Ethyl-EPA in Huntington disease: a double-blind, randomized, placebo-controlled trial.
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.
Puri
B K
BK
Imaging Sciences Department, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, London, UK.
Leavitt
B R
BR
Hayden
M R
MR
Ross
C A
CA
Rosenblatt
A
A
Greenamyre
J T
JT
Hersch
S
S
Vaddadi
K S
KS
Sword
A
A
Horrobin
D F
DF
Manku
M
M
Murck
H
H
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015331:Cohort Studies; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D015990:Placebo Effect; D016896:Treatment Outcome
D018696:Neuroprotective Agents; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid