Safety Study of Idebenone to Treat Friedreich's Ataxia

NCT00015808 | Completed Phase 1

• 2 other identifiers: 01016701-N-0167
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine the highest dose of idebonone that can safely be given to patients with Friedrich's ataxia, an inherited degenerative disease that causes loss of muscle coordination, speech problems, weakness and sensory loss. Enlargement of the left ventricle (the large pumping chamber of the heart) is also common in this disease. In studies in France and Canada, patients with Friedrich's ataxia who were given idebonone, an antioxidant similar to the dietary supplement coenzyme Q, had a decrease in the size of their left ventricle. Patients 5 years and older with Friedrich's ataxia may be eligible for this study. Pregnant and lactating women may not participate. Candidates will be screened with a medical history and physical examination and a review of genetic studies. Patients who have not had genetic studies will be offered genetic counseling and testing to confirm or rule out Friedrich's ataxia. Participants will be admitted to the NIH Clinical Center for 3 days. They will have blood and urine tests and a heart evaluation, including an echocardiogram-a procedure that uses sound waves to produce images of the heart, and an electrocardiogram-a study of the electrical activity of the heart. When these tests have been completed, patients will take an idebonone capsule. They will be monitored for side effects for 72 hours. Blood samples will be collected through an intravenous catheter (flexible plastic tube placed in a vein) 0.5, 1, 2, 3, 4, 6, 12, 24, 48 and 72 hours after the drug is taken to determine how long it takes for the drug to be eliminated from the body. Patients will return for a follow-up visit within 1 to 8 weeks. Those who experienced no serious side effects may receive another, higher dose of the drug, with at least 6 days between doses.

Conditions

Friedreich Ataxia

Keywords

Neurodegeneration; Anti-Oxidant; Neuropathy; Hereditary; Spinocerebellar; Friedreich's Ataxia; Friedreich Ataxia; FRDA

Interventions

Idebenone DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of FRDA with confirmed FRDA mutations.
• Age greater than or equal to five years old.
• No exposure to idebenone or coenzyme Q10 for a period of at least one week prior to onset of the medication phase of the study.
• Written, informed consent (and assent, if applicable).

You may not qualify if:

• History of a hypersensitivity reaction to idebenone or coenzyme
• Q10.
• Pregnant or lactating women. All women of child-bearing potential must have negative serum pregnancy prior to the medication phase of the study.
• Age less than five years old.
• Platelet count, lymphocyte count or hemoglobin below the lower limit of normal.
• Alkaline phosphatase, SGOT, SGPT greater than 1.5 times the upper limit of normal. Bilirubin greater than 1.2 g/dl.
• Creatinine greater than 1.5 times the upper limit of normal.
• 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

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institute of Neurological Disorders and Stroke (NINDS)

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Babcock M, de Silva D, Oaks R, Davis-Kaplan S, Jiralerspong S, Montermini L, Pandolfo M, Kaplan J. Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science. 1997 Jun 13;276(5319):1709-12. doi: 10.1126/science.276.5319.1709.

  PMID: 9180083 BACKGROUND

• Beal MF. Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci. 2000 Jul;23(7):298-304. doi: 10.1016/s0166-2236(00)01584-8.

  PMID: 10856939 BACKGROUND

• Campuzano V, Montermini L, Molto MD, Pianese L, Cossee M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, Zara F, Canizares J, Koutnikova H, Bidichandani SI, Gellera C, Brice A, Trouillas P, De Michele G, Filla A, De Frutos R, Palau F, Patel PI, Di Donato S, Mandel JL, Cocozza S, Koenig M, Pandolfo M. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science. 1996 Mar 8;271(5254):1423-7. doi: 10.1126/science.271.5254.1423.

  PMID: 8596916 BACKGROUND

• Di Prospero NA, Sumner CJ, Penzak SR, Ravina B, Fischbeck KH, Taylor JP. Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich ataxia. Arch Neurol. 2007 Jun;64(6):803-8. doi: 10.1001/archneur.64.6.803.

  PMID: 17562928 DERIVED

MeSH Terms

Conditions

Friedreich Ataxia; Nerve Degeneration

Interventions

idebenone

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 6, 2001
• First Posted: May 7, 2001
• Study Start: May 1, 2001
• Study Completion: April 1, 2006
• Last Updated: July 12, 2006

Record last verified: 2006-04

Locations

US (1)