Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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.
 
ClinicalTrials.gov Identifier: NCT00229632
Recruitment Status : Completed
First Posted : September 29, 2005
Last Update Posted : March 18, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Tracking Information
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
 (submitted: May 15, 2015)
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
 (submitted: May 15, 2015)
  • 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 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:

  • 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.
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.

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
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.
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 25, 2009)
51
Original Enrollment  ICMJE
 (submitted: September 28, 2005)
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
  • INCLUSION CRITERIA:

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
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
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00229632
Other Study ID Numbers  ICMJE 050245
05-N-0245
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
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
Principal Investigator: Kenneth H Fischbeck, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
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