Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis

NCT00690118 | Terminated Phase 2 DMC

• 2 other identifiers: GERP ALSEUDRACT NUMBER 2006-005410-13
• Study Type: interventional
• Target: 219
• Locations: 1 country
• Sites: 15

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Survival in patients with ALS treated with pioglitazone compared to placebo

  18 months

Secondary Outcomes (1)

• Incidence of tracheotomy or non-invasive ventilation

  18 month

Study Arms (2)

1

ACTIVE COMPARATOR

Drug: pioglitazone

2

PLACEBO COMPARATOR

Drug: placebo

Interventions

pioglitazone DRUG

45 mg/day, 18 months

Also known as: Actos

1

placebo DRUG

once daily, 18 months

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (15)

Department of Neurology, University of Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

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

Munich, Bavaria, D-81366, Germany

Location

Department of Neurology, Universty of Regensburg

Regensburg, Bavaria, D-93053, Germany

Location

Department of Neurology, University of Wuerzburg

Würzburg, Bavaria, 91054, Germany

Location

Department of Neurology, Deutsche Klinik für Diagnostik

Wiesbaden, Hesse, D-65191, Germany

Location

Department of Neurology, University of Goettingen

Göttingen, Lower Saxony, D-37073, Germany

Location

Department of Neurology, Medical School Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Department of Neurology, University of Rostock

Rostock, Mecklenburg-Vorpommern, D-18147, Germany

Location

Department of Neurology, Universty of Bonn

Bonn, Nordrhrein-Westfalen, D-53105, Germany

Location

Neurologische Universitätsklinik Bergmannsheil

Bochum, North Rhine-Westphalia, 44789, Germany

Location

Department of Neurology, Universty of Muenster

Münster, North Rhine-Westphalia, D-48149, Germany

Location

Department of Neurology, TU Dresden

Dresden, Saxony, D-01307, Germany

Location

Department of Neurology, University of Halle-Wittenberg

Halle, Saxony-Anhalt, 06097, Germany

Location

Department of Neurology, University of Jena

Jena, Thuringia, D-07747, Germany

Location

Department of Neurology, Humboldt University

Berlin, 13353, Germany

Location

Related Publications (3)

• 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.

  PMID: 16120782 BACKGROUND

• 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.

  PMID: 15649489 BACKGROUND

• 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.

  PMID: 22715372 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Albert C Ludolph, MD, Prof.

  Department of Neurology, University of Ulm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinating Investigator

Study Record Dates

• First Submitted: June 2, 2008
• First Posted: June 4, 2008
• Study Start: May 1, 2008
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: May 29, 2015

Record last verified: 2015-05

Locations

DE (15)