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PubMed2002

Migraine with aura versus migraine without aura: pain intensity and associated symptom intensities after placebo.

OBJECTIVE: To compare the intensity of pain and associated symptoms after placebo administration in patients with migraine with aura and migraine without aura. BACKGROUND: Studies that evaluate drugs used in the acute treatment of migraine ideally should include a placebo arm. The International Headache Society also recommends stratification according to age and sex but not by the presence versus absence of aura. METHODS: The study was conducted as part of a placebo controlled randomized survey comparing four active drugs against placebo in the acute treatment of migraine. Patients were blinded as to treatment received. Placebo consisted of 10 mL of normal saline (0.9%) intravenously. Pain intensity was evaluated by a 10-point analogical-verbal scale. Nausea, photophobia, and phonophobia were evaluated by a four-point analogical-verbal scale. For statistical analysis, unpaired t-test with Welch correction was used. RESULTS: After placebo administration, reduction of symptom intensity (pain, nausea, photophobia, and phonophobia) in patients with migraine without aura was significantly greater than that observed in patients with migraine with aura. CONCLUSIONS: Our findings suggest that studies comparing placebo against an active drug should use stratification according to the presence versus absence of aura.

Adult↗
PubMed2003

The impact of intensive serial plasmapheresis and iron supplementation on iron metabolism and Hb concentration in menstruating women: a prospective randomized placebo-controlled double-blind study.

BACKGROUND: Iron (Fe) depletion is common among regular whole-blood donors, but can be prevented through regular oral Fe supplementation. Little is known, however, about the Fe metabolism of donors undergoing intensive plasmapheresis. These donors lose considerable amounts of blood drawn for laboratory analyses and remaining in the disposable plastic sets. STUDY DESIGN AND METHODS: Menstruating women were enrolled in a prospective placebo- controlled double-blind study. One hundred women were randomly allocated to receive either 100 mg of elemental Fe per day or placebo over 24 weeks and asked to donate plasma at 1-week intervals. Hb was determined before each plasmapheresis. Ferritin, transferrin, and Fe concentration and reticulocyte count were measured every 4 weeks. RESULTS: Thirty donors in the placebo group and 29 receiving Fe completed the study. The total mean blood loss was 526 mL in the placebo group and 546 mL in the Fe arm (p=0.271). The number of donations with Hb values lower than 12.5 g per dL requiring prolongation of the time interval until the next plasmapheresis was significantly greater in the placebo arm. In the placebo group (n=30), ferritin levels began to decline significantly 4 weeks after entry. When the study was completed, Hb concentration and reticulocyte count also were found to be significantly lower in the placebo group than in the Fe study arm (p=0.028 and p=0.036, respectively). Hb, ferritin, and transferrin levels and reticulocyte counts did not change significantly in the Fe group during the observation period. CONCLUSION: Menstruating women undergoing regular plasmapheresis at short intervals are prone to develop Fe depletion. This can be prevented by regular Fe intake. Laboratory analyses in product plasma instead of serum gained from whole-blood samples could be an alternative to reduce blood loss.

Adult↗
PubMed1977

Effect of alcohol and benzodiazepines on performance as related to personality characteristics. Personality characteristics among healthy "placebo reactors" and nonreactors.

For 2 weeks 40 volunteers received either 5 mg diazepam, t.i.d., or 10 mg chlordiazepoxide, t.i.d., and placebo. A choice reaction test, two coordination tests, and an attention test were administered to the subjects on the 14th day of each treatment. Thirty minutes before the tests, the subjects ingested either alcohol., 5g/kg or a placebo drink, incombination with the last capsule. After the test the subjects rated the quality of their treatment as placebo, tranquilizer, or stimulant. The psychological tests taken before the treatments were Eysenck's EPIC-NESI, Taylor's Manifest Anxiety Scale (MAS), and Cattell's 16 PF inventory. A multiple regression analysis was computed. Personality factor scores found to be associated with a strong effect of the benzodiazepines were 16 PF's A, C, L, N, and Q, and EPIC's E. The effect of alcohol was associated with a high score of 16 PFs B factor. Personality factors associated with "placebo reactors" and nonreactors were investigated, as well. Those subjects on placebo indicating their treatment to be active were classified as "placebo reactors". A discriminant analysis revealed that 16PF's O and I factors discriminated effectively "placebo reactors" from nonreactors, and EPIC's SE and 16 PF's L factor nonreactors from "reactors".

