Teriflunomide and Fatigability in MS

Not yet recruiting

• Conditions: Multiple Sclerosis

• Registration Number: NCT06843382
• Lead Sponsor: TC Erciyes University

Brief Summary

The goal of this observational study is to learn about the effects of teriflunomide on walking and cognitive fatigability in individuals with relapsing multiple sclerosis (MS) who are starting this treatment as part of their routine medical care. The main question it aims to answer is:

Does teriflunomide reduce walking fatigability and cognitive fatigability in individuals with relapsing MS over a 12-month period? Participants who have recently started teriflunomide as part of their standard MS treatment will undergo clinical evaluations at baseline, 3 months, 6 months, and 12 months. These assessments will include functional tests (6-Minute Walk Test, Symbol Digit Modalities Test, 9-Hole Peg Test, EDSS, and 25-Foot Walk Test), patient-reported outcomes (HADS, TSQM, fatigue and hair-related assessments), and routine clinical data collection (MRI and laboratory tests).

Detailed Description

Study Overview

This prospective, multicenter, observational study aims to assess the real-world effectiveness and safety of teriflunomide in individuals with relapsing multiple sclerosis (MS). The study will evaluate the impact of teriflunomide on walking fatigability and cognitive fatigability over a 12-month follow-up period. As this is an observational study, no interventions will be assigned, and participants will continue their prescribed teriflunomide treatment as part of their routine MS care.

Study Objectives

The primary objective is to determine whether teriflunomide reduces walking fatigability, measured by the 6-Minute Walk Test (6MWT), and cognitive fatigability, assessed through the Symbol Digit Modalities Test (SDMT).

The secondary objectives include evaluating:

Functional performance, including the Expanded Disability Status Scale (EDSS), 25-Foot Walk Test, and 9-Hole Peg Test (9-HPT).

Patient-reported outcomes (PROMs) such as anxiety, depression, treatment satisfaction, fatigue, and hair-related concerns.

Radiological findings, including MRI-based lesion evolution over the study period.

Safety assessments, including laboratory results and adverse events classified using Common Terminology Criteria for Adverse Events (CTCAE).

Study Design \& Data Collection

Participants will be evaluated at four time points: baseline (before or at treatment initiation), 3 months, 6 months, and 12 months. The data collection includes:

Functional and cognitive tests (6MWT, SDMT, 9-HPT, EDSS, 25-Foot Walk Test). Patient-reported outcomes (HADS, TSQM, Fatigue Severity Scale, and VAS scales for hair thinning and hair loss).

Routine MRI and laboratory test results, collected as part of regular clinical care.

Adverse event reporting following the CTCAE classification system.

Data Quality and Validation

A quality assurance plan will be implemented to ensure the validity and reliability of the collected data.

Data validation procedures will include automatic range checks and logical consistency verification between data fields.

Source data verification will be performed through electronic medical records (EMRs) to ensure completeness and accuracy.

A data dictionary will be established, detailing all variables, coding systems (such as MedDRA for adverse events), and predefined normal ranges.

Registry Procedures and Standard Operating Procedures (SOPs)

The study will follow SOPs for:

Patient recruitment, ensuring adherence to inclusion/exclusion criteria. Data collection and management, with electronic case report forms (eCRFs) designed to capture all relevant clinical and patient-reported outcomes.

Adverse event monitoring and reporting, using standardized grading systems. Change management, including protocols for addressing protocol amendments and modifications.

Statistical Analysis Plan

A sample size assessment will be conducted to ensure sufficient statistical power to detect meaningful differences in walking and cognitive fatigability over the study period.

Primary analysis will involve repeated-measures mixed-effects modeling to evaluate within-subject changes in walking and cognitive fatigability from baseline to 12 months.

Secondary analyses will include linear regression models and subgroup analyses based on disease characteristics, MRI findings, and patient-reported outcomes.

Handling of missing data will follow an intent-to-treat approach, using multiple imputation techniques for sensitivity analyses.

This real-world observational study will provide critical insights into the long-term effects of teriflunomide on functional performance, patient experience, and safety in individuals with relapsing MS.

Study Timeline

• Study First Submitted: 2025-01-22
• Status Verified: 2025-02
• Study First Submitted QC: 2025-02-21
• Last Update Submitted: 2025-02-21
• Study First Posted: 2025-02-25
• Last Update Posted: 2025-02-25
• Study Start: 2025-03-01
• Primary Completion: 2027-01-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• 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.
• Ability and willingness to provide informed consent and comply with study procedures.

Exclusion Criteria

• 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.
• Pregnancy or breastfeeding at the time of enrollment.
• Inability to comply with study visits at baseline, 3 months, 6 months, and 12 months.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Walking Fatigability Index	Assessments will be conducted at baseline, at three months, at six months, and at twelve months following treatment initiation.	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)
Cognitive Fatigability Index	Baseline, 3 months, 6 months, and 12 months	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)

Secondary Outcome Measures

Name	Time	Method
Walking Performance	Baseline, 3 months, 6 months, and 12 months	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
Radiological Outcomes	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.	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
Walking Endurance	Baseline, 3 months, 6 months, and 12 months	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)
Processing Speed and Attention	Baseline, 3 months, 6 months, and 12 months	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
Hand Coordination and Dexterity	Baseline, 3 months, 6 months, and 12 months	Hand coordination and dexterity will be evaluated using the 9-Hole Peg Test (9-HPT) for both hands. The time (in seconds) required to complete the task will be recorded.; Unit of Measurement: Seconds (s) Higher Values Indicate: Worse dexterity
Fatigue Severity	Baseline, 3 months, 6 months, and 12 months	Fatigue severity will be assessed using the Fatigue Severity Scale (FSS), a validated patient-reported outcome measure. The FSS consists of nine items, each rated from 1 (no fatigue) to 7 (severe fatigue), resulting in a total score range of 9-63.; Unit of Measurement: Fatigue Severity Scale (FSS) score (range: 9-63) Higher Values Indicate: Greater fatigue severity
Treatment Satisfaction	Baseline, 3 months, 6 months, and 12 months	Treatment satisfaction will be measured using the Treatment Satisfaction Questionnaire for Medication (TSQM). This instrument assesses satisfaction with medication across different domains (effectiveness, side effects, convenience, and global satisfaction).; Unit of Measurement: TSQM Score (range to be specified) Higher Values Indicate: Greater treatment satisfaction
Anxiety and Depression	Baseline, 3 months, 6 months, and 12 months	Anxiety and depression symptoms will be assessed using the Hospital Anxiety and Depression Scale (HADS), which consists of two subscales: HADS-Anxiety (HADS-A): Scores range from 0 to 21, with higher scores indicating greater anxiety.; HADS-Depression (HADS-D): Scores range from 0 to 21, with higher scores indicating greater depressive symptoms.; Unit of Measurement: HADS Score (0-21 per subscale) Higher Values Indicate: Greater anxiety or depression

Trial Locations

Locations (1)

Erciyes University; 🇹🇷 Kayseri, Turkey