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Neuroprotection With Riluzole Patients With Early Multiple Sclerosis

Primary Purpose

Multiple Sclerosis

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Avonex (Interferon beta 1a)

Riluzole

Placebo

About this trial

This is an interventional prevention trial for Multiple Sclerosis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

UCSF MS Center , 675 Nelson Rising Lane, Suite 221

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Riluzole

Placebo

Arm Description

Riluzole + Avonex

placebo + Avonex

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Changes in Normalized White Matter Volumes (nWMV)

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)

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)

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)

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

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

Full Information

NCT ID

NCT00501943

First Posted

July 12, 2007

Last Updated

March 11, 2014

Sponsor

University of California, San Francisco

Collaborators

National Multiple Sclerosis Society, Oregon Health and Science University

1. Study Identification

Unique Protocol Identification Number

NCT00501943

Brief Title

Neuroprotection With Riluzole Patients With Early Multiple Sclerosis

Official Title

Neuroprotection With Riluzole in Patients With Early Multiple Sclerosis

Study Type

Interventional

2. Study Status

Record Verification Date

March 2014

Overall Recruitment Status

Completed

Study Start Date

July 2006 (undefined)

Primary Completion Date

October 2012 (Actual)

Study Completion Date

October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, San Francisco

Collaborators

National Multiple Sclerosis Society, Oregon Health and Science University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

43 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Riluzole

Arm Type

Active Comparator

Arm Description

Riluzole + Avonex

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

placebo + Avonex

Intervention Type

Drug

Intervention Name(s)

Avonex (Interferon beta 1a)

Intervention Type

Drug

Intervention Name(s)

Riluzole

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

MRI Parameter- Percent Brain Volume Change for 2 Years

Description

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)

Time Frame

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

Secondary Outcome Measure Information:

Title

Changes in Normalized White Matter Volumes (nWMV)

Description

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

Time Frame

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

Title

Changes in MS Functional Composite (MSFC)

Description

Time Frame

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

Title

Changes in Peripapillary Retinal Nerve Fiber Layer Thickness (RNFL)

Description

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).

Time Frame

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

Title

Changes in Symbol Digit Modality Test (SDMT)

Description

Time Frame

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

Title

Changes in Normalized Grey Matter Volume

Description

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

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Emmanuelle Waubant, MD, PhD

Organizational Affiliation

UCSF , MS Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Emmanuelle Waubant, MD PhD

Organizational Affiliation

UCSF, MS Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

UCSF MS Center , 675 Nelson Rising Lane, Suite 221

City

San Francisco

State/Province

California

ZIP/Postal Code

94158

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

28148632

Citation

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.

Results Reference

derived

PubMed Identifier

25929276

Citation

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.

Results Reference

derived

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Neuroprotection With Riluzole Patients With Early Multiple Sclerosis

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