Neuroprotection With Riluzole Patients With Early Multiple Sclerosis

This study has been completed.
Sponsor:
Collaborators:
National Multiple Sclerosis Society
Oregon Health and Science University
Information provided by (Responsible Party):
Emmanuelle Waubant, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00501943
First received: July 12, 2007
Last updated: March 11, 2014
Last verified: March 2014
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Neuroprotection With Riluzole in Patients With Early Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • MRI Parameter- Percent Brain Volume Change for 2 Years [ Time Frame: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24 ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Changes in Normalized White Matter Volumes (nWMV) [ Time Frame: Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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:

  1. To determine the effect of treatment compared to placebo on annual change in measures of normalized brain gray and white matter volume changes.
  2. 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.
  3. 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.
  4. To monitor changes on MS functional composite (MSFC) (Cutter 1999, Rudick 1998), optic coherence tomography (OCT), low contrast sensitivity and EDSS in these patients.
  5. To monitor recovery from exacerbations.
  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00501943

Locations
United States, California
UCSF MS Center , 675 Nelson Rising Lane, Suite 221
San Francisco, California, United States, 94158
Sponsors and Collaborators
University of California, San Francisco
National Multiple Sclerosis Society
Oregon Health and Science University
Investigators
Principal Investigator: Emmanuelle Waubant, MD, PhD UCSF , MS Center
Principal Investigator: Emmanuelle Waubant, MD PhD UCSF, MS Center
  More Information

No publications provided

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
Study First Received: July 12, 2007
Results First Received: November 19, 2013
Last Updated: March 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Interferon-beta
Interferons
Interferon beta 1a
Riluzole
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Protective Agents
Central Nervous System Agents
Anticonvulsants
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on April 14, 2014