Neuroprotection With Riluzole Patients With Early Multiple Sclerosis
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
| Multiple Sclerosis | Drug: Avonex (Interferon beta 1a) Drug: Riluzole Drug: Placebo | Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (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
| Enrollment: | 43 |
| Study Start Date: | July 2006 |
| Study Completion Date: | October 2012 |
| Primary Completion Date: | October 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Riluzole
Riluzole + Avonex
|
Drug: Avonex (Interferon beta 1a) Drug: Riluzole |
|
Placebo Comparator: Placebo
placebo + Avonex
|
Drug: Avonex (Interferon beta 1a) Drug: Placebo |
Detailed Description:
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).
Specific aims:
- 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.
Eligibility
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 55 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patient must give written informed consent;
- Patients with a early MS or clinically isolated syndromes (CIS) in the past 12 months as defined by an acute or sub-acute episode suggestive of demyelination affecting the optic nerves, brain stem or spinal cord or other central nervous system location.
- Entry age 18-55
- Males and females
- At least 2 silent T2 bright areas in the deep white matter on screening brain MRI.
- No riluzole, interferon, copaxone, cyclophosphamide, mitoxantrone or other off-label immunosuppressive drugs for MS prior to study entry
- No corticosteroid during the 4 weeks prior to baseline MRI exam
- No prior exposure to total lymphoid irradiation
- No history of substance abuse, including documented alcohol dependence within 6 months prior to screening or alcohol liver damage with AST , ALT > twice upper normal limits
- No pregnant or nursing patients
- No history of systemic illness or medical condition that would limit the likelihood of completing the gadolinium-enhanced MRI procedures. Automatic exclusionary conditions will include hypersensitivity reaction to riluzole or any of the tablets components, uncontrolled hypertension, epilepsy, and insulin dependent diabetes, asthma, known malignancy other than skin cancer, symptomatic cardiac disease or metallic objects on or inside the body.
- Patients willing to use birth control during the study.
- Patients willing to go on Avonex therapy 3 months after being randomized to study drug and no contra-indication to use of interferon therapy.
Exclusion Criteria:
- A history of major depression or psychosis.
- A clinically significant MS exacerbation within 30 days of the screening
- Pregnancy
- Abnormal screening liver function (AST or ALT > twice the upper normal limit).
- Patients receiving hepatotoxic medications such as drugs interfering with CYP 1A2.
Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): 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 |
More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Emmanuelle Waubant, Associate Professor of Clinical Neurology, University of California, San Francisco |
| ClinicalTrials.gov Identifier: | NCT00501943 History of Changes |
| Other Study ID Numbers: |
H9924-29155-05 |
| First Submitted: | July 12, 2007 |
| First Posted: | July 16, 2007 |
| Results First Submitted: | November 19, 2013 |
| Results First Posted: | April 9, 2014 |
| Last Update Posted: | April 9, 2014 |
| Last Verified: | March 2014 |
Additional relevant MeSH terms:
|
Riluzole Sclerosis Multiple Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases Autoimmune Diseases Immune System Diseases Interferons Interferon-beta Interferon beta-1a |
Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunologic Factors Physiological Effects of Drugs Adjuvants, Immunologic Anticonvulsants Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Neuroprotective Agents Protective Agents |