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

November 24, 2025 updated by: Charles Guttmann, MD, Brigham and Women's Hospital
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Actual)

26

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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
Three-months, longitudinal observational period
Other Names:
  • ZEPOSIA
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
Three-months, longitudinal observational period
Other Names:
  • ZEPOSIA
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Three-months change in Modified Fatigue Impact Scale (MFIS) score
Time Frame: 3 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Three-months change in Chalder Fatigue Scale (CFS) score
Time Frame: 3 months
Difference in Chalder Fatigue Scale (CFS) score between baseline (treatment initiation) and month 3. CFS 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
Three-months change in Fatigue Severity Scale (FSS) score
Time Frame: 3 months
Difference in Fatigue Severity Scale (FSS) score between baseline (treatment initiation) and month 3. FSS 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
Three-months change in NeuroQOL-fatigue questionnaire score
Time Frame: 3 months
Difference in NeuroQOL-fatigue scale score between baseline (treatment initiation) and month 3. NeuroQOL-fatigue 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
Visual Analog Scale (VAS) for fatigue score
Time Frame: 3 months
Change in VAS fatigue score over the observation period. Current fatigue level will be assessed using VAS every four hours while the patient is awake during the trial period.
3 months
Three-months change in NeuroQOL-cognitive function questionnaire score
Time Frame: 3 months
Difference in NeuroQOL-cognitive function scale score between baseline (treatment initiation) and month 3. Cognitive function 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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
NeuroQOL-depression scale
Time Frame: 3 months
Level of depression will be assessed using the NeuroQOL-depression scale score. It will be assessed at baseline, as well as on days 28, 56 and 84 of the trial period.
3 months
NeuroQOL-anxiety scale
Time Frame: 3 months
Level of anxiety will be assessed using the NeuroQOL-anxiety scale score. It will be assessed at baseline, as well as on days 28, 56 and 84 of the trial period.
3 months
Epworth Sleepiness scale
Time Frame: 3 months
Sleep abnormalities will be assessed using the Epworth Sleepiness scale score. It will be assessed at baseline, as well as on days 28, 56 and 84 of the trial period.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Charles RG Guttmann, MD, Brigham and Women's Hospital, Radiology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2022

Primary Completion (Actual)

July 23, 2024

Study Completion (Actual)

July 23, 2024

Study Registration Dates

First Submitted

April 1, 2022

First Submitted That Met QC Criteria

April 1, 2022

First Posted (Actual)

April 8, 2022

Study Record Updates

Last Update Posted (Actual)

November 28, 2025

Last Update Submitted That Met QC Criteria

November 24, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021P003284

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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