Risk Factors in Early Multiple Sclerosis
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 300
- Locations
- 1
- Primary Endpoint
- Discovery of Lesions disseminated in space on brain MRI
Study Overview
Brief Summary
The central hypothesis of this protocol is that it is possible, using First Degree Relatives (FDRs) of patients with Multiple Sclerosis (MS) and assessing a variety of both known and unknown risk factors for MS, to define a risk algorithm for earliest signs of development of MS. The plan will be to do an abbreviated brain Magnetic Resonance Imaging (MRI) scan in asymptomatic, young FDRs, analyze blood for a variety of immunological, genetic, neuroaxonal damage, metabolic, viral serology and other markers, and have FDRs fill out a detailed bioscreen questionnaire about lifestyle factors and perform a cognitive screening test. The investigators will then compare the results of the various blood/other studies in FDRs with and without an MRI showing signs signs concerning for MS, as well as age-and sex-matched NON-FDRs who will have blood drawn and fill out the questionnaire. With this preliminary cross-sectional study, the investigators hope to begin to identify a risk stratification model for those at highest risk of developing MS, ie FDRs, with a long-term goal of developing a longitudinal study to increase sensitivity and specificity of the risk model.
Detailed Description
Specific Aims, among asymptomatic first degree relatives (FDRs), aged 18-30, of multiple sclerosis (MS) patients:
- Determine the prevalence of brain MRI lesions disseminated in space (DIS), consistent with MS
- Gather data on potential risk factors or early signs related to MS development, including markers for: genes, immunological function, environmental factors, neuroaxonal damage, Vitamin D levels, lipid metabolism, activity levels, mood abnormalities, and cognitive function. From this, develop a risk factor score, incorporating all relevant potential markers of increased risk of DIS.
- To use this pilot, cross-sectional study as a base for development of a long-term, longitudinal, multi-center study to determine genetic and environmental risks for pre-symptomatic MS
- To create and maintain a biobank of specimens for future analysis as other potential biomarkers become available.
- Evaluate for potential dissemination in time (DIT) and dissemination in space (DIS) in asymptomatic FDRs through longitudinal assessment.
Sequences to include
- Whole brain T1-weighted images acquired using 3-Dimensional fast spoiled-gradient recalled acquisitions (T1-3D-FSPGR) with 1 mm slice thickness and isotropic voxel dimensions.
- Whole brain 3-Dimensional Double Inversion Recovery (DIR) acquisition with 1.5 mm slice thickness.
- Whole brain T2-weighted Fluid Attenuated Inversion Recovery (FLAIR ) images with 1 mm slice thickness and isotropic voxel dimensions will be combined with
- Whole brain T2*-weighted segmented echo-planar imaging (segEPI) images with <=1 mm slice thickness and isotropic voxel dimensions to obtain FLAIR* images.
Blood analysis for:
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 30 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •FDR Inclusion Criteria
- •Male and female
- •All races and ethnicities
- •Must have a parent, sibling or child with MS fulfilling McDonald 2017 criteria
- •No symptoms suggestive of MS on formal screen
- •Ability to undergo a non-contrast MRI and venipuncture, and perform an environmental screen, mood screen and cognitive test
- •Non-FDR Inclusion Criteria
- •Male and female
- •All races and ethnicities
- •Must NOT have a FDR (parent, sibling, child) or second degree relative (grandparent, aunt or uncle) with MS fulfilling McDonald 2017 criteria
- •No symptoms suggestive of MS on formal screen
- •Ability to undergo venipuncture and perform an environmental screen.
Exclusion Criteria
- •FDR Exclusion Criteria
- •Symptoms suggestive of MS on formal screen
- •Prior diagnosis of autoimmune disease that may be associated with CNS dysfunction and MRI lesions, e.g. Sjogren's
- •Non-FDR Exclusion Criteria
- •Symptoms suggestive of MS on formal screen
- •Prior diagnosis of autoimmune disease that may be associated with CNS dysfunction and MRI lesions, e.g. Sjogren's
Outcomes
Primary Outcomes
Discovery of Lesions disseminated in space on brain MRI
Time Frame: At the subject's Initial Visit
Lesions disseminated in space on brain MRI. The presence or absence of these lesions will only be measured once at the initial visit.
Secondary Outcomes
- Define risk stratification algorithm for prediction of MS(Within 4 months of the Initial Visit)