Clinical Trial: Idebenone to Treat Friedreich's Ataxia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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

    Detailed Summary:

    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, t
    Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

    Current Primary Outcome: 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:

    Current Secondary Outcome:

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


    Original Secondary Outcome:

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: September 29, 2005
    Date Started: September 23, 2005
    Date Completion:
    Last Updated: May 31, 2017
    Last Verified: April 28, 2017