The study objective is to determine the efficacy of coenzyme Q10 (CoQ) in Huntington's disease (HD). Although the genetic defect that causes HD has been identified, there is no known effective treatment or cure. Rational therapeutic strategies in HD include those that are targeted to improving cellular energy production and reducing oxidative stress. Coenyzme Q10, a co-factor involved in mitochondrial electron transfer and an anti-oxidant, is a compound with these properties. Coenzyme Q10 slows progression and prolongs survival in a dose-dependent manner in a transgenic mouse model of HD. In a study in people with HD, CoQ at a dosage of 600 mg per day for 2 1/2 years appeared to slow the functional decline by approximately 13% compared to placebo. Pre-clinical and clinical studies with CoQ suggest that higher dosages are more beneficial. Toxicology studies were performed in dogs that supported proceeding with 2400 mg/day in people. The study hypothesis is that chronic treatment of HD patients with CoQ will slow the progressive functional decline of HD.
The specific aim i s to test this hypothesis by conducting a multi-center randomized, double-blind placebo-controlled, parallel group, study of CoQ involving 608 ambulatory HD subjects who are each treated for 60 months. Currently, 549 participants (90%) are enrolled and it is planned that enrollment will be completed by July 2012. The Data and Safety and Monitoring Committee reviewed the first futility analysis in August 2011 and recommended continuation of the study. Eligible subjects are randomized to CoQ 2400 mg/ day or a matching placebo. The primary outcome measure is the clinical progression of HD as measured by the change in total functional capacity (TFC) between baseline and 60 months. Secondary measures include changes in the other clinical rating scales of the Unified Huntington Disease Rating Scale, time to decline in TFC by 2 and 3 points, ability to complete the study at the assigned dosages and the frequencies of clinical and laboratory adverse events.

Public Health Relevance

Despite advances in understanding the cause of Huntington's disease (HD), there is no known effective treatment or cure. Coenyzme Q10 has demonstrated efficacy in an animal model of HD and was previously shown to possibly slow disease progression in people. Any compound that slows disease course will have immediate clinical importance, and a positive outcome of this study will enhance our understanding of the underlying biology of HD.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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Sutherland, Margaret L
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Massachusetts General Hospital
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