Effect of Pioglitazone Administered to Patients With Friedreich's Ataxia: Proof of Concept

• Status: Completed
• Trial end date: 2013-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Pioglitazone

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.