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PubMed2003

Placebo effects of tobacco smoking and other nicotine intake.

Nicotine intake is a necessary but insufficient factor in maintaining tobacco smoking behavior, and nonpharmacological factors associated with smoking play a key role. Some of these factors may influence smoking behavior by eliciting placebo effects, or responses related specifically to the belief that one is consuming a drug. Greater knowledge of placebo effects of smoking would improve our understanding of factors that maintain smoking behavior, thereby aiding efforts to develop treatments to counter the influence of these factors. In addition, better understanding of placebo effects from other means of nicotine intake could help determine mechanisms of the therapeutic actions of nicotine replacement therapy, perhaps enhancing its efficacy in smoking cessation. Placebo effects of smoking or other nicotine intake have received little research attention. In this review, we first discuss common terms and methods of placebo research, especially the balanced-placebo design. We then examine the limited research directly assessing placebo effects of smoking and other nicotine intake, namely studies that manipulated instructions to subjects about the drug content of an ingested substance. Finally, we examine other studies relevant to gauging the likely magnitude of placebo smoking effects. In an effort to encourage more research on these placebo effects, we pay substantial attention to future directions. Among recommendations are testing the utility of the balanced-placebo design and other rigorously controlled designs, and including multiple measures of placebo effects in addition to self-report. Future research also should explore the moderating influences of the environmental context and of individual difference factors on placebo effects of smoking and other nicotine intake.

Clinical Trials as Topic↗
PubMed2006

Sham device v inert pill: randomised controlled trial of two placebo treatments.

OBJECTIVE: To investigate whether a sham device (a validated sham acupuncture needle) has a greater placebo effect than an inert pill in patients with persistent arm pain. DESIGN: A single blind randomised controlled trial created from the two week placebo run-in periods for two nested trials that compared acupuncture and amitriptyline with their respective placebo controls. Comparison of participants who remained on placebo continued beyond the run-in period to the end of the study. SETTING: Academic medical centre. PARTICIPANTS: 270 adults with arm pain due to repetitive use that had lasted at least three months despite treatment and who scored > or =3 on a 10 point pain scale. INTERVENTIONS: Acupuncture with sham device twice a week for six weeks or placebo pill once a day for eight weeks. MAIN OUTCOME MEASURES: Arm pain measured on a 10 point pain scale. Secondary outcomes were symptoms measured by the Levine symptom severity scale, function measured by Pransky's upper extremity function scale, and grip strength. RESULTS: Pain decreased during the two week placebo run-in period in both the sham device and placebo pill groups, but changes were not different between the groups (-0.14, 95% confidence interval -0.52 to 0.25, P = 0.49). Changes in severity scores for arm symptoms and grip strength were similar between groups, but arm function improved more in the placebo pill group (2.0, 0.06 to 3.92, P = 0.04). Longitudinal regression analyses that followed participants throughout the treatment period showed significantly greater downward slopes per week on the 10 point arm pain scale in the sham device group than in the placebo pill group (-0.33 (-0.40 to -0.26) v -0.15 (-0.21 to -0.09), P = 0.0001) and on the symptom severity scale (-0.07 (-0.09 to -0.05) v -0.05 (-0.06 to -0.03), P = 0.02). Differences were not significant, however, on the function scale or for grip strength. Reported adverse effects were different in the two groups. CONCLUSIONS: The sham device had greater effects than the placebo pill on self reported pain and severity of symptoms over the entire course of treatment but not during the two week placebo run in. Placebo effects seem to be malleable and depend on the behaviours embedded in medical rituals.

Acupuncture Analgesia↗
PubMed2001

Suicide risk in placebo-controlled studies of major depression.

OBJECTIVE: The purpose of this study was to determine if fear of an increased risk of attempted suicide in placebo groups participating in placebo-controlled studies is an argument against the performance of placebo-controlled trials in studies of major depression. METHOD: All short-term and long-term, placebo-controlled, double-blind studies that were part of a registration dossier for the indication of major depression that were submitted to the Medicines Evaluation Board, the regulatory authority of the Netherlands, from 1983 to 1997 were reviewed for attempted suicide. In addition, all long-term, placebo-controlled studies from a MEDLINE search that were conducted in the last decade in patients with major depression were assessed for attempted suicide. RESULTS: In 77 short-term studies with 12,246 patients in dossiers from the Medicines Evaluation Board, the incidence of suicide was 0.1% in both placebo groups and active compound groups. The incidence of attempted suicide was 0.4% in both placebo groups and active compound groups. In eight long-term studies with 1,949 patients, the incidence of suicide in the placebo groups was 0.0% and 0.2% in the active compound groups. Attempted suicide occurred in 0.7% of both placebo groups and active compound groups. In seven long-term MEDLINE studies, the incidence of attempted suicide in the placebo groups was not higher than in the groups treated with active compound. CONCLUSIONS: Fear of increased risk of attempted suicide in the placebo groups should not be an argument against performing short-term and long-term, placebo-controlled trials in major depression.

Antidepressive Agents↗
PubMed2004

A randomized controlled study comparing rofecoxib, diclofenac sodium, and placebo in post-bunionectomy pain.

OBJECTIVE: The relative efficacy of rofecoxib, diclofenac sodium, and placebo were compared in the treatment of acute pain after bunionectomy surgery. RESEARCH DESIGN AND METHODS: This was a double-blind, randomized, two-part study of 252 patients with moderate-to-severe pain the day after first metatarsal bunionectomy. Patients were treated with a single dose of rofecoxib 50 mg (N = 85), enteric-coated diclofenac sodium 100 mg (N = 85), or placebo (N = 82) on study Day 1 (Part I), and subsequently with daily rofecoxib 50 mg or placebo (diclofenac patients switched to placebo) over study Days 2-5 (Part II). Patients rated their pain at 16 time points over the first 24 h. Primary endpoint was total pain relief over 8 h (TOPAR8). Pre-specified secondary endpoints on Day 1 included onset of analgesia, peak pain relief, and duration of response. For Part II, supplemental analgesia use with rofecoxib compared to placebo was pre-specified for analysis over Days 2-5, with the focus on Days 2-3. Adverse experiences were recorded over Days 1-5. RESULTS: For TOPAR8 scores, rofecoxib 50 mg was significantly more effective than placebo (9.5 vs. 3.7, p < 0.001) and diclofenac (9.5 vs. 5.0, p < 0.001). Onset of analgesia was more rapid with rofecoxib than placebo (p = 0.003) and diclofenac (p = 0.019); proportion of patients achieving onset within 4 h with rofecoxib, diclofenac, and placebo was 46%, 27%, and 23%, respectively. Peak pain relief was greater with rofecoxib (1.8) than diclofenac (1.2, p = 0.004) and placebo (1.0, p < 0.001). Diclofenac and placebo patients required supplemental analgesia sooner than rofecoxib patients (2:03 h vs. 4:02 h, p < 0.001 and 1:41 h vs. 4:02 h, p < 0.001). Rofecoxib patients used significantly less (p < 0.001) supplemental analgesia than placebo patients over Days 2-3 (1.1 tablets/day vs. 2.1 tablets/day) and Days 2-5 (0.9 tablets/day vs. 1.8 tablets/day). No significant differences in adverse experiences between treatments were seen. CONCLUSION: Rofecoxib 50 mg was significantly more effective than placebo on all measures of treatment of post-bunionectomy pain. Rofecoxib 50 mg was significantly more effective than diclofenac sodium 100 mg based on Day 1 endpoints of total pain relief, onset time, and duration of response. All study medications were generally well tolerated.

Administration, Oral↗
PubMed2002

The placebo effect in alternative medicine: can the performance of a healing ritual have clinical significance?

In alternative medicine, the main question regarding placebo has been whether a given therapy has more than a placebo effect. Just as mainstream medicine ignores the clinical significance of its own placebo effect, the placebo effect of unconventional medicine is disregarded except for polemics. This essay looks at the placebo effect of alternative medicine as a distinct entity. This is done by reviewing current knowledge about the placebo effect and how it may pertain to alternative medicine. The term placebo effect is taken to mean not only the narrow effect of a dummy intervention but also the broad array of nonspecific effects in the patient-physician relationship, including attention; compassionate care; and the modulation of expectations, anxiety, and self-awareness. Five components of the placebo effect--patient, practitioner, patient-practitioner interaction, nature of the illness, and treatment and setting--are examined. Therapeutic patterns that heighten placebo effects are especially prominent in unconventional healing, and it seems possible that the unique drama of this realm may have "enhanced" placebo effects in particular conditions. Ultimately, only prospective trials directly comparing the placebo effects of unconventional and mainstream medicine can provide reliable evidence to support such claims. Nonetheless, the possibility of enhanced placebo effects raises complex conundrums. Can an alternative ritual with only nonspecific psychosocial effects have more positive health outcomes than a proven, specific conventional treatment? What makes therapy legitimate, positive clinical outcomes or culturally acceptable methods of attainment? Who decides?

Anxiety↗
PubMed1990

[Evaluation of the placebo effect on blood pressure profile during exercise in patients with mild uncomplicated hypertension].

UNLABELLED: The administration of placebo (pharmacologically inactive substance) is justified in clinical trials of antihypertensive drugs, in order to avoid the inclusion of placebo-responders. The evaluation of antihypertensive treatments during exercise is an interesting end point, since aerobic exercising is part of antihypertensive treatment. The aims of this study are to determine the placebo impact on blood pressure, heart rate and catecholamine secretion profiles during exercise testing. METHOD: 10 untreated essential mild to moderate hypertensives participated to a single blind study comprising two successive submaximal exercise testings (85% of maximal theoretical heart rate), separated by a single oral administration of placebo. Blood pressure and heart rate were measured after 10 minutes of resting position and at the end of each effort step (2 mm, 20 Watts), both before and after placebo. Blood samples (5 ml) were collected at rest and during maximal exercise before and after placebo, in order to determine the effect of placebo on circulating catecholamines. RESULTS: there was no significant variations between the "control" and exercise testings after placebo, neither on blood pressure or heart rate profiles, nor in values of circulating catecholamines [Noradrenaline at rest: 1.88 +/- 0.96, exercise: 6.43 +/- 1.93 nm/l before placebo, 1.65 +/- 0.83 nm/l and 5.71 +/- 2.12 nm/l after placebo respectively (NS)]. CONCLUSION: the placebo, which effect is generally determined on blood pressure at rest by sphygmomanometry, seems devoid of any activity on blood pressure, heart rate or catecholamine profile during exercise, in essential moderate hypertensives. Thus, antihypertensive treatments at exercise can be evaluated by comparison to baseline cardiovascular parameters without placebo groups.

Adult↗
PubMed1998

Double-blind placebo controlled trial of dextrose tablets and nicotine patch in smoking cessation.

In a placebo-controlled double-blind trial 308 smokers were individually randomly allocated to one of four groups: 1) 3 g dextrose tablets and 15 mg nicotine transdermal patch; 2) dextrose and placebo patch; 3) placebo tablets and nicotine patch; 4) placebo tablets and placebo patch. Patients were scheduled to attend weekly smokers clinic sessions starting 1 week before the quit date and continue for 4 weeks after that date. The primary outcome variable was biochemically verified abstinence at the final session, four weeks after the scheduled quit date. The proportion of smokers abstinent in the four groups was as follows: 49% - dextrose plus active patch; 44% - dextrose plus placebo patch; 36% - placebo tablet plus active patch; 30% - placebo tablet plus placebo patch. The difference between the dextrose and placebo tablets (13%) was statistically significant (P < 0.01, one-tailed); the difference between the active and placebo patches (6%) was not. There was no significant difference between the effect of the dextrose when accompanied by active versus placebo patches. There was no significant effect of dextrose on weight. The results suggest that dextrose supplementation to the diet may be a cheap and simple aid to giving up smoking. Further research is now needed to establish its long-term efficacy.

Adolescent↗
PubMed1995

Intravenous sotalol for the termination of supraventricular tachycardia and atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled study. Sotalol Multicenter Study Group.

Sotalol is an antiarrhythmic agent with combined beta-blocking and class III antiarrhythmic properties. This study was designed to assess the safety and efficacy of sotalol in terminating supraventricular tachycardia (SVT), atrial fibrillation (AFib), and atrial flutter (AFl). Ninety-three patients with spontaneous or induced SVT (n = 45) or AF (AFib or AFl; n = 48) with a ventricular rate of > or = 120 beats/min were studied. In the first phase, the double-blind phase, patients were randomly assigned to receive placebo or intravenous (i.v.) sotalol, 1.0 or 1.5 mg/kg. If SVT or AF did not convert to sinus rhythm or if the ventricular rate did not slow to < 100 beats/min within 30 minutes, patients then entered the second phase, the open-label phase, which also lasted 30 minutes, and were given 1.5 mg/kg iv sotalol. In the SVT group, during the double-blind phase conversion to sinus rhythm occurred in 2 (14%) of 14 of patients who received placebo, 10 (67%) of 15 who received sotalol, 1.0 mg/kg (p < 0.05 vs placebo), and 10 (67%) of 15 who received 1.5 mg/kg sotalol (p < 0.05 vs placebo); during the open-label phase, 1.5 mg/kg i.v. sotalol converted 7 (41%) of 17 of patients. In the AF group, during the double-blind phase conversion to sinus rhythm occurred in 2 (14%) of 14 of patients who received placebo, 2 (11%) of 18 who received 1.0 mg/kg sotalol (p not significant [NS] vs placebo), and 2 (13%) of 16 who received 1.5 mg/kg sotalol (p = NS vs placebo); in these groups, a > 20% reduction of ventricular rate without conversion to sinus rhythm occurred in 0 (0%) of 14, 13 (72%) of 18 (p < 0.05 vs placebo), and 12 (75%) of 16 of patients (p < 0.05 vs placebo), respectively; during the open-label phase, 1.5 mg/kg i.v. sotalol converted 7 (30%) of 23 of patients. The most common adverse events were hypotension and dyspnea. During the double-blind phase they occurred in 10% of patients who received placebo, 9% of those who received 1.0 mg/kg i.v. sotalol (p = NS vs placebo), and 10% of those who received 1.5 mg/kg i.v. sotalol (p = NS vs placebo). Most of these events were mild to moderate, but all were transient and clinically manageable.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2006

Safety, tolerability and efficacy of indacaterol, a novel once-daily beta(2)-agonist, in patients with COPD: a 28-day randomised, placebo controlled clinical trial.

In patients with chronic obstructive pulmonary disease (COPD) classified as moderate onwards, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines recommend regular treatment with one or more long-acting bronchodilators, such as beta(2)-agonists or anticholinergics. In contrast to currently available long-acting beta(2)-agonists, which have a duration of action of 12 h, indacaterol has demonstrated effective 24-h bronchodilation on once-daily dosing. A double-blind, randomised, placebo-controlled study was conducted to compare the safety, tolerability and efficacy of indacaterol with that of placebo, over a 28-day period, in patients with moderate COPD (as defined by GOLD 2001 criteria; equivalent to moderate-to-severe COPD in the GOLD 2005 criteria). Patients were randomised 2:2:1 to receive indacaterol 400 microg or 800 microg or placebo once-daily (between 07:00 and 11:00 h) via a single-dose dry-powder inhaler for 28 days. Assessments included monitoring of adverse events (AEs), blood chemistry (including serum potassium and blood glucose), vital signs (blood pressure and heart rate), electrocardiograms and spirometry. One hundred and sixty-three patients were randomised, with 155 (95%) completing the study. There were no statistically significant differences between treatment groups in the overall incidence of AEs, with AEs reported by 35%, 51% and 25% of patients in the indacaterol 400 microg, 800 microg and placebo groups, respectively. The majority of AEs were mild or moderate in severity, and there were no study-drug related serious AEs. There were no statistically significant differences between indacaterol groups and placebo in mean pulse rate and QTc interval, and isolated statistically significant (p<0.05) treatment-placebo differences in mean blood pressure, blood glucose and serum potassium. There was a statistically significant improvement in FEV(1) vs placebo at all post-baseline timepoints for both indacaterol treatment groups; 30 min post-dose, adjusted mean+/-SE FEV(1) indacaterol-placebo differences were: Day 1, 220+/-36 ml and 210+/-36 ml; Day 14, 320+/-50 ml and 270+/-50 ml; Day 28, 260+/-61 ml and 200+/-61 ml for 400 and 800 microg, respectively (all p<0.01 vs placebo). Bronchodilation was still apparent after 24h, with pre-dose (i.e. trough) adjusted mean+/-SE FEV(1) indacaterol-placebo differences of: Day 14, 230+/-44 ml and 210+/-44 ml; Day 28, 220+/-49 ml and 210+/-49 ml for indacaterol 400 and 800 microg, respectively (all p<0.0001 vs placebo). Once-daily indacaterol was well tolerated at doses up to 800 microg with a good overall safety profile. There was no statistical difference at any dose between the safety of indacaterol and placebo. Furthermore, this study supports the previously demonstrated 24-h bronchodilator efficacy of indacaterol.

