Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

Primary objective:

Efficacy of pioglitazone (45 mg/day) as add-on therapy to standard therapy with riluzole in patients with ALS compared to placebo in terms of survival (mortality defined exclusively as death).

This is a prospective, multicentre, randomised, stratified, parallel-group, double-blind trial comparing placebo with 45 mg pioglitazone as add-on therapy to 100 mg riluzole in ALS in 220 enrolled patients. For entry, the El Escorial Criteria for diagnosis will be used. The duration of treatment will be 18 months. The primary endpoint will be subjected to a confirmatory analyses. Secondary variables will be incidence of tracheotomy or non-invasive ventilation, ALS Functional Rating Scale, Quality of life and safety variables.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: pioglitazone; Drug: placebo	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	219 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Efficacy, Safety and Tolerability Study of 45 mg Pioglitazone in Patients With Amyotrophic Lateral Sclerosis (ALS) Receiving Standard Therapy (Riluzole)
Study Start Date :	May 2008
Actual Primary Completion Date :	June 2010
Actual Study Completion Date :	June 2010

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: 1	Drug: pioglitazone; 45 mg/day, 18 months; Other Name: Actos
Placebo Comparator: 2	Drug: placebo; once daily, 18 months

Outcome Measures

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Primary Outcome Measures :

1. Survival in patients with ALS treated with pioglitazone compared to placebo [ Time Frame: 18 months ]

Secondary Outcome Measures :

1. Incidence of tracheotomy or non-invasive ventilation [ Time Frame: 18 month ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• possible, probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria
• disease duration more than 6 months and less than 3 years
• best-sitting FVC between 50% and 95% of predicted normal
• continuously treated with 100 mg riluzole daily, for at least one month
• onset of progression weakness within 36 months prior to study
• women of childbearing age be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test
• capable of thoroughly understanding all information given and giving full informed consent according to GCP

Exclusion Criteria:

• previous participation in another clinical study within the preceding three months
• tracheotomy or assisted ventilation of any type during the preceding three months
• gastrostomy
• any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS
• presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment
• confirmed hepatic insufficiency or abnormal liver function (ASAT and/or ALAT more than 1.5 upper limit of normal)
• renal insufficiency (serum creatinine more than 2.26 mg/dl)
• evidence of major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms
• known hypersensitivity to any component of the study drugs
• likely to be not cooperative or comply with the trial requirements (as assessed by the investigator), or unable to be reached in the case of an emergency
• other antidiabetics
• heart failure or heart failure in the patients history (NYHA I to IV)
• history of macular oedema
• treatment with thiazolidinediones within 3 months prior to screening
• known or suspected history of alcohol and/or drug abuse
• treatment with gemfibrozil within 3 months prior to screening

Contacts and Locations

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Locations

Germany
Department of Neurology, University of Ulm
Ulm, Baden-Württemberg, Germany, 89081
Department of Neurology and Center for Palliative Medicine, University of Munich
Muenchen, Bayern, Germany, D-81366
Department of Neurology, Universty of Regensburg
Regensburg, Bayern, Germany, D-93053
Department of Neurology, University of Wuerzburg
Wuerzburg, Bayern, Germany, 91054
Department of Neurology, Deutsche Klinik für Diagnostik
Wiesbaden, Hessen, Germany, D-65191
Department of Neurology, University of Rostock
Rostock, Mecklenburg-Vorpommern, Germany, D-18147
Department of Neurology, University of Goettingen
Goettingen, Niedersachsen, Germany, D-37073
Department of Neurology, Medical School Hannover
Hannover, Niedersachsen, Germany, 30625
Neurologische Universitätsklinik Bergmannsheil
Bochum, Nordrhein-Westfalen, Germany, 44789
Department of Neurology, Universty of Muenster
Muenster, Nordrhein-Westfalen, Germany, D-48149
Department of Neurology, Universty of Bonn
Bonn, Nordrhrein-Westfalen, Germany, D-53105
Department of Neurology, University of Halle-Wittenberg
Halle/Saale, Sachsen-Anhalt, Germany, 06097
Department of Neurology, TU Dresden
Dresden, Sachsen, Germany, D-01307
Department of Neurology, University of Jena
Jena, Thueringen, Germany, D-07747
Department of Neurology, Humboldt University
Berlin, Germany, 13353

Sponsors and Collaborators

University of Ulm

Investigators

Principal Investigator:	Albert C Ludolph, MD, Prof.	Department of Neurology, University of Ulm

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Schütz B, Reimann J, Dumitrescu-Ozimek L, Kappes-Horn K, Landreth GE, Schürmann B, Zimmer A, Heneka MT. The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice. J Neurosci. 2005 Aug 24;25(34):7805-12.

Kiaei M, Kipiani K, Chen J, Calingasan NY, Beal MF. Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis. Exp Neurol. 2005 Feb;191(2):331-6.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dupuis L, Dengler R, Heneka MT, Meyer T, Zierz S, Kassubek J, Fischer W, Steiner F, Lindauer E, Otto M, Dreyhaupt J, Grehl T, Hermann A, Winkler AS, Bogdahn U, Benecke R, Schrank B, Wessig C, Grosskreutz J, Ludolph AC; GERP ALS Study Group. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PLoS One. 2012;7(6):e37885. doi: 10.1371/journal.pone.0037885. Epub 2012 Jun 8.

Responsible Party:	Albert Christian Ludolph, Prof., Coordinating Investigator, University of Ulm
ClinicalTrials.gov Identifier:	NCT00690118 History of Changes
Other Study ID Numbers:	GERP ALS; EUDRACT NUMBER 2006-005410-13
First Posted:	June 4, 2008
Last Update Posted:	May 29, 2015
Last Verified:	May 2015

Keywords provided by Albert Christian Ludolph, Prof., University of Ulm:

amyotrophic lateral sclerosis; survival time; ALS functioning Rating Scale; quality of life	non-invasive ventilation; clinical tolerability; survival

Additional relevant MeSH terms:

Sclerosis; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases	Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Pioglitazone; Hypoglycemic Agents; Physiological Effects of Drugs