Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT01396343
• Recruitment Status: Completed
• First Posted: July 18, 2011
• Last Update Posted: October 18, 2018
• Sponsor: University of California, San Francisco
• Collaborators: New York University; Massachusetts General Hospital; State University of New York at Buffalo; University of Alabama at Birmingham; Mayo Clinic; Children's Hospital of Philadelphia; Boston Children's Hospital; Baylor College of Medicine; Loma Linda University; Children's Hospital Colorado; University of Texas; Ann & Robert H Lurie Children's Hospital of Chicago; Washington University School of Medicine; Children's National Med Center; Primary Children's Hospital; The Cleveland Clinic
• Information provided by (Responsible Party): University of California, San Francisco

Tracking Information

• First Submitted Date: July 14, 2011
• First Posted Date: July 18, 2011
• Last Update Posted Date: October 18, 2018
• Study Start Date: October 2011
• Actual Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 14, 2011)

Identify risk factors and their respective contribution to developing pediatric multiple sclerosis [ Time Frame: 4 year data collection, 1 year analysis ]

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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis
• Official Title: Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis
• Brief Summary: 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: 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
• Study Design: Observational Model: Case-Control; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Total 41ml sample: 17ml plasma/DNA, 10ml serum, 9ml lymphocytes and 5ml RNA frozen.

• 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.
• Condition: Pediatric Multiple Sclerosis
• Intervention: Not Provided

Study Groups/Cohorts

• 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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 16, 2018): 1276
• Original Estimated Enrollment (submitted: July 14, 2011): 1920
• Actual Study Completion Date: April 2018
• Actual Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01396343
• Other Study ID Numbers: 5R01NS071463( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of California, San Francisco
• Study Sponsor: University of California, San Francisco

Collaborators

• New York University
• Massachusetts General Hospital
• State University of New York at Buffalo
• University of Alabama at Birmingham
• Mayo Clinic
• Children's Hospital of Philadelphia
• Boston Children's Hospital
• Baylor College of Medicine
• Loma Linda University
• Children's Hospital Colorado
• University of Texas
• Ann & Robert H Lurie Children's Hospital of Chicago
• Washington University School of Medicine
• Children's National Med Center
• Primary Children's Hospital
• The Cleveland Clinic

Investigators

• Principal Investigator: Emmanuelle L Waubant, MD, PhD; University of California, San Francisco

• PRS Account: University of California, San Francisco
• Verification Date: October 2018