain. PMID:25533872

The Effects of Soy Supplementation on Gene Expression in Breast Cancer: A Randomized Placebo-Controlled Study

PubMed Central

Doane, Ashley S.; Russo, Lianne; Cabal, Rafael; Reis-Filho, Jorge S.; Gerald, William; Cody, Hiram; Khanin, Raya; Bromberg, Jacqueline; Norton, Larry

2014-01-01

Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomly assigned to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString in pre- and posttreatment tumor tissue. Genome-wide expression analysis was performed on posttreatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and posttreatment samples, 21 genes (out of 202) showed altered expression (two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2-fold) of cell cycle transcripts, including those that promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein defines a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer. PMID:25190728

Randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis

PubMed Central

Siriwardena, Ajith K; Mason, James M; Balachandra, Srinivasan; Bagul, Anil; Galloway, Simon; Formela, Laura; Hardman, Jonathan G; Jamdar, Saurabh

2007-01-01

Background Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. Methods We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty‐three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE‐II score and hospital site, and delivered groups that were similar at baseline. Results Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. Conclusions This study provides no evidence to justify continued use of n‐acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study. PMID:17356040

Why does choice enhance treatment effectiveness? Using placebo treatments to demonstrate the role of personal control.

PubMed

Geers, Andrew L; Rose, Jason P; Fowler, Stephanie L; Rasinski, Heather M; Brown, Jill A; Helfer, Suzanne G

2013-10-01

In modern health care, individuals frequently exercise choice over health treatment alternatives. A growing body of research suggests that when individuals choose between treatment options, treatment effectiveness can increase, although little experimental evidence exists clarifying this effect. Four studies were conducted to test the hypothesis that exercising choice over treatment alternatives enhances outcomes by providing greater personal control. Consistent with this possibility, in Study 1 individuals who chronically desired control reported less pain from a laboratory pain task when they were able to select between placebo analgesic treatments. Study 2 replicated this finding with an auditory discomfort paradigm. In Study 3, the desire for control was experimentally induced, and participants with high desire for control benefited more from a placebo treatment when they were able to choose their treatment. Study 4 revealed that the benefit of choice on treatment efficacy was partially mediated by thoughts of personal control. This research suggests that when individuals desire control, choice over treatment alternatives improves treatment effectiveness by enhancing personal control.

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.

Salivary antioxidants of male athletes after aerobic exercise and garlic supplementation on: A randomized, double blind, placebo-controlled study.

PubMed

Damirchi, Arsalan; Saati Zareei, Alireza; Sariri, Reyhaneh

2015-01-01

Production of reactive oxygen species and reactive nitrogen species is a natural biological event in metabolism. However, the presence of antioxidants can highly reduce the negative effect of free radicals. Thus, the efficiency of antioxidant system in the physiology of exercise is very important. Considering the known antioxidant capacity of garlic, the purpose of this study was to evaluate the effect on combining 14 days aerobic exercise till exhaustion with garlic extract supplementation on the antioxidant capacity of saliva. Sixteen young men volunteered to participate in this randomized, double blind, placebo-controlled study and were randomly placed into two groups, placebo (Group I) and garlic extract (Group II). The participants performed exhaustive aerobic exercise on a treadmill before and after supplementation. Their unstimulated salivary samples were collected before, immediately after, and 1 h after the activity. The antioxidant activity in terms of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) was then measured in the collected samples using their specific substrates. A significant increase in salivary antioxidant activity of SOD, POD, and CAT was observed in saliva of the supplement group compared to the placebo group (P ≤ 0.05). The findings from this study suggest that increased activity of antioxidant enzymes could possibly decrease exercise-induced oxidative damage in male athletes.

Phytoestrogens/insoluble fibers and colonic estrogen receptor β: Randomized, double-blind, placebo-controlled study

PubMed Central

Principi, Mariabeatrice; Di Leo, Alfredo; Pricci, Maria; Scavo, Maria Principia; Guido, Raffaella; Tanzi, Sabina; Piscitelli, Domenico; Pisani, Antonio; Ierardi, Enzo; Comelli, Maria Cristina; Barone, Michele

2013-01-01

AIM: To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS: A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS: No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69 vs 37.708 ± 5.31, P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13, P = 0.04), mRNA (2.278 ± 1.19 vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67, P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06 vs 0.532 ± 0.11, P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION: The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study. PMID:23885143

Single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery: a meta-analysis of randomised placebo-controlled studies

PubMed Central

Wang, Yi-lun; Zeng, Chao; Xie, Dong-xing; Yang, Ye; Wei, Jie; Yang, Tuo; Li, Hui; Lei, Guang-hua

2015-01-01

Objectives To evaluate the efficacy and safety of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery. Design Meta-analysis. Data sources and study eligibility criteria A comprehensive literature search, using Medline (1966–2014), the Cochrane Central Register of Controlled Trials and Embase databases, was conducted to identify randomised placebo-controlled trials that used a combination of single-dose intra-articular bupivacaine and morphine for postoperative pain relief. Results 12 articles were included in this meta-analysis. The mean visual analogue scale (VAS) scores of the bupivacaine plus morphine group were significantly lower than those of the placebo group (weighted mean difference (WMD) −1.75; 95% CI −2.16 to −1.33; p<0.001). The VAS scores at the last follow-up time point (last VAS scores) of the bupivacaine plus morphine group were also significantly lower than those of the placebo group (WMD −1.46; 95% CI −1.63 to −1.29; p<0.001). The number of patients requiring supplementary analgesia was also significantly reduced (RR 0.60; 95% CI 0.39 to 0.93; p=0.02), while there was no significant difference in the time to first analgesic request (WMD 3.46; 95% CI −1.81 to 8.72; p=0.20) or short-term side effects (RR 1.67; 95% CI 0.65 to 4.26; p=0.29). Conclusions The administration of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery is effective for pain relief, and its short-term side effects remain similar to saline placebo. PMID:26078306

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: first results of ETAC. Early Treatment of the Atopic Child.

PubMed

1998-08-01

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (> or = 30 kU/l) or specific IgE (> or = 0.35 kUA/l) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the

Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study.

PubMed

Diamond, Michael P; Carr, Bruce; Dmowski, W Paul; Koltun, William; O'Brien, Chris; Jiang, Ping; Burke, Joshua; Jimenez, Roland; Garner, Elizabeth; Chwalisz, Kristof

2014-03-01

This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12. Monthly mean (standard error of the mean) reductions were greater with elagolix versus placebo (-1.19 ± 0.18, -1.25 ± 0.18, and -0.88 ± 0.18 for elagolix 150 mg, 250 mg, and placebo, respectively); differences were not statistically significant. Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix, with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo (P < .05). Minimal bone mineral density changes were observed with elagolix treatment. In women with endometriosis-associated pain, elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study.

Intravenous lysine clonixinate for the acute treatment of severe migraine attacks: a double-blind, randomized, placebo-controlled study.

PubMed

Krymchantowski, Abouch Valenty; Silva, Marcus Tulius T

2003-09-01

Several nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective in the treatment of migraine. However, few commercially available NSAIDs can be administered IV. Lysine clonixinate (LC), an NSAID derived from nicotinic acid, has been proved effective in various algesic syndromes (eg, renal colic, muscular pain, nerve compression, odontalgia). The oral formulation of LC has been shown to be effective in the treatment of migraine of moderate severity. The aim of this study was to assess the efficacy and tolerability of the IV formulation of LC in the treatment of severe migraine. This double-blind, randomized, placebo-controlled, prospective study enrolled patients with severe migraine (without aura) as defined by the criteria of the International Headache Society. When patients presented to a neurology hospital with an outpatient headache unit (Instituto de Neurologia Deolindo Couto, Rio de Janeiro, Brazil) with a severe migraine attack that had lasted <4 hours, they were randomized to 1 of 2 groups (IV placebo [25 mL of 0.9% saline] or IV LC [21 mL of 0.9% saline plus 4 mL of LC 200 mg]). Headache intensity and adverse effects (AEs) were assessed before (0 minute) and 30, 60, and 90 minutes after study drug administration. Rescue medication was available 2 hours after study drug administration, and its use was compared between groups. Thirty-two patients (23 women, 9 men; mean [SD] age, 32 [2] years; range, 18-58 years) entered the study. Twenty-nine patients (21 women, 8 men; mean [SD] age, 32 [2] years; range, 18-56 years) completed the study. Three patients (all in the placebo group) did not complete the study (1 patient was unable to rate the pain severity after drug administration and 2 patients refused IV drug administration). Among study completers, 17 patients received LC and 12 placebo. At 30 minutes, 1 patient (8.3%) in the placebo group and 5 patients (29.4%) in the LC group were pain free; the between-group difference was not

Improving depression and enhancing resilience in family dementia caregivers: a pilot randomized placebo-controlled trial of escitalopram.

PubMed

Lavretsky, Helen; Siddarth, Prabha; Irwin, Michael R

2010-02-01

This study examined the potential of an antidepressant drug, escitalopram, to improve depression, resilience to stress, and quality of life in family dementia caregivers in a randomized placebo-controlled double-blinded trial. Forty family caregivers (43-91 years of age, 25 children and 15 spouses; 26 women) who were taking care of their relatives with Alzheimer disease were randomized to receive either escitalopram 10 mg/day or placebo for 12 weeks. Severity of depression, resilience, burden, distress, quality of life, and severity of care-recipient's cognitive and behavioral disturbances were assessed at baseline and over the course of the study. The Hamilton Depression Rating Scale scores at baseline ranged between 10 and 28. The groups were stratified by the diagnosis of major and minor depression. Most outcomes favored escitalopram over placebo. The severity of depression improved, and the remission rate was greater with the drug compared with placebo. Measures of anxiety, resilience, burden, and distress improved on escitalopram compared with placebo. Among caregivers, this small randomized controlled trial found that escitalopram use resulted in improvement in depression, resilience, burden and distress, and quality of life. Our results need to be confirmed in a larger sample.

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.

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.

Atomoxetine for Hyperactivity in Autism Spectrum Disorders: Placebo-Controlled Crossover Pilot Trial

ERIC Educational Resources Information Center

Arnold, L. Eugene; Aman, Michael G.; Cook, Amelia M.; Witwer, Andrea N.; Hall, Kristy L.; Thompson, Susan; Ramadan, Yaser

2006-01-01

Objective: To explore placebo-controlled efficacy and safety of atomoxetine (ATX) for attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorders (ASD). Method: Children ages 5 to 15 with ASD and prominent ADHD symptoms were randomly assigned to order in a crossover of clinically titrated ATX and placebo, 6…

Escitalopram in the Treatment of Adolescent Depression: A Randomized, Double-Blind, Placebo-Controlled Extension Trial

PubMed Central

Robb, Adelaide; Bose, Anjana

2013-01-01

Abstract Objective The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Methods Adolescents (12–17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10–20 mg versus placebo could enroll in a 16–24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Results Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were

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

Dexmedetomidine oromucosal gel for noise-associated acute anxiety and fear in dogs-a randomised, double-blind, placebo-controlled clinical study.

PubMed

Korpivaara, M; Laapas, K; Huhtinen, M; Schöning, B; Overall, K

2017-04-08

The aim of this randomised, double-blind, placebo-controlled, clinical-field study was to evaluate the effect of dexmedetomidine oromucosal gel at subsedative doses in alleviation of noise-associated acute anxiety and fear in dogs. On New Year's Eve, 182 dogs with a history of acute anxiety and fear associated with fireworks received treatment as needed up to five times: 89 dogs received dexmedetomidine and 93 dogs received placebo. For the primary efficacy variables, dog owners assessed the overall treatment effect as well as signs and extent of anxiety and fear. The overall treatment effect was statistically significant (P<0.0001). An excellent or good treatment effect was reported for a higher proportion of dogs treated with dexmedetomidine (64/89, 72 per cent) than those receiving placebo (34/93, 37 per cent). Additionally, dexmedetomidine-treated dogs expressed significantly (P<0.0314) fewer signs of fear and anxiety despite the noise of fireworks. No local tolerance or clinical safety concerns occurred during the study. This study demonstrated that oromucosal dexmedetomidine at subsedative doses alleviates noise-associated acute anxiety and fear in dogs. British Veterinary Association.

The effects of inhaled L-methamphetamine on athletic performance while riding a stationary bike: a randomised placebo-controlled trial.

PubMed

Dufka, F; Galloway, G; Baggott, M; Mendelson, J

2009-10-01

L-methamphetamine (the non-abused isomer of methamphetamine) is banned in athletic competition because it may improve athletic performance, but there are no studies assessing its effects on performance. In the United States L-methamphetamine is formulated in the non-prescription Vick's Vapor Inhaler (VVI) nasal decongestant. VVIs sold elsewhere (we used ones from the UK) contain similar inactive ingredients (menthol, camphor and Siberian pine oil) but no L-methamphetamine. This study tested the effects of inhaled L-methamphetamine delivered from a widely available non-prescription product on athletic performance. In a 2-session double-blind placebo-controlled study 12 participants (ages 14-17) were dosed with 4 (session 1) and 12 (session 2) inhalations from VVIs with (USA) or without (UK) L-methamphetamine and then performed two 20 minute rides on a stationary bike with rides separated by a 30 minute rest. The main outcome measure was miles travelled during each 20 minute ride. Secondary outcome measures included postride urine toxicology; heart rate and blood pressure before, 1, 5 and 10 minutes postride; energy, performance, endurance, and ability to breathe; and VVI preference. Data were analysed using Excel statistical macros. After approximately 16 microg L-methamphetamine distance travelled was 5.26 (SD 0.53) miles vs 5.30 (0.55) with placebo; p = 0.81. After approximately 48 microg L-methamphetamine distance travelled was 5.30 (0.51) vs 5.35 (0.43) with placebo; p = 0.85. The approximately 16 microg dose increased systolic blood pressure from 72.6 (4.3) to 79.6 (6.6) mm Hg (p = 0.03) at 5 minutes postride but there were no other differences in outcomes. Modest doses of inhaled L-methamphetamine probably do not improve athletic performance but do minimally raise diastolic blood pressure.

A polysomnographic placebo-controlled evaluation of the efficacy and safety of eszopiclone relative to placebo and zolpidem in the treatment of primary insomnia.

PubMed

Erman, Milton K; Zammit, Gary; Rubens, Robert; Schaefer, Kendyl; Wessel, Thomas; Amato, David; Caron, Judy; Walsh, James K

2008-06-15

To evaluate the polysomnographic efficacy and the safety of a range of doses of eszopiclone relative to placebo in patients with primary insomnia. Zolpidem 10 mg was included as an active control. This multicenter, randomized, crossover study enrolled patients aged 21-64 years meeting the DSM-IV criteria for primary insomnia (n = 65). Patients received 2 nights treatment each with placebo, eszopiclone 1 mg, 2 mg, 2.5 mg, or 3 mg, and zolpidem 10 mg after randomization to one of 6 treatment sequences. Visits were separated by a 3-7 day washout. Objective efficacy was assessed by polysomnography (PSG). The primary endpoint was latency to persistent sleep (LPS); key secondary endpoints were sleep efficiency (SE) and wake time after sleep onset (WASO); other endpoints included wake time during sleep (WTDS) and number of awakenings (NAW), as well as patient-reported variables. LPS and SE were significantly different than placebo for all active treatments (p < 0.05 for all). Significant differences from placebo were noted in the 3 objective sleep maintenance measures (WASO, WTDS, and NAW) for eszopiclone 3 mg (p < 0.05), which was not the case for zolpidem 10 mg or the other eszopiclone doses. The incidence of central nervous system adverse events was 23.4% for zolpidem 10 mg, 6.2% to 12.5% for the eszopiclone doses, and 7.9% for placebo. Relative to placebo, all active treatments were effective in reducing LPS and increasing SE. Eszopiclone 3 mg was significantly different from placebo on the 3 PSG measures of sleep maintenance (WASO, WTDS, and NAW). Significant differences between zolpidem 10 mg and eszopiclone (2 mg or 3 mg) were not observed for PSG-measured outcomes, although the study was not powered to detect differences between the active drug conditions.

Duloxetine in the treatment of binge eating disorder with depressive disorders: a placebo-controlled trial.

PubMed

Guerdjikova, Anna I; McElroy, Susan L; Winstanley, Erin L; Nelson, Eric B; Mori, Nicole; McCoy, Jessica; Keck, Paul E; Hudson, James I

2012-03-01

This study evaluated duloxetine in the treatment of binge eating disorder (BED) with comorbid current depressive disorders. In this 12-week, double-blind, placebo-controlled trial, 40 patients with Diagnostic and Statistical Manual of Mental Disorders-IV-TR BED and a comorbid current depressive disorder received duloxetine (N = 20) or placebo (N = 20). The primary outcome measure was weekly binge eating day frequency. In the primary analysis, duloxetine (mean 78.7 mg/day) was superior to placebo in reducing weekly frequency of binge eating days (p = .04), binge eating episodes (p = .02), weight (p = .04), and Clinical Global Impression-Severity of Illness ratings for binge eating (p = .02) and depressive disorders (p = .01). Changes in body mass index and measures of eating pathology, depression, and anxiety did not differ between the two groups. Duloxetine may be effective for reducing binge eating, weight, and global severity of illness in BED with a comorbid current depressive disorder, but this finding needs confirmation in larger, placebo-controlled trials. Copyright © 2011 Wiley Periodicals, Inc.

Study protocol: a randomised placebo-controlled clinical trial to study the effect of vitamin D supplementation on glycaemic control in type 2 Diabetes Mellitus SUNNY trial.

PubMed

Krul-Poel, Yvonne H M; van Wijland, Hans; Stam, Frank; ten Boekel, Edwin; Lips, Paul; Simsek, Suat

2014-07-17

Besides the classical role of vitamin D on calcium and bone homeostasis, vitamin D deficiency has recently been identified as a contributing factor in the onset of insulin resistance in type 2 diabetes mellitus. However, it is uncertain whether vitamin D deficiency and poor glycaemic control are causally interrelated or that they constitute two independent features of type 2 diabetes mellitus. There are limited clinical trials carried out which measured the effect of vitamin D supplementation on glycaemic control.The objective of this study is to investigate the effect of vitamin D supplementation on glycaemic control and quality of life in patients with type 2 diabetes mellitus. In a randomised double-blind placebo-controlled trial conducted in five general practices in the Netherlands three hundred patients with type 2 diabetes mellitus treated with lifestyle advises or metformin or sulphonylurea-derivatives are randomised to receive either placebo or 50,000 IU Vitamin D3 at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and six months. Secondary outcome measures include blood pressure, anthropometric parameters, lipid profile, insulin resistance, quality of life, advanced glycation end products and safety profiles. Quality of life will be measured by The Short Form (SF-36) Health Survey questionnaire. Advanced glycation end products are measured by an AGE-reader. This trial will be the first study exploring the effect of vitamin D supplementation on both glycaemic control and quality of life in patients with type 2 diabetes mellitus. Our findings will contribute to the knowledge of the relationship between vitamin D status and insulin resistance in patients with type 2 diabetes mellitus. The Netherlands trial register: NTR3154.

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.

Effects of subtle cognitive manipulations on placebo analgesia - An implicit priming study.

PubMed

Rosén, A; Yi, J; Kirsch, I; Kaptchuk, T J; Ingvar, M; Jensen, K B

2017-04-01

Expectancy is widely accepted as a key contributor to placebo effects. However, it is not known whether non-conscious expectancies achieved through semantic priming may contribute to placebo analgesia. In this study, we investigated if an implicit priming procedure, where participants were unaware of the intended priming influence, affected placebo analgesia. In a double-blind experiment, healthy participants (n = 36) were randomized to different implicit priming types; one aimed at increasing positive expectations and one neutral control condition. First, pain calibration (thermal) and a credibility demonstration of the placebo analgesic device were performed. In a second step, an independent experimenter administered the priming task; Scrambled Sentence Test. Then, pain sensitivity was assessed while telling participants that the analgesic device was either turned on (placebo) or turned off (baseline). Pain responses were recorded on a 0-100 Numeric Response Scale. Overall, there was a significant placebo effect (p < 0.001), however, the priming conditions (positive/neutral) did not lead to differences in placebo outcome. Prior experience of pain relief (during initial pain testing) correlated significantly with placebo analgesia (p < 0.001) and explained 34% of placebo variance. Trait neuroticism correlated positively with placebo analgesia (p < 0.05) and explained 21% of placebo variance. Priming is one of many ways to influence behaviour, and non-conscious activation of positive expectations could theoretically affect placebo analgesia. Yet, we found no SST priming effect on placebo analgesia. Instead, our data point to the significance of prior experience of pain relief, trait neuroticism and social interaction with the treating clinician. Our findings challenge the role of semantic priming as a behavioural modifier that may shape expectations of pain relief, and affect placebo analgesia. © 2016 The Authors. European Journal of Pain published by John

Preventing ICU Subsyndromal Delirium Conversion to Delirium with Low Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study

PubMed Central

Al-Qadheeb, Nada S.; Skrobik, Yoanna; Schumaker, Greg; Pacheco, Manuel; Roberts, Russel; Ruthazer, Robin; Devlin, John W

2016-01-01

Objective To compare the efficacy and safety of scheduled low-dose, haloperidol vs. placebo for the prevention of delirium [Intensive Care Delirium Screening Checklist (ICDSC) ≥ 4)] administered to critically ill adults with subsyndromal delirium (ICDSC = 1-3). Design Randomized, double-blind, placebo-controlled trial. Setting Three 10-bed ICUs (2 medical; 1 surgical) at an academic medical center in the U.S. Patients Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery or requiring deep sedation. Interventions Patients were randomly assigned to receive intravenous haloperidol 1 mg or placebo every six hours until either delirium (ICDSC ≥ 4 with psychiatric confirmation), therapy ≥ 10 days or ICU discharge occurred. Measurements and Main Results Baseline characteristics were similar between the haloperidol (n=34) and placebo (n=34) groups. A similar number of patients given haloperidol [12/34 (35%)] and placebo [8/34 (23%)] patients developed delirium (p=0.29). Haloperidol use reduced the hours per study day spent agitated (SAS ≥ 5) (p=0.008), but did not influence the proportion of 12-hour ICU shifts patients’ spent alive without coma (SAS ≤ 2) or delirium (p=0.36), the time to first delirium occurrence (p=0.22) nor delirium duration (p=0.26). Days of mechanical ventilation (p=0.80), ICU mortality (p=0.55) and ICU patient disposition (p=0.22) were similar in the two groups. The proportion of patients who developed QTc-interval prolongation (p=0.16), extrapyramidal symptoms (p=0.31), excessive sedation (p=0.31) or new-onset hypotension (p=1.0) that resulted in study drug discontinuation was comparable between the two groups. Conclusions Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium. PMID:26540397

Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low-Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study.

PubMed

Al-Qadheeb, Nada S; Skrobik, Yoanna; Schumaker, Greg; Pacheco, Manuel N; Roberts, Russel J; Ruthazer, Robin R; Devlin, John W

2016-03-01

To compare the efficacy and safety of scheduled low-dose haloperidol versus placebo for the prevention of delirium (Intensive Care Delirium Screening Checklist ≥ 4) administered to critically ill adults with subsyndromal delirium (Intensive Care Delirium Screening Checklist = 1-3). Randomized, double-blind, placebo-controlled trial. Three 10-bed ICUs (two medical and one surgical) at an academic medical center in the United States. Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery, or requiring deep sedation. Patients were randomly assigned to receive IV haloperidol 1 mg or placebo every 6 hours until delirium occurred (Intensive Care Delirium Screening Checklist ≥ 4 with psychiatric confirmation), 10 days of therapy had elapsed, or ICU discharge. Baseline characteristics were similar between the haloperidol (n = 34) and placebo (n = 34) groups. A similar number of patients given haloperidol (12/34 [35%]) and placebo (8/34 [23%]) developed delirium (p = 0.29). Haloperidol use reduced the hours per study day spent agitated (Sedation Agitation Scale ≥ 5) (p = 0.008), but it did not influence the proportion of 12-hour ICU shifts patients spent alive without coma (Sedation Agitation Scale ≤ 2) or delirium (p = 0.36), the time to first delirium occurrence (p = 0.22), nor delirium duration (p = 0.26). Days of mechanical ventilation (p = 0.80), ICU mortality (p = 0.55), and ICU patient disposition (p = 0.22) were similar in the two groups. The proportion of patients who developed corrected QT-interval prolongation (p = 0.16), extrapyramidal symptoms (p = 0.31), excessive sedation (p = 0.31), or new-onset hypotension (p = 1.0) that resulted in study drug discontinuation was comparable between the two groups. Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults

Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials.

PubMed

Carpenter, Joseph K; Andrews, Leigh A; Witcraft, Sara M; Powers, Mark B; Smits, Jasper A J; Hofmann, Stefan G

2018-06-01

The purpose of this study was to examine the efficacy of cognitive behavioral therapy (CBT) for anxiety-related disorders based on randomized placebo-controlled trials. We included 41 studies that randomly assigned patients (N = 2,843) with acute stress disorder, generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD), panic disorder (PD), posttraumatic stress disorder (PTSD), or social anxiety disorder (SAD) to CBT or a psychological or pill placebo condition. Findings demonstrated moderate placebo-controlled effects of CBT on target disorder symptoms (Hedges' g = 0.56), and small to moderate effects on other anxiety symptoms (Hedges' g = 0.38), depression (Hedges' g = 0.31), and quality of life (Hedges' g = 0.30). Response rates in CBT compared to placebo were associated with an odds ratio of 2.97. Effects on the target disorder were significantly stronger for completer samples than intent-to-treat samples, and for individuals compared to group CBT in SAD and PTSD studies. Large effect sizes were found for OCD, GAD, and acute stress disorder, and small to moderate effect sizes were found for PTSD, SAD, and PD. In PTSD studies, dropout rates were greater in CBT (29.0%) compared to placebo (17.2%), but no difference in dropout was found across other disorders. Interventions primarily using exposure strategies had larger effect sizes than those using cognitive or cognitive and behavioral techniques, though this difference did not reach significance. Findings demonstrate that CBT is a moderately efficacious treatment for anxiety disorders when compared to placebo. More effective treatments are especially needed for PTSD, SAD, and PD. © 2018 Wiley Periodicals, Inc.

Tapentadol immediate-release for acute postbunionectomy pain: a phase 3, randomized, double-blind, placebo-controlled, parallel-group study in Taiwan.

PubMed

Chen, Yeung-Jen; Chiang, Chao-Ching; Huang, Peng-Ju; Huang, Jason; Karcher, Keith; Li, Honglan

2015-11-01

To evaluate the efficacy and safety of tapentadol immediate-release (IR) for treating acute pain following orthopedic bunionectomy surgery in a Taiwanese population. This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group bridging study in which Taiwanese patients (N = 60) with moderate-to-severe pain following bunionectomy were randomized (1:1:1) to receive tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours over a 72 hour period. The primary endpoint was the sum of pain intensity difference over 48 hours (SPID48), analyzed using analysis of variance. Out of 60 patients randomized (mainly women [96.7%]; median age 44 years), 41 (68.3%) completed the treatment. Mean SPID48 values were significantly higher for tapentadol IR (p ≤ 0.006: 50 mg, p ≤ 0.004: 75 mg) compared with placebo. Between-group differences in LS means of SPID48 (vs. placebo) were tapentadol IR 50 mg: 105.6 (95% CI: 32.0; 179.2); tapentadol IR 75 mg: 126.6 (95% CI: 49.5; 203.7). Secondary endpoints including SPID at 12, 24, and 72 hours, time to first use of rescue medication, cumulative distribution of responder rates, total pain relief and sum of total pain relief and sum of pain intensity difference at 12, 24, 48, and 72 hours, and patient global impression of change showed numerically better results supporting that tapentadol IR (50 and 75 mg) was more efficacious than placebo in relieving acute pain. The most frequent treatment emergent adverse events reported in ≥ 10% patients in either group were dizziness, nausea, and vomiting. A limitation of this study may possibly include more controlled patient monitoring through 4-6 hour dosing intervals, which reflects optimal conditions and thus may not approximate real-world clinical practice. However, all treatment groups would be equally affected by such bias of frequent monitoring, if any, since it was a randomized and double-blind study. Tapentadol IR treatment significantly relieved acute postoperative

Lansoprazole 15 mg once daily for 14 days is effective for treatment of frequent heartburn: results of 2 randomized, placebo-controlled, double-blind studies.

PubMed

Kushner, Pamela R; Snoddy, Andrew M; Gilderman, Larry; Peura, David A

2009-07-01

To investigate the efficacy and safety of a 14-day treatment period with lansoprazole 15 mg for frequent heartburn in patients who are likely to select a nonprescription medication before consulting a prescriber. Adults with untreated frequent heartburn > or = 2 days a week over the past month were recruited for 2 identical multicenter, double-blind studies conducted with a 1-week screening and heartburn medication washout, a 1-week placebo run-in, a 2-week placebo-controlled treatment, and a 1-week placebo follow-up. After the washout and placebo run-in, subjects were randomly assigned to receive lansoprazole 15 mg or placebo once daily for 14 days in a double-blind fashion. Antacid tablets were permitted as rescue medication. Endpoints included percentage of 24-hour days without heartburn (primary), percentage of night-times without heartburn, and percentage of subjects without heartburn during day 1 of treatment (secondary endpoints). Data were collected daily via an interactive voice response system. In studies 1 and 2, 282 and 288 subjects, respectively, were randomly assigned to lansoprazole, and 282 in each study received placebo. The mean percentage of days without heartburn was greater among lansoprazole recipients compared with placebo recipients (P < 0.0001). Significantly more subjects treated with lansoprazole also reported no night-time heartburn and no heartburn during day 1 of the 14-day treatment. Adverse events were infrequent and were similar for lansoprazole and placebo groups. During the 14-day treatment period in a population with frequent heartburn who were likely to select a medication without consulting a prescriber, lansoprazole 15 mg once daily showed rapid and sustained effectiveness throughout a 24-hour period and was well tolerated.

Sildenafil citrate as a medical expulsive therapy for distal ureteric stones: A randomised double-blind placebo-controlled study.

PubMed

Shokeir, Ahmed A; Tharwat, Mohamed A; Abolazm, Ahmed Elhussein; Harraz, Ahmed

2016-03-01

To study the effect of sildenafil citrate on spontaneous passage of distal ureteric stones (DUS). This was a randomised double-blinded placebo-controlled study of 100 patients with DUS. Inclusion criteria were: male, age 18-65 years, normal renal function, and a single radiopaque unilateral DUS of 5-10 mm. Patients were randomly allocated into two equal groups, one that received placebo and the other that received 50 mg sildenafil citrate once daily. Both investigators and patients were masked to the type of treatment. Patients self-administered the medication until spontaneous passage of the DUS. In patients where there was uncontrolled pain, fever, an increase in serum creatinine of >1.8 mg/dL, progressive hydronephrosis or no further progress after 4 weeks, a decision was taken for further treatment. In all, 47 and 49 patients were available for analysis in both the placebo and sildenafil citrate groups; respectively. Both groups were comparable for age and stone characteristics. Spontaneous expulsion occurred in 19 of 47 patients (40.4%) in the placebo group and in 33 of 49 (67.3%) in the sildenafil citrate group (P = 0.014). The mean time to stone expulsion was significantly shorter in the sildenafil citrate group (P < 0.001). A multivariable Cox proportional hazards model showed that receiving sildenafil citrate was the only independent factor that had a significant impact on stone passage with a hazard ratio of 2.7 (95% confidence interval 1.5-4.8; P < 0.001). Sildenafil citrate enhances spontaneous passage of 5-10 mm DUS.

Effect of low-level laser therapy in the treatment of cochlear tinnitus: a double-blind, placebo-controlled study.

PubMed

Dehkordi, Mahboobeh Adami; Einolghozati, Sasan; Ghasemi, Seyyed Mohsen; Abolbashari, Samaneh; Meshkat, Mojtaba; Behzad, Hadi

2015-01-01

Many treatments for chronic tinnitus have been attempted, but the condition remains difficult to cure, especially in the case of cochlear tinnitus. We conducted a prospective, double-blind, placebo-controlled study to assess the effect of low-dose laser therapy on chronic cochlear tinnitus. Our study population was made up of 66 patients-33 who received active laser treatment (case group) and 33 who received inactive dummy treatment (control group). Patients in the laser group received 5 mV with a wavelength of 650 nm for 20 minutes a day, 5 days a week, for 4 weeks. The controls followed the same schedule, but they were "treated" with an inactive device. The degree of tinnitus was evaluated before and after treatment in each group in three ways: (1) the Tinnitus Severity Index (TSI), (2) a subjective 10-point self-assessment scale for tinnitus loudness, and (3) the Tinnitus Evaluation Test (TET). At study's end, we found no statistically significant differences between the case and control groups in the number of patients who experienced a reduction in TSI values (p = 0.589) or a reduction in subjective self-assessment scores (p = 0.475). Nor did we find any significant reductions in the loudness (p = 0.665) and frequency (p = 0.396) of tinnitus as determined by the TET. We conclude that 5-mV laser therapy with a wavelength of 650 nm is no better than placebo for improving hearing thresholds overall or for treating tinnitus with regard to age, sex, environmental noise level, and the duration of tinnitus.

Efficacy and Safety of Pueraria lobata Extract in Gray Hair Prevention: A Randomized, Double-Blind, Placebo-Controlled Study

PubMed Central

Jo, Seong Jin; Shin, Hyoseung; Paik, Seung Hwan; Na, Sun Jae; Jin, Yingji; Park, Won Seok; Kim, Su Na

2013-01-01

Background Graying of hair-a sign of aging-raises cosmetic concerns. Individuals with gray hair often look older than others their age; therefore, some dye their hair for aesthetic purposes. However, hair colorants can induce many problems including skin irritation, allergic reaction and hair-breakage. Objective This randomized, double-blind clinical trial was performed in order to examine the effects of APHG-1001, a compound including an extract from Pueraria lobata, on graying hair. Methods A total of 44 female subjects were randomly treated with either APHG-1001 or placebo twice daily for 24 weeks. Using the phototrichogram analysis, a count of newly developed gray hair was estimated. Investigator assessment and subject self-assessment were also performed in order to evaluate the efficacy of the compound. Results The mean number of newly developed gray hair at 24 weeks was 6.3/cm2 in the APHG-1001 group and 11.4/cm2 in the placebo group; the difference was statistically significant (p<0.05). However, the investigator assessment and subject self-assessment did not show any significant change in the gross appearance of hair grayness by the end of the study. No severe adverse events in either group were observed. Moreover, the incidence of adverse events did not differ between the groups. Conclusion This clinical trial revealed that APHG-1001, which contains an extract of P. lobata, could prevent the development of new gray hair without any remarkable adverse effects. Thus, it can be considered as a viable treatment option for the prevention of gray hair. PMID:23717015

Glucosamine-containing supplement improves locomotor functions in subjects with knee pain: a randomized, double-blind, placebo-controlled study.

PubMed

Kanzaki, Noriyuki; Ono, Yoshiko; Shibata, Hiroshi; Moritani, Toshio

2015-01-01

The aim of this study was to investigate the ability of a glucosamine-containing supplement to improve locomotor functions in subjects with knee pain. A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted for 16 weeks in 100 Japanese subjects (age, 51.8±0.8 years) with knee pain. Subjects were randomly assigned to one of the two supplements containing 1) 1,200 mg of glucosamine hydrochloride, 60 mg of chondroitin sulfate, 45 mg of type II collagen peptides, 90 mg of quercetin glycosides, 10 mg of imidazole peptides, and 5 μg of vitamin D per day (GCQID group, n=50) or 2) a placebo (placebo group, n=50). Japanese Knee Osteoarthritis Measure, visual analog scale score, normal walking speed, and knee-extensor strength were measured to evaluate the effects of the supplement on knee-joint functions and locomotor functions. In subjects eligible for efficacy assessment, there was no significant group × time interaction, and there were improvements in knee-joint functions and locomotor functions in both groups, but there was no significant difference between the groups. In subjects with mild-to-severe knee pain at baseline, knee-extensor strength at week 8 (104.6±5.0% body weight vs 92.3±5.5% body weight, P=0.030) and the change in normal walking speed at week 16 (0.11±0.03 m/s vs 0.05±0.02 m/s, P=0.038) were significantly greater in the GCQID group than in the placebo group. Further subgroup analysis based on Kellgren-Lawrence (K-L) grade showed that normal walking speed at week 16 (1.36±0.05 m/s vs 1.21±0.02 m/s, P<0.05) was significantly greater in the GCQID group than in the placebo group in subjects with K-L grade I. No adverse effect of treatment was identified in the safety assessment. In subjects with knee pain, GCQID supplementation was effective for relieving knee pain and improving locomotor functions.

Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period

PubMed Central

Oe, Mariko; Sakai, Seigo; Yoshida, Hideto; Okado, Nao; Kaneda, Haruna; Masuda, Yasunobu; Urushibata, Osamu

2017-01-01

Background 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. Methods 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. Results 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. Conclusion The results suggest that oral HA (both HA 2 k and HA 300 k) inhibits skin wrinkles and improves skin condition. PMID:28761365

The Effect of Buffering High Acid Load Meal with Sodium Bicarbonate on Postprandial Glucose Metabolism in Humans-A Randomized Placebo-Controlled Study.

PubMed

Kozan, Pinar; Blythe, Jackson C; Greenfield, Jerry R; Samocha-Bonet, Dorit

2017-08-11

Background: High dietary acid load relates to increased risk of type 2 diabetes in epidemiological studies. We aimed to investigate whether buffering a high acid load meal with an alkalizing treatment changes glucose metabolism post meal. Methods: Non-diabetic participants ( n = 32) were randomized to receive either 1680 mg NaHCO₃ or placebo, followed by a high acid load meal in a double-blind placebo-controlled crossover (1-4 weeks apart) study. Thirty (20 men) participants completed the study. Venous blood pH, serum bicarbonate, blood glucose, serum insulin, C -peptide, non-esterified fatty acid (NEFA), and plasma glucagon-like peptide-1 (GLP-1) concentrations were measured at baseline (fasting) and at 15-30 min intervals for 3 h post meal. Results: The treatment was well tolerated. Venous blood pH declined in the first 15 min post meal with the placebo ( p = 0.001), but not with NaHCO₃ ( p = 0.86) and remained decreased with the placebo for 3 h ( p interaction = 0.04). On average over the 3 h blood pH iAUC was greater with NaHCO₃ compared with placebo ( p = 0.02). However, postprandial glucose, insulin, C -peptide, NEFA and GLP-1 were not different between treatments ( p interaction ≥ 0.07). Conclusions: An alkalizing medication administered pre-meal has no acute effect on glycaemia and insulin response in healthy individuals. Long-term interventions in at-risk populations are necessary to investigate the effect of sustained alkalization on glucose metabolism.

Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia in Japan: A 6-week, randomized, double-blind, placebo-controlled study.

PubMed

Ishigooka, Jun; Iwashita, Shuichi; Tadori, Yoshihiro

2018-05-18

This study aimed to evaluate the efficacy, safety, and tolerability of brexpiprazole compared to placebo in Japanese patients with acute schizophrenia. We conducted a 6-week, multicenter, double-blind, placebo-controlled, phase 2/3 study in Japan. Patients with acute schizophrenia were randomized (1:1:1:1) to receive brexpiprazole 1, 2, or 4 mg or placebo once a day. The primary endpoint was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total scores. In the 459 patients that were randomized, brexpiprazole 2 mg showed a significant improvement versus placebo (treatment difference: -7.32, p = 0.0124), although brexpiprazole 4 mg showed numerical improvements (treatment difference: -3.86, p = 0.1959), and brexpiprazole 1 mg showed only minimal change (treatment difference: -0.63, p = 0.8330). The treatment-emergent adverse events (TEAEs) with an incidence of ≥5% and ≥2 times the rate of placebo in the brexpiprazole groups were vomiting, elevated blood prolactin, diarrhoea, nausea, and dental caries. Most TEAEs were mild or moderate in severity. There were no clinically significant changes in electrocardiogram parameters, body weight, laboratory values, and vital signs in the brexpiprazole groups. Brexpiprazole was efficacious and well tolerated in Japanese adult patients with acute schizophrenia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A randomized and placebo-controlled study to compare the skin-lightening efficacy and safety of lignin peroxidase cream vs. 2% hydroquinone cream.

PubMed

Mauricio, Tess; Karmon, Yoram; Khaiat, Alain

2011-12-01

  Historically, the most effective treatments for skin lightening have contained hydroquinone. However, there is a need for an effective alternative.   The purpose of this study was to evaluate the skin-lightening efficacy and safety of lignin peroxidase (LIP) creams using a regimen of both day and night products compared with twice-daily application of 2% hydroquinone cream and placebo in Asian women.   This was a randomized, double-blind, placebo-controlled, split-face, single-center study of 51 patients. Patients were randomized to receive day and night LIP cream on one randomly selected side of their face and either 2% hydroquinone cream or placebo on the other.   A statistically significant change from baseline in the melanin index was observed in LIP-treated skin, with a mean reduction of 7.6% (P < 0.001) on Day 31. Conversely, hydroquinone and placebo did not provide a statistically significant lightening effect when instrumentally measured. Dermatologist scoring demonstrated a significant improvement in overall fairness as early as 8 days after treatment initiation in the LIP-treated group, which was not observed in the other groups. Overall, patients preferred the LIP creams.   The application of day/night LIP cream provided a significantly more rapid and observable skin-lightening effect than hydroquinone 2% cream or placebo. © 2011 Wiley Periodicals, Inc.

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.

Diuretic versus placebo in normotensive acute pulmonary embolism with right ventricular enlargement and injury: a double-blind randomised placebo controlled study. Protocol of the DiPER study.

PubMed

Gallet, Romain; Meyer, Guy; Ternacle, Julien; Biendel, Caroline; Brunet, Anne; Meneveau, Nicolas; Rosario, Roger; Couturaud, Francis; Sebbane, Mustapha; Lamblin, Nicolas; Bouvaist, Helene; Coste, Pierre; Maitre, Bernard; Bastuji-Garin, Sylvie; Dubois-Rande, Jean-Luc; Lim, Pascal

2015-05-22

In acute pulmonary embolism (PE), poor outcome is usually related to right ventricular (RV) failure due to the increase in RV afterload. Treatment of PE with RV failure without shock is controversial and usually relies on fluid expansion to increase RV preload. However, several studies suggest that fluid expansion may worsen acute RV failure by increasing RV dilation and ischaemia, and increase left ventricular compression by RV dilation. By reducing RV enlargement, diuretic treatment may break this vicious circle and provide early improvement in normotensive patients referred for acute PE with RV failure. The Diuretic versus placebo in Pulmonary Embolism with Right ventricular enlargement trial (DiPER) is a prospective, multicentre, randomised (1:1), double-blind, placebo controlled study assessing the superiority of furosemide as compared with placebo in normotensive patients with confirmed acute PE and RV dilation (diagnosed on echocardiography or CT of the chest) and positive brain natriuretic peptide result. The primary end point will be a combined clinical criterion derived from simplified Pulmonary Embolism Severity Index (PESI) score and evaluated at 24 h. It will include: (1) urine output >0.5 mL/kg/min for the past 24 h; (2) heart rate <110 bpm; (3) systolic blood pressure >100 mm Hg and (4) arterial oxyhaemoglobin level >90%. Thirty-day major cardiac events defined as death, cardiac arrest, mechanical ventilation, need for catecholamine and thrombolysis, will be evaluated as a secondary end point. Assuming an increase of 30% in the primary end point with furosemide and a β risk of 10%, 270 patients will be required. Ethical approval was received from the ethical committee of Ile de France (2014-001090-14). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations. NCT02268903. Published by the BMJ Publishing Group Limited. For permission to use (where not already

Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: a pooled analysis.

PubMed

Tonstad, Serena; Davies, Simon; Flammer, Martina; Russ, Cristina; Hughes, John

2010-04-01

Varenicline (Chantix), Champix) has shown efficacy and tolerability as an aid to smoking cessation. In postmarketing surveillance, neuropsychiatric symptoms have appeared; however, their incidence and causal relationship to varenicline is not known. We assessed the incidence and relative risk (RR) of psychiatric disorders in ten randomized, double-blind, placebo-controlled trials of varenicline for smoking cessation. All smoking cessation phase II, III and IV randomized controlled clinical trials of varenicline versus placebo completed as of 31 December 2008, on file with the manufacturer (Pfizer, Inc.), were included. All studies have been published. All 3091 participants who received at least one dose of varenicline and all 2005 participants who received placebo were included in this analysis. These were men and women smoking > or =10 cigarettes/day, aged 18-75 years and without current psychiatric disease who received varenicline or placebo for 6 (one study), 12 (eight studies) or 52 (one study) weeks. Adverse events were recorded at each study visit and classified according to standard Medical Dictionary for Regulatory Activities (MedDRA) terms (version 11.0). The incidence of psychiatric disorders other than solely sleep disorders and disturbances was 10.7% in subjects treated with varenicline and 9.7% in subjects treated with placebo, with an RR of 1.02 (95% CI 0.86, 1.22). The RRs (95% CI) versus placebo of psychiatric adverse events with an incidence > or =1% in the varenicline group were 0.86 (0.67, 1.12) for anxiety disorders and symptoms, 0.76 (0.42, 1.39) for changes in physical activity, 1.42 (0.96, 2.08) for depressed mood disorders and disturbances, 1.21 (0.79, 1.83) for mood disorders and disturbances not elsewhere classified and 1.70 (1.50, 1.92) for sleep disorders and disturbances. There were no cases of suicidal ideation or behaviour in varenicline-treated subjects in the ten placebo-controlled studies analysed. However, among three trials that

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.

Safety and metabolic outcomes of resveratrol supplementation in older adults: results of a twelve-week, placebo-controlled pilot study

PubMed Central

Anton, Stephen D.; Embry, Chelsea; Marsiske, Michael; Lud, Xiaomin; Doss, Hani; Leeuwenburgh, Christiaan; Manini, Todd M.

2014-01-01

Resveratrol has been found to have potent antioxidant, anti-inflammatory, and anticarcinogenic effects. The safety and efficacy of resveratrol supplementation in older adults are currently unknown. We conducted a double-blind, randomized, placebo-controlled trial to examine the safety and metabolic outcomes in 32 overweight, older adults (mean age, 73 ± 7 years). Participants were randomized into one of three treatment groups: (1) placebo, (2) moderate dose resveratrol (300 mg/day), and (3) high dose resveratrol (1000 mg/day). Both resveratrol and placebo were orally ingested in capsule form twice daily for 90 days. Blood chemistry values remained within the normal range, and there were no significant differences in the number of participants reporting adverse events across conditions. Compared to placebo, glucose levels were significantly lower at post-treatment among participants randomized to both resveratrol conditions, with and without adjustment for the corresponding baseline values (ps < 0.05). Glucose values of participants in the treatment groups, however, were not significantly different from baseline levels. These findings suggest that short-term resveratrol supplementation at doses of 300 mg/day and 1000 mg/day does not adversely affect blood chemistries and is well tolerated in overweight, older individuals. These findings support the study of resveratrol for improving cardio-metabolic health in older adults in larger clinical trials. PMID:24866496

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.

Extracorporeal shock wave therapy in Peyronie's disease: results of a placebo-controlled, prospective, randomized, single-blind study.

PubMed

Hatzichristodoulou, Georgios; Meisner, Christoph; Gschwend, Jürgen E; Stenzl, Arnulf; Lahme, Sven

2013-11-01

Extracorporeal shock wave therapy (ESWT) for treatment of Peyronie's disease (PD) is controversial. To study the efficacy of ESWT by a placebo-controlled, randomized trial. Patients with PD (n=102) were randomly assigned (n=51) to each group (ESWT or placebo). All patients were given 6 weekly treatments. Patients in the ESWT-group received 2,000 shock waves per session, using the Piezoson 100 lithotripter (Richard Wolf, Knittlingen, Germany). Patients in the placebo-group were treated with interposition of a plastic membrane, which prevented any transmission of shock waves. Primary end point was decrease of pain between baseline and after 4 weeks follow-up. Secondary end points were changes in deviation, plaque size, and sexual function. Pain was assessed by a visual analog scale. Deviation was measured by a goniometer after artificial erection using Alprostadil (Viridal®, Schwarz Pharma, Monheim, Germany). Plaque size was measured with a ruler and sexual function assessed by a scale regarding the ability to perform sexual intercourse. Overall, only 45 patients experienced pain at baseline. In the subgroup analysis of these patients, pain decreased in 17/20 (85.0%) patients in the ESWT group and 12/25 (48.0%) patients in the placebo group (P=0.013, relative risk [RR]=0.29, 95% confidence interval: 0.09-0.87). Penile deviation was not reduced by ESWT (P=0.66) but worsened in 20/50 (40%) and 12/49 (24.5%) patients of the ESWT and placebo-group, respectively (P=0.133). Plaque size reduction was not different between the two groups (P=0.33). Additional, plaque size increased in five patients (10.9%) of the ESWT group only. An improvement in sexual function could not be verified (P=0.126, RR=0.46). Despite some potential benefit of ESWT in regard to pain reduction, it should be emphasized that pain usually resolves spontaneously with time. Given this and the fact that deviation may worsen with ESWT, this treatment cannot be recommended. © 2013 International Society

A Prospective, Randomized, Masked, and Placebo-Controlled Efficacy Study of Intraarticular Allogeneic Adipose Stem Cells for the Treatment of Osteoarthritis in Dogs

PubMed Central

Harman, Robert; Carlson, Kim; Gaynor, Jamie; Gustafson, Scott; Dhupa, Sarit; Clement, Keith; Hoelzler, Michael; McCarthy, Tim; Schwartz, Pamela; Adams, Cheryl

2016-01-01

Osteoarthritis (OA) is a degenerative joint disease with a high prevalence in dogs. Mesenchymal stem cells (MSCs) have been used to treat humans, dogs, and horses with OA. This report describes a prospective, randomized, blinded, and placebo-controlled clinical efficacy study of intraarticular allogeneic adipose stem cells for the treatment of dogs with OA. Health assessments and measurements of pain and activity impairment were performed at baseline and at selected time points through day 60. The primary outcome variable was the owner Client-Specific Outcome Measurement (CSOM) and secondary measures included veterinary pain on manipulation, veterinary global score, and owner global score. The dogs were treated with either a saline placebo or a single dose of allogeneic adipose-derived MSCs in either one or two joints. Seventy-four dogs were statistically analyzed for efficacy outcomes. Success in the primary outcome variable, CSOM, was statistically improved in the treated dogs compared to the placebo dogs (79.2 versus 55.4%, p = 0.029). The veterinary pain on manipulation score (92.8 versus 50.2%, p = 0.017) and the veterinary global score (86.9 versus 30.8%, p = 0.009) were both statistically improved in treated dogs compared to placebo. There was no detected significant difference between treated and placebo dogs in the incidence of adverse events or negative health findings. Allogeneic adipose-derived stem cell treatment was shown to be efficacious compared to placebo. This large study of dogs also provides valuable animal clinical safety and efficacy outcome data to our colleagues developing human stem cell therapy. PMID:27695698

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

PubMed

Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

2017-07-01

Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. Pharmacological

BASALIT trial: double-blind placebo-controlled allergen immunotherapy with rBet v 1-FV in birch-related soya allergy.

PubMed

Treudler, R; Franke, A; Schmiedeknecht, A; Ballmer-Weber, B; Worm, M; Werfel, T; Jappe, U; Biedermann, T; Schmitt, J; Brehler, R; Kleinheinz, A; Kleine-Tebbe, J; Brüning, H; Ruëff, F; Ring, J; Saloga, J; Schäkel, K; Holzhauser, T; Vieths, S; Simon, J C

2017-08-01

Conflicting results exist on the effect of allergen immunotherapy (AIT) on pollen-related food allergy. We aimed to investigate the efficacy of one-year AIT with the folding variant (FV) of recombinant (r) Bet v 1 on birch-related soya allergy. Of 138 subjects with Bet v 1 sensitization, 82 were positive at double-blind placebo-controlled food challenge (DBPCFC) with soya. A total of 56 of 82 were randomized in the ratio of 2:1 (active: placebo). Per-protocol population (PPP) had received ≥150 μg of allergen or placebo preparation. lowest observed adverse effect levels (LOAEL), postinterventional occurrence of objective signs (objS) at any dose level, sIgE/IgG4 against Bet v 1 and Gly m 4. Between-group changes were investigated (ancova, Mann-Whitney U-test, Fisher exact test). Baseline characteristics including LOAELs were comparable in both groups with objS and subjS occurring in 82% and 95% of active (n = 38) vs 78% and 83% of placebo group (n = 18). After AIT, objS occurred in 24% and 47%, respectively. LOAEL group differences showed a beneficial tendency (P = 0.081) for LOAEL objective in PPP (30 active, 15 placebo). sIgG4 raised only in active group (Bet v 1: P = 0.054, Gly m 4: P = 0.037), and no relevant changes occurred for sIgE. Only 56% of the intended sample size was recruited. For the first time, we present data on the effect of rBet v 1-FV on birch-related soya allergy. rBet v 1-FV AIT induced significant immunogenic effects. Clinical assessment showed a tendency in favour of the active group but did not reach statistical significance. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Homeopathy for Depression - DEP-HOM: study protocol for a randomized, partially double-blind, placebo controlled, four armed study

PubMed Central

2011-01-01

Background Homeopathy is often sought by patients with depression. In classical homeopathy, the treatment consists of two main elements: the case history and the prescription of an individually selected homeopathic remedy. Previous data suggest that individualized homeopathic Q-potencies were not inferior to the antidepressant fluoxetine in a sample of patients with moderate to severe depression. However, the question remains whether individualized homeopathic Q-potencies and/or the type of the homeopathic case history have a specific therapeutical effect in acute depression as this has not yet been investigated. The study aims to assess the two components of individualized homeopathic treatment for acute depression, i.e., to investigate the specific effect of individualized Q-potencies versus placebo and to investigate the effect of different approaches to the homeopathic case history. Methods/Design A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2 × 2 factorial design with a six-week study duration per patient will be performed. 228 patients diagnosed with major depression (moderate episode) by a psychiatrist will be included. The primary endpoint is the total score on the 17-item Hamilton Depression Rating Scale after six weeks. Secondary end points are: Hamilton Depression Rating Scale total score after two and four weeks; response and remission rates, Beck Depression inventory total score, quality of life and safety at two, four and six weeks. Statistical analyses will be by intention-to-treat. The main endpoint will be analysed by a two-factorial analysis of covariance. Within this model generalized estimation equations will be used to estimate differences between verum and placebo, and between both types of case history. Discussion For the first time this study evaluates both the specific effect of homeopathic medicines and of a homeopathic case taking in patients with depression. It is an attempt to deal with the

Impact of maternal probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration: a prospective, randomized, placebo-controlled study.

