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Idebenone to Treat Friedreich's Ataxia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00229632
Recruitment Status : Completed
First Posted : September 29, 2005
Last Update Posted : March 18, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

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:

  • Medical interview and physical examination. Tests include blood and urine tests, an electrocardiogram, or EKG (recording of the electrical activity of the heart), echocardiogram (ultrasound test showing the pumping action of the heart, thickness of the heart walls, and any valve leakage), and a detailed neurological examination, including maneuvers such as copying a drawing and putting pegs in a board. Patients' parents are asked questions about how they feel their child's disease affects the child's quality of life.
  • Magnetic resonance imaging (MRI) to examine the heart muscle and blood flow to the heart. MRI uses a magnetic field and radio waves to produce images of body tissues and organs. The patient lies on a table that is moved into the doughnut-shaped MRI scanner, wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. A catheter (plastic tube) is placed in a vein in the child's arm so that a chemical called gadolinium can be injected during the MRI study. Gadolinium brightens areas of the heart, improving the ability to see the heart and blood flow.
  • Physical medicine and rehabilitation evaluations to test the child's physical functioning. These tests include gait evaluation, measurements of the ability to exert and maintain a constant force, assessment of visual-motor control and fine motor control, aerobic exercise endurance testing, and measurement of the ability of the child's heart and lungs to increase their effectiveness with exercise.
  • Idebenone/placebo treatment. Patients are given a 6-month supply of either idebenone pills or placebo (pills that look like the study drug but have no active ingredient) to take three times a day. Patients are seen by their primary care physician after 1 and 3 months on the study medication for a brief physical examination. In addition, they have blood and urine tests once a month while on medication to check for any abnormalities.
  • 6-month examination. After 6 months on the study drug, patients return to NIH to repeat all the tests listed above to determine the effects of idebenone treatment.

Condition or disease Intervention/treatment Phase
Friedreich Ataxia Drug: Idebenone Phase 2

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 : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Study Start Date : September 27, 2005
Actual Primary Completion Date : December 17, 2007
Actual Study Completion Date : December 17, 2007

Intervention Details:
  • 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.

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. To evaluate the safety and tolerability of idebenone [ Time Frame: baseline and after 6 months ]
  2. To explore the effects of idebenone on cardiac parameters [ Time Frame: baseline and after 6 months ]
  3. To explore the effects of idebenone on neurological function [ Time Frame: baseline and after 6 months ]
  4. To assess the effects of idebenone on patients quality of life [ Time Frame: baseline and after 6 months ]
  5. To explore the effects of idebenone on functional capacity [ Time Frame: baseline and after 6 months ]
  6. To evaluate metabolic alterations, gene expression changes and markers of mitochondrial DNA damage [ Time Frame: baseline and after 6 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   9 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
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.


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00229632

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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Principal Investigator: Kenneth H Fischbeck, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS) Identifier: NCT00229632    
Other Study ID Numbers: 050245
First Posted: September 29, 2005    Key Record Dates
Last Update Posted: March 18, 2019
Last Verified: March 14, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Friedreich's Ataxia
Drug Trial
Randomized Trial
Friedreich Ataxia
Additional relevant MeSH terms:
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Cerebellar Ataxia
Friedreich Ataxia
Neurologic Manifestations
Nervous System Diseases
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinocerebellar Degenerations
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs