Neuroprotection With Riluzole Patients With Early Multiple Sclerosis
This is a double blind, randomized, parallel group design placebo-controlled mono-center study. Patients will be evaluated within twelve months of CIS onset. Patients with at least 2 silent ovoid T2 bright areas in the deep white matter on their clinic brain MRI scan will be offered participation in the study. Patients will be randomized to oral riluzole or placebo (1:1). Patient will take 50 mg of riluzole or placebo once a day for one month. If 50 mg once a day is well tolerated, patients will then go on 50 mg twice daily for the rest of the study. They will start Avonex (Interferon beta 1a) therapy 30 mcg IM once weekly 3 months after study drug (riluzole or placebo) is initiated if their liver function has remained normal.
Forty patients within twelve months of onset CIS onset will be enrolled at UCSF MS Center. Patients will be evaluated every month for the first 12 months and every three months thereafter for a total study duration of 24-month. Enrollment period will last six months.
|Multiple Sclerosis||Drug: Avonex (Interferon beta 1a) Drug: Riluzole Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Prevention
|Official Title:||Neuroprotection With Riluzole in Patients With Early Multiple Sclerosis|
- MRI Parameter- Percent Brain Volume Change for 2 Years [ Time Frame: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24 ]Baseline MRI is compared to MRI images collected during subsequent timepoints. The percent brain volume change is measured using SIENAX (Structural Image Evaluation using Normalization of Atrophy-X)
- Changes in Normalized White Matter Volumes (nWMV) [ Time Frame: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24 ]The baseline data of white matter volume obtained from the MRI images is compared to data obtained at time points using SIENA (Structural Image Evaluation using Normalization of Atrophy) and SIENAX
- Changes in MS Functional Composite (MSFC) [ Time Frame: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24 ]Baseline MSFC data is compared to MSFC data collected during the timepoints. The MSFC is a three-part, standardized, quantitative, assessment instrument that measures the clinical dimensions of leg function, arm/hand function and cognitive function and the components include Timed 25-Foot walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test.
- Changes in Peripapillary Retinal Nerve Fiber Layer Thickness (RNFL) [ Time Frame: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24 ]Baseline RNFL data is compared to the RNFL data collected during the timepoint, and the changes in RNFL is measured using optical coherence tomography (OCT).
- Changes in Symbol Digit Modality Test (SDMT) [ Time Frame: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24 ]Baseline SDMT data were compared to SDMT data collected during the timepoints. A simple substitution task, the SDMT gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The total score is the total number of correctly completed boxes in the time allowed. The test score range is from 0(worst outcome) to 110 (best outcome).
- Changes in Normalized Grey Matter Volume [ Time Frame: Baseline, Month-3, Month-6, Month-12 and Month-24 ]The baseline data of grey matter volume obtained from the MRI images is compared to data obtained at time points using SIENA (Structural Image Evaluation using Normalization of Atrophy) and SIENAX
|Study Start Date:||July 2006|
|Study Completion Date:||October 2012|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Riluzole
Riluzole + Avonex
|Drug: Avonex (Interferon beta 1a) Drug: Riluzole|
Placebo Comparator: Placebo
placebo + Avonex
|Drug: Avonex (Interferon beta 1a) Drug: Placebo|
To determine the effect of riluzole up to 50 mg bid on MRI parameters, including T1 lesions load, atrophy of gray and white matter, and 1H-MRSI; and to determine safety of riluzole when administered orally up to 50 mg bid for 2 years in double blinded clinical trial of patients with clinically isolated syndromes (CIS) and at least 2 silent T2-bright areas in the deep white matter. These patients have a high risk of conversion to MS within 2 years and faster rate of atrophy (Dalton 2004).
- To determine the effect of treatment compared to placebo on annual change in measures of normalized brain gray and white matter volume changes.
- To determine the effect of riluzole compared to placebo on annual change in proton spectroscopic intensities of N-acetyl aspartate (NAA) and glutamate in normal appearing white matter (NAWM), in acute and chronic lesions.
- To determine the safety of riluzole up to 50 mg bid in patients with CIS in association to Avonex (Interferon beta 1a) 30 mcg IM once a week.
- To monitor changes on MS functional composite (MSFC) (Cutter 1999, Rudick 1998), optic coherence tomography (OCT), low contrast sensitivity and EDSS in these patients.
- To monitor recovery from exacerbations.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00501943
|United States, California|
|UCSF MS Center , 675 Nelson Rising Lane, Suite 221|
|San Francisco, California, United States, 94158|
|Principal Investigator:||Emmanuelle Waubant, MD, PhD||UCSF , MS Center|
|Principal Investigator:||Emmanuelle Waubant, MD PhD||UCSF, MS Center|