Multiple Sclerosis, Retinal Degeneration, Tomography, Optical Coherence, Visual Acuity
Conditions
Brief summary
This study aims to assess whether, and the degree to which, ofatumumab modulates or reduces rates of retinal atrophy in people with relapsing-remitting MS (RMS), according to baseline serum neurofilament light chain (sNfL) levels.
Detailed description
Seventy-five people with RMS who due to commence or already receiving ofatumumab therapy within 60 days of baseline will be recruited. All recruited participants will be tracked prospectively over a two-year period. Participants will complete an optical coherence tomography (OCT) scan, visual acuity (VA) assessments, EDSS, and sNfL blood level at baseline and every 6 months. Participants will be tracked prospectively for 2 years. OCT scans, sNfL levels, disability score determinations, 100% high-contrast, 2.5% and 1.25% low-contrast letter acuities will be performed every 6 months. Results from an existing cohort of approximately 75 healthy controls (HC) from a separate study undergoing annual OCT and visual function assessments will be used for comparison purposes.
Interventions
DRUGOfatumumab
Ofatumumab therapy is part of the patient's clinical care and is not given as part of the study
Sponsors
Johns Hopkins University
Novartis
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Between 18 - 70 years of age 2. Have RMS as confirmed by the treating neurologist based on the 2017 revised McDonald criteria AND Either * be due to commence ofatumumab within 60 days of baseline OCT/VA/phlebotomy or * be existing patients attending the center and already receiving ofatumumab, be eligible for inclusion, and already undergoing all of the proposed study procedures. 3. Willing to sign informed consent 4. Willing to undergo phlebotomy
Exclusion criteria
* Uncontrolled Diabetes * Uncontrolled Hypertension * Glaucoma * Refractive errors of +/- 6 diopters * Other neurologic or ophthalmologic disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ganglion cell inner plexiform (GCIP) atrophy in RMS relative to HCs, according to baseline sNfL levels | at least 12 months for up to 2 years | Rates of of GCIP layer thinning (µm/year) will be assessed according to baseline sNfL levels using mixed-effects linear regression models with random subject and eye-specific random intercepts and random slopes in time, using time from baseline OCT visit (in years) as a continuous variable in both unadjusted models (including time, sNfL group and their interaction) and models adjusted for the cross-sectional and longitudinal effects of covariates (age, sex, race, and history of optic neuritis) by including these variables and their respective interactions with time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inner nuclear layer (INL) atrophy in RMS relative to HCs | at least 12 months for up to 2 years | Rates of INL layer thinning (µm/year) will be assessed according to baseline sNfL levels using mixed-effects linear regression models with random subject and eye-specific random intercepts and random slopes in time, using time from baseline OCT visit (in years) as a continuous variable in both unadjusted models (including time, sNfL group and their interaction) and models adjusted for the cross-sectional and longitudinal effects of covariates (age, sex, race, and history of optic neuritis) by including these variables and their respective interactions with time. |
| Outer nuclear layer (ONL) atrophy in RMS relative to HCs | at least 12 months for up to 2 years | Rates of INL and ONL layer thinning (µm/year) will be assessed according to baseline sNfL levels using mixed-effects linear regression models with random subject and eye-specific random intercepts and random slopes in time, using time from baseline OCT visit (in years) as a continuous variable in both unadjusted models (including time, sNfL group and their interaction) and models adjusted for the cross-sectional and longitudinal effects of covariates (age, sex, race, and history of optic neuritis) by including these variables and their respective interactions with time. |
| Differences in the visual function scores | at least 12 months for up to 2 years | Exploratory analyses within the ofatumumab group will assess changes in visual function scores by baseline sNfL levels utilizing logistic regression. |
| Differences in expanded disability status scale (EDSS) scores | at least 12 months for up to 2 years | Exploratory analyses within the ofatumumab group will assess changes in EDSS scores by baseline sNfL levels utilizing logistic regression. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORShiv Saidha, MBBCh
Johns Hopkins University
Outcome results
None listed