Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis (IPPoMS)

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: NCT00950248
Recruitment Status : Completed
First Posted : July 31, 2009
Last Update Posted : August 8, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:


  • 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.


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


- Individuals between 18 and 65 years of age who have been diagnosed with primary progressive multiple sclerosis.


  • 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.

Condition or disease Intervention/treatment Phase
Primary Progressive Multiple Sclerosis Drug: Idebenone Phase 1 Phase 2

Detailed Description:

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. All defined outcome measures collected in the first 30 enrolled patients will be transformed into z-scores and compared for the robustness of longitudinal change over the coefficient of variation. This will permit to select the most sensitive and most accurate outcome measure for detecting progression of CNS tissue damage. As a result, the primary outcome measure of this trial will be the comparison of individualized rates of brain atrophy progression between the idebenone and placebo groups after 2 years of treatment, unless the predetermined analysis of the pre-treatment baseline period in the first 30 enrolled subjects determines that one of the predefined secondary outcome measures has a higher z-score than brain atrophy measurement. In this case, the primary outcome would be the efficacy of idebenone versus placebo in inhibiting patient-specific slopes of functional or structural deterioration as measured by this more sensitive biomarker of CNS tissue destruction, yet to be defined by the analysis of the 1-year longitudinal data from pre-treatment baseline.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis
Study Start Date : July 22, 2009
Actual Primary Completion Date : April 30, 2018
Actual Study Completion Date : August 6, 2018

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. The primary outcome measure of the IPPOMS is the rate of disability progression, assessed with the Area Under the Curve (AUC) of the CombiWISE scores during the 2-year treatment period.

Secondary Outcome Measures :
  1. Inhibition of individualized rates of enlargement of ventricular volume: effect of idebenone versus placebo on individualized rates of enlargement of segmented volume of lateral and 3rd ventricles

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

    1. PP-MS as determined by the 2005 modification of McDonald s diagnostic criteria
    2. Age from 18-65 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. 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
    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


  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 a 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) <30

    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

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): NCT00950248

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator: Bibiana Bielekova, M.D. National Institute of Neurological Disorders and Stroke (NINDS)

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00950248     History of Changes
Other Study ID Numbers: 090197
First Posted: July 31, 2009    Key Record Dates
Last Update Posted: August 8, 2018
Last Verified: August 6, 2018

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Magnetic Resonance Imaging (MRI)
Magnetic Resonance Spectroscopy
Mitochondrial Enhancer
Multiple Sclerosis
Primary Progressive Multiple Sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Growth Substances