A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis
| Autor: | Ulrich Bogdahn, Reinhard Dengler, Andreas Hermann, Eva Lindauer, Jan Kassubek, Stephan Zierz, Torsten Grehl, Markus Otto, Julian Grosskreutz, Thomas Meyer, Jens Dreyhaupt, Bertold Schrank, Albert C. Ludolph, Carsten Wessig, Reiner Benecke, Wilhelm Fischer, Michael T. Heneka, Luc Dupuis, Andrea Sylvia Winkler, Franziska Steiner |
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| Přispěvatelé: | GERP ALS Study Group, Borisow, N., Holm, T., Maier, A., Meyer, T., Budde, P., Grehl, T., Guettsches, AK., Bewersdorff, M., Heneka, M., Hermann, A., Storch, A., Frank, T., Göricke, B., Weishaupt, J., Eger, K., Hanisch, F., Zierz, S., Cordes, AL., Dengler, R., Koerner, S., Kollewe, K., Petri, S., Grosskreutz, J., Kunze, A., Prell, T., Ringer, T., Zinke, J., Anneser, J., Borasio, GD., Chahli, C., Winkler, AS., Boentert, M., Stubbe-Draeger, B., Young, P., Bogdahn, U., Franz, S., Haringer, V., Weidner, N., Benecke, R., Meister, S., Prudlo, J., Wittstock, M., Dorst, J., Hendrich, C., Ludolph, AC., Sperfeld, AD., Weiland, U., Neidhardt, S., Schrank, B., Beck, M., Kraft, P., Toyka, K., Ulzheimer, J., Wessig, C. |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Placebo-controlled study lcsh:Medicine Biochemistry Motor Neuron Diseases Mice Drug Discovery Clinical endpoint lcsh:Science Multidisciplinary Riluzole Hazard ratio Clinical Pharmacology Neurodegenerative Diseases Neuromuscular Diseases Middle Aged Survival Rate Neurology Medicine Anticonvulsants Drug Therapy Combination Female medicine.drug Research Article Biotechnology medicine.medical_specialty Drugs and Devices Drug Research and Development Clinical Research Design Placebo Disease-Free Survival Neuropharmacology Double-Blind Method Internal medicine medicine Animals Humans Hypoglycemic Agents Clinical Trials ddc:610 Survival rate Biology Aged Pioglitazone business.industry Amyotrophic Lateral Sclerosis lcsh:R Interim analysis Surgery Thiazolidinediones lcsh:Q business |
| Zdroj: | PLoS ONE, Vol 7, Iss 6, p e37885 (2012) PLoS ONE Plos One, vol. 7, no. 6, pp. e37885 |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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