Placebo-controlled Parallel Study Research Articles

Effects of wheat bran and olestra on objective measures of stool and subjective reports of GI symptoms

OBJECTIVE: The aim of this study was to compare the effects of two nondigested, nonabsorbed dietary components on objective and subjective measures of gastrointestinal (GI) function. METHODS: A placebo-controlled parallel study compared the effects of wheat bran (20 g/day or 40 g/day in cereal), a well-known dietary fiber, with those of olestra (20 g or 40 g/day in potato chips), a nonabsorbed fat, on stool output, stool apparent viscosity (log peak force for extrusion [PF]), stool water content, and GI symptoms. Sixty subjects resided on a metabolic ward for 9 days: 3 days baseline and 6 days treatment. RESULTS: Compared with placebo, consumption of 20 g/day wheat bran for 6 days resulted in a rapid (within 38 h) increase in mean (±SE) stool output (placebo, 150 ± 29 g/day; bran, 246 ± 35 g/day, p < 0.05), a directional increase in mean stool water content (placebo, 81.2 ± 0.8%; bran, 83.9 ± 0.8%), stool water output (placebo, 159 ± 54 g/day; bran, 238 ± 30 g/day), and bowel movement frequency (BM/day) (placebo, 2.2 ± 0.4; bran, 2.6 ± 0.4), and no stool-softening effect (placebo log PF, 2.9 ± 0.1 g; bran log PF, 2.9 ± 0.1 g). Wheat bran 40 g/day results were not significantly different from wheat bran 20 g/day. Compared with placebo, consumption of olestra 20 g/day and 40 g/day for 6 days showed no significant difference in mean stool output (151 ± 18 g/day and 204 ± 28 g/day, respectively), mean BM frequency (1.8 ± 0.2 BM/day and 2.1 ± 0.3 BM/day, respectively), and stool water output (138 ± 13 g/day and 184 ± 31 g/day, respectively), a significant ( p < 0.05) decrease in stool water content (75.5 ± 1.7% and 72.6 ± 2.2%, respectively), and either no effect on stool apparent viscosity (olestra 20 g/day, mean log PF, 3.0 ± 0.1 g) or a gradual stool-softening effect beginning study day 6 (olestra 40 g/day, log PF, 2.7 ± 0.1 g). None of the treatment groups showed a significant increase in GI symptoms compared with placebo. CONCLUSIONS: Consumption of wheat bran in excess of levels in a typical Western diet significantly increased stool output, but did not soften normal-viscosity stool nor result in an increase in common GI symptoms. The observed plateau effect for wheat bran at 40 g/day suggests a maximal mechanical stimulatory effect. Consumption of olestra in excess of usual snacking conditions did not result in a significant increase in stool output or common GI symptoms. At the highest level tested, olestra resulted in a gradual stool-softening effect after several days of consumption.

Ozone-induced inflammation assessed in sputum and bronchial lavage fluid from asthmatics:: A new noninvasive tool in epidemiologic studies on air pollution and asthma

We investigated correlations between ozone-induced increases in inflammatory markers in induced sputum and in bronchial lavage fluid. Sixteen volunteers with intermittent asthma participated in a placebo-controlled parallel study with two exposures. Six days before and 16 h after the first exposure to ozone (0.4 ppm during 2 h) sputum was induced with hypertonic saline. This resulted in a significant increase in the sputum levels of eosinophil cationic protein (ECP; 1.8-fold; p = .03), neutrophil elastase (5.0-fold; p = .005) and the total cell number (1.6-fold; p = .02). After 4 weeks, a second exposure was randomized for air or ozone. Six days before and 16 h after the second exposure a bronchial lavage was performed. ECP values in sputum and in bronchial lavage fluid obtained after ozone correlated significantly (Rs = .79; p = .04), as did interleukin-8 (IL-8) values (Rs = .86; p = .01), and the percentage eosinophils (Rs = .89; p = .007). Moreover, the ozone-induced changes in percentage eosinophils observed in sputum and lavage fluid were highly correlated (Rs = .93; p = .003). In conclusion, changes in eosinophils, IL-8, and ECP markers induced by ozone and measured in sputum reflect the inflammatory responses in the lower airways of asthmatics, and may provide a noninvasive tool in epidemiologic studies on air pollution and asthma.

