Active Neuromuscular Clinical Trials & Studies Selective Listing
DISEASE CLASSIFICATION(S):
Friedreich’s ataxia
NAME OF CLINICAL TRIAL/STUDY:
Idebenone — Phase 1 Clinical Trial to Establish the Maximum Tolerated Dose of Idebenone in People with Friedreich’s Ataxia
PURPOSE AND RATIONALE:
This study will determine the highest dose of idebenone that can safely be given to people with Friedreich's ataxia (FA), 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 FA who were given idebenone, an antioxidant similar to the dietary supplement coenzyme Q, had a decrease in the size of their left ventricle.
FA is a progressive, autosomal recessive (takes two flawed genes to cause symptoms), 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 (cardiac muscle degeneration).
This will be a phase 1a, unblinded, dose-escalation trial examining the toxicity and tolerability of the antioxidant idebenone in patients with FA. The primary objective is to determine the maximum tolerated single dose of idebenone in patients with FA.
The secondary objective is to document the pharmacokinetics (what happens to the drug in the body) of single-dose idebenone in this population. The investigators 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 participants from each cohort will receive a single dose 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 participants 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 1a trial, the investigators plan to further refine the MTD for each age group in a phase 1b trial, in which they will examine multiple-dose regimens over a longer study period.
They hope to follow these phase 1 studies with a double-blinded, placebo-controlled, phase 2 trial to further evaluate safety and to estimate the efficacy of idebenone, using cardiac parameters (values) as the primary end points. In addition, they are currently in the process of validating a clinical evaluation scale for FA that they hope to employ in measuring neurological parameters as a secondary end point in the phase 2 trial.
OPENING/CLOSING DATES: Opened May 2001; closing not determined.
TARGET NUMBER OF PARTICIPANTS: 100
RECRUITMENT STATUS: Active
ELIGIBILITY REQUIREMENTS:
At present, recruitment has ended for adolescents and adults; only children ages 5 to 11 with Friedreich’s ataxia are still being actively recruited. 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 FA.
Participants will be admitted to the NIH Clinical Center for three days. They will have blood and urine tests and a heart evaluation, including an echocardiogram, which is a procedure that uses sound waves to produce images of the heart, and an electrocardiogram, which is a study of the electrical activity of the heart.
When these tests have been completed, patients will take an idebenone 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, one, two, three, four, six, 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 one to eight weeks. Those who experienced no serious side effects may receive another, higher dose of the drug, with at least six days between doses.
Inclusion Criteria:
- Diagnosis of Friedreich’s ataxia with confirmed FA mutations
- Age greater than or equal to 5 years old; as of July 2002, only children ages 5 to 11 are being recruited
- 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 (or assent, a modified form of consent that applies to minors, if applicable)
- History of a hypersensitivity reaction to idebenone or coenzyme Q10
- Pregnant or lactating (breast-feeding) women; all women of childbearing age must have negative serum pregnancy test 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 grams per decliter
- 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
CONTACT INFORMATION FOR PROSPECTIVE PARTICIPANTS:
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, MD 20892
phone: (800) 411-1222
TTY (for hearing-impaired callers): (866) 411-1010
e-mail: prpl@mail.cc.nih.gov