Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis

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.

Study Overview

• Status: Completed
• Conditions: Pediatric Multiple Sclerosis

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 1276

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Center for pediatric-onset demyelinating diseases at the Children's Hospital of Alabama, Birmingham
  • California
    • San Bernardino, California, United States, 92408
      • Pediatric MS Clinic, Children's Hospital, Loma Linda University
    • San Francisco, California, United States, 94143
      • UCSF Pediatric MS Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado, University of Colorado School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Pediatric MS Clinic, Children's National Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Pediatric MS Clinic, Ann & Robert H. Lurie Children's Hospital of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Partners Pediatric MS Center at the Massachusetts General Hospital for Children
    • Boston, Massachusetts, United States, 02115
      • Pediatric MS Clinic, Children's Hospital Boston
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Regional Pediatric MS Center at Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Pediatric MS Clinic, Washington University School of Medicine
  • New York
    • Buffalo, New York, United States, 14203
      • Pediatric MS Center of the Jacobs Neurological Institute, University of Buffalo
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Pediatric MS Clinic, Children's Hospital of Philadelphia
  • Texas
    • Dallas, Texas, United States, 75390
      • Pediatric MS Center, University of Texas, Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • The Blue Bird Circle Clinic for MS at Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Pediatric Neurology Clinic, Primary Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Case patients seen at the 16 participating Pediatric MS Center Clinics. Control patients seen at the Pediatric Clinics of the same institution as MS cases.

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Pediatric MS Case; Demographic and Medical History Questionnaire, Environmental Exposure Questionnaire, Food Frequency Questionnaire, Blood Sample Collection
Pediatric Control; Demographic and Medical History Questionnaire, Environmental Exposure Questionnaire, Food Frequency Questionnaire, Blood Sample Collection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Massachusetts General Hospital; Mayo Clinic; Baylor College of Medicine; Children's Hospital of Philadelphia; Washington University School of Medicine; University of Alabama at Birmingham; New York University; Children's Hospital Colorado; Boston Children's Hospital; The Cleveland Clinic; Ann & Robert H Lurie Children's Hospital of Chicago; University of Texas; Loma Linda University; Primary Children's Hospital; State University of New York at Buffalo; Children's National Med Center
• Investigators: Principal Investigator: Emmanuelle L Waubant, MD, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: July 14, 2011
• First Submitted That Met QC Criteria: July 14, 2011
• First Posted (Estimate): July 18, 2011

Study Record Updates

• Last Update Posted (Actual): October 18, 2018
• Last Update Submitted That Met QC Criteria: October 16, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Clinically Isolated Syndrome; Relapsing Remitting Multiple Sclerosis; Demyelinating Disease; Pediatric Multiple Sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 5R01NS071463 (U.S. NIH Grant/Contract)