Experimental rhinovirus 16 infection causes variable airway obstruction in subjects with atopic asthma.

Exacerbations of asthma are often associated with rhinovirus infections. However, it has not been investigated whether rhinovirus infection can induce variable airway obstruction in asthma. We examined the effect of experimental rhinovirus 16 (RV16) infection on daily home recordings of FEV(1) in 27 subjects (nonsmoking, atopic, mildly asthmatic) who participated in a parallel placebo-controlled study. The subjects used a microspirometer to record FEV(1) three times daily from 4 d before until 10 d after RV16 (n = 19) or placebo (n = 8) inoculation. In addition, symptoms of asthma and symptoms of common cold were scored. Airway hyperresponsiveness to histamine was measured 3 d before and on Days 4 and 11 after RV16/placebo administration. Home recordings of FEV(1) decreased significantly after RV16 infection, reaching a minimum 2 d after inoculation (ANOVA, p </= 0.005), which was significantly different from placebo (p </= 0.004). In the RV16 group the lowest FEV(1) (expressed as a percentage of personal best) during Days 0-3 after infection (mean +/- SEM: 78.7 +/- 2.6% versus baseline: 85.6 +/- 1.2%, p = 0.008) correlated significantly with the cold score (r = -0.47, p = 0.04), asthma score (r = -0.47, p = 0.04), and with the decrease in airway hyperresponsiveness on Day 4 as compared with baseline (r = 0.50, p = 0.03). We conclude that experimental RV16 infection augments variable airway obstruction in subjects with asthma. This favors a causative role for rhinovirus colds in asthma exacerbations, and is in keeping with rhinovirus-induced worsening of airway inflammation.

A randomized, double-masked, placebo-controlled parallel study of loteprednol etabonate 0.2% in patients with seasonal allergic conjunctivitis

Objective To evaluate the effects of loteprednol etabonate (LE) 0.2% in reducing the signs and symptoms of seasonal allergic conjunctivitis. Design Randomized, double-masked, placebo-controlled, parallel group multicenter study of 6 weeks duration. Participants A total of 135 patients with signs and symptoms of seasonal allergic conjunctivitis participated. Intervention All patients received either LE 0.2% or placebo (vehicle) four times a day in both eyes for 42 days. Main outcome measures Bulbar conjunctival injection (primary sign) and itching (primary symptom) over the first 2 weeks of treatment was measured. Results A reduction in severity was seen in both LE and placebo groups for bulbar conjunctival injection (1.5 vs. 1.0 units on a 0–3 scale) and itching (3.4 vs. 3.0 units on a 0–4 scale) over the first 2 weeks. The treatment effect by these measures was −0.5 and −0.4 units in favor of LE ( P ≤ 0.008). Resolution (i.e., the proportion of patients with signs or symptoms no longer present) at day 14 strongly favored LE-treated patients (36% and 15%; 58% and 38%, for injection and itching, respectively). Both treatments were well tolerated. One patient in each treatment group (1 of 67 and 1 of 68, respectively) had an elevation of intraocular pressure of 10 mmHg or greater during the 6 weeks of treatment. Conclusions Loteprednol etabonate 0.2% was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate 0.2% had a safety profile comparable to placebo.

A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis

Background: Loteprednol etabonate is a site-active corticosteroid with efficacy and safety in treating ocular inflammation at the 0.5% concentration. Evidence from dose-response studies suggested that the 0.2% concentration might be effective in treating ocular allergy. Objectives: The objective of this study was to evaluate the effects of 0.2% loteprednol etabonate in reducing the signs and symptoms of seasonal allergic conjunctivitis. Methods: This was a randomized, double-masked, placebo-controlled, parallel-group multicenter study. Patients with signs and symptoms of environmental seasonal allergic conjunctivitis received either loteprednol etabonate or placebo bilaterally four times daily for 42 days. Results: Enrolled were 133 patients (66 receiving loteprednol etabonate; 67 receiving placebo). A reduction in severity was seen in both loteprednol etabonate and placebo groups for bulbar conjunctival injection (1.3 vs 0.9 units on a 0 to 3 scale) and itching (3.5 vs 3.1 units on a 0 to 4 scale) over the first 2 weeks. The treatment effect was –0.5 and –0.6 units in favor of loteprednol etabonate ( P < .001). Resolution (the proportion of patients with the sign or symptom no longer present) at visit 4 (day 14) strongly favored loteprednol etabonate-treated patients over placebo-treated patients (31% and 9%, and 54% and 38%, for injection and itching, respectively). Both treatments were well tolerated. No patients in either treatment group (0 for loteprednol etabonate and 0 for vehicle) had an elevation of intraocular pressure of 10 mm Hg or greater during the 6 weeks of treatment. Conclusions: Loteprenol etabonate (0.2%) was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate (0.2%) had a safety profile comparable to placebo during this 6-week trial. (J Allergy Clin Immunol 1998;102:251-5.)

Nebulized flunisolide in infants and young children with asthma: A pilot study

The role of nebulized flunisolide solution in controlling recurrent respiratory symptoms was assessed in a double-blind placebo-controlled parallel study on 23 infants and small children (mean age, 14.2 months) with bronchial asthma. Five of the 12 children in the placebo group and 1 of the 11 patients on active treatment had to be withdrawn from the study. Flunisolide significantly improved symptom scores of wheezing and cough. The rescue treatments with salbutamol did not differ between the two groups during the study. Parents considered the active treatment effective in all the patients, while the placebo was considered useful in 4 of 7 children. No side effects were detected with either treatments. This study indicates that nebulized flunisolide may be an effective treatment for infants with recurrent wheezing and cough.

Acute hemodynamic and long-term clinical effects of isradipine in patients with coronary artery disease and chronic heart failure. A double-blind, placebo-controlled study

To assess the acute hemodynamic and long-term clinical effects of isradipine, a calcium antagonist of the dihydropyridine class, we performed a double-blind, placebo-controlled parallel study in 19 patients with coronary artery disease (CAD) and stable chronic heart failure (CHF). Their mean age was 56 ± 5 years, and left ventricular ejection fraction (LVEF) was 0.18 ± 0.05. Patients were treated with diuretics and digoxin only. All were clinically stable and in sinus rhythm. The acute hemodynamic study showed that (intravenous) isradipine increased cardiac index (+36%) and stroke volume index (+30%) (both P < 0.001), while systemic vascular resistance (−33%) and mean arterial pressure (−10%) decreased (both P < 0.005). Filling pressures and heart rate were not affected. Of the 19 patients, 17 completed the 12 week study; 2 patients on placebo (1 death, 1 side-effects), but no patient on isradipine (5 mg 3 times daily) dropped out. After 12 weeks, peak oxygen consumption (VO 2), LVEF, echocardiographic indices, and other clinical parameters were unaffected by treatment. Repeat invasive hemodynamic measurements showed that the initial improvement by isradipine was not present anymore. In conclusion, despite a beneficial acute hemodynamic effect, isradipine has no favorable clinical influence during prolonged treatment in patients with mild to moderate CHF.

Sucrose polyester and plasma carotenoid concentrations in healthy subjects

A double-blind, placebo-controlled crossover study of the effects of the nonabsorbable fat analogue sucrose polyester (SPE; 12.4 g/d) on plasma concentrations of five different carotenoids and vitamin E in 21 volunteers, and a double-blind, placebo-controlled parallel comparison study in 53 subjects of the effect of 3 g SPE/d on plasma concentrations of two different carotenoids were undertaken. SPE-containing margarine added to the main meal was used. SPE (12.4 g/d) reduced plasma of beta-carotene concentrations by 0.13 mumol/L (34%, P = 0.0001) and concentrations of lycopene by 0.14 mumol/L (52%, P = 0.0001). Smaller but significant reductions were found for plasma concentrations of beta-cryptoxanthin, lutein, zeaxanthin, and vitamin E. SPE (3 g/d) reduced plasma concentrations of beta-carotene by 0.094 mumol/L (20% P = 0.0001) and concentrations of lycopene by 0.12 mumol/L (38%, P = 0.0001). Even at low doses, SPE strongly reduces plasma carotenoid concentrations. This finding merits careful consideration in assessing the long-term health effects of SPE-containing consumer foods.

A placebo-controlled parallel study of the effect of two types of coffee oil on serum lipids and transaminases: identification of chemical substances involved in the cholesterol-raising effect of coffee

In a randomized double-blind parallel study in 36 subjects the effect on serum cholesterol of a daily dose of 2 g lipid extracted from green Arabica and Robusta coffee beans was studied. Arabica oil elevated serum total cholesterol by 1.1 mmol/L (95% CI for the difference from placebo: 0.41, 1.73 mmol/L); the effect of robusta oil (+0.5 mmol/L) was not statistically significant (95% CI: -0.01, 0.92 mmol/L). Arabica oil also raised plasma triglycerides by 0.8 mmol/L (95% CI: 0.26, 1.25 mmol/L). The effect of robusta oil on triglycerides was +0.14 mmol/L and not significant (95% CI: -0.26, 0.42 mmol/L). In the 12 subjects taking arabica oil an average serum alanine amino-transferase elevation of 18 U/L (95% CI: 9.4, 28.4 U/L) was observed. Because only arabica oil contains kahweol and arabica coffee contains more cafestol than does robusta oil, this is further evidence for the role of diterpenes in the rise of serum cholesterol and alanine aminotransferase after consumption of boiled coffee.

Treatment of Diabetic Neuropathy With γ-Linolenic Acid

Objective— To compare the effects of placebo and GLA on the course of mild diabetic neuropathy over 1 yr. Research Design and Methods— We entered 111 patients with mild diabetic neuropathy from seven centers into a randomized, double-blind, placebo-controlled parallel study of GLA at a dose of 480 mg/day. MNCV, SNAP, CMAP, hot and cold thresholds, sensation, tendon reflexes, and muscle strength were assessed by standard tests in upper and lower limbs. Results— For all 16 parameters, the change over 1 yr in response to GLA was more favorable than the change with placebo, and for 13 parameters, the difference was statistically significant. Sex, age, and type of diabetes did not influence the result, but treatment was more effective in relatively well-controlled than in poorly-controlled diabetic patients. Conclusions— GLA had a beneficial effect on the course of diabetic neuropathy.

Effects of captopril on left ventricular systolic and diastolic function after acute myocardial infarction

The left ventricle progressively dilates in some patients after acute myocardial infarction (AMI). Both systolic and diastolk left ventricular (LV) dysfunction can be of significance in the development of heart failure. Captopril has been shown to prevent dilatation, but the effect on LV diastolic function is unknown. In a placebo-controlled double-blind parallel study, 58 AMI patients with heart failure or low ejection fraction, or both, were consecutively randomized at day 7 to either placebo or captopril (25 mg twice daily). No differences were present between the groups at baseline. Fifty-three patients completed the 6-month study period. Both LV diastolic and systolic volume indexes increased significantly in the placebo group (17 and 14%, respectively); in the captopril group there was no change in LV diastolic volume index, but a 13% reduction in LV systolic volume index. Ejection fraction increased significantly in the captopril group. The peak flow velocities of the early and atrial filling phases were measured, and the ratio between the velocities was calculated. A significant reduction was observed during the study period in early peak flow velocity (65 to 52 cm/s) and in the ratio between early and atrial peak flow velocity (1.3 to 0.8) in the placebo group (p < 0.05), but no significant changes occurred in the captopril group. No correlation was found between dilatation of the left ventricle and reduction in early peak flow velocity or the ratio between early and atrial peak flow velocity. In conclusion, captopril prevented LV dilatation, improved ejection fraction and prevented LV diastolic dysfunction in AMI patients with early signs of LV systolic dysfunction.

Cholesterol-Lowering Effects of Psyllium Hydrophilic Mucilloid

Psyllium hydrophilic mucilloid was examined for its ability to lower serum cholesterol levels in hypercholesterolemic patients. Seventy-five patients with mild to moderate hypercholesterolemia were evaluated in this randomized, double-blind, placebo-controlled parallel study. Patients were treated with a Step I diet for 12 weeks before receiving placebo or 3.4 g of psyllium (equivalent to 1 teaspoon) three times per day for 8 weeks. Compared with placebo, psyllium achieved an additional 4.8% reduction in total cholesterol level, 8.2% reduction in low-density lipoprotein cholesterol level, and 8.8% reduction in apolipoprotein B level. Psyllium did not significantly affect blood pressure or levels of high-density cholesterol, triglycerides, serum glucose, or iron. Reported adherence to diet and treatment was excellent, and no significant adverse side effects were noted. These results indicate psyllium hydrophilic mucilloid is an effective and well-tolerated adjunct to diet in the management of mild to moderate hypercholesterolemia. (<i>JAMA</i>. 1989;261:3419-3423)

The efficacy of benorylate in postoperative dental pain

The efficacy of a single pre-operative dose of benorylate (4 g) was determined in a double-blind, randomized, placebo-controlled parallel study in patients undergoing removal of a single impacted lower third molar. Patients treated with benorylate 4 g reported significantly less pain between 3-6 h after dosage than those treated with placebo. Overall pain scores at 6 h were significantly less in the benorylate group than the placebo group. However, overall pain scores at 12 h did not differ significantly between treatment groups. It is concluded from this study that a single dose of benorylate 4 g given immediately prior to the removal of an impacted lower third molar provides limited pain control during the postoperative period.

Cholesterol-Lowering Effects of Psyllium Hydrophilic Mucilloid for Hypercholesterolemic Men

The effect of psyllium hydrophilic mucilloid on serum cholesterol levels was investigated in 26 men with mild to moderate hypercholesterolemia (range of cholesterol level, 4.86 to 8.12 mmol/L [188 to 314 mg/dL]) in a double-blind, placebo-controlled parallel study. Following a two-week baseline period, subjects were treated for eight weeks with 3.4 g of psyllium or cellulose placebo at mealtimes (three doses per day). All subjects maintained their usual diets, which provided less than 300 mg of cholesterol per day and approximately 20% of energy from protein, 40% from carbohydrate, and 40% from fat. Eight weeks of treatment with psyllium reduced serum total cholesterol levels by 14.8%, low-density lipoprotein (LDL) cholesterol by 20.2%, and the ratio of LDL cholesterol to high-density lipoprotein cholesterol by 14.8% relative to baseline values. The reductions in total cholesterol and LDL cholesterol became progressively larger with time, and this trend appeared to be continuing at the eighth week. Psyllium treatment did not affect body weight, blood pressure, or serum levels of high-density lipoprotein cholesterol, triglycerides, glucose, iron, or zinc. No significant changes in serum lipid levels, body weight, blood pressure, or other serum parameters were observed with placebo treatment. Subject adherence to psyllium treatment was excellent, and no adverse effects were observed. Results of this study show that psyllium is an effective and well-tolerated therapy for mild to moderate hypercholesterolemia.