The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: Oxidative stress has been suggested to play a role in the development of diabetes, hypertension and vascular dysfunction. Vitamin E, a major lipid-soluble dietary antioxidant, has two major dietary forms, alpha-tocopherol and gamma-tocopherol. The potential importance of gamma-tocopherol has largely been overlooked. Our aim was to investigate the effect of alpha-tocopherol and gamma-tocopherol supplementation on 24-h ambulatory blood pressure (BP) and heart rate, vascular function and oxidative stress in individuals with type 2 diabetes. METHOD: Fifty-eight individuals with type 2 diabetes were randomized in a double-blind, placebo-controlled trial. Participants were randomized to a daily dose of 500 mg/day RRR-alpha-tocopherol, 500 mg/day mixed tocopherols (60% gamma-tocopherol) or placebo for 6 weeks. Primary endpoints were 24-h ambulatory BP and heart rate, endothelium-dependent and independent vasodilation and plasma and urinary F2-isoprostanes. RESULTS: Treatment with alpha-tocopherol significantly increased systolic BP [7.0 (5.2, 8.8) mmHg, P < 0.0001], diastolic BP [5.3 (4.0, 6.5) mmHg, P < 0.0001], pulse pressure [1.8 (0.6, 3.0) mmHg, P < 0.005] and heart rate [2.0 (0.6, 3.3) bpm, P < 0.005] versus placebo. Treatment with mixed tocopherols significantly increased systolic BP [6.8 (4.9, 8.6) mmHg, P < 0.0001], diastolic BP [3.6 (2.3, 4.9) mmHg, P < 0.0001], pulse pressure [3.2 (2.0, 4.4) mmHg, P < 0.0001] and heart rate [1.8 (0.5, 3.2) bpm, P < 0.01] versus placebo. Treatment with alpha-tocopherol or mixed tocopherols significantly reduced plasma F2-isoprostanes versus placebo, but had no effect on urinary F2-isoprostanes. Endothelium-dependent and independent vasodilation was not affected by either treatment. CONCLUSION: In contrast to our initial hypothesis, treatment with either alpha- or mixed tocopherols significantly increased BP, pulse pressure and heart rate in individuals with type 2 diabetes.     

Effect of dietary fiber intake on blood pressure: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To examine the effect of dietary fiber intake on blood pressure (BP). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING AND PARTICIPANTS: A total of 110 trial participants aged 30 to 65 years who had untreated, but higher than optimal BP or stage-1 hypertension were recruited from the community in New Orleans, Louisiana, USA. INTERVENTIONS: Study participants were randomly assigned to receive 8 g/day of water-soluble fiber from oat bran or a control intervention. MAIN OUTCOME MEASURES: Nine BP measurements were obtained by trained observers using random-zero sphygmomanometers, over three clinical visits, at the baseline and termination visits of the trial. An average of the nine measurements was used to determine mean BP at the baseline and termination visits. RESULTS: The net changes [95% confidence interval, (CI)] in systolic blood pressure were -1.8 mmHg (-4.3 to 0.8, P = 0.17) following 12 weeks, -2.2 mmHg (-5.3 to 1.0, P = 0.18) following 6 weeks, and -2.0 mmHg (-4.4 to 0.3, P = 0.09) for an average of the 6- and 12-week visits. The corresponding net changes (95% CI) in diastolic blood pressure were -1.2 mmHg (-3.0 to 0.5, P = 0.17) following 12 weeks, -0.8 mmHg (-3.1 to 1.4, P = 0.47) following 6 weeks, and -1.0 mmHg (-2.6 to 0.5, P = 0.19) for an average of the 6- and 12-week visits. CONCLUSIONS: Our findings suggest that a diet rich in fiber may have a moderate BP-lowering effect and indicate the need for further investigation of this important question.     

Daily multivitamin supplementation and vitamin blood levels in the elderly: a randomized, double-blind, placebo-controlled trial

Despite the many questions being raised about multivitamin use by the elderly, it has not been proven that consuming an oral multivitamin alters vitamin blood levels in the aged. To address this question, we performed a randomized, prospective, placebo-controlled study of daily multivitamin supplementation in 101 noninstitutionalized ambulatory elderly persons (median age, 64 years). Vitamin levels were assayed at baseline, and at two and four months of supplementation. At four months, those taking multivitamins had statistically significant increased levels of water soluble vitamins (C, B2, B12, plasma, and erythrocyte folate) that were greater than changes noted for the placebo group. This was not true for fat soluble vitamins A and E. Greater storage pools of fat soluble vitamins help explain this discrepancy. We conclude that in the ambulatory elderly, oral multivitamins can raise levels of water soluble vitamins but the effect on fat soluble vitamins remains uncertain.     

