Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

Efficacy, Safety and Tolerability Study of 45 mg Pioglitazone in Patients With Amyotrophic Lateral Sclerosis (ALS) Receiving Standard Therapy (Riluzole)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00690118
• Other study ID #: GERP ALS
• Secondary ID: EUDRACT NUMBER 2
• Status: Terminated
• Phase: Phase 2
• First received: June 2, 2008
• Last updated: May 28, 2015
• Start date: May 2008
• Est. completion date: June 2010

Study information

• Verified date: May 2015
• Source: University of Ulm
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 219
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• pioglitazone
45 mg/day, 18 months
• placebo
once daily, 18 months

Locations

Country	Name	City	State
Germany	Department of Neurology, Humboldt University	Berlin
Germany	Neurologische Universitätsklinik Bergmannsheil	Bochum	Nordrhein-Westfalen
Germany	Department of Neurology, Universty of Bonn	Bonn	Nordrhrein-Westfalen
Germany	Department of Neurology, TU Dresden	Dresden	Sachsen
Germany	Department of Neurology, University of Goettingen	Goettingen	Niedersachsen
Germany	Department of Neurology, University of Halle-Wittenberg	Halle/Saale	Sachsen-Anhalt
Germany	Department of Neurology, Medical School Hannover	Hannover	Niedersachsen
Germany	Department of Neurology, University of Jena	Jena	Thueringen
Germany	Department of Neurology and Center for Palliative Medicine, University of Munich	Muenchen	Bayern
Germany	Department of Neurology, Universty of Muenster	Muenster	Nordrhein-Westfalen
Germany	Department of Neurology, Universty of Regensburg	Regensburg	Bayern
Germany	Department of Neurology, University of Rostock	Rostock	Mecklenburg-Vorpommern
Germany	Department of Neurology, University of Ulm	Ulm	Baden-Württemberg
Germany	Department of Neurology, Deutsche Klinik für Diagnostik	Wiesbaden	Hessen
Germany	Department of Neurology, University of Wuerzburg	Wuerzburg	Bayern

Sponsors (1)

Lead Sponsor	Collaborator
University of Ulm

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival in patients with ALS treated with pioglitazone compared to placebo		18 months	No
Secondary	Incidence of tracheotomy or non-invasive ventilation		18 month	Yes