Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis (IPPoMS)
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ClinicalTrials.gov Identifier: NCT00950248 |
Recruitment Status
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Active, not recruiting
First Posted
: July 31, 2009
Last Update Posted
: March 29, 2018
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Tracking Information | ||||
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First Submitted Date ICMJE | July 30, 2009 | |||
First Posted Date ICMJE | July 31, 2009 | |||
Last Update Posted Date | March 29, 2018 | |||
Study Start Date ICMJE | July 22, 2009 | |||
Estimated Primary Completion Date | April 30, 2018 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
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. | |||
Original Primary Outcome Measures ICMJE |
Inhibition of development of brain atrophy: comparison of individualized rates of progression of brain atrophy (as detected by SIENA methodology) between idebenone and placebo | |||
Change History | Complete list of historical versions of study NCT00950248 on ClinicalTrials.gov Archive Site | |||
Current Secondary Outcome Measures ICMJE |
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 | |||
Original Secondary Outcome Measures ICMJE |
Inhibition of individualized rates of development of brain atrophy: effect of idebenone versus placebo on individualized rates of development of brain atrophy | |||
Current Other Outcome Measures ICMJE | Not Provided | |||
Original Other Outcome Measures ICMJE | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis (IPPoMS) | |||
Official Title ICMJE | Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis | |||
Brief Summary | Background:
Objectives: - To evaluate the safety and effectiveness of using idebenone to treat primary progressive MS. Eligibility: - Individuals between 18 and 65 years of age who have been diagnosed with primary progressive multiple sclerosis. Design:
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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. |
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Study Type ICMJE | Interventional | |||
Study Phase | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment |
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Condition ICMJE | Primary Progressive Multiple Sclerosis | |||
Intervention ICMJE | Drug: Idebenone | |||
Study Arms | Not Provided | |||
Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Active, not recruiting | |||
Actual Enrollment ICMJE |
85 | |||
Original Enrollment ICMJE |
80 | |||
Estimated Study Completion Date | August 1, 2018 | |||
Estimated Primary Completion Date | April 30, 2018 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE |
EXCLUSION CRITERIA:
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Sex/Gender |
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Ages | 18 Years to 65 Years (Adult) | |||
Accepts Healthy Volunteers | 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 | NCT00950248 | |||
Other Study ID Numbers ICMJE | 090197 09-N-0197 |
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Has Data Monitoring Committee | Not Provided | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement | 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 |
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PRS Account | National Institutes of Health Clinical Center (CC) | |||
Verification Date | August 3, 2017 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |