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

NCT06843382 | Not Yet Recruiting

• 1 other identifier: ROOF-MS
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Teriflunomide; Fatigability; Real-world study

Outcome Measures

Primary Outcomes (2)

• 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)

  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)

  Baseline, 3 months, 6 months, and 12 months

Secondary Outcomes (8)

• Walking Performance

  Baseline, 3 months, 6 months, and 12 months

• 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.

• Walking Endurance

  Baseline, 3 months, 6 months, and 12 months

• Processing Speed and Attention

  Baseline, 3 months, 6 months, and 12 months

• Hand Coordination and Dexterity

  Baseline, 3 months, 6 months, and 12 months

Other Outcomes (1)

• Safety outcomes

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

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• TC Erciyes University: lead
• Sakarya University: collaborator
• Kocaeli University: collaborator
• Bursa Yuksek Ihtisas Training and Research Hospital: collaborator

Study Sites (1)

Erciyes University

Kayseri, Turkey (Türkiye)

Location

Related Publications (11)

• 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.

  PMID: 33023488 BACKGROUND

• 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.

  PMID: 36566698 BACKGROUND

• 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.

  PMID: 35631424 BACKGROUND

• 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.

  PMID: 38275509 BACKGROUND

• 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.

  PMID: 37861931 BACKGROUND

• 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.

  PMID: 36297360 BACKGROUND

• 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.

  PMID: 34486382 BACKGROUND

• 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.

  PMID: 30273841 BACKGROUND

• 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.

  PMID: 35696880 BACKGROUND

• 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.

  PMID: 33291032 BACKGROUND

• 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.

  PMID: 24198223 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Husnu Efendi, Prof.

  Kocaeli University

  STUDY CHAIR

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

  TC Erciyes University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

905428203060; drfatihmehmet@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Head of Multiple Sclerosis Unit of Erciyes University

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: February 25, 2025
• Study Start: November 20, 2025
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): June 15, 2027
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 3 months and ending 3 years after the publication of results

Locations

TU (1)