Obesity and Pediatric Multiple Sclerosis

Study Overview
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Brief Summary
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Obesity is one possible contributor to severity of multiple sclerosis and progression of the disease. We already know that obesity is a risk determinant for acquiring MS, yet the impact of obesity on pediatric MS disease expression and course is unknown. This study will evaluate the relationship between obesity, obesity-derived inflammatory mediators, and imaging metrics of MS severity in children. Understanding how childhood obesity contributes to MS severity/progression may yield fundamental insights into disease pathobiology - which may thereby lead to effective strategies for halting its progression in its earliest stages.

Official Title
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Obesity as a Driver of Inflammation and Brain Volume Loss in Pediatric Multiple Sclerosis.

Conditions
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Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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Pediatric MS subjects will meet below inclusion and exclusion criteria: Inclusion Criteria: Ability to provide informed consent (or assent for minors) Relapsing-remitting MS diagnosis per 2017 McDonald criteria Ages ≥ 10 years to ≤ 20 years Diagnosis of MS or first clinical symptom of MS (whichever comes first) within ≤ 36 months from the time of enrollment. Exclusion Criteria: Progressive form of MS Patients with an active, chronic disease of the immune system other than MS Conditions affecting the central nervous system (CNS) white matter (e.g. leukodystrophy) or for whom another condition may better explain imaging abnormalities (e.g. lupus) Myelin oligodendrocyte glycoprotein (MOG) antibodies on serologic testing Corticosteroid exposure within 30 days of study enrollment Control subjects (Aim 2) will meet the below inclusion and exclusion criteria: Inclusion Criteria: Ability to provide informed consent (or assent for minors) Age-, sex-, & BMI-matched to pediatric MS subjects (1:1 allocation) Healthy children and young adults from the local communities Exclusion Criteria: History of past imaging or neurologic event raising concern for any inflammatory CNS process Medical history or previous/current diagnosis consistent with an autoimmune disorder pertaining to any system of the body (e.g. diabetes mellitus type 1, Crohn's disease, lupus)

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pediatric MS Subjects<br>Subjects with pediatric MS will undergo fasting lab work, non-contrasted MRI, DEXA scan, and surveys. | |
| Healthy controls<br>Non-MS pediatric control subjects who will undergo fasting lab work, DEXA scan, and surveys for comparison to control group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole brain volumes and focal demyelinating lesion volumes | 58 patients with a recent MS diagnosis, stratified by weight category (29 normal weight and 29 overweight/obese). Subjects will undergo MRI to quantify total brain and lesion volume. Z-scores for volumetrics will be determined using age- and sex-matched normative data from the NIH-sponsored ABCD dataset. We will compare mean Z-scores of whole brain volume and focal demyelinating lesion volumes between the two groups. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adipo-cytokine profiles | Fasting adipo-cytokines from MS cohort will be compared to age-, sex-, and BMI-matched controls. | 3 years | 
| Adipo-cytokines correlation with brain volume loss and neuroaxonal injury | We will measure serum NfL in MS subjects and controls. We will determine if leptin (a pro-inflammatory adipo-cytokine) predicts degree of brain volume loss and/or neuroaxonal injury in subjects with MS. This exploratory, mechanistic aim has potential to provide the first link between obesity-derived inflammation and neuronal cell injury/loss. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, Obesity, Neurodegeneration, Inflammation