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

Sponsor

Brigham and Women's Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05319093

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fatigue Multiple Sclerosis	Drug: Ozanimod

Detailed Description

Primary objectives:

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).
To assess the impact of fronto-striatal damage on the association between Ozanimod treatment and fatigue.

Secondary objectives:

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.
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.
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.
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 Design

Study Type:

Observational

Anticipated Enrollment :

40 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Apr 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	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)

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Three-months change in Chalder Fatigue Scale (CFS) score [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.
Three-months change in Fatigue Severity Scale (FSS) score [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.
Three-months change in NeuroQOL-fatigue questionnaire score [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.
Visual Analog Scale (VAS) for fatigue score [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.
Three-months change in NeuroQOL-cognitive function questionnaire score [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.

Other Outcome Measures

NeuroQOL-depression scale [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.
NeuroQOL-anxiety scale [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.
Epworth Sleepiness scale [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

neurodegenerative disorders other than MS
terminal medical condition
currently treated for active malignancy
alcohol or substance abuse in the past year, except marijuana
diagnosis of major depressive disorder based on DSM V criteria
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.