Administration, Inhalation↗
PubMed1996

Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study.

BACKGROUND/AIMS: Small, uncontrolled studies of ribavirin for patients with chronic hepatitis C have reported efficacy in chronic hepatitis C. We have evaluated the efficacy and safety of a 24-week course of oral ribavirin in patients with chronic hepatitis C, compared to placebo. METHODS: A total of 114 patients were randomised to ribavirin or placebo. Ribavirin was administered in doses of 1000 or 1200 mg/day for 24 weeks. Efficacy was determined in the intention-to-treat population: 76 received ribavirin and 38 placebo. RESULTS: Ribavirin was significantly more effective than placebo in reducing and normalising serum ALT levels: 42/76 (55%) of ribavirin-treated patients vs 2/38 (5%) placebo recipients had either normalisation of the ALT levels or a reduction from baseline of at least 50% (p < 0.001). ALT levels were normal in 22/76 (29%) of ribavirin-treated patients vs 0/38 placebo recipients (p < 0.001). Twenty-four weeks after stopping ribavirin, the majority of patients had abnormal ALT levels. There was no difference between the treatment groups in reduction or disappearance of HCV-RNA levels. HCV RNA disappeared during treatment in 3% of ribavirin-treated patients and 3% of placebo recipients. More ribavirin than placebo patients showed improvement in total Knodell score (45% vs 31%), but these differences were not statistically significant. Analysis of each component of a histology activity index revealed no statistically significant differences between treatment groups. Ribavirin patients had fewer lymphoid aggregates than did placebo recipients at the post-treatment assessment (p = 0.05). Ribavirin was associated with reversible haemolytic anaemia: a fall in haemoglobin occurred in 3% of placebo- and 32% (25/78) of ribavirin-treated patients, respectively (p < 0.001). CONCLUSIONS: These data indicate that ribavirin was no more effective than placebo in reducing or eliminating HCV-RNA levels, and was not significantly more effective than placebo in improving hepatic histology after 6 months of treatment. The role of a 6-month treatment of chronic hepatitis C with ribavirin alone, without a significant effect on HCV RNA, is therefore limited.

Administration, Oral↗
PubMed1999

A double-blind, placebo-controlled study of topical tetracaine in the treatment of herpes labialis.

BACKGROUND: Before the September 1996 approval of 1% penciclovir cream for the treatment of herpes labialis, no other prescription topical therapy was approved for the treatment of this recurrent viral disease affecting approximately 20% of the adult population of the United States. Local anesthetics, such as tetracaine, have been used in over-the-counter topical products, but are only labeled for the relief of pain and itching associated with cold sores and fever blisters. OBJECTIVE: The purpose of this study was to determine whether a topical preparation of a tetracaine cream is safe and effective in the treatment of recurrent herpes labialis in immunocompetent patients. METHODS: A double-blind, placebo-controlled study was conducted to assess the relative effectiveness and safety of 1.8% tetracaine equivalent in a cream base versus placebo in the treatment of herpes labialis in immunocompetent adults. In this study, patients applied medication up to 6 times daily until the lesions healed (scab loss), but for no more than 12 days. The patients were monitored on the day of enrollment, once during the course of treatment, and at a final visit after the lesions had healed. Patients assessed themselves the day of scab formation and the day the scab fell off. They also graded, on a daily basis, their perception of relief from itching and pain and the overall benefit. RESULTS: The results from 72 patients (35 = placebo; 37 = active) showed that scab formation occurred in a mean of 2.4 +/- 0.27 days for the placebo group and 2. 3 +/- 0.26 days for the active group. Healing time (scab loss) occurred in a mean 7.2 +/- 0.36 days for the placebo group and in 5. 1 +/- 0.35 days in the active group. The difference observed for healing time between the placebo and the active tetracaine cream was statistically significant (P =.0002). This represents an approximately 30% reduction in the healing time for the active group compared with the placebo group. In addition, the study patients ranked the benefit of their treatment on a daily basis and graded the overall benefit of the therapy at their final visit. The ranking was on a 1 to 10 index scale (1 = no benefit at all; 10 = very effective treatment). At the final visit there was a statistically significant difference in the benefit index for active preparation versus placebo for this subjective evaluation (placebo index, 5.9 +/- 0.6; active index, 7.3 +/- 0.48 [P =.0359]). The subjects also evaluated relief from itching and pain on a daily basis. Relief from itching was significantly greater in the active group than in the placebo group on days 2 and 3 after initiation of the treatment. Pain was not found to be severe in either the placebo or active treatment groups. At day 2 of treatment and beyond, pain scores never were greater than 3.2 +/- 0.28 for active on a scale in which 1.0 represented "no pain at all" and 10 represented "most severe pain imaginable." Although mean values for pain were always less for the active therapy, lesional pain scores never reached statistically significant lower values for active compared with placebo. CONCLUSION: Our findings indicate that a 1.8% topical tetracaine cream, when applied frequently, significantly reduces the healing time of recurrent herpes labialis lesions. Additionally, it is perceived by the study subjects to reduce itching of the lesions and to have a beneficial overall effect.

