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

NCT00811681 | Completed Phase 3 DMC

• 1 other identifier: P070123
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Friedreich's Ataxia

Keywords

Friedreich's ataxia; Pioglitazone

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (4)

• tolerance of Pioglitazone

  2 years

• efficacy of Pioglitazone on neurological function

  2 years

• efficacy of Pioglitazone on functional handicap and quality of life

  2 years

• effect of Pioglitazone on cardiac parameters

  2 years

Study Arms (2)

Pioglitazone

EXPERIMENTAL

pioglitazone

Drug: pioglitazone

Control

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

pioglitazone DRUG

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

Pioglitazone

Placebo DRUG

a placebo administered orally once a day after the first visit and for a total of 2 years.

Also known as: Control

Control

Eligibility Criteria

• Age: 7 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Robert Debré

Paris, 75019, France

Location

Related Publications (1)

• Simon AL, Meyblum J, Roche B, Vidal C, Mazda K, Husson I, Ilharreborde B. Scoliosis in Patients With Friedreich Ataxia: Results of a Consecutive Prospective Series. Spine Deform. 2019 Sep;7(5):812-821. doi: 10.1016/j.jspd.2019.02.005.

  PMID: 31495483 DERIVED

MeSH Terms

Conditions

Friedreich Ataxia

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Isabelle Husson

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2008
• First Posted: December 19, 2008
• Study Start: December 1, 2008
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: September 4, 2013

Record last verified: 2013-08

Locations

FR (1)