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Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis

Primary Purpose

Amyotrophic Lateral Sclerosis

Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
pioglitazone
placebo
Sponsored by
University of Ulm
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring amyotrophic lateral sclerosis, survival time, ALS functioning Rating Scale, quality of life, non-invasive ventilation, clinical tolerability, survival

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Neurology, University of Ulm
  • Department of Neurology and Center for Palliative Medicine, University of Munich
  • Department of Neurology, Universty of Regensburg
  • Department of Neurology, University of Wuerzburg
  • Department of Neurology, Deutsche Klinik für Diagnostik
  • Department of Neurology, University of Rostock
  • Department of Neurology, University of Goettingen
  • Department of Neurology, Medical School Hannover
  • Neurologische Universitätsklinik Bergmannsheil
  • Department of Neurology, Universty of Muenster
  • Department of Neurology, Universty of Bonn
  • Department of Neurology, University of Halle-Wittenberg
  • Department of Neurology, TU Dresden
  • Department of Neurology, University of Jena
  • Department of Neurology, Humboldt University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

1

2

Arm Description

Outcomes

Primary Outcome Measures

Survival in patients with ALS treated with pioglitazone compared to placebo

Secondary Outcome Measures

Incidence of tracheotomy or non-invasive ventilation

Full Information

First Posted
June 2, 2008
Last Updated
May 28, 2015
Sponsor
University of Ulm
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1. Study Identification

Unique Protocol Identification Number
NCT00690118
Brief Title
Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis
Official Title
Efficacy, Safety and Tolerability Study of 45 mg Pioglitazone in Patients With Amyotrophic Lateral Sclerosis (ALS) Receiving Standard Therapy (Riluzole)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Terminated
Why Stopped
The interim analysis showed no tendency in favour of the verum group. Therefore it was decided to stop the study prematurely.
Study Start Date
May 2008 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Ulm

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
amyotrophic lateral sclerosis, survival time, ALS functioning Rating Scale, quality of life, non-invasive ventilation, clinical tolerability, survival

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
219 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Title
2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
pioglitazone
Other Intervention Name(s)
Actos
Intervention Description
45 mg/day, 18 months
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
once daily, 18 months
Primary Outcome Measure Information:
Title
Survival in patients with ALS treated with pioglitazone compared to placebo
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Incidence of tracheotomy or non-invasive ventilation
Time Frame
18 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albert C Ludolph, MD, Prof.
Organizational Affiliation
Department of Neurology, University of Ulm
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurology, University of Ulm
City
Ulm
State/Province
Baden-Württemberg
ZIP/Postal Code
89081
Country
Germany
Facility Name
Department of Neurology and Center for Palliative Medicine, University of Munich
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
D-81366
Country
Germany
Facility Name
Department of Neurology, Universty of Regensburg
City
Regensburg
State/Province
Bayern
ZIP/Postal Code
D-93053
Country
Germany
Facility Name
Department of Neurology, University of Wuerzburg
City
Wuerzburg
State/Province
Bayern
ZIP/Postal Code
91054
Country
Germany
Facility Name
Department of Neurology, Deutsche Klinik für Diagnostik
City
Wiesbaden
State/Province
Hessen
ZIP/Postal Code
D-65191
Country
Germany
Facility Name
Department of Neurology, University of Rostock
City
Rostock
State/Province
Mecklenburg-Vorpommern
ZIP/Postal Code
D-18147
Country
Germany
Facility Name
Department of Neurology, University of Goettingen
City
Goettingen
State/Province
Niedersachsen
ZIP/Postal Code
D-37073
Country
Germany
Facility Name
Department of Neurology, Medical School Hannover
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
Facility Name
Neurologische Universitätsklinik Bergmannsheil
City
Bochum
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
44789
Country
Germany
Facility Name
Department of Neurology, Universty of Muenster
City
Muenster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
D-48149
Country
Germany
Facility Name
Department of Neurology, Universty of Bonn
City
Bonn
State/Province
Nordrhrein-Westfalen
ZIP/Postal Code
D-53105
Country
Germany
Facility Name
Department of Neurology, University of Halle-Wittenberg
City
Halle/Saale
State/Province
Sachsen-Anhalt
ZIP/Postal Code
06097
Country
Germany
Facility Name
Department of Neurology, TU Dresden
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
D-01307
Country
Germany
Facility Name
Department of Neurology, University of Jena
City
Jena
State/Province
Thueringen
ZIP/Postal Code
D-07747
Country
Germany
Facility Name
Department of Neurology, Humboldt University
City
Berlin
ZIP/Postal Code
13353
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
16120782
Citation
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.
Results Reference
background
PubMed Identifier
15649489
Citation
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.
Results Reference
background
PubMed Identifier
22715372
Citation
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.
Results Reference
derived

Learn more about this trial

Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis

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