Ethyl-EPA in Huntington disease: a double-blind, randomized, placebo-controlled trial

Neurology. 2005 Jul 26;65(2):286-92. doi: 10.1212/01.wnl.0000169025.09670.6d.


Background: Preliminary evidence suggests beneficial effects of pure ethyl-eicosapentaenoate (ethyl-EPA) in Huntington disease (HD).

Methods: A total of 135 patients with HD were randomized to enter a multicenter, double-blind, placebo-controlled trial on the efficacy of 2 g/d ethyl-EPA vs placebo. The Unified Huntington's Disease Rating Scale (UHDRS) was used for assessment. The primary end point was outcome at 12 months on the Total Motor Score 4 subscale (TMS-4). Analysis of covariance (ANCOVA) and a chi2 test on response, defined as absence of increase in the TMS-4, were performed.

Results: A total of 121 patients completed 12 months, and 83 did so without protocol violations (PP cohort). Intent-to-treat (ITT) analysis revealed no significant difference between ethyl-EPA and placebo for TMS-4. In the PP cohort, ethyl-EPA proved better than placebo on the chi2 test on TMS-4 (p < 0.05), but missed significance on ANCOVA (p = 0.06). Secondary end points (ITT cohort) showed no benefit of ethyl-EPA but a significantly worse outcome in the behavioral severity and frequency compared with placebo. Exploring moderators of the efficacy of ethyl-EPA on TMS-4 showed a significant interaction between treatment and a factor defining patients with high vs low CAG repeats. Reported adverse events were distributed equally between treatment arms.

Conclusions: Ethyl-eicosapentaenoate (ethyl-EPA) (purity > 95%) had no benefit in the intent-to-treat cohort of patients with Huntington disease, but exploratory analysis revealed that a significantly higher number of patients in the per protocol cohort, treated with ethyl-EPA, showed stable or improved motor function. Further studies of the potential efficacy of ethyl-EPA are warranted.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Cohort Studies
  • Double-Blind Method
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / adverse effects
  • Eicosapentaenoic Acid / analogs & derivatives*
  • Female
  • Humans
  • Huntington Disease / drug therapy*
  • Huntington Disease / genetics
  • Huntington Disease / physiopathology
  • Male
  • Middle Aged
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Movement / drug effects
  • Movement / physiology
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / prevention & control
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / adverse effects
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Placebo Effect
  • Treatment Outcome


  • Neuroprotective Agents
  • eicosapentaenoic acid ethyl ester
  • Eicosapentaenoic Acid