A Multicenter Observational Study to Evaluate Pediatric Multiple Sclerosis in Brazil

Study Overview
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Brief Summary
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Pediatric Multiple sclerosis (MS) is a chronic inflammatory disease defined by multiple episodes of demyelination of the central nervous system (CNS) separated by time and space as specified in adults not explained by acute disseminated encephalomyelitis (ADEM). Several studies have indicated that at least 5% of MS patients are in the pediatric population, but no prospective study was performed in Brazil. There are particular characteristics of Pediatric MS that differs from the adult population and have been focus of interest in the last years. However, we still lack high evidence data, specially concerning treatment, of this age group. This is an observational non-interventional multicenter study in pediatric MS patients in which participating subjects will be characterized by their clinical, MRI and immunological features. In this observational study, we will select 8 MS centers in Brazil to recruit at least 100 pediatric patients currently followed on each center with idiopathic inflammatory CNS disorders over a 2-year study period. We will collect retrospective and prospective clinical and MRI data to determine the proportion of patients who fulfill the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for MS,7 especially on those below 10 years where the use of McDonald 2010 criteria is not recommended routinely. Following the inclusion on the study, subjects will be followed for at least 2 years. All subjects enrolled in this study will have serum collected to test autoantibodies including anti-AQP4 and anti-MOG using cell-based assays with transfected cells.8 Pediatric patients with positive testing for these autoantibodies will be analyzed separately. Exploratory MRI sub-study In 10 patients recruited at Hospital São Lucas PUCRS, we will perform an exploratory substudy with advanced MRI using q-space diffusion protocol on a 3-Tesla MRI (GE Signa HDx 3.0T, General Electric, Milwaukee, WI, USA) and a 8-channel head coil to visualize remyelinating brain MS lesions. Normalized leptokurtic diffusion (NLD) data will be acquired using diffusion-weighted echo planar imaging. All MRI scans from this exploratory study will be performed at the Brain Institute of Rio Grande do Sul (BraIns). Only patients with previous brain demyelinating lesions will be included in this exploratory sub-study.

Official Title
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A Multicenter Observational Study to Evaluate Pediatric Multiple Sclerosis in Brazil

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Diagnostic Test: anti-aquaporin-4 antibody
* Diagnostic Test: anti-myelin oligodendrocyte glycoprotein


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parents / patient have an understanding, ability and willingness to fully comply with study procedures Parents / patient have the ability to provide voluntary written, signed and dated informed consent to participate in the study Be 6 months - 18 years of age at screening Have clinical evidence of at least 1 attack suggestive of idiopathic inflammatory CNS disorder Have at least one brain MRI with available images (for review) For the exploratory MRI study, parents / patients have to agree to perform 2 MRI scans (at baseline and at the end of the study). Considering the age of the study subjects, sedation may be required during the acquisition of the MRI. Exclusion Criteria: Current evidence or known history of clinically significant infection including: - Chronic or ongoing active infectious disease requiring long-term systemic treatment such as active hepatitis B or C, HIV or tuberculosis Current malignancy or history of malignancy in the past 5 years Significant concurrent, uncontrolled medical condition that could affect subject's safety or impair the subject's participation in the study. Current participation in any interventional trial. Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: anti-aquaporin-4 antibody|Serum anti-aquaporin-4 antibody|
|Diagnostic Test: anti-myelin oligodendrocyte glycoprotein|Serum anti-myelin oligodendrocyte glycoprotein|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Convertion rate to MS | To evaluate the proportion of patients (below and above 10 years-old) with idiopathic inflammatory CNS disorders converting to pediatric MS in Brazilian MS referral centers. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical features | • To compare the clinical and MRI features between pediatric MS patients with disease onset < 10 and > 10 years | 2 years | 
| epidemiology | • To analyze the influence of latitude, ethnicity and past viral infections on the development of pediatric MS | 2 years | 
| autoantibodies | • To determine the proportion of patients with pediatric MS and other inflammatory demyelinating CNS disorders with autoantibodies (anti-AQP4 and anti-MOG) | 2 years | 
| treatments | • To identify the disease-modifying treatments used in pediatric MS cases by the treating physician and the occurrence of adverse events | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple sclerosis, pediatric