A futility study of minocycline in Huntington's disease

Authors

  • Dr. Merit Cudkowicz,

    Corresponding author
    1. Massachusetts General Hospital, Neurology Clinical Trial Unit, 149 13th Street, Room 2274, Charlestown, MA 02129, USA
    • Massachusetts General Hospital, Neurology Clinical Trial Unit, 149 13th Street, Room 2274, Charlestown, MA 02129, USA
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  • The Huntington Study Group DOMINO Investigators

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    • See Appendix for a complete list of participating Huntington Study Group authors of this report and their affiliations.


  • Potential conflict of interest: The authors have no personal conflicts of interest related to the study or study drug. There was no ghost writing.

Abstract

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. © 2010 Movement Disorder Society

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