Trials of Idebeone in Progressive MS.

For those of you interested in studies aimed at PPMS, there are clinical trials (NCT00950248) are being performed in Progressive MSers

Idebenone is a drug developed as a synthetic analog of coenzyme Q10 (CoQ10) which is an ant-oxidant that was originally targeted to congnitive behaviour therapy.

Objective: The goal of this study is to assess the safety, therapeutic efficacy and mechanism of action of idebenone in primary-progressive multiple sclerosis (PP-MS) patients.

Study Population: Adult, untreated patients with PP-MS with disability ranging from none to moderately severe will be included in the trial. The upper age limit in this study has been set at 65; setting an age limit should permit us to focus on the potential neuroprotective effect of idebenone in PP-MS and limit the confounding factor of the natural aging process and its known negative influence on neuro-regeneration. Published data indicate that higher doses (10-50 mg/kg) of idebenone per day are required for beneficial effects on neurological disability in comparison to the lower doses (5-10mg/kg) that are sufficient for beneficial effects on cardiac/systemic functions in Friedreich's ataxia (FRDA) patients. Therefore, in order to target the CNS compartment, we will use a daily dose of 2250mg (750mg 3 times per day), which will provide target values of 10-50mg/kg for virtually all adult patients.

Design: This is a Phase I/II safety/efficacy trial with an adaptive trial design: one year of pretreatment baseline period serves the dual purpose of collecting patient-specific biomarkers of disease progression and collecting longitudinal neuroimaging and clinical data for selection of primary outcome measures. This baseline period is then followed by a double-blind, idebenone versus placebo treatment phase for a total of 2 years. Based on preliminary sample size estimates, current enrollment calls for a total of 66 patients (33 per arm). Outcome Measures: Quantitative neuroimaging measures of central nervous system (CNS: i.e. brain and spinal cord) tissue destruction and clinical and functional (i.e. electrophysiological) measures of neurological disability will be collected every 6-12 months. Additionally, biomarkers focusing on analysis of reactive oxygen species (ROS) and oxidative stress will be collected every 12 months. The trial is currently powered using progression of brain atrophy as detected by SIENA methodology as the primary outcome measure. However, this may not be the most sensitive outcome available. In recognition of this, the trial has an adaptive design: i.e. it incorporates analysis of progression of CNS tissue destruction as measured by quantitative MRI markers and clinical/paraclinical markers defined as secondary outcome measures in the first 30 enrolled patients during the one year pre-treatment baseline, before randomization.

Ages Eligible for Study: 18 Years to 65 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

PP-MS as determined by the 2005 modification of McDonald's diagnostic criteria
Age from 18-65 years (inclusive)
EDSS measure of neurological disability from 1 (no disability, clinical signs only) to 7 (ambulatory with bilateral support)
Able to provide informed consent
Willing to participate in all aspects of trial design and follow-up
If able to become pregnant or to father a child, agreeing to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation, or vasectomy in a partner)) for the duration of treatment arm of the study
Not receiving any immunomodulatory/immunosuppressive therapies for a period of at least 3 months before enrollment in the study
No exposure to idebenone, coenzyme-Q(10) or other dietary supplements (such as antioxidants, mitochondrial-function promoting supplements or vitamins in excess of 3 times recommended daily doses) for a period of at least 1 month before enrollment in the study

Alternative diagnoses that can explain neurological disability and MRI findings
Clinically significant medical disorders that, in the judgment of the investigators, could cause CNS tissue damage or limit its repair, or might expose the patient to undue risk of harm or prevent the patient from completing the study
History of hypersensitivity reaction to idebenone or coenzyme-Q
Pregnant or lactating women. All women of child-bearing potential must have a negative pregnancy test prior to the medication phase of the study.
Abnormal screening/baseline blood tests exceeding any of the limits defined below:

i. Serum alanine transaminase or aspartate transaminase levels greater than 3 times the upper limit of normal values
ii. Total white blood cell count < 3,000/mm(3)
iii. Platelet count < 85,000/mm(3)
iv. Serum creatinine level > 2.0 mg/dl or eGFR (glomerular filtration rate) < 30
v. Positive pregnancy test
Patients who are receiving any immunosuppressive therapies (including cytostatic agents) due to the concern that these drugs may contribute to neurodegeneration or limit CNS repair

Please refer to this study by its identifier: NCT00950248


Contact: Joan M Ohayon, C.R.N.P. (301) 496-0064
Contact: Bibiana Bielekova, M.D. (301) 496-1801

CoI None 

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