Observational Study of the Effect of Ozanimod on Fatigue in Multiple Sclerosis Patients

NCT05319093 | Terminated FDA Drug

• 1 other identifier: 2021P003284
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Multi-center observational study to assess the short-term response of multiple sclerosis (MS) patients initiated on Ozanimod with respect to fatigue. Patterns of brain changes on brain magnetic resonance imaging (MRI) that might modulate the effect of Ozanimod treatment on fatigue will also be assessed.

Conditions

Fatigue; Multiple Sclerosis

Keywords

fatigue; multiple sclerosis; brain; ozanimod; diffusion MRI

Outcome Measures

Primary Outcomes (1)

• Three-months change in Modified Fatigue Impact Scale (MFIS) score

  Difference in Modified Fatigue Impact Scale (MFIS) score between baseline (treatment initiation) and month 3. MFIS score will be assessed at baseline, as well as on days 28, 56 and 84 of the trial period. Should the 84-day measurement not be available, the three-months change will be estimated by linear regression extrapolation using available measurements.

  3 months

Secondary Outcomes (5)

• Three-months change in Chalder Fatigue Scale (CFS) score

  3 months

• Three-months change in Fatigue Severity Scale (FSS) score

  3 months

• Three-months change in NeuroQOL-fatigue questionnaire score

  3 months

• Visual Analog Scale (VAS) for fatigue score

  3 months

• Three-months change in NeuroQOL-cognitive function questionnaire score

  3 months

Other Outcomes (3)

• NeuroQOL-depression scale

  3 months

• NeuroQOL-anxiety scale

  3 months

• Epworth Sleepiness scale

  3 months

Study Arms (4)

Early Ozanimod treatment

In this group the effect of Ozanimod will be assessed in patients who initiated on Ozanimod treatment at study baseline (n=10). Treatment schedule and dosage of Ozanimod and the other disease-modifying treatments (DMTs) will be solely based on clinical indication and will be instituted by the patient's treating neurologist at Brigham and Women's Hospital or Massachusetts General Hospital.

Drug: Ozanimod

Medium-term Ozanimod treatment

In this group, the effect of Ozanimod will be assessed in patients treated with Ozanimod for ≥6 months at study baseline (n=10). Treatment schedule and dosage of Ozanimod and the other disease-modifying treatments (DMTs) will be solely based on clinical indication and will be instituted by the patient's treating neurologist at Brigham and Women's Hospital or Massachusetts General Hospital.

Drug: Ozanimod

Non-Ozanimod treatment

In this group, investigators will involve patients initiated on any disease-modifying drug (other than Ozanimod) at study initiation (n=10). Treatment schedule and dosage of the disease-modifying treatments (DMTs) will be solely based on clinical indication and will be instituted by the patient's treating neurologist at Brigham and Women's Hospital or Massachusetts General Hospital. The proposed study is purely observational and will not influence the selection, schedule or dosage of patient treatments.

Untreated

In this group, MS patient will be involved who did not receive any disease-modifying drug for at least 3 months before study initiation (i.e., untreated patients, n=10)

Interventions

Ozanimod DRUG

Three-months, longitudinal observational period

Also known as: ZEPOSIA

Early Ozanimod treatment; Medium-term Ozanimod treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All MS patients seen at Brigham and Women's Hospital and Massachusetts General Hospital who fit our selection criteria (see below) will be eligible to participate in this study. Since MS is 2-3 times more common in women, investigators expect that more women than men will participate.

You may qualify if:

• age≥18
• diagnosis of MS (according to the 2010 McDonald criteria)

You may not qualify if:

• neurodegenerative disorders other than MS
• terminal medical condition
• currently treated for active malignancy
• alcohol or substance abuse in the past year, except marijuana
• non-English speakers (the mobile application is not available in other languages)
• inability to undergo MRI scan
• Patients undergoing COVID-19 vaccination will be allowed to participate in the study if at least 2 weeks have elapsed from their last dose of vaccine.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (18)

• Palotai M, Wallack M, Kujbus G, Dalnoki A, Guttmann C. Usability of a Mobile App for Real-Time Assessment of Fatigue and Related Symptoms in Patients With Multiple Sclerosis: Observational Study. JMIR Mhealth Uhealth. 2021 Apr 16;9(4):e19564. doi: 10.2196/19564.

  PMID: 33861208 BACKGROUND

• Cella M, Chalder T. Measuring fatigue in clinical and community settings. J Psychosom Res. 2010 Jul;69(1):17-22. doi: 10.1016/j.jpsychores.2009.10.007. Epub 2009 Dec 11.

  PMID: 20630259 BACKGROUND

• Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989 Oct;46(10):1121-3. doi: 10.1001/archneur.1989.00520460115022.

  PMID: 2803071 BACKGROUND

• Cella D, Lai JS, Nowinski CJ, Victorson D, Peterman A, Miller D, Bethoux F, Heinemann A, Rubin S, Cavazos JE, Reder AT, Sufit R, Simuni T, Holmes GL, Siderowf A, Wojna V, Bode R, McKinney N, Podrabsky T, Wortman K, Choi S, Gershon R, Rothrock N, Moy C. Neuro-QOL: brief measures of health-related quality of life for clinical research in neurology. Neurology. 2012 Jun 5;78(23):1860-7. doi: 10.1212/WNL.0b013e318258f744. Epub 2012 May 9.