Adult↗
PubMedDate not supplied

[Placebos in clinic and research: experimental findings and theoretical concepts].

The placebo response in medicine and psychology is incompletely understood, and is usually either mystified or down-played; a rational approach to the understanding of the placebo response, however, can be deduced from the scientific literature. We present 3 theories that may explain most of the placebo response in medical and psychological interventions: a) Regression to the mean (RTM): This refers to "errors" in measuring the outcome of therapies, that are due to small samples sizes, global assessment variables, spontaneous variability of symptoms, and other methodological reasons. b) Pavlovian Conditioning (PC): here the placebo response occurs as the consequence of successful association of diagnostic and therapeutic procedures in the past (illness history) of the individuum that resulted in symptom improvement. Neutral stimuli in the context of a treatment can thus gain therapeutic potency (become conditioned stimuli), e. g. the procedure of an injection or the colour of a drug. c) Signal detection theory (SDT): manipulation of expectencies and cognitions of the patient by suggestions and verbal instructions of the health care system will change the willingness of the patient to perceive symptoms as improved/worsened, specifically if this happens under "noisy" circumstances, e. g. with high spontaneous variability of symptoms. All three models are illustrated with examples from medical and psychological treatments or experiments, including recent findings of cortical correlates of the placebo response in functional brain imaging investigations. Potential biological mechanisms for the placebo response are discussed, including the possibility of genetic predisposition to be a placebo responder.

Clinical Trials as Topic↗
PubMed2006

[Placebo response in functional bowel disorders].

The placebo response in functional bowel disorders is incompletely understood, and is usually either mystified or down-played; a rational approach to the understanding of the placebo response, however, can be deduced from the scientific literature. We present 3 theories that may explain most of the placebo response in medical and psychological interventions. a) Regression to the Mean (RTM): This refers to "errors" in measuring the outcome of therapies that are due to small samples sizes, global assessment variables, spontaneous variability of symptoms, and other methodological reasons. b) Pavlovian Conditioning (PC): Here the placebo response occurs as the consequence of successful association of diagnostic and therapeutic procedures in the past (illness history) of the individual that resulted in symptom improvement. Stimuli in the context of a treatment can thus gain therapeutic potency (become conditioned stimuli), e. g., the procedure of an injection or the colour of a drug. c) Signal Detection theory (SDT): Manipulation of expectations and cognitions of the patient by suggestions and verbal instructions of the health-care system will change the willingness of the patient to perceive symptoms as improved/worsened, specifically if this happens under "noisy" circumstances, e. g., with high spontaneous variability of symptoms. All three models are illustrated with examples from the medical and psychological treatments or experiments, including recent findings of cortical correlates of the placebo response in functional brain imaging investigations. Potential biological mechanisms for the placebo response are discussed, including he possibility of the genetic predisposition to be a placebo responder.

Clinical Trials as Topic↗
PubMed2001

Gender and the placebo analgesic effect in acute pain.

OBJECTIVE: Our objective was to examine the placebo arms from a series of clinical trials in which the post-third molar extraction dental pain model was used to elucidate the time course of the placebo effect and the proportion of the population that are responders, as well as to evaluate whether the placebo analgesic response of female subjects may differ from that of male subjects. METHODS: We performed a meta-analysis of 596 subjects included in the placebo treatment arm of 16 double-blind, post-third molar extraction dental pain (moderate to severe) studies submitted to the Food and Drug Administration electronically. The inclusion and exclusion criteria were practically identical in all studies. Pain relief and pain intensity measurements used the same metrics in all studies. The measurements were recorded just before drug administration and at least at postdose hours 0.5, 1, 1.5, 2, 3, 4, 5, and 6. RESULTS: There were 325 female subjects and 271 male subjects. They were all otherwise healthy, with a mean age of 21.6 years for female subjects and 22.3 years for male subjects. The postoperative baseline pain was greater in female subjects than in male subjects, and this difference was statistically significant. Both pain intensity and pain relief scores demonstrate the well-established placebo effect in 10% of the pooled subjects, as well as in all the individual studies. Over time, however, the mean pain intensity and pain relief scores for the female and male treatment groups were not noticeably different at any time point after medication. Further analysis of the data showed no gender difference in duration of action of the placebo. CONCLUSIONS: The results demonstrated no gender difference in response to placebo. These results were obtained from the post-third molar extraction situation, in which the least possible confounding factors were present. To fully establish the generality of this phenomenon, studies should be carried out in other pain models.

