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

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02651545

Enrollment

Registered

2016-01-11

Start date

2014-02-28

Completion date

2020-11-30

Last updated

2021-09-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple Sclerosis

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.

Interventions

None listed

Study design

Observational model

CASE_CONTROL

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Nine-hole Peg Test	0, 12, and 24 months	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.
Expanded Disability Status Scale Score (EDSS)	0, 12, and 24 months	The Expanded Disability Status Scale (EDSS). 0-10 scale with higher scores indicating more severe disability.
Timed 25-foot Walk.	0, 12, and 24 months	Time it takes in seconds for patient to walk 25 feet. Higher times indicate slower ambulation.
Symbol Digit Modalities Test Total Correct	0, 12, and 24 months	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.
California Verbal Learning Test 2nd Edition Total Learning Score	0, 12, and 24 months	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.
Brief Visuospatial Memory Test Revised Total Learning Score	0, 12, and 24 months	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.

Secondary

Measure	Time frame	Description
Change in Vocational Status	0, 12, and 24 months	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
MS Group Multiple Sclerosis Patients Prescribed Aubagio	30
Healthy Control Group Healthy controls matched to the MS group	30
Total	60

Baseline characteristics

Characteristic	Total	MS Group	Healthy Control Group
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	60 Participants	30 Participants	30 Participants
Age, Continuous	48.65 years STANDARD_DEVIATION 10.14	49.53 years STANDARD_DEVIATION 8.97	47.77 years STANDARD_DEVIATION 11.27
Race/Ethnicity, Customized African American	8 Participants	7 Participants	1 Participants
Race/Ethnicity, Customized Caucasian	50 Participants	23 Participants	27 Participants
Race/Ethnicity, Customized Other	2 Participants	0 Participants	2 Participants
Region of Enrollment United States	60 participants	30 participants	30 participants
Sex: Female, Male Female	51 Participants	25 Participants	26 Participants
Sex: Female, Male Male	9 Participants	5 Participants	4 Participants
Symbol Digit Modalities Test Total correct	54.3 score on a scale STANDARD_DEVIATION 10.6	49.7 score on a scale STANDARD_DEVIATION 10.6	58.9 score on a scale STANDARD_DEVIATION 8.5

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 30	0 / 30
other Total, other adverse events	10 / 30	0 / 30
serious Total, serious adverse events	0 / 30	0 / 30

Outcome results

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.