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Neuroprotection With Riluzole Patients With Early Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT00501943
Recruitment Status : Completed
First Posted : July 16, 2007
Results First Posted : April 9, 2014
Last Update Posted : April 9, 2014
Sponsor:
Collaborators:
National Multiple Sclerosis Society
Oregon Health and Science University
Information provided by (Responsible Party):
Emmanuelle Waubant, University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE July 12, 2007
First Posted Date  ICMJE July 16, 2007
Results First Submitted Date  ICMJE November 19, 2013
Results First Posted Date  ICMJE April 9, 2014
Last Update Posted Date April 9, 2014
Study Start Date  ICMJE July 2006
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2014)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2007)
Safety and efficacy of Riluzole vs placebo [ Time Frame: 2 years ]
Change History Complete list of historical versions of study NCT00501943 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2014)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2007)
Evaluate neuroprotection of Riluzole [ Time Frame: data analysis ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neuroprotection With Riluzole Patients With Early Multiple Sclerosis
Official Title  ICMJE Neuroprotection With Riluzole in Patients With Early Multiple Sclerosis
Brief 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.

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE
  • Drug: Avonex (Interferon beta 1a)
  • Drug: Riluzole
  • Drug: Placebo
Study Arms  ICMJE
  • Active Comparator: Riluzole
    Riluzole + Avonex
    Interventions:
    • Drug: Avonex (Interferon beta 1a)
    • Drug: Riluzole
  • Placebo Comparator: Placebo
    placebo + Avonex
    Interventions:
    • Drug: Avonex (Interferon beta 1a)
    • Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 24, 2013)
43
Original Estimated Enrollment  ICMJE
 (submitted: July 13, 2007)
40
Actual Study Completion Date  ICMJE October 2012
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE 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 NCT00501943
Other Study ID Numbers  ICMJE H9924-29155-05
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Emmanuelle Waubant, University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE
  • National Multiple Sclerosis Society
  • Oregon Health and Science University
Investigators  ICMJE
Principal Investigator: Emmanuelle Waubant, MD, PhD UCSF , MS Center
Principal Investigator: Emmanuelle Waubant, MD PhD UCSF, MS Center
PRS Account University of California, San Francisco
Verification Date March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP