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A futility study of minocycline in Huntington's disease.

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.

SUBMITTER: Huntington Study Group DOMINO Investigators

PROVIDER: S-EPMC8801051 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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A futility study of minocycline in Huntington's disease.

Movement disorders : official journal of the Movement Disorder Society 20101001 13

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 me ...[more]

PMID: 20721920

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Project description:BackgroundHuntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III) and controls.MethodsControl (n = 15), premanifest (n = 14) and stage II/III (n = 13) participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a), fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test.ResultsWe found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine) there is a suggestion (p values between 0.02 and 0.05) that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious.ConclusionsContrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that the majority of these markers do not differ markedly by disease status.

Dataset Information

A futility study of minocycline in Huntington's disease.

Publications

A futility study of minocycline in Huntington's disease.

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