Idebenone to Treat Friedreich's Ataxia
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ClinicalTrials.gov Identifier: NCT00229632 |
Recruitment Status :
Completed
First Posted : September 29, 2005
Last Update Posted : March 18, 2019
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Tracking Information | ||||
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First Submitted Date ICMJE | September 29, 2005 | |||
First Posted Date ICMJE | September 29, 2005 | |||
Last Update Posted Date | March 18, 2019 | |||
Study Start Date ICMJE | September 27, 2005 | |||
Actual Primary Completion Date | December 17, 2007 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
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 [ Time Frame: baseline and after 6 months ] | |||
Original Primary Outcome Measures ICMJE | Not Provided | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Not Provided | |||
Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Idebenone to Treat Friedreich's Ataxia | |||
Official Title ICMJE | 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 | |||
Brief Summary | 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:
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Detailed Description | 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. |
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 2 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Single Group Assignment Masking: Triple (Participant, Care Provider, Investigator) Primary Purpose: Treatment |
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Condition ICMJE | Friedreich Ataxia | |||
Intervention ICMJE | Drug: Idebenone
Idebenone is a short-chain benzoquinone derivative of similar structure to ubiquinone (coenzyme Q10). This compound was synthesized and developed initially by Takeda Chemical Industries, Ltd. (Osaka, Japan) and designated as CV-2619. The chemical name for idebenone is 6-(10-Hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benxoquinone. Santhera Pharmaceuticals (Liestal, Switzerland) LLC, will supply drug for this study as specified by a clinical trial agreement.
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Study Arms ICMJE | Not Provided | |||
Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
51 | |||
Original Enrollment ICMJE |
60 | |||
Actual Study Completion Date ICMJE | December 17, 2007 | |||
Actual Primary Completion Date | December 17, 2007 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE |
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. |
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Sex/Gender ICMJE |
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Ages ICMJE | 9 Years to 17 Years (Child) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | United States | |||
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Administrative Information | ||||
NCT Number ICMJE | NCT00229632 | |||
Other Study ID Numbers ICMJE | 050245 05-N-0245 |
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Has Data Monitoring Committee | Not Provided | |||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | |||
Responsible Party | National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ) | |||
Study Sponsor ICMJE | National Institute of Neurological Disorders and Stroke (NINDS) | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | National Institutes of Health Clinical Center (CC) | |||
Verification Date | March 14, 2019 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |