Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial.

IMPORTANCE: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. OBJECTIVE: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. DESIGN, SETTING, AND PATIENTS: The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. INTERVENTIONS: Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). MAIN OUTCOMES AND MEASURES: The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. RESULTS: The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. CONCLUSIONS AND RELEVANCE: Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00449865.

Treatment with omega-3 fatty acid ethyl-ester alters fatty acid composition of lipoproteins in overweight or obese adults with insulin resistance.

INTRODUCTION: The effects of dietary fatty acid supplementation on lipoprotein fatty acid composition have rarely been described. PATIENTS AND METHODS: Sixty-one overweight and obese adults with dyslipidemia and insulin resistance were randomized to placebo, 2g/day extended-release nicotinic acid (ERN), 4g/day prescription omega-3 fatty acid ethyl ester (P-OM3), or combination therapy for 16 weeks. Lipoprotein fatty acid composition was analyzed by gas chromatography pre- and post-treatment. RESULTS: Treatment with P-OM3 or combination, but not ERN, increased proportions of eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid, and reduced those for arachidonic acid in all lipoprotein fractions, with greatest impact in the high-density lipoprotein fraction. P-OM3-induced changes in eicosapentaenoic acid within low-density lipoproteins and very low-density lipoproteins were associated with beneficial effects on mean arterial pressure and pulse pressure. CONCLUSIONS: P-OM3 supplementation, with or without ERN, was associated with differentially altered lipoprotein fatty acid composition and improved blood pressure parameters.