Phase 1 Trial of Idebenone to Treat Patients With Friedreich's Ataxia

NCT00078481 | Completed Phase 1

• 2 other identifiers: 04012904-N-0129
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine the highest amount of idebenone that can be taken without harmful side effects in children, teenagers, and adults with Friedreich's ataxia, a progressive degenerative disease that affects several body systems. Studies in France and Canada showed that patients with Friedreich's ataxia who took idebenone had a decrease in the size of their left ventricle (main pumping chamber of the heart), which is often enlarged in this disease. It is possible that idebenone may also prevent the progression of nervous system degeneration in Friedreich's ataxia. Patients 5 years of age and older with Friedreich's ataxia may be eligible for this study. Candidates are screened with a blood test and review of their medical records, including genetic studies. Participants undergo the following procedures during a 6-day hospital admission to the NIH Clinical Center:

• Placement of an intravenous catheter (plastic tube inserted into a vein) for collecting blood samples after drug administration
• Blood and urine tests
• Heart examination, including electrocardiogram (EKG), to assess heart function and size.
• Idebenone therapy: Patients take three tablets a day (at 7 AM, 1 PM and 7 PM) on days 2, 3 and 4 of hospitalization. Blood samples are collected through the IV tube at 0.5, 1, 2, 4, and 6 hours after the first dose on day 2, then at 1 hour after the first and third doses every day, and then at 1, 2, 4, 8, 12, 24, 36, and 48 hours after the last dose on day 4 to determine how the body uses and eliminates the drug.
• Monitoring for drug side effects: Patients have frequent checks of vital signs (blood pressure, pulse, temperature, breathing rate) and a brief physical examination to check for drug side effects from the start of drug therapy on day 2 until at least 43 hours after the last dose on day 4. Patients who experience no difficulties are discharged from the hospital after the sixth day with a 1-month supply of medication to take 3 times a day at home. They are contacted by phone every 2 weeks while taking the medication to check side effects. Blood tests are also done every 2 weeks to check for any abnormalities.

Conditions

Friedreich Ataxia

Keywords

Neurodegeneration; Anti-Oxidant; Neuropathy; Hereditary; Spinocerebellar; 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.
• No exposure to idebenone or coenzyme Q(10) for a period of at least one week before onset of the medication phase of the study.
• Written, informed consent (and assent, if applicable).

You may not qualify if:

• History of hypersensitivity reaction to idebenone or coenzyme Q(10).
• Pregnant or lactating women. All women of child-bearing potential must have negative serum pregnancy prior to the medication phase of the study. If a minor has a positive pregnancy test, we will inform her but not inform her parents unless we are asked to by the minor.
• Lactose intolerant individuals (because of the lactose content in the tablet ingredients).
• Age less than five years old.
• Platelet count, lymphocyte count or hemoglobin below the lower limit of normal.
• Alkaline phosphatase, SGOT, or SGPT greater than 1.5 x the upper limit of normal. Bilirubin greater than 1.2 g/dl.
• Creatinine greater than 1.5 x 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)

• Artuch R, Aracil A, Mas A, Colome C, Rissech M, Monros E, Pineda M. Friedreich's ataxia: idebenone treatment in early stage patients. Neuropediatrics. 2002 Aug;33(4):190-3. doi: 10.1055/s-2002-34494.

  PMID: 12368988 BACKGROUND

• 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

• 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: February 27, 2004
• First Posted: March 1, 2004
• Study Start: February 1, 2004
• Study Completion: April 1, 2006
• Last Updated: March 4, 2008

Record last verified: 2006-04

Locations

US (1)