Acute Disease↗
PubMed2000

Randomised, double blind, placebo controlled trial of penicillin V in the treatment of acute maxillary sinusitis in adults in general practice.

OBJECTIVE: To compare the effectiveness of penicillin V with placebo in the treatment of adult patients with acute maxillary sinusitis in general practice. DESIGN: Randomised, double blind, placebo controlled trial. SETTING: 26 Danish general practices. PATIENTS: 133 adult patients with a clinical diagnosis of acute maxillary sinusitis based on maxillary pain and raised values of either C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR). MAIN OUTCOME MEASURES: Pain score and illness score as well as measurement of CRP and ESR values after initiation of treatment. RESULTS: Penicillin V led to a better recovery than did placebo. The difference was statistically significant 3 days after the initiation of treatment with regard to pain reduction, whereas no significant difference was found with regard to the reduction in the sense of illness. At the end of the study, significantly more patients in the penicillin group were completely free of pain compared to the placebo group. This difference was only found in patients with an initial pain score of more than three. The cure rate was 71% in the penicillin group and 37% in the placebo group. Significantly more patients achieved normal CRP values when treated with penicillin (88%) as opposed to placebo (75%). CONCLUSION: Penicillin V is more effective than placebo in the treatment of acute maxillary sinusitis in adults in general practice, but only in patients with pronounced pain.

Acute Disease↗
PubMed1993

An experimental study of the placebo effect in African traditional medicine.

In an experimental study on the placebo effect in Malawi, an independent East African nation, 21 Malawian college students were tested individually in two 1-hour sessions on successive afternoons, using a one-group, two-condition before-after counterbalanced experimental design. Subjects were falsely told that a physiologically neutral substance they consumed would arouse the body, affecting oral temperature and pulse. Before-after measurements were taken during each day's session. On one of the days, the placebo resembled a traditional African herbal concoction, whereas on the other day, the placebo appeared to be a commercial Western-style medicine. The placebo effect was evaluated for each medication by comparing pre- and posttreatment scores. After the session, the subjects completed a questionnaire on their beliefs in the power of each style of medication. The placebo response was demonstrated in both medication conditions for oral temperature, but the strength of the placebo effect did not vary between medication styles. No significant relationship was found between the placebo effects and self-reported attitudes toward the two types of medication.

Adult↗
PubMed1998

Zidovudine treatment in patients with primary (acute) human immunodeficiency virus type 1 infection: a randomized, double-blind, placebo-controlled trial. DATRI 002 Study Group. Division of AIDS Treatment Research Initiative.

A multicenter, double-blind, placebo-controlled trial randomized 28 patients with primary (acute) human immunodeficiency virus (HIV)-1 infection (PHI) to receive zidovudine, 1000 mg daily, or placebo for 24 weeks. At week 48, compared with placebo patients, zidovudine-treated patients had significantly higher CD4 cell counts (zidovudine, 666 cells/mm3; placebo, 362; P = .004) and lower peripheral blood mononuclear cell (PBMC) culture titers (zidovudine, 0.58 log infectious units per million cells; placebo, 1.68; P = .02) but no difference in plasma RNA (zidovudine, 3.93 log copies/mL; placebo, 4.00; P = .83). Serious adverse events and minor clinical events were infrequent and comparable in both arms. There were two deaths: 1 patient died of sepsis and renal disease (zidovudine arm), and 1 patient died of sepsis and tension pneumothorax (placebo arm). Six months of high-dose zidovudine initiated during PHI results in higher CD4 cell counts and lower PBMC culture titers but no difference in plasma HIV-1 RNA. Further studies with more potent antiretroviral combination therapies are warranted.

Adolescent↗
PubMed2005

In vitro and in vivo characterization of a potential universal placebo designed for use in vaginal microbicide clinical trials.

