Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis

NCT ID: NCT00690118

Last Updated: 2015-05-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2010-06-30

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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Group Type: ACTIVE_COMPARATOR

pioglitazone

Intervention Type: DRUG

45 mg/day, 18 months

2

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

once daily, 18 months

Interventions

pioglitazone

45 mg/day, 18 months

Intervention Type: DRUG

placebo

once daily, 18 months

Intervention Type: DRUG

Other Intervention Names

Actos

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Ulm

OTHER

Sponsor Role: lead

Responsible Party

Albert Christian Ludolph, Prof.

Coordinating Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Albert C Ludolph, MD, Prof.

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, University of Ulm

Locations

Department of Neurology, University of Ulm

Ulm, Baden-Wurttemberg, Germany

Department of Neurology and Center for Palliative Medicine, University of Munich

Munich, Bavaria, Germany

Department of Neurology, Universty of Regensburg

Regensburg, Bavaria, Germany

Department of Neurology, University of Wuerzburg

Würzburg, Bavaria, Germany

Department of Neurology, Deutsche Klinik für Diagnostik

Wiesbaden, Hesse, Germany

Department of Neurology, University of Goettingen

Göttingen, Lower Saxony, Germany

Department of Neurology, Medical School Hannover

Hanover, Lower Saxony, Germany

Department of Neurology, University of Rostock

Rostock, Mecklenburg-Vorpommern, Germany

Department of Neurology, Universty of Bonn

Bonn, Nordrhrein-Westfalen, Germany

Neurologische Universitätsklinik Bergmannsheil

Bochum, North Rhine-Westphalia, Germany

Department of Neurology, Universty of Muenster

Münster, North Rhine-Westphalia, Germany

Department of Neurology, TU Dresden

Dresden, Saxony, Germany

Department of Neurology, University of Halle-Wittenberg

Halle, Saxony-Anhalt, Germany

Department of Neurology, University of Jena

Jena, Thuringia, Germany

Department of Neurology, Humboldt University

Berlin, , Germany

Countries

Germany

References

Schutz B, Reimann J, Dumitrescu-Ozimek L, Kappes-Horn K, Landreth GE, Schurmann 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. doi: 10.1523/JNEUROSCI.2038-05.2005.

Reference Type: BACKGROUND

PMID: 16120782 (View on PubMed)

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. doi: 10.1016/j.expneurol.2004.10.007.

Reference Type: BACKGROUND

PMID: 15649489 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22715372 (View on PubMed)

Other Identifiers

EUDRACT NUMBER 2006-005410-13

Identifier Type: -

Identifier Source: secondary_id

GERP ALS

Identifier Type: -

Identifier Source: org_study_id