Effects of Teriflunomide (Aubagio) on Cognitive and Vocational Outcomes in Multiple Sclerosis

Study Overview
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Brief Summary
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Cognitive impairment is common in MS and has devastating impact on functional activities. There is a great demand for medications that will enhance cognitive capacity in MS patients. The effect of teriflunomide on cognition and vocational capacity is unknown. The investigators will address these questions in a sample of 30 relapsing MS patients treated with teriflunomide. Cognitive impairment will be measured by calculating an information processing speed index and a memory composite index from conventional, validated neuropsychological tests as recommended by consensus opinion publications. Vocational performance will be monitored using a newly developed online survey called the Multiple Sclerosis Vocational Monitoring Survey (MSVMS). This study will elucidate the effect of teriflunomide on these important outcomes.

Detailed Description
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Summary: Objectives: The primary aim of this study is to define the effect of teriflunomide (Aubagio®) on cognitive abilities in patients with relapsing multiple sclerosis (MS). There are two secondary objectives, to [a] relate changes in cognition to vocational problems, and [b] determine MRI correlates of change in cognition, more specifically gray-matter (GM) volume metrics which the investigators believe reflect neurodegeneration. Design: This is a prospective, observational, single-blinded, longitudinal study of teriflunomide effects on cognitive performance in MS patients over 24 months. Neuropsychological status and 3T (3 Tesla) MRI will be assessed at baseline, 12 months and 24 months. Vocational status will be assessed every three months via the internet. Statistical analysis will emphasize within-subjects changes in all metrics to maximize statistical power. Study Population: Thirty (30) relapsing MS patients and 30 healthy controls (HC) will be enrolled in the study. Outcomes: An information processing speed index and a memory composite index will be calculated from conventional, validated neuropsychological tests as recommended by consensus opinion publications. Conventional clinical metrics for overall neurological disability will also be assessed. Vocational performance will be monitored using a newly developed online survey called the Multiple Sclerosis Vocational Monitoring Survey (MSVMS). Regional GM atrophy, as defined by measurement of thalamic and cortical atrophy, will serve as neurodegeneration outcomes. Significance of the research: The effect of teriflunomide on the development of cognitive impairment and vocational capacity is unknown. This study will elucidate the effect of teriflunomide on these important outcomes.

Official Title
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Teriflunomide (Aubagio) Effects on Cognitive and Vocational Outcomes, as Related to Neurodegeneration in Multiple Sclerosis: A Prospective, Observational, Single-blinded Study.

Conditions
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Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient diagnosed with MS according to McDonald criteria Age 18-60 Have a relapsing disease course Have Expanded Disability Status Scale scores of 0-6.5 Have a disease duration <20 years Treatment naïve to teriflunomide Be willing and able to comply with the study procedures for the duration of the trial Have given written informed consent and signed Health Insurance Portability and Accountability Act (HIPAA) Authorization before any study-related activities are carried out Normal kidney functioning (creatinine clearance >59) None of the exclusion criteria Exclusion Criteria: MS patients with hepatic impairment Nursing mothers or pregnant women who will need to undergo 12 months follow-up Women of childbearing potential not using reliable contraception Patients currently treated with teriflunomide A clinically significant infectious or neurological (for Healthy Controls only) illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to treatment assignment Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the study protocol History of neurological disorder other than MS History of developmental learning disorder or other developmental anomaly History of major depressive disorder, or other psychiatric disorder that could impact cognitive capacity, preceding diagnosis of MS Current major depressive episode Other pathology related to MRI abnormalities

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Relapsing MS patients<br>Thirty (30) relapsing MS patients new to teriflunomide therapy will be enrolled. | |
| Healthy Controls<br>A sample of 30 healthy control volunteers, matched on demographics with the treated group will be enrolled. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expanded Disability Status Scale Score (EDSS) | The Expanded Disability Status Scale (EDSS). 0-10 scale with higher scores indicating more severe disability. | 0, 12, and 24 months | 
| Timed 25-foot Walk. | Time it takes in seconds for patient to walk 25 feet. Higher times indicate slower ambulation. | 0, 12, and 24 months | 
| Nine-hole Peg Test | The Nine-Hole Peg test is a measure of manual dexterity, where the time in seconds that it takes for patient to fill pegboard holes with pegs and remove them is recorded. Longer times indicate slower motor ability. The range in seconds to complete the nine-hole peg test ranges from 0-seconds to the ceiling value of 300 seconds. | 0, 12, and 24 months | 
| California Verbal Learning Test 2nd Edition Total Learning Score | A measure of verbal learning and memory. Patient is read a list of 16 words 5 times and asked to recall the list each time. Score 0-80 with higher scores indicating better performance. | 0, 12, and 24 months | 
| Brief Visuospatial Memory Test Revised Total Learning Score | A measure of visual-spatial learning and memory. Patient is shown a display 3 times and asked to recall figures from the display. Score 0-36 with higher scores indicating better performance. | 0, 12, and 24 months | 
| Symbol Digit Modalities Test Total Correct | A measure of cognitive processing speed. Patient is shown a key with symbol-digit pairings and several rows of symbols with empty boxes beneath them. Patient is asked to respond with the numbers that are paired with each of the symbols as quickly and accurately as they can. Score 0-120 with higher scores indicating better performance. | 0, 12, and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Vocational Status | Vocational Status assessed by the Buffalo Vocational Monitoring Survey (BVMS). BVMS includes four sections: [a] demographics and disease characteristics, [b] self-reported symptom inventories, [c] general employment information, and [d] work-related problems/accommodations. Vocational status (employed vs. unemployed) will be taken from this survey. | 0, 12, and 24 months |