Neuroprotection With Riluzole Patients With Early Multiple Sclerosis

NCT00501943 | Completed Phase 2 Results DMC

• 1 other identifier: H9924-29155-05
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• MRI Parameter- Percent Brain Volume Change for 2 Years

  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)

  Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24

Secondary Outcomes (5)

• Changes in Normalized White Matter Volumes (nWMV)

  Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24

• Changes in MS Functional Composite (MSFC)

  Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24

• Changes in Peripapillary Retinal Nerve Fiber Layer Thickness (RNFL)

  Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24

• Changes in Symbol Digit Modality Test (SDMT)

  Baseline, Month-3, Month-6, Month-12, Month-18 and Month-24

• Changes in Normalized Grey Matter Volume

  Baseline, Month-3, Month-6, Month-12 and Month-24

Study Arms (2)

Riluzole

ACTIVE COMPARATOR

Riluzole + Avonex

Drug: Avonex (Interferon beta 1a); Drug: Riluzole

Placebo

PLACEBO COMPARATOR

placebo + Avonex

Drug: Avonex (Interferon beta 1a); Drug: Placebo

Interventions

Avonex (Interferon beta 1a) DRUG

Placebo; Riluzole

Riluzole DRUG

Riluzole

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Multiple Sclerosis Society: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

UCSF MS Center , 675 Nelson Rising Lane, Suite 221

San Francisco, California, 94158, United States

Location

Related Publications (2)

• Kuhle J, Nourbakhsh B, Grant D, Morant S, Barro C, Yaldizli O, Pelletier D, Giovannoni G, Waubant E, Gnanapavan S. Serum neurofilament is associated with progression of brain atrophy and disability in early MS. Neurology. 2017 Feb 28;88(9):826-831. doi: 10.1212/WNL.0000000000003653. Epub 2017 Feb 1.

  PMID: 28148632 DERIVED

• Maghzi AH, Graves J, Revirajan N, Spain R, Liu S, McCulloch CE, Pelletier D, Green AJ, Waubant E. Retinal axonal loss in very early stages of multiple sclerosis. Eur J Neurol. 2015 Jul;22(7):1138-41. doi: 10.1111/ene.12722. Epub 2015 Apr 29.

  PMID: 25929276 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Interferon beta-1a; Riluzole

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr Emmanuelle Waubant, MD
• Organization: UCSF

Emmanuelle.Waubant@ucsf.edu

415- 514 2468

Study Officials

• Emmanuelle Waubant, MD, PhD

  UCSF , MS Center

  PRINCIPAL INVESTIGATOR

• Emmanuelle Waubant, MD PhD

  UCSF, MS Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Neurology

Study Record Dates

• First Submitted: July 12, 2007
• First Posted: July 16, 2007
• Study Start: July 1, 2006
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: April 9, 2014
• Results First Posted: April 9, 2014

Record last verified: 2014-03

Locations

US (1)