Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial

A futility study of minocycline in Huntington's disease

Huntington Study Group DOMINO Investigators. Mov Disord. .

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.

PubMed Disclaimer

Conflict of interest statement

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

Figures

Figure 1:
Figure 1:
Participant Flow
Figure 2:
Figure 2:
Change in TFC
See this image and copyright information in PMC

References

    1. Marshall F, Shoulson I. Huntington’s disease: clinical features and therapy. In: Watts R, Kollers W, editors. Movement disorders: neurologic principles and practice. New York: McGraw HIll; 1997. p.491–502.
    1. Wang X, Zhu S, Drozda M, et al. Minocycline inhibits caspase-independent and -dependent mitochondrial cell death pathways in models of Huntington’s disease. PNAS 2003;100:10483–10487. - PMC - PubMed
    1. Zhu S, Stavrovskiaya I, Drozda M, et al. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 2002;417:74–78. - PubMed
    1. Chen M, Ona C, Li M, et al. Minocycline inhibits caspase-1 andcaspase-2 expression and delays mortality in a transgenic mouse model of Huntington disease. Nature Med 2000;6:797–801. - PubMed
    1. Stack E, Smith K, Ryu H, et al. Combination therapy using minocycline and coenzyme Q10 in R6/2 transgenic Huntington’s disease mice. Biochim Biophys Acta 2006;1762:373–380. - PubMed

Publication types