Clinical Trial: Effect of Pioglitazone Administered to Patients With Friedreich's Ataxia: Proof of Concept
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Effect of Pioglitazone Administered to Patients With Friedreich's ATAXIA:Proof of Concept
Brief 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.
Detailed Summary:
State of the art 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. The cardinal feature is a progressive gait and limb ataxia. Other commonly associated clinical signs include: dysarthria, sensory loss, distal weakness, pyramidal signs, absent reflexes, nystagmus and cardiomyopathy. Pes caves, scoliosis, diabetes and decline of vision or audition are also found in many patients. The disease often reveals before adulthood and leads to a progressive loss of autonomy about ten years after disease onset. FA is recessively inherited with a GAA trinucleotide repeat expansion in the first intron of a gene encoding frataxin a mitochondrial protein. Decreased frataxin leads to a mitochondrial iron-sulfur protein deficiency and hampered signalling pathways for superoxide dismutases, key enzymes of early antioxidant defences of the cells. As a result, cultured patient cells are particularly sensitive to oxidative insult. One aspect of the pathogenesis in vivo might be explained by this phenomenon.
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. A clinical study has shown that a daily treatment with Pioglitazone during three years induced apparent clinical improvement without adverse events in multiple sclerosis patients. Pioglitazone has been shown to possibly act on neurodegeneration in humans and animals models thus it appears a promising agent to be tested in F
Sponsor: Assistance Publique - Hôpitaux de Paris
Current Primary Outcome: 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 ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- tolerance of Pioglitazone [ Time Frame: 2 years ]
- efficacy of Pioglitazone on neurological function [ Time Frame: 2 years ]
- efficacy of Pioglitazone on functional handicap and quality of life [ Time Frame: 2 years ]
- effect of Pioglitazone on cardiac parameters [ Time Frame: 2 years ]
Original Secondary Outcome: Same as current
Information By: Assistance Publique - Hôpitaux de Paris
Dates:
Date Received: December 18, 2008
Date Started: December 2008
Date Completion:
Last Updated: September 2, 2013
Last Verified: August 2013