PubMed

Luoto, Raakel; Laitinen, Kirsi; Nermes, Merja; Isolauri, Erika

2012-06-01

The breast milk bioactive substances such as adiponectin, have a presumably long-term impact upon the health and well-being of a child. To determine the impact of probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration. Altogether 256 pregnant women were randomized into three study groups: dietary intervention with probiotics (diet/probiotics) or with placebo (diet/placebo) and a control group (control/placebo). The intervention group received dietary counseling provided by a nutritionist, the main focus being the amount and the type of dietary fat. The probiotics used were Lactobacillus rhamnosus GG and Bifidobacterium lactis in combination. Dietary intake was evaluated by food records at every trimester of pregnancy. Breast milk samples were collected after birth (colostrum) for adiponectin concentration analysis (n=181). The dietary intervention increased the colostrum adiponectin concentration (ng/mL, geometric mean [95% CI]), the difference being significant when comparing to the control group; 12.7 [10.6-29.7] vs. 10.2 [9.9-13.2], P=0.024. Maternal weight gain during pregnancy (kg) correlated inversely with colostrum adiponectin concentration; β (SE)=-1.7 (0.1), P=0.020, and gestational diabetes mellitus was associated with the likelihood of adiponectin concentration falling into the lowest quartile; OR 2.36, 95% CI 1.1-3.2, P=0.028. In showing that the colostrum adiponectin concentration is markedly dependent on maternal diet and nutritional status during pregnancy, and considering that colostrum adiponectin has potential effects on metabolism, nutrition, and immune function in the neonates, the results of this study underscore the importance of the metabolic homeostasis of the mother for the child's initial nutritional environment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Sex-specific effects of intranasal oxytocin on thermal pain perception: A randomised, double-blind, placebo-controlled cross-over study.

PubMed

Tracy, Lincoln M; Labuschagne, Izelle; Georgiou-Karistianis, Nellie; Gibson, Stephen J; Giummarra, Melita J

2017-09-01

Chronic neck and shoulder pain (CNSP) is a common musculoskeletal disorder in adults, which is linked to hypersensitivity to noxious stimuli. The hormone oxytocin has been implicated as a potential therapeutic for the management of chronic pain disorders, and has been suggested to have sex-specific effects on the salience of threatening stimuli. This study investigated the influence of intranasal oxytocin on the perception of noxious thermal stimuli. Participants were 24 individuals with CNSP lasting >12months (eight women), and 24 age- and sex-matched healthy, pain-free controls. In a randomised double-blind, placebo-controlled, cross-over study, participants attended two sessions, self-administering intranasal oxytocin (24 IU) in one session, and placebo in another. Participants rated intensity and unpleasantness of thermal heat stimuli at three body sites: the cervical spine, deltoid, and tibialis anterior, on 11-point numerical rating scales. Compared with placebo, intranasal oxytocin increased the perceived intensity of noxious heat stimuli in women with CNSP (Cohen's d=0.71), but not in men with CNSP, or healthy, pain-free controls. Men and women displayed divergent sensitivity across target sites for ratings of pain intensity (partial eta squared=0.12) and pain unpleasantness (partial eta squared=0.24), irrespective of drug condition. Men were more sensitive at the cervical spine and deltoid, whereas women were more sensitive at the tibialis. These findings suggest that oxytocin and endogenous sex hormones may interact to influence the salience of noxious stimuli. The hyperalgesic effects of oxytocin in women suggest that caution should be taken when considering oxytocin in the management of chronic pain. CT-2016-CTN-01313-1; ACTRN12616000532404. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

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.

[Placebo effect in Parkinson's disease].

PubMed

Miwa, Hideto

2007-02-01

"Placebo" is Latin for "I shall please". The placebo effect has been widely documented by randomized placebo-controlled drug studies. One of the best examples of placebo effectiveness is that have been shown in clinical trials of anti-parkinsonian drugs. The placebo effect is observable not only in drug trials but also with deep brain stimulation. Recent advances in research on the placebo effect in Parkinson's disease (PD) have suggested that motor symptoms of PD can be essentially improved by placebo. A recent study using positron emission tomography (PET) with raclopride demonstrated that release of endogeneous dopamine in the dorsal striatum occurs in placebo-responsive patients with PD. This suggests that placebo-induced expectation of clinical improvement may activate endogenous dopamine in the striatum, and that placebo effectiveness is thus achieved by endogenous dopamine supplementation. Indeed, decreased neuronal activities in the subthalamic nucleus (STN), that were recorded during surgery to implant deep brain stimulation electrodes, correlated well with placebo-induced clinical improvement in patients with PD. Although the detailed pathophysiological mechanism underlying the placebo effects remains uncertain, theoretically, the placebo effect has generally been explained by two different mechanisms: one is conditioning theory (pavlovian conditioning), and the other is cognitive theory (expectation of clinical improvement). Although both mechanisms may contribute to placebo effects, the placebo effect in PD may be attributed more to cognitive mechanisms such as expectation of improvement, because the placebo effect can be obtained in de novo PD patients. There have been accumulating findings that suggest a functional relationship between dopamine and the expectation of clinical improvement (reward). Further basic studies are required to clarify the complex link between dopamine and the reward system, but such findings will contribute to a better

Effect of Royal Jelly on premenstrual syndrome among Iranian medical sciences students: a randomized, triple-blind, placebo-controlled study.

PubMed

Taavoni, Simin; Barkhordari, Fatemeh; Goushegir, Ashrafeddin; Haghani, Hamid

2014-08-01

Premenstrual syndrome (PMS) may have negative effects on women's health and sometimes need therapeutic non-pharmacological management. To determine the effect of oral consumption of 1000 mg Royal Jelly capsule on premenstrual syndrome. This is a randomized, triple-blind, placebo-controlled clinical trial, which was conducted in Tehran University of Medical Sciences female dormitories between December 2011 and October 2012. The study population comprised 110 medical sciences student with PMS, whom were randomly assigned to an intervention or a control group. Each participant in the intervention group took one Royal jelly capsule orally per day, starting on the first day of menstruation and continued the same treatment daily throughout two consecutive menstrual cycles, while participants in the intervention group took placebo capsules as same method. The outcome measure in this study was PMS score as obtained through the Premenstrual Profile 2005. The mean of personal characteristics and baseline level of the premenstrual score before intervention did not differ between groups. After two consecutive months consumption of Royal Jelly, PMS score had decreased from 23.17 ± 17.43 to 11.42 ± 14.58 (mean change: 11.75; 95% confidence interval [CI]: 8.31-15.19) and in Placebo, PMS score changed from 21.48 ± 16.39 to 20.27 ± 15.76 (mean change: 1.20; 95% CI: -1.69 to 4.10). Also difference between mean changes was significant (mean difference: 10.54; 95% CI: 6.10-14.98). The results of the study have demonstrated that 2 months consumption of Royal Jelly was effective in reducing PMS. Copyright © 2014. Published by Elsevier Ltd.

Bright light therapy decreases winter binge frequency in women with bulimia nervosa: a double-blind, placebo-controlled study.

PubMed

Braun, D L; Sunday, S R; Fornari, V M; Halmi, K A

1999-01-01

The study objective was to determine the effect of winter bright light therapy on binge and purge frequencies and depressive symptoms in subjects with bulimia nervosa. Thirty-four female bulimic outpatients were treated with either 10,000 lux bright white light or 50 lux dim red light (placebo control) during the winter months. In this double-blind study, the placebo group (n = 18) and the bright light group (n = 16) were matched for age, degree of seasonality (measured by the Seasonal Patterns Assessment Questionnaire [SPAQ]), and concurrent depression (measured by Structured Clinical Interview for DSM-IV [SCID]). Three weeks of baseline data collection were followed by 3 weeks of half-hour daily morning light treatment and 2 weeks of follow-up evaluation. There was a significant light-treatment by time interaction (Wilks' lambda = .81, F(2,28) = 3.31, P = .05). The mean binge frequency decreased significantly more from baseline to the end of treatment for the bright light group (F(1,29) = 6.41, P = .017) than for the placebo group. The level of depression (measured by daily Beck Depression Inventory [BDI] scores) did not significantly differ between the groups during any phase, and neither depression nor seasonality affected the response to light treatment. In this double-blind study, bulimic women who received 3 weeks of winter bright light treatment reported a reduced binge frequency between baseline and the active treatment period in comparison to subjects receiving dim red light.

Effect of Salsalate on Insulin Action, Secretion, and Clearance in Nondiabetic, Insulin-Resistant Individuals: A Randomized, Placebo-Controlled Study

PubMed Central

Liu, Alice; Ariel, Danit; Abbasi, Fahim; Lamendola, Cindy; Grove, Kaylene; Tomasso, Vanessa; Ochoa, Hector; Reaven, Gerald

2014-01-01

OBJECTIVE Salsalate treatment has been shown to improve glucose homeostasis, but the mechanism remains unclear. The aim of this study was to evaluate the effect of salsalate treatment on insulin action, secretion, and clearance rate in nondiabetic individuals with insulin resistance. RESEARCH DESIGN AND METHODS This was a randomized (2:1), single-blind, placebo-controlled study of salsalate (3.5 g daily for 4 weeks) in nondiabetic individuals with insulin resistance. All individuals had measurement of glucose tolerance (75-g oral glucose tolerance test), steady-state plasma glucose (SSPG; insulin suppression test), and insulin secretion and clearance rate (graded-glucose infusion test) before and after treatment. RESULTS Forty-one individuals were randomized to salsalate (n = 27) and placebo (n = 14). One individual from each group discontinued the study. Salsalate improved fasting (% mean change −7% [95% CI −10 to −14] vs. 1% [−3 to 5], P = 0.005) but not postprandial glucose concentration compared with placebo. Salsalate also lowered fasting triglyceride concentration (−25% [−34 to −15] vs. −6% [−26 to 14], P = 0.04). Salsalate had no effect on SSPG concentration or insulin secretion rate but significantly decreased insulin clearance rate compared with placebo (−23% [−30 to −16] vs. 3% [−10 to 15], P < 0.001). Salsalate was well tolerated, but four individuals needed a dose reduction due to symptoms. CONCLUSIONS Salsalate treatment in nondiabetic, insulin-resistant individuals improved fasting, but not postprandial, glucose and triglyceride concentration. These improvements were associated with a decrease in insulin clearance rate without change in insulin action or insulin secretion. PMID:24963111

Paroxetine in the treatment of dysthymic disorder without co-morbidities: A double-blind, placebo-controlled, flexible-dose study.

PubMed

Ravindran, Arun V; Cameron, Colin; Bhatla, Raj; Ravindran, Lakshmi N; da Silva, Tricia L

2013-04-01

Few published studies have evaluated selective serotonin reuptake inhibitors in dysthymia without current co-morbid major depression. In this 12-week study, 40 dysthymic patients were randomly assigned to either placebo (n=19) or 20-40 mg/day of paroxetine (n=21). At endpoint, the paroxetine group showed significantly greater improvement on the Clinical Global Impression Scale, Beck Depression Inventory, and Quality of Life Enjoyment and Satisfaction Questionnaire (p<0.05), and a trend to superiority over placebo on the Hamilton Depression Rating Scale. Response and remission were significantly higher with paroxetine than placebo (p<0.05). There were no significant differences in drop out rates or frequency of adverse effects, except for excessive sweating (greater with paroxetine, p=0.04). Reporting of multiple side effects was also higher with paroxetine than with placebo (p=0.02). Paroxetine is more effective than placebo in improving symptoms and quality of life in dysthymia, and is generally tolerable. Copyright © 2012 Elsevier B.V. All rights reserved.

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial

PubMed Central

2011-01-01

Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis. Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR): NTR2768 PMID:22070744

Placebo - More hatred than love.

PubMed

Zhang, Hong-Liang

2011-01-01

A placebo is a sham medical intervention that can produce a placebo effect. Laboratory evidence supports the existence of several mechanisms of placebo effects in both healthy population and patients with a variety of medical conditions. The ethics of placebos have long been debated. However, accumulating ethical concern has arisen from the worldwide use of placebo in randomized control trials (RCTs), which may render their participants without early and optimal treatment. Although the pilgrimage of placebo is still on the way, refinement of controls in RCTs is worth paying new attention to.

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.

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.

N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

ERIC Educational Resources Information Center

Bloch, Michael H.; Panza, Kaitlyn E.; Grant, Jon E.; Pittenger, Christopher; Leckman, James F.

2013-01-01

Objective: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method: A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary…

Efficacy and safety of diclofenac diethylamine 1.16% gel in acute neck pain: a randomized, double-blind, placebo-controlled study

PubMed Central

2013-01-01

Background Neck pain (NP) is a common musculoskeletal disorder in primary care that frequently causes discomfort. Non-steroidal anti-inflammatory drugs (NSAIDs) may be used to reduce neck pain and associated inflammation and facilitate earlier recovery. Topical diclofenac diethylamine (DDEA) 1.16% gel is clinically proven to be effective and well tolerated in acute and chronic musculoskeletal conditions, but until now no clinical data existed for its use in acute NP. The aim of this study was to assess the efficacy and safety of DDEA 1.16% gel compared with placebo gel in acute NP. Methods In a randomized, double-blind, placebo-controlled study, patients with acute NP (n = 72) were treated with DDEA 1.16% gel (2 g, 4x/day, for 5 days) or placebo. Efficacy assessments included pain-on-movement (POM), pain-at-rest (PAR), functional neck disability index (NDI) and response to treatment (decrease in POM by 50% after 48 h). Adverse events (AEs) were recorded throughout the study. Results The primary outcome, POM at 48 h, was statistically significantly lower with DDEA gel (19.5 mm) vs. placebo (56.9 mm) (p < 0.0001), representing a clinically relevant decrease from baseline (75% vs. 23%, respectively). All POM scores were significantly lower with DDEA gel vs. placebo from 1 h, as were PAR and NDI scores from first assessment (24 h) onwards (all p < 0.0001). Response to treatment was significantly higher with DDEA gel (94.4%) vs. placebo (8.3%) (p < 0.0001). There were no AEs with DDEA gel. Conclusions DDEA 1.16% gel, which is available over-the-counter, was effective and well tolerated in the treatment of acute neck pain. The tools used to assess efficacy suggest that it quickly reduced neck pain and improved neck function. However, questions remain regarding the comparability and validity of such tools. Further studies will help ascertain whether DDEA 1.16% gel offers an alternative treatment option in this common, often debilitating condition

Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study.

PubMed

Lauria, Giuseppe; Dalla Bella, Eleonora; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Fazio, Raffaella; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; La Bella, Vincenzo; Logroscino, Giancarlo; Mandrioli, Jessica; Mazzini, Letizia; Monsurrò, Maria Rosaria; Mora, Gabriele; Pietrini, Vladimiro; Quatrale, Rocco; Rizzi, Romana; Salvi, Fabrizio; Siciliano, Gabriele; Sorarù, Gianni; Volanti, Paolo; Tramacere, Irene; Filippini, Graziella

2015-08-01

To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40,000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. RhEPO 40,000 IU fortnightly did not change the course of ALS. 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.

A Randomized, Double-Blind, Single-Dose, Placebo-Controlled, Multicenter, Polysomnographic Study of Gabapentin in Transient Insomnia Induced by Sleep Phase Advance

PubMed Central

Rosenberg, Russell P.; Hull, Steven G.; Lankford, D. Alan; Mayleben, David W.; Seiden, David J.; Furey, Sandy A.; Jayawardena, Shyamalie; Roth, Thomas

2014-01-01

Study Objectives: To evaluate the effects of single doses of gabapentin 250 and 500 mg on polysomnographic (PSG) and participant-reported sleep measures in a 5-h phase advance insomnia model. Methods: Adults reporting occasional disturbed sleep received gabapentin 500 mg (n = 125), 250 mg (n = 125), or placebo (n = 127) 30 min prior to bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, post-sleep questionnaire, and the Karolinska Sleep Diary (KSD). Next-day residual effects (Digit Symbol Substitution Test [DSST] and Stanford Sleepiness Scale [SSS]) and tolerability were assessed. Results: Demographics were comparable among groups. Among PSG endpoints, wake after sleep onset (primary endpoint) (135.7 [placebo], 100.7 [250 mg], and 73.2 [500 mg] min) was significantly lower and total sleep time (TST) (311.4, 356.5, and 378.7 min) significantly greater in both gabapentin groups versus placebo. Latency to persistent sleep was not significantly different among groups. Percent slow wave sleep (12.6%, 15.4%, and 17.0%, respectively) was significantly greater and percent stage 1 (15.1%, 11.8%, and 10.8%, respectively) significantly lower relative to placebo. Gabapentin was associated with significantly higher values of KSD Sleep Quality Index and reported TST versus placebo; no other reported outcomes were significant. Neither gabapentin dose produced evidence of next-day residual effects as measured by DSST and SSS. Adverse events were infrequent (< 5%). Conclusion: Participants with occasional disturbed sleep treated with gabapentin showed significantly longer sleep duration and greater depth (versus placebo) in response to a phase advance manipulation known to disrupt sleep maintenance. Citation: Rosenberg RP, Hull SG, Lankford DA, Mayleben DW, Seiden DJ, Furey SA, Jayawardena S, Roth T. A randomized, double-blind, single-dose, placebo-controlled, multicenter, polysomnographic study of gabapentin in transient

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

Placebo Trends across the Border: US versus Canada