Administration, Topical↗
PubMed2000

Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study.

AIM: To assess the efficacy and tolerability of sibutramine 15 mg once daily as a weight reduction agent in overweight and obese patients (body mass index (b.m.i.) > 26 kg/m2) with type 2 diabetes when given with a customised, reduced-calorie diet, and to evaluate the influence of weight loss on diabetic control. METHODS: Randomised, placebo-controlled, double-blind, parallel-group, 12-week study conducted at two hospital-based obesity/diabetes clinics. Patients were men and women aged 30-65 years, with b.m.i. > 26 kg/m2 and < or = 35 kg/m2 and treated or untreated type 2 diabetes diagnosed > or = 6 months previously. Each patient was given sibutramine 15 mg or placebo once daily and advised to follow a customised diet of 500 kcal/day less than the individual's energy needs. The principal measure of efficacy was change in body weight (b.w.). Additional efficacy measurements were changes in b.m.i., body composition as measured by dual-energy X-ray absorptiometry, and change in waist and hip measurements. Changes in diabetic control were assessed by blood glucose levels fasting and after a standard test meal, fasting insulin level, and glycosylated haemoglobin level. Adverse events (AEs) were monitored at each visit, and routine laboratory safety tests were done at 4-week intervals. RESULTS: Ninety-one patients were randomised into the study, 44 to placebo and 47 to sibutramine 15 mg once daily. Eighty-three patients (91%) completed the study, 40 (91%) on placebo and 43 (91%) on sibutramine. Mean weight reduction from baseline was statistically significantly greater with sibutramine than with placebo at every measurement and at the end of the study (2.4 vs. 0.1 kg at week 12; p < 0.001; intent-to-treat). The proportion of patients who lost > 5% of their baseline b.w. was 19% in the sibutramine group and 0% in the placebo group (p < 0.001; 95% confidence interval: 9, 30). Patients receiving sibutramine lost significantly more fat mass compared with those receiving placebo, as a percentage (1.0% vs. 0.1%; p < 0.05) and in absolute terms (1.8 vs. 0.2 kg, p < 0.001). Loss of lean mass was not significantly different between the groups. Mean peak blood glucose concentration after a standard test meal decreased by 1.1 mmol/l in the sibutramine treatment group but increased by 0.5 mmol/l in the placebo group (p = 0.04; difference in means, 1.6, 95% confidence interval: -3.3, -0.1). Mean fasting blood glucose decreased by 0.3 mmol/l with sibutramine and increased by 1.4 mmol/l with placebo. Mean glycosylated haemoglobin levels decreased by 0.3% units with sibutramine treatment, and were unchanged with placebo. However, more sibutramine-treated patients (33%) than placebo-treated patients (5%) achieved decreases in glycosylated haemoglobin of 1% unit or more (p < 0.05). Sibutramine 15 mg was safe and well tolerated, and AEs were mostly mild or moderate in severity. No significant differences were found between treatment groups in blood pressure. No clinically significant conduction or rhythm abnormalities were observed on ECG. CONCLUSIONS: Sibutramine 15 mg once daily with a customised, reduced-calorie diet significantly reduced weight compared with placebo in overweight and obese patients (b.m.i. > 26 kg/m2) with type 2 diabetes. Sibutramine was well tolerated, and significant improvement in diabetic control was seen in conjunction with weight reduction on sibutramine treatment.

Absorptiometry, Photon↗
PubMed2006

Evaluation of levalbuterol metered dose inhaler in pediatric patients with asthma: a double-blind, randomized, placebo- and active-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of levalbuterol metered dose inhaler (MDI) in children aged 4-11 years (n = 173). RESEARCH DESIGN AND METHODS: Multicenter, randomized, double-blind 28-day study of QID levalbuterol 90 microg, racemic albuterol 180 mug, and placebo (2:1:1 ratio). Serial spirometry was performed on Days 0, 14, and 28. The primary endpoint was the double-blind average peak percent (%) change in FEV(1) from visit pre-dose; the primary comparison was with placebo. Secondary endpoints included the area under the FEV(1) percent change from pre-dose curve and peak % predicted FEV(1). Safety endpoints included adverse events, laboratory tests, rescue medication use, and electrocardiograms. RESULTS: Levalbuterol significantly improved the least square mean peak percent change in FEV(1) compared with placebo (levalbuterol 25.6% +/- 1.3% [p < 0.001]; racemic albuterol 21.8% +/- 1.8% [p = ns]; placebo 16.8% +/- 1.9%). Results for levalbuterol were similar for the other spirometry endpoints (p < 0.05 vs. placebo). No levalbuterol-treated patients had a peak percent change in FEV(1) < 10% (compared with 15.8% of racemic albuterol-treated patients and 30.3% of placebo-treated patients). The incidence of adverse events was 43.4% for levalbuterol, 56.4% for racemic albuterol, and 51.4% for placebo. The rate of discontinuation was 1.3% for levalbuterol, 2.6% for racemic albuterol, and 8.6% for placebo. The rate of asthma attacks (10.5%, 12.8%, 14.3%, respectively) was similar among treatments. Levalbuterol and racemic albuterol both reduced rescue medication use (p < 0.01 vs. placebo) and produced changes in ventricular heart rate and QT(c-F) that were similar to placebo. CONCLUSIONS: In this study, levalbuterol administered via MDI significantly improved airway function in comparison with placebo in asthmatic children aged 4-11 years with a safety profile that was similar to placebo.

Administration, Inhalation↗
PubMed2005

Etoricoxib provides analgesic efficacy to patients after knee or hip replacement surgery: a randomized, double-blind, placebo-controlled study.

UNLABELLED: In this randomized, double-blind, placebo-controlled, multicenter study we assessed the analgesic effect of etoricoxib (a new cyclooxygenase-2 inhibitor) in patients having had knee or hip replacement surgery. A total of 228 patients with moderate or severe pain were randomly allocated within 72 h after surgery to receive etoricoxib 120 mg, controlled-release naproxen sodium 1100 mg, or placebo (1:1:1) on day 1 followed by etoricoxib and placebo (1:2) on days 2 to 7. Patients reported pain scores, rescue (opioid-combination) medication use, and the response to study drug. On day 1, etoricoxib provided an analgesic effect superior to placebo and similar to controlled-release naproxen sodium as demonstrated by the total pain relief score over 8 h, the primary end-point; least-squares mean scores were 11.0, 11.5, and 5.6, respectively (P < 0.001 versus placebo). Similarly, a larger percentage of patients receiving etoricoxib and naproxen sodium than those receiving placebo reported good to excellent responses to study drug: 53%, 60%, and 26% respectively. On days 2-7, etoricoxib demonstrated a significant reduction of rescue medication use, 35% (P < 0.001 versus placebo). The clinical relevance of the decrease was confirmed by Patient's Global Evaluation (P < 0.05 versus placebo). Patients receiving etoricoxib also experienced significantly less "worst" and "average" pain than did those on placebo. Etoricoxib was generally well tolerated in this study; the incidence of adverse experiences was infrequent and similar across treatment groups. In summary, etoricoxib provided analgesia that was similar to controlled-release naproxen sodium on day 1 and superior to placebo with reduced supplemental opioid use over 7 days. IMPLICATIONS: In a postsurgery setting (knee and hip replacements), etoricoxib 120 mg provided analgesia superior to placebo and similar to controlled-release naproxen sodium 1100 mg. Patients receiving etoricoxib suffered less pain and took less opioid rescue medication compared with patients on placebo.

Adult↗
PubMed1996

Clinical Trials: Design Flaws Associated with Use of a Placebo.

BACKGROUND: The placebo arm of a trial, although it controls for psychological placebo effects and natural history of a disease and facilitates effective blinding, is susceptible to bias just like the true treatment arm is. The placebo arm of a trial may even be particularly vulnerable to specific types of bias. The present article focuses on design flaws associated with the use of a placebo. RESULTS: (1) Placebo-controlled trials using mortality rather than morbidity as the end point may have both ethical and statistical problems. (2) Bias may affect placebo data to a larger extent than active treatment data. (3) Trials may provide an atmosphere of exaggerated placebo effects and, consequently, inadequate power to determine differences between placebo and active treatment groups. (4) A biased placebo period due to carryover effect is a common problem of controlled trials with a crossover or self-controlled design. (5) Adjustment for asymmetries between placebo and treatment group in a parallel-group trial is inappropriate if such asymmetries are not completely independent on the main variables of the study. (6) Samples may not be representative when a large number of patients inappreciative of a possible treatment with placebo refuse randomization. CONCLUSIONS: It is emphasized that routinely accounting for design flaws associated with use of placebo may further improve the powerful method of controlled clinical trials.

Journal Article↗
PubMed1987

Effect of ketanserin in the treatment of patients with intermittent claudication: results from 13 placebo-controlled parallel group studies.

The effect of ketanserin on intermittent claudication was assessed in 13 placebo-controlled parallel group studies following basically the same protocol. After a single-blind placebo run-in period of 1-2 months, the patients randomly received either ketanserin (n = 152) or placebo (n = 158) for 3-6 months. Data on walking distance, assessed on the treadmill, were available in 12 centers (239 patients). Walking distance significantly increased in seven centers with ketanserin and in two centers with placebo. In two centers, the intergroup comparison between ketanserin and placebo was significantly in favor of ketanserin; in one center, it was in favor of placebo. A pooled analysis of all data on walking distance showed that ketanserin significantly increased walking distance by 65%, whereas placebo significantly increased it by 25%. However, the intergroup comparison does not show significant differences. Comparison of individual responses, on the other hand, showed that more patients experienced a doubling of walking distance on ketanserin than on placebo (25 versus 13%), and fewer patients deteriorated on ketanserin than on placebo (23 versus 32%); this difference in response rate is significant (p less than 0.05). In these studies there was a striking difference in drop-out rate between ketanserin and placebo. In total, 25 patients dropped out during placebo treatment versus 14 during ketanserin treatment. Nine of the 25 dropouts on placebo suffered severe "cardiovascular events," whereas no such events were observed in the ketanserin group. This difference is highly significant and suggests that ketanserin may have a vascular protective effect in patients with intermittent claudication. This possibility is being investigated in a prospective trial (PACK trial).

Blood Pressure↗
PubMedDate not supplied

The placebo effect.

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.

Clinical Trials as Topic↗
PubMed1997

Classical conditioning and the placebo effect.

Stimulus substitution models posit that placebo responses are due to pairings of conditional and unconditional stimuli. Expectancy theory maintains that conditioning trials produce placebo response expectancies, rather than placebo responses, and that the expectancies elicit the responses. We tested these opposing models by providing some participants with information intended to impede the formation of placebo expectancies during conditioning trials and by assessing placebo expectancies. Although conditioning trials significantly enhanced placebo responding, this effect was eliminated by adding expectancies to the regression equation, indicating that the effect of pairing trials on placebo response was mediated completely by expectancy. Verbal information reversed the effect of conditioning trials on both placebo expectancies and placebo responses, and the magnitude of the placebo effect increased significantly over 10 extinction trials. These data disconfirm a stimulus substitution explanation and provide strong support for an expectancy interpretation of the conditioned placebo enhancement produced by these methods.

Adolescent↗