Clinical trial NCT06843382: Teriflunomide and Fatigability in MS
Official title: The Effect of Teriflunomide on Fatigability in Individuals with Multiple Sclerosis: a Multicenter Real-World Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Teriflunomide
Fatigability
Real-world study
Lead sponsor: TC Erciyes University
Sponsor class: OTHER
Collaborators: name: Karadeniz Technical University
name: Bursa Yüksek İhtisas Education and Research Hospital
name: Sakarya University
First posted: 2025-02-25
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Walking Fatigability Index
timeFrame: Assessments will be conducted at baseline, at three months, at six months, and at twelve months following treatment initiation.
measure: Cognitive Fatigability Index
timeFrame: Baseline, 3 months, 6 months, and 12 months
Secondary outcomes:
measure: Walking Performance
timeFrame: Baseline, 3 months, 6 months, and 12 months
measure: Radiological Outcomes
timeFrame: 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.
measure: Walking Endurance
timeFrame: Baseline, 3 months, 6 months, and 12 months
measure: Processing Speed and Attention
timeFrame: Baseline, 3 months, 6 months, and 12 months
measure: Hand Coordination and Dexterity
timeFrame: Baseline, 3 months, 6 months, and 12 months
measure: Fatigue Severity
timeFrame: Baseline, 3 months, 6 months, and 12 months
measure: Treatment Satisfaction
timeFrame: Baseline, 3 months, 6 months, and 12 months
measure: Anxiety and Depression
timeFrame: Baseline, 3 months, 6 months, and 12 months
Other outcomes:
measure: Safety outcomes
timeFrame: From enrollment through study completion at 12 months, with assessments at baseline, 3 months, 6 months, and 12 months
Locations:
city: Kayseri
country: Turkey
facility: Erciyes University
Study officials:
affiliation: Karadeniz Technical University
name: Cavit Boz Prof. Dr. MD, Prof. Dr.
role: STUDY_CHAIR
affiliation: TC Erciyes University
name: Mehmet Fatih Yetkin Assoc. Prof. MD, Assoc. Prof.
role: PRINCIPAL_INVESTIGATOR
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