Interferon and amantadine in naive chronic hepatitis C: a double-blind, randomized, placebo-controlled trial

Recent controlled trials on the efficacy of an amantadine/interferon combination in treatment-naive patients with chronic hepatitis C yielded contradictory results. We therefore conducted a large, double-blind, placebo-controlled, multicenter trial in naive patients with chronic hepatitis C: 246 patients were randomized to receive interferon alfa-2a (6 MIU sc thrice weekly for 20 weeks, then 3 MIU sc thrice weekly) and either amantadine sulphate (2 x 100 mg p.o. QD) or placebo. Treatment continued for a total of 52 weeks, if HCV-RNA in serum polymerase chain reaction (PCR) had fallen below detection limit (1,000 copies/mL) at treatment week 10, and stopped otherwise. All patients were followed for 24 weeks off therapy. After 10 weeks of treatment, 66/121 patients treated with amantadine (55%) and 78/125 treated with placebo (62%) had lost HCV-RNA (n.s.). After 24 weeks of follow-up, 25 patients in the amantadine (21%) and 17 (14%) in the placebo group remained HCV-RNA negative (n.s.). During therapy, virologic breakthroughs occurred less often in the amantadine than in the placebo group [14 (12%) vs. 27 (22%) patients; P =.04]. Multivariate logistic regression analysis revealed genotype, viremia level, age, and amantadine therapy [risk ratio 0.4 (95%CI 0.2-1.0), P =.05] as predictors of sustained virologic response. Adverse events and impact of therapy on quality of life were similar in amantadine and placebo treated patients. Compared with current standard treatment (interferon/ribavirin), the interferon/amantadine combination was not cost-effective. In conclusion, amantadine does not add to a clinically relevant extent to the treatment of naive patients with chronic hepatitis C.     

A new active vitamin D, ED-71, increases bone mass in osteoporotic patients under vitamin D supplementation: a randomized, double-blind, placebo-controlled clinical trial

CONTEXT: ED-71 has been shown to increase lumbar bone mineral density (BMD) in osteoporotic subjects. However, vitamin D insufficiency might have influenced the effect of ED-71 on BMD. OBJECTIVE: Our objective was to examine whether ED-71 can increase BMD in osteoporotic patients under vitamin D supplementation. DESIGN, SETTING, AND PATIENTS: We conducted a randomized, double-blind, placebo-controlled clinical trial of 219 osteoporotic patients (49-87 yr of age). Interventions: Subjects were randomly assigned to receive placebo or 0.5, 0.75, or 1.0 microg/d ED-71 for 12 months. All the subjects received 200 or 400 IU/d vitamin D(3). MAIN OUTCOME MEASURES: We assessed changes in lumbar and hip BMD and bone turnover markers from baseline. RESULTS: Lumbar BMD increased with ED-71 treatment for 12 months (2.2, 2.6, and 3.1% from baseline and 2.9, 3.4, and 3.8% vs. placebo group in subjects receiving 0.5, 0.75, and 1.0 microg ED-71, respectively). Total hip BMD also increased with 0.75 and 1.0 microg ED-71 (-0.8, 0.6, and 0.9% from baseline and 0.1, 1.5, and 1.8% vs. placebo group in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively). Bone formation and resorption markers were suppressed by approximately 20% after 12 months of 0.75 and 1.0 microg ED-71 treatment. Transient hypercalcemia over 2.6 mmol/liter occurred in 7, 5, and 23% of subjects in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively, but none of them developed sustained hypercalcemia. CONCLUSIONS: These results demonstrate that ED-71 treatment at around 0.75 microg/d can effectively and safely increase lumbar and hip BMD in osteoporotic patients with vitamin D supplementation.     

Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial

Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). A randomized, double-blind, placebo-controlled trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet surgical guidelines or refused surgery. Forty-four patients randomized to placebo or active treatment arms were stratified for gender. At 12 months, patients taking placebo crossed over to active treatment. All patients were on active treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS), femoral neck, total hip, and distal one third radius was measured every 6 months by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2 yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P < 0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77% se; P < 0.001) from baseline and remained stable over the next 12 months of therapy. BMD at the one third radius site did not show any statistically significant change in the alendronate-treated group at 12 or 24 months of therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) = 0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in comparison with baseline. The placebo group, when crossed over to alendronate at 12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the total hip site in comparison with baseline. There was no statistically significant change seen in the placebo group at 12 months at any BMD site and no significant change at 24 months for the distal one third radius or femoral neck sites. Alendronate was associated with marked reductions in bone turnover markers with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5% se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = -15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11; +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively) of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum calcium (total and ionized), PTH, and urine calcium did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS at 12 and 24 months from baseline values. Significant reductions in bone turnover occur with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.     

Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial

BACKGROUND: Nicotine replacement therapy is an effective treatment for nicotine-dependent smokers. However, cessation rates are modest, and preliminary studies suggest that combination therapy may be superior. We compared the efficacy of the nicotine inhaler plus nicotine patch vs nicotine inhaler plus placebo patch for smoking cessation. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in 400 subjects who had smoked 10 or more cigarettes per day for 3 years or longer. Group 1 (n = 200) received the nicotine inhaler plus nicotine patch (delivering 15 mg of nicotine per 16 hours) for 6 weeks, then inhaler plus placebo patch for 6 weeks, then inhaler alone for 14 weeks. Group 2 (n = 200) received the nicotine inhaler plus placebo patch for 12 weeks, then inhaler for 14 weeks. Inhaler was used at a rate of 6 to 12 cartridges per day ad libitum for 3 months and then tapered off. Main outcome measures were complete abstinence (self-reported) and expired carbon dioxide concentration less than 10 ppm. RESULTS: Group 1 vs group 2 complete abstinence rates were 60.5% and 47.5% at 6 weeks (P =.009), 42.0% and 31.0% at 12 weeks (P =.02), 25.0% and 22.5% at 6 months (P =.56), and 19.5% and 14.0% at 12 months (P =. 14). One-year survival analysis showed a significant association between abstinence and treatment with nicotine inhaler plus nicotine patch (P =.04). Mean nicotine substitution at week 6 was 60.1% (group 1) and 24.6% (group 2) (P<.001). At 12 months, the frequency of respiratory symptoms in abstinent subjects fell significantly and lung function showed a trend toward improvement. The most common adverse events were throat irritation (inhaler) and itching (patch). CONCLUSIONS: Treatment with the nicotine inhaler plus nicotine patch resulted in significantly higher cessation rates than inhaler plus placebo patch.     

Nebulized lidocaine for flexible bronchoscopy: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: Topical anesthesia for flexible bronchoscopy can be administered via transcricoid injection, nebulizer, or directly through the bronchoscope in a "spray as you go" fashion. We performed a prospective, randomized, double-blind, placebo-controlled trial to evaluate whether nebulized lidocaine provides additional benefit and reduces the total anesthetic dose required during bronchoscopy. SETTING: Tertiary care university hospital. METHODS: One hundred fifty patients (93 men; age, 20 to 89 years) undergoing diagnostic flexible bronchoscopy were randomized to receive either 4 mL of 4% lidocaine (160 mg) or 4 mL of saline solution as placebo via nebulization. Combined sedation was achieved using 5 mg of IV hydrocodone and midazolam boluses. Supplemental lidocaine doses and total midazolam required as judged by the bronchoscopist were recorded for each patient. After the procedure, both bronchoscopists and patients charted their perception of cough on a 10-cm visual analog scale (VAS). Similarly, patients recorded their discomfort related to the procedure on a 10-cm VAS. RESULTS: The most common procedures were BAL in 77 cases (51%), transbronchial biopsy in 40 cases (27%), and transbronchial needle aspiration in 34 cases (23%). Outcome parameters, including hemodynamic findings, duration of the procedure, cough scores for physicians and patients, discomfort score for patients, midazolam doses, and supplemental lidocaine doses, were similar in both groups. Mean total lidocaine dose required in the lidocaine group was 318 +/- 41 mg and was significantly higher than the total dose required in the placebo group (157 +/- 44 mg [+/- SD]) [p < 0.001]. CONCLUSION: Additional nebulized lidocaine cannot be recommended for flexible bronchoscopy performed under combined sedation.     

Effects of anthocyanins on blood pressure and stress reactivity: a double-blind randomized placebo-controlled crossover study

High intakes of flavonoids are associated with reduced cardiovascular risk, and flavonoids such as cocoa and soy protein isolate have shown beneficial effects on blood pressure (BP). Anthocyanins constitute a flavonoid subgroup consumed in regular diets, but few studies have assessed the antihypertensive potential of anthocyanins. We aimed to assess whether high concentrations of relatively pure anthocyanins reduce BP and alter cardiovascular and catecholamine reactivity to stress. A total of 31 healthy men between 35-51 years of age with screening BP >140/90 mm Hg, not on antihypertensive or lipid-lowering medication, were randomised in a double-blind crossover study to placebo versus 320-mg anthoycanins twice daily. Treatment duration was 4 weeks, with a 4-week washout. Sitting and supine BP measurements, ambulatory BP recording and stress reactivity were assessed and analyzed by a paired sample t-test. In all, 27 patients completed all visits. Sitting systolic BP (primary endpoint) was 133 mm Hg after placebo versus 135 mm Hg after anthocyanin treatment (P=0.25). Anthocyanins did neither affect semiautomatic oscillometric BP measurements in the sitting or supine position nor 24-h ambulatory BP. No significant differences in stress reactivity were found across treatment periods. Overall, we conclude that high concentrations of these relatively pure anthocyanins do not reduce BP in healthy men with a high normal BP.     

