Effect of Pioglitazone Administered to Patients With Friedreich's Ataxia: Proof of Concept - Full Text View

Sponsor:	Assistance Publique - Hôpitaux de Paris
Information provided by (Responsible Party):	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00811681

Purpose

Friedreich's ataxia (FA) is a rare progressive neurological disorder affecting approximately 1/30, 000 individuals. No treatment is presently available to counteract the neurodegeneration of this extremely severe disease.

Pioglitazone, a well known PPAR gamma (peroxysome proliferators-activated receptor gamma) ligand induces the expression of many enzymes involved in the mitochondrial metabolism, including the superoxide dismutases. This agent may be therapeutic by counteracting the disabled recruitment of antioxidant enzymes in FA patients. This potential neuroprotective agent crosses the brain blood barrier in human.

Primary objective: To explore the effects of Pioglitazone on neurological function in FA patients. We expect neurological benefits taking into account the natural course of the disease.

Population: Subjects for this study will be limited to patients not older than 25 years Methodology: Prospective, randomized double-blind trial of Pioglitazone versus placebo in FA patients. Patients will be treated two years and will undergo clinical exams and testing during three days each six months at the clinical investigation centre.

Condition	Intervention	Phase
Friedreich's Ataxia	Drug: pioglitazone Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Effect of Pioglitazone Administered to Patients With Friedreich's ATAXIA:Proof of Concept

Resource links provided by NLM:

Genetics Home Reference related topics: ataxia neuropathy spectrum childhood myocerebrohepatopathy spectrum deoxyguanosine kinase deficiency Friedreich ataxia infantile-onset spinocerebellar ataxia Marinesco-Sjögren syndrome mitochondrial neurogastrointestinal encephalopathy disease myoclonic epilepsy myopathy sensory ataxia spinocerebellar ataxia type 1 spinocerebellar ataxia type 2 spinocerebellar ataxia type 3 spinocerebellar ataxia type 6

MedlinePlus related topics: Friedreich's Ataxia

Drug Information available for: Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

evaluate the efficacy of Pioglitazone on the neurological function of FA patients. Success will be defined as a stabilisation or improvement on ICARS designed as no more than 2 points maximum increment on this scale in two year. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

tolerance of Pioglitazone [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
efficacy of Pioglitazone on neurological function [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
efficacy of Pioglitazone on functional handicap and quality of life [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
effect of Pioglitazone on cardiac parameters [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment:	40
Study Start Date:	December 2008
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Pioglitazone	Drug: pioglitazone administered orally once a day after the first visit and for a total of 2 years. Initially, Pioglitazone will be started at 15mg /day. Dosage will then increase by 15mg /d/ week up to the maximal dose of 45mg /day Other Name: pioglitazone
Placebo Comparator: Control	Drug: Placebo a placebo administered orally once a day after the first visit and for a total of 2 years. Other Name: Control

Show Detailed Description

Eligibility

Ages Eligible for Study:	7 Years to 24 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of FA with confirmed FRDA mutations
GAA repeat length of the shorter allele of frataxin gene > 300
Age ≤ 24 years
Ambulatory (assistance devices permitted) or able to stand up without support
Neurologically symptomatic
All subjects agree and commit to the use of 2 reliable methods of birth control for the duration of the study if sexually active
Willing (and parents if minor) to participate in all aspects of trial design and follow-up
No modification of the usual treatment 6 months before inclusion and agree to stay with the same treatment during the trial (idebenone with a stable dosage, cardiologic therapeutic)

Exclusion Criteria:

Composite heterozygote
Patients unable to stand up even with support
Pregnant women
Cardiac insufficiency NYHA III to IV and heart ejection fraction> 50%
Alkaline phosphatase, SGOT or SGPT greater than 1.5 X the upper limit of normal
Patients with diabetes
Modification of the concomitant medications taken by the patient within the 6 months before inclusion or during the trial
Clinically significant medical disease that, in the judgment of the investigators, would expose the patient to undue risk of harm or prevent the patient from completing the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00811681

Locations

France
Hôpital Robert Debré
Paris, France, 75019

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator:

Isabelle Husson

Assistance Publique - Hôpitaux de Paris

More Information

No publications provided

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00811681 History of Changes
Other Study ID Numbers:	P070123
Study First Received:	December 18, 2008
Last Updated:	January 9, 2012
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Friedreich's ataxia
Pioglitazone

Additional relevant MeSH terms:

Ataxia
Friedreich Ataxia
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinocerebellar Degenerations
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases

Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012