Clinical trial NCT00690118: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: amyotrophic lateral sclerosis
survival time
ALS functioning Rating Scale
quality of life
non-invasive ventilation
clinical tolerability
survival
Lead sponsor: University of Ulm
Sponsor class: OTHER
First posted: 2008-06-04
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Survival in patients with ALS treated with pioglitazone compared to placebo
timeFrame: 18 months
Secondary outcomes:
measure: Incidence of tracheotomy or non-invasive ventilation
timeFrame: 18 month
Other outcomes:
Locations:
city: Ulm
country: Germany
facility: Department of Neurology, University of Ulm
state: Baden-Württemberg
city: Muenchen
country: Germany
facility: Department of Neurology and Center for Palliative Medicine, University of Munich
state: Bayern
city: Regensburg
country: Germany
facility: Department of Neurology, Universty of Regensburg
state: Bayern
city: Wuerzburg
country: Germany
facility: Department of Neurology, University of Wuerzburg
state: Bayern
city: Wiesbaden
country: Germany
facility: Department of Neurology, Deutsche Klinik für Diagnostik
state: Hessen
city: Rostock
country: Germany
facility: Department of Neurology, University of Rostock
state: Mecklenburg-Vorpommern
city: Goettingen
country: Germany
facility: Department of Neurology, University of Goettingen
state: Niedersachsen
city: Hannover
country: Germany
facility: Department of Neurology, Medical School Hannover
state: Niedersachsen
city: Bochum
country: Germany
facility: Neurologische Universitätsklinik Bergmannsheil
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: Department of Neurology, Universty of Muenster
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Department of Neurology, Universty of Bonn
state: Nordrhrein-Westfalen
city: Halle/Saale
country: Germany
facility: Department of Neurology, University of Halle-Wittenberg
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Department of Neurology, TU Dresden
state: Sachsen
city: Jena
country: Germany
facility: Department of Neurology, University of Jena
state: Thueringen
city: Berlin
country: Germany
facility: Department of Neurology, Humboldt University
Study officials:
affiliation: Department of Neurology, University of Ulm
name: Albert C Ludolph, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.