Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis

This study has been terminated.
(The interim analysis showed no tendency in favour of the verum group. Therefore it was decided to stop the study prematurely.)
Sponsor:
Information provided by:
University of Ulm
ClinicalTrials.gov Identifier:
NCT00690118
First received: June 2, 2008
Last updated: June 1, 2010
Last verified: August 2009
  Purpose

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 Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: pioglitazone
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by University of Ulm:

Primary Outcome Measures:
  • Survival in patients with ALS treated with pioglitazone compared to placebo [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of tracheotomy or non-invasive ventilation [ Time Frame: 18 month ] [ Designated as safety issue: Yes ]

Enrollment: 219
Study Start Date: May 2008
Estimated Study Completion Date: March 2011
Estimated Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: pioglitazone
45 mg/day, 18 months
Other Name: Actos
Placebo Comparator: 2 Drug: placebo
once daily, 18 months

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00690118

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

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Albert C Ludolph, Prof. MD, Department of Neurology, University of Ulm, Oberer Eselsberg 45, D-89081 Ulm
ClinicalTrials.gov Identifier: NCT00690118     History of Changes
Other Study ID Numbers: GERP ALS, EUDRACT NUMBER 2006-005410-13
Study First Received: June 2, 2008
Last Updated: June 1, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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

ClinicalTrials.gov processed this record on April 16, 2014