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| Sponsor: | National Institute of Neurological Disorders and Stroke (NINDS) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00229632 |
Purpose
This study will determine whether a drug called idebenone is safe and effective in reducing the level of oxidants that are believed to damage the nervous system and hearts in patients with Friedreich's ataxia. Friedreich's ataxia is caused by an abnormality in the gene that makes a protein called frataxin, which is necessary for the proper functioning of energy-producing parts of cells called mitrochondria. In Friedreich's ataxia, the mitochondria become overloaded with iron, and high levels of harmful compounds called oxidants are formed. These oxidants are believed to damage the cells of the nervous system and hearts of people with Friedreich's ataxia. Idebenone is a man-made drug similar to a naturally occurring compound known as Coenzyme Q10. This study will test whether idebenone can alleviate some of the symptoms of Friedreich's ataxia and slow or halt the progression of the disease.
Patients with genetically confirmed Friedreich's ataxia who are between 9 and 18 years of age, weigh between 65 and 175 pounds and can walk 25 feet with or without an assistive device may be eligible for this study. Candidates are screened with blood tests and a review of their medical records.
Participants undergo the following tests and procedures:
| Condition | Intervention | Phase |
|---|---|---|
|
Friedreich Ataxia |
Drug: Idebenone |
Phase II |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Safety/Efficacy Study |
| Official Title: | A Six Month Double-Blind, Placebo-Controlled Phase 2 Clinical Trial to Determine the Safety and Efficacy of Idebenone Administered to Patients With Friedreich's Ataxia |
| Enrollment: | 51 |
| Study Start Date: | September 2005 |
| Study Completion Date: | December 2007 |
| Primary Completion Date: | December 2007 (Final data collection date for primary outcome measure) |
Background: Friedreich's ataxia (FA) is a progressive, autosomal recessive, multisystem degenerative disease for which there is currently no effective treatment. Recent studies have suggested that lipid-soluble antioxidants lead to a modest reversal of cardiomyopathy in patients with FA. It is possible that antioxidants may also prevent the progression of neurodegeneration.
Objective: This will be a 6 month phase 2 double-blind, placebo-controlled trial to assess the safety and efficacy of idebenone administered to adolescents and children with FA.
Study Population: We aim to enroll 48 subjects composed of children (ages 9-11) and adolescents (ages 12-17) with FA divided evenly among 4 treatment arms (placebo, low, intermediate, and high dose idebenone).
Design: Our primary objective is to examine the change in the level of oxidative stress by measuring the oxidative marker 8-hydroxy-2-deoxyguanosine from baseline and after 6 months of treatment with placebo or varying doses of idebenone. Following informed consent and assent, patients will undergo an initial medical history and physical followed by specific neurological, functional, and cardiac testing over a two-day outpatient visit. Patients will provide blood and urine samples for safety laboratory and biochemical analysis. Each patient will be randomized to one of 4 treatment arms and will be provided with a 6 month supply of study drug or placebo which will be administered three times a day. Patients will have follow-up laboratory monitoring after 1 and 3 months and at the end of the study. Additionally, patients will also have an EKG, vital signs, including orthostatics, and a physical examination performed after 1 and 3 months by their primary care physician. Patients will return after 6 months for follow-up exam, testing, and laboratory monitoring over a two-day outpatient visit.
Outcome Parameters: The primary endpoint in this phase 2 trial is the change in the level of the oxidative stress marker 8-hydroxy-2-deoxyguanosine. Secondary endpoints include types and frequency of adverse events, if any, compliance with the dosing regimen, and measurements of the following: International Cooperative Ataxia Rating Scale (ICARS), Friedreich's ataxia Rating Scale (FARS), force control, gait analysis, quantitative sensation testing, fine motor control, health related quality of life score (SF-10), functional capacity, aerobic capacity, left ventricular wall mass, noninvasive measures of systolic and diastolic ventricular function, metabolic markers, markers of mitochondrial DNA damage, and gene expression profiling.
Future Directions: We hope that the results of this phase 2 study will assist us in developing a multi-center, double-blinded, placebo-controlled phase III trial.
Eligibility| Ages Eligible for Study: | 9 Years to 17 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Diagnosis of FA with confirmed FRDA mutations.
Age from nine up to but not over eighteen years.
Weight between 30 to 80 kilograms.
Ambulatory (assistance devices permitted).
Willing to participate in all aspects of trial design and follow-up.
All subjects agree and commit to the use of 2 reliable methods of birth control for the duration of the study if sexually active.
Neurologically symptomatic.
No exposure to idebenone, coenzyme Q10, or other dietary supplements for a period of at least one month before enrollment in the study.
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. 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.
Platelet count, white blood cell count or hemoglobin below the lower limit of normal.
Alkaline phosphatase, SGOT, or SGPT greater than 1.5 times the upper limit of normal. Bilirubin greater than 1.5 g/dl.
Creatinine greater than 1.5 times the upper limit of normal based upon the pediatric reference range provided by the testing laboratory.
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.
Contacts and Locations More Information
| Responsible Party: | National Institutes of Health ( Audrey S. Penn, M.D./National Institute of Neurological Disorders and Stroke ) |
| Study ID Numbers: | 050245, 05-N-0245 |
| Study First Received: | September 29, 2005 |
| Last Updated: | November 25, 2009 |
| ClinicalTrials.gov Identifier: | NCT00229632 History of Changes |
| Health Authority: | United States: Federal Government |
|
Friedreich's Ataxia Idebenone Ataxia Drug Trial |
Randomized Trial Friedreich Ataxia FA |
|
Antioxidants Metabolic Diseases Molecular Mechanisms of Pharmacological Action Spinal Cord Diseases Physiological Effects of Drugs Nervous System Diseases Central Nervous System Diseases Idebenone Mitochondrial Diseases Brain Diseases Neurodegenerative Diseases |
Protective Agents Dyskinesias Pharmacologic Actions Signs and Symptoms Heredodegenerative Disorders, Nervous System Genetic Diseases, Inborn Friedreich Ataxia Ataxia Neurologic Manifestations Cerebellar Diseases Spinocerebellar Degenerations |
