[en] BACKGROUND: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS).
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.
CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole.
TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118.
Disciplines :
Neurology
Author, co-author :
Dupuis, Luc; Department of Neurology, University of Ulm, Ulm, Germany
Dengler, Reinhard; Department of Neurology, Hannover Medical School, Hannover, Germany
HENEKA, Michael ; Department of Neurology, University of Bonn, Bonn, Germany
Meyer, Thomas; Department of Neurology, Charité University Hospital, Berlin, Germany
Zierz, Stephan; Department of Neurology, University of Halle-Wittenberg, Halle, Germany
Kassubek, Jan; Department of Neurology, University of Ulm, Ulm, Germany
Fischer, Wilhelm; Department of Neurology, University of Ulm, Ulm, Germany
Steiner, Franziska; Department of Neurology, University of Ulm, Ulm, Germany
Lindauer, Eva; Department of Neurology, University of Ulm, Ulm, Germany
Otto, Markus; Department of Neurology, University of Ulm, Ulm, Germany
Dreyhaupt, Jens; Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
Grehl, Torsten; Department of Neurology, Ruhr-Universität, Bochum, Germany
Hermann, Andreas; Department of Neurology, Dresden University of Technology, Dresden, Germany
Winkler, Andrea S; Department of Neurology, Technical University, Munich, Germany
Bogdahn, Ulrich; Department of Neurology, University of Regensburg, Regensburg, Germany
Benecke, Reiner; Neurology clinic, University of Rostock, Rostock, Germany
Schrank, Bertold; Deutsche Klinik für Diagnostik, Wiesbaden, Germany
Wessig, Carsten; Department of Neurology, University of Würzburg, Würzburg, Germany
Grosskreutz, Julian; Department of Neurology, University Hospital, Jena, Germany
Ludolph, Albert C; Department of Neurology, University of Ulm, Ulm, Germany
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