The development of vaginal microbicides for the prevention of sexual transmission of HIV is becoming an increasingly important strategy in the battle against the AIDS epidemic. Several first generation microbicide candidates are entering Phase III efficacy trials, and several other candidates are in earlier stages of clinical development. The capacity to make accurate clinical assessments of the safety and efficacy of microbicide formulations is critical. Since microbicide trials will rely on a blinded, randomized, placebo-controlled design, it is important to employ a placebo formulation that does not distort either safety or efficacy assessments. Efficacy of the microbicide would be underestimated if the placebo itself provided a degree of protection. Conversely, a placebo with epithelial toxicity that increased susceptibility would cause an overestimation of microbicide efficacy. To address these issues, a hydroxyethylcellulose (HEC) placebo formulation has been developed and has been adopted for use in clinical evaluations of investigational microbicides as a "universal" placebo. In this report, the chemical and physical properties of this formulation are described, as well as its in vitro and in vivo effects on safety and efficacy. The results show that this "universal" placebo has adequate physical properties, is sufficiently stable as a vaginal gel formulation, and is safe and sufficiently inactive for use in the clinical study of investigational microbicides.

Animals↗
PubMed2005

A randomized, double-blind and placebo-controlled study of a Ganoderma lucidum polysaccharide extract in neurasthenia.

Ganoderma lucidum has been widely used to treat various diseases, including cancer, diabetes, and neurasthenia in many Asian countries. This randomized, double-blind, placebo-controlled parallel study aimed to investigate the efficacy and safety of a polysaccharide extract of G. lucidum (Ganopoly) in Chinese patients with neurasthenia. One hundred thirty-two patients with neurasthenia according to the diagnosis criteria of the 10th International Classification of Diseases were included in this study. Written consents were obtained from the patients, and the study was conducted in accordance with Good Clinical Practice guidelines. Patients were randomized to receive Ganopoly or placebo orally at 1,800 mg three times a day for 8 weeks. Efficacy assessments comprised the Clinical Global Impression (CGI) improvement of severity scale and the Visual Analogues Scales for the sense of fatigue and well-being. In 123 assessable patients in two treatment groups at the end of the study, Ganopoly treatment for 8 weeks resulted in significantly lower scores after 8 weeks in the CGI severity score and sense of fatigue, with a respective reduction of 15.5% and 28.3% from baseline, whereas the reductions in the placebo group were 4.9% and 20.1%, respectively. The score at day 56 in the sense of well-being increased from baseline to 38.7% in the Ganopoly group compared with 29.7% in the placebo group. The distribution of the five possible outcomes from very much improved to minimally worse was significantly different (X (2) = 10.55; df = 4; P = .0322) after treatment with Ganopoly or placebo. There was a percentage of 51.6% (32 of 62) in the Ganopoly group rated as more than minimally improved compared with 24.6% (15 of 61) in the placebo group (X (2) = 9.51; df = 1; P = .002). Ganopoly was well tolerated in the study patients. These findings indicated that Ganopoly was significantly superior to placebo with respect to the clinical improvement of symptoms in neurasthenia.

Administration, Oral↗
PubMed1998

Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: a randomized, double-blind, placebo-controlled, clinical trial.

To examine the role of recombinant human follicle stimulating hormone (rhFSH) in male idiopathic infertility a randomized, double-blind, placebo-controlled study was performed. Of 211 patients screened, 67 were finally included. After two pre-examinations, patients were randomized and treated for 12 weeks, either with 150 IU rhFSH or with placebo. Examinations (physical examination, scrotal ultrasonography, semen analysis, hormone measurements, and in 31 patients electron microscopy (EM) of spermatozoa were performed 6 and 12 weeks after treatment initiation and 6 and 12 weeks after completion of treatment. Pregnancies were recorded for a further 3 months after the last examination. Of the 67 patients included in the study, 34 treated and 31 placebo patients could be analysed. In the treated group, FSH was elevated compared to baseline values (P < 0.001). At the end of treatment testicular volume in the treated group was increased compared to placebo (P < 0.05) and baseline (P < 0.001). Apart from an increase in sperm motility (P < 0.05) in the placebo group and in sperm DNA condensation (P < 0.001) in the treated group no significant changes were observed in semen parameters. Two spontaneous pregnancies in partners of men in the treated group and none in the placebo group occurred. However, two pregnancies occurred in partners of men in the placebo group induced by intrauterine insemination or intracytoplasmic sperm injection. In conclusion, at the chosen dose and duration, rhFSH did not lead to an improvement of conventional or EM sperm parameters nor to an increase in pregnancy rates. However, the increased testicular volume and sperm DNA condensation give reason for further investigations.

DNA↗
PubMed2002

Repeat-cycle study of high-dose intravenous 4162W94 anti-CD4 humanized monoclonal antibody in rheumatoid arthritis. A randomized placebo-controlled trial.

OBJECTIVE: Results of an earlier open-label pilot study showed that 4162W94 was a relatively non-depleting anti-CD4 monoclonal antibody that induced >80% down-modulation of CD4 molecules from the surface of T lymphocytes. This placebo-controlled repeat-cycle study was conducted in active rheumatoid arthritis (RA) patients to determine the duration of CD4 blockade required to achieve lasting clinical benefit. METHODS: Following DMARD washout, 48 patients (i.e. three cohorts of 16 patients) with ACR-defined RA were to be dosed with 1 (cohort 1), 2 (cohort 2) or 3 (cohort 3) cycles of 5x300 mg 4162W94 or placebo (12 and 4 patients per cohort respectively) at monthly intervals. There was at least 3 months of follow-up after dosing. Clinical outcome was assessed in evaluable patients (receiving at least 80% of each dose course) using ACR20 criteria (required on two consecutive visits). CD4 lymphocyte counts and adverse events were also monitored. RESULTS: Sixteen patients were dosed in each of the first two cohorts; however, the dose was reduced in cohort 3 after five patients had received up to two dose cycles due to accumulating evidence of a high frequency of skin rash. These patients were analysed according to the number of cycles received. A further eight patients received 5x100 mg for one to three cycles prior to stopping the study for administrative reasons. Four of 13 (P=0.119 vs placebo) and 7/13 (P=0.015 vs placebo) in cohorts 1 and 2 respectively achieved ACR20 response on at least two consecutive occasions. No patient receiving 5x100 mg/day or placebo achieved ACR20. Four patients were still responding at the end of the 3-month follow-up period. CD4 lymphocyte suppression (<0.2x10(9)/l on at least two successive occasions) occurred in 11/34 patients who received 4162W94 vs none on placebo. Rash occurred in 21/34 monoclonal antibody-treated patients, including one case of biopsy-confirmed cutaneous vasculitis and 1/11 placebo patients. CONCLUSION: 4162W94 demonstrated significant clinical efficacy in this study. However, because of unacceptable CD4 lymphopenia and rash, the original hypothesis that prolonged CD4 blockade would give lasting clinical benefit was not tested.

Adult↗
PubMed1995

The utility of comparative local anesthetic blocks versus placebo-controlled blocks for the diagnosis of cervical zygapophysial joint pain.

BACKGROUND: The development of target-specific local anesthetic blocks has enabled pain physicians to explore the anatomical source of chronic spinal pain. However, such blocks rely on subjective responses and may be subject to the placebo effect. Comparative local anesthetic blocks have been advocated as a means of identifying true-positive cases and excluding placebo responders. This paradigm employs two local anesthetics with different durations of action; only patients who obtain reproducible relief and correctly identify the longer-acting agent are considered positive. OBJECTIVE: Our objective was to evaluate the reliability of comparative blocks of the medial branches of the cervical dorsal rami in the diagnosis of cervical zygapophysial joint pain. DESIGN: We compared comparative blocks and the criterion-standard of randomized, double-blind, placebo-controlled blocks. SETTING: The study was conducted at a tertiary referral center. PATIENTS: We studied the first 50 consecutive patients referred for assessment of chronic neck pain (> 3 months' duration) after a motor vehicle accident, who completed a series of placebo-controlled blocks after an initial positive response. Patients were 41 +/- 11 years (mean +/- SD) old with a male/female ratio of 1:2. METHODS: Patients underwent three blocks using three different agents-lignocaine, bupivacaine, and normal saline--administered on separate occasions, in random order and under double-blind conditions. The diagnostic decision based on comparative blocks alone was compared with that based on placebo-controlled blocks. RESULTS: Comparative blocks were found to have a specificity of 88%, but only marginal sensitivity (54%). Although comparative blocks result in few false-positive diagnoses, their liability is that they result in a high proportion of false-negative diagnoses. Expanding the comparative blocks diagnostic criteria to include all patients with reproducible relief, irrespective of duration, increases sensitivity to 100% but lowers specificity to 65%. CONCLUSIONS: Whether physicians use comparative or placebo-controlled blocks depends upon the implications of their results. If innocuous therapy will be prescribed, comparative blocks might suffice. However, when diagnostic certainty is critical, such as in a medicolegal context or when surgical intervention is contemplated, placebo-controlled blocks are recommended.

Adult↗
PubMed1999

Effect of the immunomodulating agent, pentoxifylline, in the treatment of sepsis in prematurely delivered infants: a placebo-controlled, double-blind trial.

OBJECTIVE: To evaluate the influence of the methylxanthine derivative, pentoxifylline, on plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6 in prematurely delivered infants with generalized bacterial infections and to assess the effect of this immunomodulating drug on the clinical outcome in newborns with sepsis. DESIGN: A prospective, randomized, double-blind trial. SETTING: The neonatal intensive therapy units in university teaching hospitals. PATIENTS: One hundred patients with sepsis admitted during a 1.5-yr period. INTERVENTIONS: Patients were randomly assigned to receive pentoxifylline (pentoxifylline group) in a dose of 5 mg/kg/hr for 6 hrs on 6 successive days or an identically presented placebo (placebo group). MEASUREMENTS AND MAIN RESULTS: Only infants with sepsis confirmed by positive blood culture were recruited into the study. There were no significant differences at randomization between the pentoxifylline and placebo groups with regard to the birth weight, gestational age, gender, Apgar score, hypotension, neutropenia, thrombocytopenia, metabolic acidosis, plasma levels of cytokines, and occurrence of shock. Plasma levels of TNF, IL-1, and IL-6 were evaluated before and after the drug or placebo administration on the first, third, and sixth days of therapy. Cytokines were determined by immunoenzymetric test EASIA (TNF) and Endogen Interleukin-Elisa (IL-1, IL-6). The frequency of gram-negative sepsis was similar in both groups (37.5% and 36.8%). Pentoxifylline significantly diminished plasma TNF levels (p = .009) but had no effect on plasma IL-1 levels. Mean plasma IL-6 levels, which were measured in the pentoxifylline group on the 6th day of the study, were significantly lower compared with respective data obtained in the placebo group. Only 1 of 40 infants with sepsis in the pentoxifylline group died, whereas 6 of 38 infants in the placebo group did not survive (p = .046). An increased incidence of disordered peripheral circulation and metabolic acidosis (p = .048), anuria or oliguria (p = .03), disseminated intravascular coagulation (p = .043), and the occurrence of clinical symptoms of necrotizing enterocolitis (p = .025) was observed in the course of sepsis in infants in the placebo group. CONCLUSION: Pentoxifylline significantly affects the synthesis of TNF and IL-6 as well as reduces the mortality rate in premature infants with sepsis. The dosage and schedule of drug administration in this study attenuated the severity of the clinical course of sepsis in this group of patients.

Adjuvants, Immunologic↗
PubMed2000

Side effects and time course of response in a placebo-controlled trial of fluoxetine for the treatment of geriatric depression.

A high rate of improvement among patients who receive placebo in controlled trials of antidepressants can complicate the evaluation of true drug effect. Placebo response may be a reaction to the psychosocial factors of study participation or a function of changes in the natural course of depression. Drug side effects may also influence patients' expectations, and they should be distinguished from the somatic symptoms associated with major depression. The authors reanalyzed data from a large, multicenter, placebo-controlled clinical trial of fluoxetine treatment of geriatric depression to evaluate similarities and differences between responders and nonresponders in both treatment groups. Specifically, the authors examined weekly somatic complaints as possible predictors of response and of dropout, as well as the time course and onset of response. Fluoxetine was superior to placebo on all outcome measures. Among somatic complaints associated with fluoxetine response, headache before and after randomization was associated with a good response and anxiety after randomization was associated with a poor response. Somnolence before and after randomization was associated with a good placebo response. Early and persistent improvement occurred among similar proportions of responders in both groups. The difference between fluoxetine and placebo seemed to be a persistent response beginning during the 4th week. Pretreatment somnolence was associated with early, persistent improvement in both groups and may serve as a marker for placebo response.

Aged↗
PubMed1987

Long-term treatment of severe chronic heart failure with captopril: a double-blind, randomized, placebo-controlled, long-term study.

Twenty-three patients with severe heart failure (NYHA classes III and IV) on treatment with digitalis and diuretics were additionally treated in a randomized double-blind study over a 6-month period with captopril (n = 12; mean daily dose 84 mg) or a placebo (n = 11) and were then reexamined. In the captopril group, the left-ventricular filling pressure decreased by 9 mm Hg (from 23 to 14) at rest and 6 mm Hg (from 35 to 29) during exercise. In the placebo group, there was an increase of 4 mm Hg (from 25 to 29) at rest and 7 mm Hg (from 33 to 40) during exercise; p less than 0.01 (p less than 0.01). In the captopril group, the cardiac index at rest increased 0.7 1/min/m2 (from 2.1 to 2.8) and during exercise 1.2 1/min/m2 (from 2.8 to 4.0). In the placebo group, the increase in cardiac index was considerably less pronounced at rest (= 0.2 1/min/m2; from 1.9 to 2.1) and during exercise (= 0.1 1/min/m2; from 2.7 to 2.8); p less than 0.02 (p less than 0.01). The improved cardiac output had a beneficial effect on the renal blood flow. Hippuran clearance increased by 46 ml/min (from 271 to 318), whereas in the control group it decreased 25 ml/min (from 259 to 234) (p less than 1.02). Both the heart rate and the arterial blood pressure remained constant, whereas the decrease in peripheral vascular resistance was definitely more pronounced in the captopril group (= 562 dyne X s X cm-5, from 1,841 to 1,279) than in the placebo group (= 123 dyne X s X cm-5, from 1,834 to 1,710; p less than 0.02). The heart volume, assessed radiographically, increased slightly in the placebo group, and the left-ventricular end-diastolic diameter remained constant in both groups. In the course of the study, two patients died in the captopril group and three in the placebo group. After six months, eight patients in the captopril group and three in the placebo group had improved by at least one NYHA category. The beneficial effects of captopril are due to its inhibitory effect on the renin-angiotensin system as well as to the inhibition of sympathetic stimulation. Consequently, in the captopril group the quantity of plasma norepinephrine decreased by 188 ng/ml (from 430 to 618); p less than 0.03. The indirect vasodilation caused by this mechanism leads to persistent unloading of the myocardium and an improvement in heart failure without loss of action by counterregulatory mechanisms.

Captopril↗
PubMed2001

Evaluation of omeprazole in the treatment of reflux laryngitis: a prospective, placebo-controlled, randomized, double-blind study.

OBJECTIVES: Proton-pump inhibitors are often recommended in the treatment of laryngitis secondary to gastric reflux. Despite prospective treatment studies reporting high efficacy, only one previous report has been placebo-controlled and blinded. The objective of this study was to determine the efficacy of omeprazole in treating proven reflux laryngitis. STUDY DESIGN: Prospective, placebo-controlled, randomized, double-blind clinical trial. METHODS: Fifty-three patients with one or more reflux laryngitis symptoms were recruited to undergo 24-hour dual-channel pH probe testing. Thirty patients with more than four episodes of laryngopharyngeal reflux were enrolled. By random assignment, 15 patients received 40 mg omeprazole twice a day and the other 15 received placebo for a period of 2 months. Symptoms (hoarseness, throat pain, lump in throat sensation, throat clearing, cough, excessive phlegm, dysphagia, odynophagia, and heartburn) and endoscopic laryngeal signs (erythema, edema, and mucus accumulation) were recorded initially, at 1 month, and 2 months. RESULTS: In general, most symptom scores improved over time for both the omeprazole and placebo groups. Hoarseness, when patients begin with low hoarseness symptom scores, and throat clearing improved significantly more in patients on omeprazole than in those on placebo during the 2-month study. Throat pain, lump in throat sensation, excessive phlegm, difficulty swallowing, pain with swallowing, and heartburn showed improvement in both treatment arms, signifying the possibility of a placebo effect. Endoscopic laryngeal signs did not change significantly over the course of the study for either treatment group. CONCLUSIONS: A placebo effect appears to exist in the treatment of reflux laryngitis. However, hoarseness, when initially scored low, and throat clearing resulting from reflux laryngitis are effectively treated by omeprazole.

Adult↗