Protocol Number: 09-N-0197

Title:

Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients with Primary Progressive Multiple Sclerosis

Number:

09-N-0197

Summary:

Background:

- Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system that progressively weakens and destroys the pathways of the nervous system. About 10 percent to 15 percent of patients develop primary-progressive MS (PP-MS), characterized by progressive accumulation of disability from the disease onset, without any marked improvements or relapses. There are currently no effective treatments for PP-MS.

- Idebenone is a manmade drug that is similar to a naturally occurring compound known as coenzyme Q10, a common dietary supplement. Research data suggest that idebenone may be able to limit demyelination and death of brain cells and thereby slow or halt the progression of neurological dysfunction such as that occurring in MS.

Objectives:

- To evaluate the safety and effectiveness of using idebenone to treat primary progressive MS.

Eligibility:

- Individuals between 18 and 55 years of age who have been diagnosed with primary progressive multiple sclerosis.

Design:

- The study will last 3 years and will be divided into two parts: a 1-year pretreatment baseline and 2 years of treatment with either idebenone or a placebo.

- Pre-treatment study: approximately 5 clinic visits over 1 year.

- Visit 1: Comprehensive medical history and neurological examination, with brain scans and neurological tests.

- Visit 2: Magnetic resonance imaging (MRI) scan of the spine and lymphocytapheresis (withdrawal of white blood cells for testing).

- Visit 3: Lumbar puncture.

- Visit 4: Skin biopsy.

- Visit 5: Repeat MRI of the brain and spinal cord, as well as neurological tests; these tests will be scheduled over 2 days.

- After the five pretreatment visits, patients will receive a 6-month supply of study medication (either idebenone or a placebo) to take three times a day with food

- Patients will continue to have regular followup clinic visits with brain MRI scans, blood tests, and other evaluations of brain and nervous system function. Randomly selected participants will have additional MRI scans for further safety precautions.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

1. PP-MS as determined by the 2005 modification of McDonald's diagnostic criteria

2. Age from 18-55 years (inclusive)

3. EDSS measure of neurological disability from 1 (no disability, clinical signs only) to 7 (ambulatory with bilateral support)

4. Able to provide informed consent

5. Willing to participate in all aspects of trial design and follow-up

6. 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

7. Not receiving any immunomodulatory/immunosuppressive therapies for a period of at least 3 months before enrollment in the study

8. 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

EXCLUSION CRITERIA:

1. Alternative diagnoses that can explain neurological disability and MRI findings

2. 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

3. History of hypersensitivity reaction to idebenone or coenzyme-Q (10)

4. Pregnant or lactating women. All women of child-bearing potential must have negative pregnancy test prior to the medication phase of the study.

5. 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) < 60

v. Positive pregnancy test

6. 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

Special Instructions:

Currently Not Provided

Keywords:

Idebenone

Magnetic Resonance Imaging (MRI)

Magnetic Resonance Spectroscopy

Mitochondrial Enhancer

Multiple Sclerosis

Recruitment Keyword(s):

Multiple Sclerosis

MS

Primary Progressive Multiple Sclerosis

Condition(s):

Primary Progressive Multiple Sclerosis

Investigational Drug(s):

Idebenone

Investigational Device(s):

None

Intervention(s):

Drug: Idebenone

Supporting Site:

National Institute of Neurological Disorders and Stroke

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Artuch R, Aracil A, Mas A, ColomŽ C, Rissech M, Monr—s E, Pineda M. Friedreich's ataxia: idebenone treatment in early stage patients. Neuropediatrics. 2002 Aug;33(4):190-3.

Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, Waldmann TA, McFarland H, Henkart PA, Martin R. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5941-6. Epub 2006 Apr 3.

Bieniek M, Altmann DR, Davies GR, Ingle GT, Rashid W, Sastre-Garriga J, Thompson AJ, Miller DH. Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006 Sep;77(9):1036-9. Epub 2006 Jun 22.

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