A futility study of minocycline in Huntington's disease

Mov Disord. 2010 Oct 15;25(13):2219-24. doi: 10.1002/mds.23236.


This study assessed the futility of proceeding with a Phase 3 clinical trial of minocycline as a disease-modifying treatment for Huntington's disease (HD). One hundred fourteen research participants with HD were randomized, 87 to minocycline (200 mg/d) and 27 to placebo. The change in Total Functional Capacity (TFC) score from baseline to Mo 18 was prespecified as the primary measure of HD progression. By using a futility design, we tested the null hypothesis that minocycline would reduce the mean decline in TFC score by at least 25% compared to a fixed value obtained from a historical database, with a one-tailed significance level of 10%. The placebo group was included to facilitate blinding. Rejection of the null hypothesis would discourage a major definitive trial of minocycline in HD. For the primary analysis, missing data were handled by carrying forward the last available observation; a secondary analysis used multiple imputations. The mean TFC decline in the minocycline group was 1.55 (SD 1.85), and futility was not declared (P = 0.12) for the primary analysis. When multiple imputation was used to handle missing data, the mean TFC decline in the minocycline group of 1.71 (SD 1.96, P = 0.07) suggested futility, as was the case for prespecified secondary outcome measures. There were no safety abnormalities attributable to minocycline. Based on the threshold of 25% improvement in TFC, further study of minocycline 200 mg/d in HD was not warranted. Futility designs aid in screening potential therapies for HD.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activities of Daily Living
  • Adult
  • Anti-Bacterial Agents / therapeutic use*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Huntington Disease / drug therapy*
  • Male
  • Medical Futility
  • Middle Aged
  • Minocycline / therapeutic use*
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Minocycline