Neuroprotection With Riluzole Patients With Early Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Avonex (Interferon beta 1a); Riluzole; Placebo
Intervention MeSH terms: Interferons; Interferon-beta; Interferon beta-1a; Riluzole
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient must give written informed consent;

          2. 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.

          3. Entry age 18-55

          4. Males and females

          5. At least 2 silent T2 bright areas in the deep white matter on screening brain MRI.

          6. No riluzole, interferon, copaxone, cyclophosphamide, mitoxantrone or other off-label
             immunosuppressive drugs for MS prior to study entry

          7. No corticosteroid during the 4 weeks prior to baseline MRI exam

          8. No prior exposure to total lymphoid irradiation

          9. 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

         10. No pregnant or nursing patients

         11. 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.

         12. Patients willing to use birth control during the study.

         13. 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:

          1. A history of major depression or psychosis.

          2. A clinically significant MS exacerbation within 30 days of the screening

          3. Pregnancy

          4. Abnormal screening liver function (AST or ALT > twice the upper normal limit).

          5. Patients receiving hepatotoxic medications such as drugs interfering with CYP 1A2.