  PMID: 22573626 BACKGROUND

• Palotai M, Guttmann CR. Brain anatomical correlates of fatigue in multiple sclerosis. Mult Scler. 2020 Jun;26(7):751-764. doi: 10.1177/1352458519876032. Epub 2019 Sep 19.

  PMID: 31536461 BACKGROUND

• Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec;14(6):540-5. doi: 10.1093/sleep/14.6.540.

  PMID: 1798888 BACKGROUND

• Godin G, Shephard RJ. A simple method to assess exercise behavior in the community. Can J Appl Sport Sci. 1985 Sep;10(3):141-6.

  PMID: 4053261 BACKGROUND

• Palotai M, Weiner HL, Chitnis T, Duffy JF, and Guttmann CR, SLEEP APNEA AND PERIODIC LIMB MOVEMENTS ARE HIGHLY PREVALENT IN PATIENTS WITH MULTIPLE SCLEROSIS in 34th Annual Meeting of the Associated Professional Sleep Societies; Sleep, Volume 43, Issue Supplement_1, April 2020, Pages A429-A430, 1122. 2020.

  BACKGROUND

• Billiard M, Broughton R. Modafinil: its discovery, the early European and North American experience in the treatment of narcolepsy and idiopathic hypersomnia, and its subsequent use in other medical conditions. Sleep Med. 2018 Sep;49:69-72. doi: 10.1016/j.sleep.2018.05.027. Epub 2018 Jun 6.

  PMID: 30174215 BACKGROUND

• Miller P, Soundy A. The pharmacological and non-pharmacological interventions for the management of fatigue related multiple sclerosis. J Neurol Sci. 2017 Oct 15;381:41-54. doi: 10.1016/j.jns.2017.08.012. Epub 2017 Aug 12.

  PMID: 28991714 BACKGROUND

• Yang TT, Wang L, Deng XY, Yu G. Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis. J Neurol Sci. 2017 Sep 15;380:256-261. doi: 10.1016/j.jns.2017.07.042. Epub 2017 Jul 28.

  PMID: 28870581 BACKGROUND

• Induruwa I, Constantinescu CS, Gran B. Fatigue in multiple sclerosis - a brief review. J Neurol Sci. 2012 Dec 15;323(1-2):9-15. doi: 10.1016/j.jns.2012.08.007. Epub 2012 Aug 27.

  PMID: 22935407 BACKGROUND

• Kos D, Kerckhofs E, Nagels G, D'hooghe MB, Ilsbroukx S. Origin of fatigue in multiple sclerosis: review of the literature. Neurorehabil Neural Repair. 2008 Jan-Feb;22(1):91-100. doi: 10.1177/1545968306298934. Epub 2007 Apr 4.

  PMID: 17409388 BACKGROUND

• Palotai M, Cavallari M, Healy BC, Guttmann CR. A novel classification of fatigue in multiple sclerosis based on longitudinal assessments. Mult Scler. 2020 May;26(6):725-734. doi: 10.1177/1352458519898112. Epub 2020 Jan 23.

  PMID: 31971067 BACKGROUND

• Palotai M, Cavallari M, Koubiyr I, Morales Pinzon A, Nazeri A, Healy BC, Glanz B, Weiner HL, Chitnis T, Guttmann CR. Microstructural fronto-striatal and temporo-insular alterations are associated with fatigue in patients with multiple sclerosis independent of white matter lesion load and depression. Mult Scler. 2020 Nov;26(13):1708-1718. doi: 10.1177/1352458519869185. Epub 2019 Aug 16.

  PMID: 31418637 BACKGROUND

• Palotai M, Nazeri A, Cavallari M, Healy BC, Glanz B, Gold SM, Weiner HL, Chitnis T, Guttmann CRG. History of fatigue in multiple sclerosis is associated with grey matter atrophy. Sci Rep. 2019 Oct 14;9(1):14781. doi: 10.1038/s41598-019-51110-2.

  PMID: 31611598 BACKGROUND

• Cavallari M, Palotai M, Glanz BI, Egorova S, Prieto JC, Healy BC, Chitnis T, Guttmann CR. Fatigue predicts disease worsening in relapsing-remitting multiple sclerosis patients. Mult Scler. 2016 Dec;22(14):1841-1849. doi: 10.1177/1352458516635874. Epub 2016 Feb 26.

  PMID: 26920374 BACKGROUND

• Palotai M, Mike A, Cavallari M, Strammer E, Orsi G, Healy BC, Schregel K, Illes Z, Guttmann CR. Changes to the septo-fornical area might play a role in the pathogenesis of anxiety in multiple sclerosis. Mult Scler. 2018 Jul;24(8):1105-1114. doi: 10.1177/1352458517711273. Epub 2017 May 26.

  PMID: 28548605 BACKGROUND

Related Links

• MotionWatch 8
• Nox T3s Home Sleep Device

MeSH Terms

Conditions

Fatigue; Multiple Sclerosis

Interventions

ozanimod

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Charles RG Guttmann, MD

  Brigham and Women's Hospital, Radiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for Neurological Imaging

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 8, 2022
• Study Start: April 1, 2022
• Primary Completion: July 23, 2024
• Study Completion: July 23, 2024
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)