Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis

Study Overview
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Brief Summary
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The purpose of this study is to better understand multiple sclerosis (MS) in children and adolescents, to learn if it differs from adult MS and to investigate if genes or environmental exposures or a combination of both put children and adolescents at risk for getting MS.

Detailed Description
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The overall goal of this project is to determine whether well-established environmental and genetic risk factors for adult onset MS play an important role in susceptibility to pediatric-onset MS. Our study design is based on the hypothesis that genetic influences, specifically variation at HLA-DRB1 and other confirmed non-MHC MS loci, as well as environmental exposures including EBV infection and tobacco smoke, contribute to disease risk. In addition, we will also examine the relationship between serum levels of 25(OH) vitamin D3 and prior vitamin D status, and risk for pediatric onset MS. Finally, we will investigate whether specific G x E, and other multivariable relationships influencing risk exist for pediatric-onset MS. There are 16 collaborating sites other than UCSF that will enroll cases and controls for this study.

Official Title
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Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis

Conditions
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Pediatric Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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Children are eligible for this study as cases if: They have MS or clinically isolated syndrome (CIS): MS: As defined by the 2010 McDonald criteria for diagnosis of MS (Polman 2010), CIS: A first demyelinating event indicating high risk for MS (i.e., one clinical event involving the spinal cord, the optic nerve, the brainstem or cerebellum, or occasionally the hemispheres) and at least 2 silent T2 bright areas on a brain or spinal cord MRI (at least one must be in the brain); AND They are three years of age or older; AND Disease onset occurred before 18 years of age. Patients are not eligible for study participation if: Disease onset occurred more than 4 years prior to the opportunity to enroll; OR They have had an organ transplant; OR They are known to have neuromyelitis optica (NMO). Children are not eligible to participate as pediatric controls if: They are two years of age or younger; OR They are 22 years of age or older; OR They are known to have MS or another demyelinating disease (for example, neuromyelitis optica or acute disseminated encephalomyelitis); OR They have a biological family member who has been enrolled as a control; OR They have an immediate, biological family member (parent/sibling) who has been diagnosed with MS; OR They have an autoimmune disorder (except asthma or eczema); OR They have had an organ transplant; OR They have a chronic neurological condition with major disability (this does not include, for example, migraine, controlled seizures, and mild learning disabilities such as ADD or ADHD).

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 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 Case<br>Demographic and Medical History Questionnaire, Environmental Exposure Questionnaire, Food Frequency Questionnaire, Blood Sample Collection | |
| Pediatric Control<br>Demographic and Medical History Questionnaire, Environmental Exposure Questionnaire, Food Frequency Questionnaire, Blood Sample Collection | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify risk factors and their respective contribution to developing pediatric multiple sclerosis | The primary objective of this study is to determine if risk factors identified for adult MS such as HLA-DRB1*1501/1503, EBV, 25(OH) vitamin D3 insufficiency, and exposure to cigarette smoking are also risk factors for pediatric MS, and if there are interactions between them analyzing data collected from questionnaires for environmental exposure, demographic and food frequency as well as sample blood specimens. | 4 year data collection, 1 year analysis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis, Clinically Isolated Syndrome, Demyelinating Disease