Multiple SclerosisROOF-MSNCT06843382
Real-world Experience of Oral Agents On Fatigability in Multiple Sclerosis
An observational study of Multiple Sclerosis, run by TC Erciyes University at 1 site in Turkey (Türkiye).
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Sclerosis
- How many people
- 100 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 20 Nov 2025to 15 Jun 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site
Erciyes University
Kayseri
Mehmet Fatih Yetkin Assoc. Prof. MD, Assoc. Prof. MD, 905428203060, drfatihmehmet@gmail.com
About this study
Official title: Real-World Comparative Effects of Teriflunomide and Dimethyl Fumarate on Physical and Cognitive Fatigability in Multiple Sclerosis: The ROOF-MS Multicenter Prospective Cohort Study
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.
Read more
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.
Read the detailed description
This investigator-initiated, multicenter, prospective observational cohort study examines longitudinal changes in physical and cognitive fatigability among adults with multiple sclerosis (MS) initiating teriflunomide or dimethyl fumarate as part of routine clinical care. The study integrates standardized fatigability assessments into real-world clinical workflows across participating neurology centers.
Fatigability represents an objective performance decline during sustained motor or cognitive activity and provides information that is complementary to subjective fatigue ratings. To quantify physical fatigability, the study applies a structured 6-Minute Walk Test protocol in which distance covered during each minute is recorded. The primary physical fatigability index (DWI6-1) is calculated as the percentage change between the first and sixth minutes, enabling sensitive detection of time-dependent gait deterioration. Cognitive fatigability is quantified via a timed Symbol Digit Modalities Test procedure in which correct responses are recorded at three consecutive 30-second intervals. The Cognitive Fatigability Index (CFI-SDMT) reflects the proportional change between early and late test performance. Both indices allow continuous modeling of longitudinal trajectories and group differences.
All assessments are performed at baseline (within 30 days of treatment initiation) and at months 3, 6, 9, and 12. Functional performance measures (6MWT total distance, Timed 25-Foot Walk, Nine-Hole Peg Test), clinical evaluations (EDSS), patient-reported outcomes (FIS, TSQM, HADS), and MRI findings obtained during routine care are incorporated to contextualize patterns of fatigability. Test administration is standardized across centers through written manuals and joint training sessions. To minimize diurnal variability, fatigability tests are scheduled at approximately the same time of day for each participant.
Because the study is non-interventional, treatment decisions-including drug choice, dosing, and management of side effects-are determined solely by treating physicians. Data are recorded in a secure electronic capture platform using coded identifiers, with center-level access restrictions and prospective time-locked entry to maintain data integrity. All analyses follow a predefined statistical plan using mixed-effects modeling with participant- and center-level random effects to account for repeated measures and between-center heterogeneity.
This study aims to clarify real-world differences in fatigability trajectories between teriflunomide and dimethyl fumarate and to determine how these trajectories relate to functional performance, symptomatic burden, radiological disease activity, and treatment adherence in routine MS care.
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Teriflunomide, Fatigability, Real-world study
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Teriflunomide Cohort | Participants with relapsing multiple sclerosis who initiate teriflunomide as part of routine clinical care. Individuals in this cohort undergo standardized assessments of physical and cognitive fatigability, functional performance, clinical status, patient-reported outcomes, and routinely obtained MRI findings at baseline and at 3, 6, 9, and 12 months. No experimental treatment is administered, and all therapeutic decisions remain under the responsibility of the treating physician. | |
| Dimethyl Fumarate Cohort | Participants with relapsing multiple sclerosis who initiate dimethyl fumarate as part of routine clinical care. Individuals in this cohort complete standardized evaluations of physical and cognitive fatigability, functional performance, clinical status, patient-reported outcomes, and routinely acquired MRI measures at baseline and at 3, 6, 9, and 12 months. No experimental intervention is provided, and all treatment decisions are made independently by the treating physician. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: Baseline, 3 months, 6 months, and 12 months
Secondary outcomes (8)
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
Measured: 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
Measured: 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)
Measured: 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
Measured: Baseline, 3 months, 6 months, and 12 months
Hand Coordination and Dexterity
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
Measured: Baseline, 3 months, 6 months, and 12 months
Fatigue Severity
Fatigue severity will be evaluated using the Fatigue Impact Scale (FIS), a validated patient-reported measure assessing the perceived impact of fatigue on cognitive, physical, and psychosocial functioning. Participants rate the extent to which fatigue has affected daily activities during the previous month. Higher scores indicate greater fatigue-related impact.
Time Frame: Baseline, Month 3, Month 6, Month 9, Month 12 Type of Outcome: Patient-Reported Outcome Measure Method of Aggregation: Mean change from baseline and longitudinal trajectory over 12 months.
Measured: Baseline, 3 months, 6 months, and 12 months
Treatment Satisfaction
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
Measured: Baseline, 3 months, 6 months, and 12 months
Anxiety and Depression
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
Measured: Baseline, 3 months, 6 months, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2025
- Study start20 Nov 2025 (estimated)
- Primary completion15 Jun 2027 (estimated)
- Study completion15 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by TC Erciyes UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TC Erciyes University
- Sponsor type
- University, hospital or other
- Collaborators
- Sakarya University, Kocaeli University, Bursa Yuksek Ihtisas Training and Research Hospital
- Responsible party
- Principal investigator, Mehmet Fatih Yetkin, TC Erciyes University
- Investigators
- Husnu Efendi, Prof., Study chair, Kocaeli UniversityMehmet Fatih Yetkin Assoc. Prof. MD, Assoc. Prof., Principal investigator, TC Erciyes University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06843382
- Sponsor's protocol ID
- ROOF-MS
- Acronym
- ROOF-MS
- Status last verified
- Nov 2025
- First submitted
- 22 Jan 2025
- Last updated
- 21 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPD that underlie results in a publication
Publications
Comi G, Freedman MS, Meca-Lallana JE, Vermersch P, Kim BJ, Parajeles A, Edwards KR, Gold R, Korideck H, Chavin J, Poole EM, Coyle PK. Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis. BMC Neurol. 2020 Oct 6;20(1):364. doi: 10.1186/s12883-020-01937-4.
PubMed 33023488Berkovich R, Negroski D, Wynn D, Sellers D, Bzdek KG, Lublin AL, Rawlings AM, Quach C, Wells DP, Dumlao M, Bora A, Ranno AE, Luo KL, Chavin J, Hua LH, Becker D. Effectiveness and safety of switching to teriflunomide in older patients with relapsing multiple sclerosis: A real-world retrospective multicenter analysis. Mult Scler Relat Disord. 2023 Feb;70:104472. doi: 10.1016/j.msard.2022.104472. Epub 2022 Dec 18.
PubMed 36566698Bencsik K, Dobos E, Jobbagy Z, Birkas AJ, Kovacs K, Satori M, Lencses G, Bartok G, Losonczi E, Vecsei L, On Behalf Of The Teri-Real Investigators. Real-World Evidence for Favourable Quality-of-Life Outcomes in Hungarian Patients with Relapsing-Remitting Multiple Sclerosis Treated for Two Years with Oral Teriflunomide: Results of the Teri-REAL Study. Pharmaceuticals (Basel). 2022 May 13;15(5):598. doi: 10.3390/ph15050598.
PubMed 35631424Elkhooly M, Bao F, Bernitsas E. Impact of Disease Modifying Therapy on MS-Related Fatigue: A Narrative Review. Brain Sci. 2023 Dec 20;14(1):4. doi: 10.3390/brainsci14010004.
PubMed 38275509Meca-Lallana JE, Prieto Gonzalez JM, Caminero Rodriguez AB, Olascoaga Urtaza J, Alonso AM, Duran Ferreras E, Espinosa R, Dotor J, Romera M, Ares Luque A, Perez Ruiz D, Calles C, Hernandez MA, Hervas Garcia M, Mendoza Rodriguez A, Berdei Montero Y, Tellez N, Herrera Varo N, Sotoca J, Presas-Rodriguez S, Querol Gutierrez LA, Hervas Pujol M, Batlle Nadal J, Martin Ozaeta G, Gubieras Lillo L, Martinez Yelamos S, Ramio-Torrenta L, Mallada Frechin J, Belenguer Benavides A, Gascon-Gimenez F, Casanova B, Landete Pascual L, Berenguer L, Navarro L, Gomez Gutierrez M, Duran C, Rodriguez Regal A, Alvarez E, Garcia-Estevez DA, Lopez Real AM, Llaneza Gonzalez MA, Marzo Sola ME, Sanchez-Menoyo JL, Oterino A, Villaverde Gonzalez R, Castillo-Trivino T, Alvarez de Arcaya A, Llarena C. Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study. Neurol Ther. 2023 Dec;12(6):2177-2193. doi: 10.1007/s40120-023-00557-7. Epub 2023 Oct 20.
PubMed 37861931Strosova D, Tuzil J, Turkova BV, Pilnackova BF, de Souza LL, Dolezalova H, Raskova M, Dufek M, Dolezal T. Relationship between Patient Preferences, Attitudes to Treatment, Adherence, and Quality of Life in New Users of Teriflunomide. Pharmaceuticals (Basel). 2022 Oct 11;15(10):1248. doi: 10.3390/ph15101248.
PubMed 36297360Miller AE. An updated review of teriflunomide's use in multiple sclerosis. Neurodegener Dis Manag. 2021 Oct;11(5):387-409. doi: 10.2217/nmt-2021-0014. Epub 2021 Sep 16.
PubMed 34486382Coyle PK, Khatri B, Edwards KR, Meca-Lallana JE, Cavalier S, Rufi P, Benamor M, Thangavelu K, Robinson M, Gold R; Teri-PRO Trial Group. Patient-reported outcomes in patients with relapsing forms of MS switching to teriflunomide from other disease-modifying therapies: Results from the global Phase 4 Teri-PRO study in routine clinical practice. Mult Scler Relat Disord. 2018 Nov;26:211-218. doi: 10.1016/j.msard.2018.09.017. Epub 2018 Sep 15.
PubMed 30273841Hestvik ALK, Frederiksen JL, Nielsen HH, Torkildsen O, Eek C, Huang-Link Y, Haghighi S, Tsai JA, Kant M. Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes. Mult Scler Relat Disord. 2022 Jul;63:103892. doi: 10.1016/j.msard.2022.103892. Epub 2022 May 16.
PubMed 35696880de Seze J, Devy R, Planque E, Delabrousse-Mayoux JP, Vandhuick O, Kabir M, Gherib A. Fatigue in teriflunomide-treated patients with relapsing remitting multiple sclerosis in the real-world Teri-FAST study. Mult Scler Relat Disord. 2021 Jan;47:102659. doi: 10.1016/j.msard.2020.102659. Epub 2020 Nov 28.
PubMed 33291032Garnock-Jones KP. Teriflunomide: a review of its use in relapsing multiple sclerosis. CNS Drugs. 2013 Dec;27(12):1103-23. doi: 10.1007/s40263-013-0118-2.
PubMed 24198223
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real-World Comparative Effects of Teriflunomide and Dimethyl Fumarate on Physical and Cognitive Fatigability in Multiple Sclerosis: The ROOF-MS Multicenter Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT06843382
- Acronym / sponsor ID
- ROOF-MS / ROOF-MS
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Teriflunomide, Fatigability, Real-world study
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- TC Erciyes UniversityUniversity, hospital or other
- Collaborators
- Sakarya University, Kocaeli University, Bursa Yuksek Ihtisas Training and Research Hospital
- Study start
- 20 Nov 2025 (estimated)
- Primary completion
- 15 Jun 2027 (estimated)
- Study completion
- 15 Jun 2027 (estimated)
- First posted
- 25 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This investigator-initiated, multicenter, prospective observational cohort study examines longitudinal changes in physical and cognitive fatigability among adults with multiple sclerosis (MS) initiating teriflunomide or dimethyl fumarate as part of routine clinical care. The study integrates standardized fatigability assessments into real-world clinical workflows across participating neurology centers.
Fatigability represents an objective performance decline during sustained motor or cognitive activity and provides information that is complementary to subjective fatigue ratings. To quantify physical fatigability, the study applies a structured 6-Minute Walk Test protocol in which distance covered during each minute is recorded. The primary physical fatigability index (DWI6-1) is calculated as the percentage change between the first and sixth minutes, enabling sensitive detection of time-dependent gait deterioration. Cognitive fatigability is quantified via a timed Symbol Digit Modalities Test procedure in which correct responses are recorded at three consecutive 30-second intervals. The Cognitive Fatigability Index (CFI-SDMT) reflects the proportional change between early and late test performance. Both indices allow continuous modeling of longitudinal trajectories and group differences.
All assessments are performed at baseline (within 30 days of treatment initiation) and at months 3, 6, 9, and 12. Functional performance measures (6MWT total distance, Timed 25-Foot Walk, Nine-Hole Peg Test), clinical evaluations (EDSS), patient-reported outcomes (FIS, TSQM, HADS), and MRI findings obtained during routine care are incorporated to contextualize patterns of fatigability. Test administration is standardized across centers through written manuals and joint training sessions. To minimize diurnal variability, fatigability tests are scheduled at approximately the same time of day for each participant.
Because the study is non-interventional, treatment decisions-including drug choice, dosing, and management of side effects-are determined solely by treating physicians. Data are recorded in a secure electronic capture platform using coded identifiers, with center-level access restrictions and prospective time-locked entry to maintain data integrity. All analyses follow a predefined statistical plan using mixed-effects modeling with participant- and center-level random effects to account for repeated measures and between-center heterogeneity.
This study aims to clarify real-world differences in fatigability trajectories between teriflunomide and dimethyl fumarate and to determine how these trajectories relate to functional performance, symptomatic burden, radiological disease activity, and treatment adherence in routine MS care.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Teriflunomide Cohort | – | –Participants with relapsing multiple sclerosis who initiate teriflunomide as part of routine clinical care. Individuals in this cohort undergo standardized assessments of physical and cognitive fatigability, functional performance, clinical status, patient-reported outcomes, and routinely obtained MRI findings at baseline and at 3, 6, 9, and 12 months. No experimental treatment is administered, and all therapeutic decisions remain under the responsibility of the treating physician. |
| Dimethyl Fumarate Cohort | – | –Participants with relapsing multiple sclerosis who initiate dimethyl fumarate as part of routine clinical care. Individuals in this cohort complete standardized evaluations of physical and cognitive fatigability, functional performance, clinical status, patient-reported outcomes, and routinely acquired MRI measures at baseline and at 3, 6, 9, and 12 months. No experimental intervention is provided, and all treatment decisions are made independently by the treating physician. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Walking Fatigability Index
Time frame: 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
Time frame: 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)
8 secondary outcomes
Walking Performance
Time frame: Baseline, 3 months, 6 months, and 12 months
Radiological Outcomes
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
Time frame: Baseline, 3 months, 6 months, and 12 months
Processing Speed and Attention
Time frame: Baseline, 3 months, 6 months, and 12 months
Hand Coordination and Dexterity
Time frame: Baseline, 3 months, 6 months, and 12 months
Fatigue Severity
Time frame: Baseline, 3 months, 6 months, and 12 months
Treatment Satisfaction
Time frame: Baseline, 3 months, 6 months, and 12 months
Anxiety and Depression
Time frame: Baseline, 3 months, 6 months, and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2025.
- Background: PubMed 33023488Comi G, Freedman MS, Meca-Lallana JE, Vermersch P, Kim BJ, Parajeles A, Edwards KR, Gold R, Korideck H, Chavin J, Poole EM, Coyle PK. Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis. BMC Neurol. 2020 Oct 6;20(1):364. doi: 10.1186/s12883-020-01937-4.
- Background: PubMed 36566698Berkovich R, Negroski D, Wynn D, Sellers D, Bzdek KG, Lublin AL, Rawlings AM, Quach C, Wells DP, Dumlao M, Bora A, Ranno AE, Luo KL, Chavin J, Hua LH, Becker D. Effectiveness and safety of switching to teriflunomide in older patients with relapsing multiple sclerosis: A real-world retrospective multicenter analysis. Mult Scler Relat Disord. 2023 Feb;70:104472. doi: 10.1016/j.msard.2022.104472. Epub 2022 Dec 18.
- Background: PubMed 35631424Bencsik K, Dobos E, Jobbagy Z, Birkas AJ, Kovacs K, Satori M, Lencses G, Bartok G, Losonczi E, Vecsei L, On Behalf Of The Teri-Real Investigators. Real-World Evidence for Favourable Quality-of-Life Outcomes in Hungarian Patients with Relapsing-Remitting Multiple Sclerosis Treated for Two Years with Oral Teriflunomide: Results of the Teri-REAL Study. Pharmaceuticals (Basel). 2022 May 13;15(5):598. doi: 10.3390/ph15050598.
- Background: PubMed 38275509Elkhooly M, Bao F, Bernitsas E. Impact of Disease Modifying Therapy on MS-Related Fatigue: A Narrative Review. Brain Sci. 2023 Dec 20;14(1):4. doi: 10.3390/brainsci14010004.
- Background: PubMed 37861931Meca-Lallana JE, Prieto Gonzalez JM, Caminero Rodriguez AB, Olascoaga Urtaza J, Alonso AM, Duran Ferreras E, Espinosa R, Dotor J, Romera M, Ares Luque A, Perez Ruiz D, Calles C, Hernandez MA, Hervas Garcia M, Mendoza Rodriguez A, Berdei Montero Y, Tellez N, Herrera Varo N, Sotoca J, Presas-Rodriguez S, Querol Gutierrez LA, Hervas Pujol M, Batlle Nadal J, Martin Ozaeta G, Gubieras Lillo L, Martinez Yelamos S, Ramio-Torrenta L, Mallada Frechin J, Belenguer Benavides A, Gascon-Gimenez F, Casanova B, Landete Pascual L, Berenguer L, Navarro L, Gomez Gutierrez M, Duran C, Rodriguez Regal A, Alvarez E, Garcia-Estevez DA, Lopez Real AM, Llaneza Gonzalez MA, Marzo Sola ME, Sanchez-Menoyo JL, Oterino A, Villaverde Gonzalez R, Castillo-Trivino T, Alvarez de Arcaya A, Llarena C. Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study. Neurol Ther. 2023 Dec;12(6):2177-2193. doi: 10.1007/s40120-023-00557-7. Epub 2023 Oct 20.
- Background: PubMed 36297360Strosova D, Tuzil J, Turkova BV, Pilnackova BF, de Souza LL, Dolezalova H, Raskova M, Dufek M, Dolezal T. Relationship between Patient Preferences, Attitudes to Treatment, Adherence, and Quality of Life in New Users of Teriflunomide. Pharmaceuticals (Basel). 2022 Oct 11;15(10):1248. doi: 10.3390/ph15101248.
- Background: PubMed 34486382Miller AE. An updated review of teriflunomide's use in multiple sclerosis. Neurodegener Dis Manag. 2021 Oct;11(5):387-409. doi: 10.2217/nmt-2021-0014. Epub 2021 Sep 16.
- Background: PubMed 30273841Coyle PK, Khatri B, Edwards KR, Meca-Lallana JE, Cavalier S, Rufi P, Benamor M, Thangavelu K, Robinson M, Gold R; Teri-PRO Trial Group. Patient-reported outcomes in patients with relapsing forms of MS switching to teriflunomide from other disease-modifying therapies: Results from the global Phase 4 Teri-PRO study in routine clinical practice. Mult Scler Relat Disord. 2018 Nov;26:211-218. doi: 10.1016/j.msard.2018.09.017. Epub 2018 Sep 15.
- Background: PubMed 35696880Hestvik ALK, Frederiksen JL, Nielsen HH, Torkildsen O, Eek C, Huang-Link Y, Haghighi S, Tsai JA, Kant M. Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes. Mult Scler Relat Disord. 2022 Jul;63:103892. doi: 10.1016/j.msard.2022.103892. Epub 2022 May 16.
- Background: PubMed 33291032de Seze J, Devy R, Planque E, Delabrousse-Mayoux JP, Vandhuick O, Kabir M, Gherib A. Fatigue in teriflunomide-treated patients with relapsing remitting multiple sclerosis in the real-world Teri-FAST study. Mult Scler Relat Disord. 2021 Jan;47:102659. doi: 10.1016/j.msard.2020.102659. Epub 2020 Nov 28.
- Background: PubMed 24198223Garnock-Jones KP. Teriflunomide: a review of its use in relapsing multiple sclerosis. CNS Drugs. 2013 Dec;27(12):1103-23. doi: 10.1007/s40263-013-0118-2.
- Individual participant dataSharing planned: Yes. all IPD that underlie results in a publication
Related trials for Multiple Sclerosis
RecruitingPhase 2
Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS)
Multiple Sclerosis
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
RecruitingPhase 3
Dalfampridine Combined With Physical Therapy for Mobility Impairment in Multiple Sclerosis
Multiple Sclerosis
RecruitingPhase 2
Targeting Agonists of Glucagon-like Peptide-1 Receptor for Multiple Sclerosis
Multiple Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Husnu Efendi, Prof. study chair
Kocaeli University
Mehmet Fatih Yetkin Assoc. Prof. MD, Assoc. Prof. principal investigator
TC Erciyes University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by TC Erciyes University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 21 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mehmet Fatih Yetkin Assoc. Prof. MD, Assoc. Prof. (905428203060, drfatihmehmet@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Walking Fatigability Index (time frame: Assessments will be conducted at baseline, at three months, at six months, and at twelve months following treatment initiation.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06843382, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2025.