Outlook: Clinical Trials

JANUARY 13, 2011
Michele Reed, PharmD
B Vitamins and Omega-3 Fatty Acids in Cardiovascular Disease
Recent data from a randomized, placebo-controlled, clinical trial does not support the routine use of dietary supplements containing B vitamins or omega-3 fatty acids for prevention of cardiovascular (CV) disease in people with previous ischemic heart disease events.1  Study subjects (n = 2501) included patients with a history of myocardial infarction (MI), unstable angina, or ischemic stroke. The primary outcomes of the study were major CV events defined as a composite of nonfatal MI, stroke, or death from CV disease.

Results showed that B vitamins had no significant effects on major CV events compared with placebo (75 vs 82 patients; hazard ratio, 0.90; 95% confidence interval [CI], 0.66 to 1.23; P = .50). Additionally, whereas omega-3 fatty acids increased plasma concentrations of omega-3 fatty acids by 37% compared with placebo, they showed no significant effect on major CV events (81 vs 76 patients; hazard ratio, 1.08; 95% CI, 0.79 to 1.47; P = .64).

Inhaled Montelukast in the Treatment of Chronic Asthma
Results from a recent clinical trial showed that inhaled montelukast provided significant bronchodilation that persisted for 24 hours as early as 20 minutes after administration.2 This randomized, double-blind, crossover study compared single-dose inhaled montelukast with placebo in patients aged 15 to 65 years with chronic asthma (n = 68). Study subjects were treated with montelukast via dry powder inhaler at doses of 25, 250, or 1000 mcg. Doses of 50, 100, and 500 mcg were available on an as-needed basis through a prespecified dose-response algorithm. A washout period of 4 to 7 days followed each administration before the patient crossed over to the next treatment. The primary end point of the study was the change from baseline in a forced expiratory volume in 1 second (FEV1) over the first 4 hours after administration, calculated as a time-weighted average (ΔFEV1 [0-4 hours]). Secondary end points included the onset and duration of bronchodilation and the effect of albuterol when added to inhaled montelukast.

Results showed that inhaled montelukast 100 mcg (0.13 L, P ≤.001), 250 mcg (0.10 L, P <.01), and 1000 mcg (0.12 L, P ≤.001) had significantly greater ΔFEV1 (0-4 hours). Additionally, inhaled montelukast 100 mcg (0.10 L) and 1000 mcg (0.09 L) had significantly greater bronchodilation compared with placebo (0.02 L, P <.05 vs montelukast) at 24 hours postdose. Montelukast 1000 mcg provided significant bronchodilation versus placebo within 20 minutes of administration (0.03 L vs -0.05 L), whereas montelukast 100 mcg provided significant bronchodilation relative to placebo within 2 hours of dosing (0.09 L vs 0.01 L). When compared with montelukast plus placebo, montelukast plus albuterol was significantly more effective for ΔFEV1 (0-90 min) (0.34 L vs 0.15 L, P = .015). No serious adverse events were reported in this study.

Long-Term Effect of Dihydrotestosterone Treatment on Prostate Growth
In a recent randomized, placebo-controlled trial, the long-term effects of dihydrotestosterone (DHT) treatment on prostate growth in healthy middle-aged men were evaluated.3 Study subjects (n = 114) included healthy men older than 50 years without known prostate disease. Subjects received transdermal DHT 70 mg or placebo gel daily for 2 years. Investigators used ultrasonography to measure prostate volume. Additionally, bone mineral density (BMD) and body composition were measured by dualenergy x-ray absorptiometry. Blood samples and questionnaires were collected
every 6 months.

Study results showed that over 24 months total prostate volume increased (29%; 95% CI, 23% to 34%; P <.01). Central prostate volume also increased (75%; 95% CI, 64% to 86%; P <.01). Additionally, serum prostate-specific antigen level increased with time on study (15%; 95% CI, 6% to 24%). However, DHT had no effect on these increases (P <0.2). DHT treatment decreased spinal BMD (1.4%; 95% CI, 0.6% to 2.3%; P <.001) at 24 months, but it did not decrease hip BMD (P <0.2). Investigators concluded that DHT treatment for 24 months has no beneficial or adverse effect on prostate growth; however, it does decrease spinal BMD.

Modafinil for Excessive Daytime Sleepiness
Recent data from a clinical trial demonstrated that modafinil is effective and well tolerated in the treatment of excessive daytime sleepiness (EDS) after traumatic brain injury (TBI).4 This randomized, double-blind study included 20 patients with fatigue, EDS, or both following TBI. Baseline examinations included the Epworth Sleepiness Scale, the Fatigue Severity Scale, actigraphy, polysomnography, maintenance of wakefulness, and the psychomotor vigilance test. Following baseline examinations, 10 patients received modafinil 100 to 200 mg daily in the morning and 10 patients received placebo for 6 weeks, at which time all examinations were repeated.

Results showed that patients treated with modafinil experienced significantly improved EDS compared with placebo. Modafinil improved maintenance of wakefulness, but it did not significantly affect fatigue. There were no clinically relevant side effects observed in the study. Investigators concluded that modafinil improves posttraumatic EDS compared with placebo. PT


1. Galan P, Kesse-Guyot E, Czernichow S, Briancon S, Blacher J, Hercberg S. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ. 2010;341:c6273.
2. Idan A, Griffiths KA, Harwood DT, et al. Long-term effects of dihydrotestosterone treatment on prostate growth in healthy, middle-aged men without prostate disease: a randomized, placebo-controlled trial. Ann Intern Med. 2010;153(10):621-632.
3. Kaiser PR, Valko PO, Werth E, et al. Modafinil ameliorates excessive daytime sleepiness after traumatic brain injury. Neurology. 2010;75(20):1780-1785.
4. Philip G, Pedinoff A, Vandormael K, et al. A phase I randomized, placebo-controlled, dose-exploration study of single-dose inhaled montelukast in patients with chronic asthma. J Asthma. 2010;47(10):1078-1084.

Dr. Reed received her Doctor of Pharmacy degree from the University of the Sciences in Philadelphia, Pennsylvania, and currently works as a medical editor in the greater Philadelphia area.


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