A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis

作者：Dupuis Luc^*; Dengler Reinhard; Heneka Michael T; Meyer Thomas; Zierz Stephan; Kassubek Jan; Fischer Wilhelm; Steiner Franziska; Lindauer Eva; Otto Markus; Dreyhaupt Jens; Grehl Torsten; Hermann Andreas; Winkler Andrea S; Bogdahn Ulrich; Benecke Reiner; Schrank Bertold; Wessig Carsten; Grosskreutz Julian; Ludolph Albert C

来源：PLos One, 2012, 7(6): e37885.

DOI：10.1371/journal.pone.0037885

Background: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). %26lt;br%26gt;Methods/Principal Findings: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. %26lt;br%26gt;Conclusion/Significance: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole.

• 出版日期2012-6-8