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

NCT ID: NCT06843382

Last Updated: 2025-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-11-20

Study Completion Date

2027-06-15

Brief Summary

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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

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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

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Multiple Sclerosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sakarya University

OTHER

Sponsor Role collaborator

Kocaeli University

OTHER

Sponsor Role collaborator

Bursa Yuksek Ihtisas Training and Research Hospital

OTHER_GOV

Sponsor Role collaborator

TC Erciyes University

OTHER

Sponsor Role lead

Responsible Party

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Mehmet Fatih Yetkin

Principal Investigator, Head of Multiple Sclerosis Unit of Erciyes University

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Husnu Efendi, Prof.

Role: STUDY_CHAIR

Kocaeli University

Mehmet Fatih Yetkin Assoc. Prof. MD, Assoc. Prof.

Role: PRINCIPAL_INVESTIGATOR

TC Erciyes University

Locations

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Erciyes University

Kayseri, , Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

Central Contacts

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Mehmet Fatih Yetkin Assoc. Prof. MD, Assoc. Prof.

Role: CONTACT

905428203060

Facility Contacts

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Mehmet Fatih Yetkin Assoc. Prof. MD, Assoc. Prof. MD

Role: primary

905428203060

References

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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.

Reference Type BACKGROUND
PMID: 33023488 (View on PubMed)

Berkovich 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.

Reference Type BACKGROUND
PMID: 36566698 (View on PubMed)

Bencsik 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.

Reference Type BACKGROUND
PMID: 35631424 (View on PubMed)

Elkhooly 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.

Reference Type BACKGROUND
PMID: 38275509 (View on PubMed)

Meca-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.

Reference Type BACKGROUND
PMID: 37861931 (View on PubMed)

Strosova 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.

Reference Type BACKGROUND
PMID: 36297360 (View on PubMed)

Miller 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.

Reference Type BACKGROUND
PMID: 34486382 (View on PubMed)

Coyle 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.

Reference Type BACKGROUND
PMID: 30273841 (View on PubMed)

Hestvik 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.

Reference Type BACKGROUND
PMID: 35696880 (View on PubMed)

de 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.

Reference Type BACKGROUND
PMID: 33291032 (View on PubMed)

Garnock-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.

Reference Type BACKGROUND
PMID: 24198223 (View on PubMed)

Other Identifiers

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ROOF-MS

Identifier Type: -

Identifier Source: org_study_id

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