Real-world Experience of Oral Agents On Fatigability in Multiple Sclerosis

ConditionMultiple Sclerosis

Trial statusNot yet recruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18-75

SponsorTC Erciyes University

About this trial

This multicenter, prospective, real-world study evaluates how two commonly used oral disease-modifying therapies-teriflunomide and dimethyl fumarate-affect physical and cognitive fatigability in adults with multiple sclerosis (MS). Fatigability refers to an objective decline in physical or cognitive performance during sustained activity and represents a major barrier to daily functioning for many individuals with MS.

Participants starting either teriflunomide or dimethyl fumarate as part of routine clinical care will be followed for 12 months at regular visits (baseline, 3, 6, 9, and 12 months). At each visit, standardized assessments will measure walking endurance, gait performance, hand function, and information-processing speed. Patient-reported outcomes about fatigue, mood, quality of life, and daily functioning will also be collected. Brain MRI scans performed as part of usual care will be reviewed to document disease activity.

The goal of the ROOF-MS study is to understand whether these two therapies differ in their impact on physical and cognitive fatigability, functional outcomes, symptom burden, and real-world treatment adherence. Because this is an observational study, no experimental treatments are given, and all clinical decisions remain the responsibility of the treating physicians.

By examining fatigability in everyday clinical settings, this study aims to generate evidence that can help patients, families, and health care providers make more informed treatment decisions.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Relapsing Multiple Sclerosis (RRMS or active SPMS) diagnosis, confirmed according to the 2017 revised McDonald criteria.

18 years or older at the time of enrollment.

Newly initiated teriflunomide treatment as part of routine clinical care.

Ambulatory status (EDSS ≤ 7.0), capable of completing study assessments.

Disqualifiers

Diagnosis of Primary Progressive Multiple Sclerosis (PPMS).

Severe comorbidities affecting mobility or cognitive function (e.g., advanced cardiovascular, pulmonary, or neuromuscular disease).

Neurological or psychiatric conditions that prevent cognitive testing (e.g., advanced cognitive impairment, untreated severe depression).

Severe upper extremity motor dysfunction, limiting 9-Hole Peg Test (9-HPT) or Symbol Digit Modalities Test (SDMT) completion.

Trial population

The study population will consist of adult patients aged 18 years or older with a confirmed diagnosis of relapsing Multiple Sclerosis (MS), including relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS), according to the 2017 revised McDonald criteria. Participants will be selected from routine clinical settings where teriflunomide has been prescribed as part of standard care. Eligible individuals must be ambulatory, with an Expanded Disability Status Scale (EDSS) score of 7.0 or lower, and capable of performing the 6-Minute Walk Test (6MWT). This population will represent a real-world cohort reflective of patients receiving teriflunomide in typical clinical practice.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Not listed

Trial groups

100 Participants

are grouped into 2 trial groups

Group A: Teriflunomide Cohort

Group B: Dimethyl Fumarate Cohort

Trial outcomes

Primary outcomes

Walking Fatigability Index

Walking fatigability will be quantified using the Distance Walk Index (DWI), calculated with the following formula: DWI=(Distance at minute 6-Distance at minute 1Distance at minute 1)×100 DWI=(Distance at minute 1Distance at minute 6-Distance at minute 1 )×100 A DWI decline of \>10% will be classified as abnormal, based on prior relapsing-remitting MS studies. Unit of Measurement: Percentage (%) Time Frame: Baseline, 3 months, 6 months, and 12 months Higher Values Indicate: Better walking endurance (lower fatigability)

Time frame

Assessments will be conducted at baseline, at three months, at six months, and at twelve months following treatment initiation.

Cognitive Fatigability Index

Cognitive fatigability will be quantified using the Cognitive Fatigability Index (CFI), calculated with the following formula: CFI=(SDMT3-SDMT1SDMT1)×100 CFI=(SDMT1SDMT3-SDMT1 )×100 A negative CFI value will indicate cognitive fatigability, with a decline greater than 10% classified as abnormal. Unit of Measurement: Percentage (%) Higher Values Indicate: Better cognitive endurance (lower fatigability)

Time frame

Baseline, 3 months, 6 months, and 12 months

Secondary outcomes

Walking Performance

Walking performance will be assessed using the 6-Minute Walk Test (6MWT). The total distance walked (meters) and walking speed (meters per minute, m/min) will be recorded. Unit of Measurement: Meters (m), Meters per minute (m/min) Higher Values Indicate: Better walking endurance

Time frame

Baseline, 3 months, 6 months, and 12 months

Radiological Outcomes

Radiological outcomes will assess MRI changes at baseline, 6 months, and 12 months to evaluate disease progression and lesion activity in MS. T2 Lesions: Total number of T2-weighted hyperintense lesions. Gadolinium-Enhancing Lesions: Presence and count of Gd-enhancing lesions. New Lesions: Number of newly developed brain and spinal cord lesions. Upper Cervical Spinal Lesions: Presence of lesions in C1-C4 spinal cord region. Brainstem Lesions: Identification of lesions in the brainstem. Unit: Lesion count per MRI scan Higher Values Indicate: Increased disease activity

Time frame

Radiological outcomes will be assessed at three time points: baseline (prior to treatment initiation), 6 months after starting treatment, and 12 months after starting treatment.

Walking Endurance

Walking endurance will be assessed using the 6-Minute Walk Test (6MWT). Participants will walk at their fastest pace to cover the maximum distance within six minutes, following the standardized protocol by Goldman et al. The total distance walked (meters) will be recorded as the primary measure of endurance. Unit of Measurement: Meters (m) Higher Values Indicate: Better walking endurance (lower fatigability)

Time frame

Baseline, 3 months, 6 months, and 12 months

Processing Speed and Attention

Processing speed and sustained attention will be assessed using the Symbol Digit Modalities Test (SDMT), a validated neurocognitive test. Participants will complete the SDMT in a 90-second timed format following the standardized protocol. Correct responses will be recorded at three consecutive 30-second intervals, and the total number of correct responses will be reported. Unit of Measurement: Number of correct responses Higher Values Indicate: Better cognitive processing speed and sustained attention

Time frame

Baseline, 3 months, 6 months, and 12 months

Other outcomes

Safety outcomes

The safety profile of teriflunomide will be assessed by monitoring the incidence, severity, and type of adverse events (AEs), including laboratory abnormalities, hair thinning or loss, and other treatment-related side effects. Serious adverse events (SAEs) will be categorized according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0), assessing their severity and relationship to treatment. Unit: Incidence count of AEs/SAEs Higher Values Indicate: Increased treatment-related adverse events

Time frame

From enrollment through study completion at 12 months, with assessments at baseline, 3 months, 6 months, and 12 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

TC Erciyes University

Lead sponsor

Sakarya University

Collaborator

Kocaeli University

Collaborator

Bursa Yuksek Ihtisas Training and Research Hospital

Collaborator

Source ClinicalTrials.gov

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