Effect of potassium supplementation on blood pressure in Chinese: a randomized, placebo-controlled trial.

OBJECTIVE: To examine the effect of potassium supplementation on blood pressure (BP) in a Chinese population who consume a habitual high sodium and low potassium diet. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Community sample from Beijing, China. PARTICIPANTS: A total of 150 men and women aged 35-64 years with an initial systolic BP 130-159 mmHg and/or diastolic BP 80-94 mmHg. INTERVENTIONS: Participants were randomly assigned to take 60 mmol potassium chloride supplement or placebo for 12 weeks. MAIN OUTCOME MEASURE(S): BP measurements were obtained at baseline, and at 6 weeks and 12 weeks during the trial, using random-zero sphygmomanometers. RESULTS: The average baseline urinary excretion of sodium and potassium was 182 mmol/24 h and 36 mmol/24 h. Baseline BP and other measured variables were similar between the potassium supplementation and placebo groups. In the active compared to the placebo treatment group, the urinary excretion of potassium was significantly increased by 20.6 mmol/24 h (P< 0.001) during 12 weeks of intervention. Compared to placebo, active treatment was associated with a significant reduction in systolic BP (-5.00 mmHg, 95% CI: -2.13 to -7.88 mmHg, P < 0.001) but not diastolic BP (-0.63 mmHg, 95% CI: -2.49 to1.23 mmHg, P = 0.51) during 12-week intervention. CONCLUSION: These data indicate that moderate potassium supplementation resulted in a substantial reduction in systolic BP. Our findings suggest that increased potassium intake may play an important role in the prevention and treatment of hypertension in China.     

Onercept for moderate-to-severe Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: Onercept is a recombinant, soluble human p55 receptor to tumor necrosis factor-alpha. METHODS: A randomized, double-blind, placebo-controlled, dose-ranging trial was performed to evaluate the efficacy of onercept induction therapy in patients with Crohn's disease (CD). Patients (n = 207) with moderate-to-severe acute or chronic active CD were randomized to receive subcutaneous onercept (10, 25, 35, or 50 mg) or placebo 3 times weekly for 8 weeks. Primary analysis was induction of remission (defined as a CD activity index score < or = 150) at week 8. RESULTS: A total of 104 patients had acute active CD. Remission rates at week 8 were 23.5% for placebo (n = 17), and 34.8%, 20.0%, 26.1%, and 28.6% for onercept 10 mg (n = 23), 25 mg (n = 20), 35 mg (n = 23), and 50 mg (n = 21), respectively (P = .98). A total of 103 patients had chronic active CD. Remission rates at week 8 were 23.8% for placebo (n = 21), and 23.8%, 9.1%, 35.3%, and 13.6% for onercept 10 mg (n = 21), 25 mg (n = 22), 35 mg (n = 17), and 50 mg (n = 22), respectively (P = .66). There were no differences between treatment groups in the incidence of adverse events. However, mild-to-moderate injection-site reactions occurred in up to 12% of onercept-treated patients. CONCLUSIONS: Onercept was well tolerated but was not effective at the doses studied in patients with active CD.     

Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: We evaluated etanercept, a human soluble tumor necrosis factor receptor: Fc fusion protein, for the treatment of active Crohn's disease. METHODS: Forty-three patients with moderate to severe Crohn's disease were enrolled in an 8-week placebo-controlled trial. Patients were randomized to subcutaneous etanercept 25 mg or placebo twice weekly. The primary outcome measure was clinical response at week 4, defined as a decrease in the baseline Crohn's Disease Activity Index score > or =70 points or a Crohn's Disease Activity Index score <150 points. RESULTS: At week 4, 39% of etanercept-treated patients had clinical response as compared with 45% of placebo-treated patients (P = 0.763). The frequency of common adverse events including headache, new injection site reaction, asthenia, abdominal pain, Crohn's disease-related anemia, and skin disorders was similar in both groups. Likewise, the frequency of severe or serious adverse events was similar in both groups. CONCLUSIONS: Subcutaneous etanercept at a dose of 25 mg twice weekly is safe, but not effective, for the treatment of patients with moderate to severe Crohn's disease. The dose of etanercept administered in this study is that approved for rheumatoid arthritis. Higher doses or more frequent dosing may be required to attain a response in patients with active Crohn's disease.