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

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05319093
• Other study ID #: 2021P003284
• Status: Not yet recruiting
• Start date: April 2022
• Est. completion date: December 2023

Study information

• Verified date: April 2022
• Source: Brigham and Women's Hospital
• Contact: Diana Pintye, MD
• Phone: +18574239507
• Email: dpintye[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. diagnosis of major depressive disorder based on DSM V criteria

6. non-English speakers (the mobile application is not available in other languages)

7. 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.

Related Conditions & MeSH terms

• Fatigue
• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Ozanimod
Three-months, longitudinal observational period

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Bristol-Myers Squibb

References & Publications (18)

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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. — View Citation

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. — View Citation

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. — View Citation

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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. — View Citation

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	NeuroQOL-depression scale	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
Other	NeuroQOL-anxiety scale	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
Other	Epworth Sleepiness scale	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
Primary	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	Three-months change in Chalder Fatigue Scale (CFS) score	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
Secondary	Three-months change in Fatigue Severity Scale (FSS) score	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
Secondary	Three-months change in NeuroQOL-fatigue questionnaire score	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
Secondary	Visual Analog Scale (VAS) for fatigue score	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
Secondary	Three-months change in NeuroQOL-cognitive function questionnaire score	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

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