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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Relapsing MS patients | Thirty (30) relapsing MS patients new to teriflunomide therapy will be enrolled. | ||
| Healthy Controls | A sample of 30 healthy control volunteers, matched on demographics with the treated group will be enrolled. |
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| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Ralph HB Benedict, PhD | State University of New York at Buffalo | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Buffalo General Hospital, D3 | Buffalo | New York | 14203 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Relapsing MS Patients | Thirty (30) relapsing MS patients new to teriflunomide therapy will be enrolled. |
| FG001 | Healthy Controls | A sample of 30 healthy control volunteers, matched on demographics with the treated group will be enrolled. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | MS Group | Multiple Sclerosis Patients Prescribed Aubagio |
| BG001 | Healthy Control Group | Healthy controls matched to the MS group |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Expanded Disability Status Scale Score (EDSS) | The Expanded Disability Status Scale (EDSS). 0-10 scale with higher scores indicating more severe disability. | Posted | Median | Inter-Quartile Range | EDSS Score | 0, 12, and 24 months |
|
|
6 years total of study activity.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MS Group | Multiple Sclerosis Patients Prescribed Aubagio | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Jaworski | UBMD Neurology | 716-323-0550 | mgjawors@buffalo.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 6, 2020 | Jul 13, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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| 0, 12, and 24 months |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Symbol Digit Modalities Test Total correct | The Symbol Digit Modalities Test (SDMT) is a measure to assess cognitive processing speed. The SDMT presents a series of 9 symbols, each paired to a single digit in a key at the top of a stimulus page. Subjects say the number associated with each symbol as rapidly as possible. The examiner records the responses. The task continues for 90 seconds with staff recording responses. The total number of correct responses is known as "Total Correct" and is used as the unit of measure. Score may range from 0 correct (slow processing speed) to 110 correct (faster processing speed). | Mean | Standard Deviation | score on a scale |
|
|
| Primary | Timed 25-foot Walk. | Time it takes in seconds for patient to walk 25 feet. Higher times indicate slower ambulation. | Posted | Mean | Standard Deviation | Seconds | 0, 12, and 24 months |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | Seconds | 0, 12, and 24 months |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | score on a scale | 0, 12, and 24 months |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | score on a scale | 0, 12, and 24 months |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | score on a scale | 0, 12, and 24 months |
|
|
|
| Secondary | 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. | Patient discontinuations, withdrawals, and loss-to-follow-ups account for declining numbers in each group as study progressed. | Posted | Count of Participants | Participants | 0, 12, and 24 months |
|
|
|
| 30 |
| 0 |
| 30 |
| 10 |
| 30 |
| EG001 | Healthy Controls | This sample 30 healthy control volunteers, matched on demographics with the multiple sclerosis group. This healthy control group was not prescribed Aubagio. | 0 | 30 | 0 | 30 | 0 | 30 |
| Minor Hair Loss | General disorders | Non-systematic Assessment |
|
| Headache | General disorders | Non-systematic Assessment |
|
| Swelling in legs and feet | General disorders | Non-systematic Assessment |
|
| Weight gain | General disorders | Non-systematic Assessment |
|
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| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| Month 24 |
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| Month 24 |
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| Month 24 |
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| Month 24 |
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| Month 24 |
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| Unemployed |
|
| Month 12 |
|
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| Month 24 |
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