Clinical trial NCT02651545: Effects of Teriflunomide (Aubagio) on Cognitive and Vocational Outcomes in Multiple Sclerosis
Official title: Teriflunomide (Aubagio) Effects on Cognitive and Vocational Outcomes, as Related to Neurodegeneration in Multiple Sclerosis: A Prospective, Observational, Single-blinded Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
First posted: 2016-01-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A sample of 30 relapsing MS patients new to teriflunomide therapy will be enrolled. A sample 30 healthy control volunteers, matched on demographics with the treated group will be enrolled.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Expanded Disability Status Scale Score (EDSS)
timeFrame: 0, 12, and 24 months
measure: Timed 25-foot Walk.
timeFrame: 0, 12, and 24 months
measure: Nine-hole Peg Test
timeFrame: 0, 12, and 24 months
measure: California Verbal Learning Test 2nd Edition Total Learning Score
timeFrame: 0, 12, and 24 months
measure: Brief Visuospatial Memory Test Revised Total Learning Score
timeFrame: 0, 12, and 24 months
measure: Symbol Digit Modalities Test Total Correct
timeFrame: 0, 12, and 24 months
Secondary outcomes:
measure: Change in Vocational Status
timeFrame: 0, 12, and 24 months
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Buffalo General Hospital, D3
state: New York
Study officials:
affiliation: State University of New York at Buffalo
name: Ralph HB Benedict, PhD
role: PRINCIPAL_INVESTIGATOR
References: