Safety Study of Idebenone to Treat Friedreich's Ataxia

July 11, 2006 updated by: National Institute of Neurological Disorders and Stroke (NINDS)

Phase I Clinical Trial to Establish the Maximum Tolerated Dose of Idebenone in Children, Adolescents, and Adults With Friedreich's Ataxia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Friedreich's ataxia (FRDA) is a progressive, autosomal recessive, multisystem degenerative disease for which there is currently no effective treatment. Recent studies suggest that lipid-soluble antioxidants may prevent the progression of neurodegeneration and lead to some reversal of cardiomyopathy.

This will be a phase Ia, unblinded, dose-escalation trial examining the toxicity and tolerability of the antioxidant idebenone in patients with FRDA. Our primary objective is to determine the maximum tolerated single dose of idebenone in patients with FRDA. Our secondary objective is to document the pharmacokinetics of single-dose idebenone in this population. We aim to enroll 48 patients divided evenly among three age cohorts: children (ages 5-11), adolescents (ages 12-17), and adults (age greater than or equal to 18). Each age cohort will be studied independently. Three patients from each cohort will receive one day of oral idebenone followed by inpatient monitoring for 72 hours. If dose-limiting toxicity (DLT) is not observed during the 72-hour study period, three new patients will receive the next highest dose. If one of three patients experiences DLT, three new patients will receive the same dose. Within each cohort, the dose will be escalated until the maximum tolerated dose (MTD) is established. The MTD will be defined as one dose below that which resulted in DLT in any two patients within a cohort.

Subsequent to the completion of this phase Ia trial, we plan to further refine the MTD for each age group in a phase Ib trial in which we will examine multiple-dose regimens over a longer study period. We hope to follow these phase I studies with a double-blinded, placebo-controlled phase II trial to further evaluate safety and to estimate the efficacy of idebenone using cardiac parameters as our primary endpoints. In addition, we are currently in the process of validating a clinical evaluation scale for FRDA that we hope to employ in measuring neurological parameters as a secondary endpoint in the phase II trial.

Study Type

Interventional

Enrollment

100

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institute of Neurological Disorders and Stroke (NINDS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

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).

EXCLUSION CRITERIA:

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2001

Study Completion

April 1, 2006

Study Registration Dates

First Submitted

May 6, 2001

First Submitted That Met QC Criteria

May 5, 2001

First Posted (Estimate)

May 7, 2001

Study Record Updates

Last Update Posted (Estimate)

July 12, 2006

Last Update Submitted That Met QC Criteria

July 11, 2006

Last Verified

April 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 010167
  • 01-N-0167

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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