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

NCT ID: NCT05319093

Last Updated: 2025-11-28

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

TERMINATED

Total Enrollment

26 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-04-01

Study Completion Date

2024-07-23

Brief Summary

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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.

Detailed Description

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Primary objectives:

1. To assess the effect of Ozanimod treatment on the impact of fatigue on physical, cognitive, and psychosocial functions, as measured by the modified fatigue impact scale (MFIS).
2. To assess the impact of fronto-striatal damage on the association between Ozanimod treatment and fatigue.

Secondary objectives:

1. To assess the effect of Ozanimod treatment on fatigue severity, mood symptoms (ie, depression and anxiety), sleep quality, physical activity, reward responsiveness and cognitive functions over the first 3-month after treatment initiation with Ozanimod.
2. To assess the time course of changes by daily administration of visual analogue scales of fatigue, depression, anxiety, and pain, and monthly administration of self-assessment questionnaires for fatigue, depression and anxiety using a mobile application.
3. In addition to the hypothesis-driven analyses specifically targeting the fronto-striatal system, the investigators will also perform analyses designed to discover other potential brain MRI predictors of Ozanimod treatment response (ie, change in primary and/or secondary endpoints during the 3-month Ozanimod treatment). The investigators will perform global and regional (e.g., cerebral cortical, deep grey matter, hippocampal) volumetric measurements as well as well-established voxel-based image statistics to seek other potential patterns of brain atrophy that identify responders to Ozanimod. Resting state functional MRI (rsfMRI) will also be performed to seek potential markers of fatigue related to functional brain connectivity changes.
4. To establish patient compliance in using the aforementioned mobile app, and the robustness of app-based phenotypic characterization of fatigue and related symptoms on real-world patients. These observations will lay the basis for future prospective studies on larger patient cohorts. For this purpose, recruitment will also be expanded to patients treated with disease modifying drugs other than Ozanimod.

Primary hypothesis:

Patients without significant damage to fronto-striatal circuitry (ie, fronto-striatal fractional anisotropy (FA)≥0.26 on diffusion tensor MRI (DT-MRI)) show significant decrease in fatigue score over the first 3-month after treatment initiation with Ozanimod.

Study assessments:

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. The proposed study is purely observational and will not influence the selection, schedule or dosage of patient treatments. Therefore, no safety assessment will be performed within the study.

All endpoints and confounders will be assessed using state-of-the art mobile/wearable technology, while the patient is on her/his/their normal routine at home and/or at work, including self-isolated quarantine. All patient-reported outcomes (PROs) will be assessed using a mobile application developed by the study team. The first version of the mobile application was already tested and used in a prospective brain MRI study of MS-related fatigue (MGB IRB Protocol number: 2017P001239). The mobile application will be modified and adapted to make it specifically suitable for the proposed study. The application will be installed on an Android smartphone that will be provided to each subject. The application will communicate using end-to-end encryption (https protocol) with a server inside the MGB firewall. Data will be transmitted between the mobile app and the server in deidentified and coded form.

Continuous actigraphy will be performed using wrist-worn actigraphic watches to assess quantitative physical activity (during daytime) and sleep measures (at night) during the entire 3-months period of the trial. These devices also measure other bio-signals as for instance skin conductivity and heart rhythm, as well as light exposure.

Presence/absence of obstructive sleep apnea and restless leg syndrome will be assessed once between day 0 and day 3 of the trial period using a home sleep test (HST) device.

Subjects will receive the study devices in person or via postal mail and will be instructed how to use the devices in person or via video conference call in compliance with COVID-19 regulations.

Each patient will undergo 3 Tesla brain Magnetic Resonance Imaging, including diffusion tensor, T1-weighted, T2-weighted, FLAIR and rsfMRI imaging at Brigham and Women's Hospital at baseline.

Conditions

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Fatigue Multiple Sclerosis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Ozanimod

Intervention Type DRUG

Three-months, longitudinal observational period

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.

Ozanimod

Intervention Type DRUG

Three-months, longitudinal observational period

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.

No interventions assigned to this group

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)

No interventions assigned to this group

Interventions

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Ozanimod

Three-months, longitudinal observational period

Intervention Type DRUG

Other Intervention Names

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ZEPOSIA

Eligibility Criteria

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Inclusion Criteria

1. age≥18
2. diagnosis of MS (according to the 2010 McDonald criteria)

Exclusion Criteria

1. neurodegenerative disorders other than MS
2. terminal medical condition
3. currently treated for active malignancy
4. alcohol or substance abuse in the past year, except marijuana
5. non-English speakers (the mobile application is not available in other languages)
6. 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Charles Guttmann, MD

Director, Center for Neurological Imaging

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Charles RG Guttmann, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital, Radiology

Locations

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Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 2803071 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20630259 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33861208 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22573626 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31536461 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1798888 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 4053261 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 30174215 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28991714 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28870581 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22935407 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17409388 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31971067 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31418637 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31611598 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26920374 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28548605 (View on PubMed)

Other Identifiers

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2021P003284

Identifier Type: -

Identifier Source: org_study_id

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