Genes and Environment in Multiple Sclerosis (GEMS)

• ClinicalTrials.gov Identifier: NCT01353547
• Recruitment Status: Recruiting
• First Posted: May 13, 2011
• Last Update Posted: September 19, 2022
• Sponsor: Columbia University
• Collaborators: University of Pittsburgh; Brigham and Women's Hospital
• Information provided by (Responsible Party): Columbia University

Tracking Information

• First Submitted Date: May 11, 2011
• First Posted Date: May 13, 2011
• Last Update Posted Date: September 19, 2022
• Actual Study Start Date: October 1, 2017
• Estimated Primary Completion Date: October 2040 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 24, 2020)

Total number of subjects who are diagnosed with MS [ Time Frame: 20 years ]

For each subject, weighted integrated risk score will be calculated, combining genetic burden and environmental exposure. A distribution of the risk score will be generated for the cohort. At this stage, the study will assess whether there is an increase in subjects with a diagnosis of MS (validated by a letter or copy of clinical records from the subject's neurologist) within the higher end vs. the lower end of the risk score distribution.

Original Primary Outcome Measures (submitted: May 12, 2011)

Brain MRI after recruiting 2200 subjects and calculating their genetic and environmental risk score of Multiple Sclerosis. [ Time Frame: 5 years ]

Genetic and Environmental Risk Score (GERS) will be calculated based on answers given in subject questionnaire and DNA collected from saliva sample. The questionnaire is about their neurologic and family history and potential environmental exposures. Subjects with the top and bottom 10% of GERS will undergo a single draw of up to 120 cc blood for analysis of immunologic markers. Subjects with the top and bottom 2.5% of GERS will undergo brain MRI to assess for asymptomatic MS-like lesions.

• 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: Genes and Environment in Multiple Sclerosis
• Official Title: Integrating Genetic and Environmental Risk Scores Into an Algorithm to Predict Multiple Sclerosis Susceptibility
• Brief Summary: The purpose of the research study is to identify the genetic, environmental and immune profiles that may increase a person's risk of developing multiple sclerosis (MS). While MS is not a disease caused by a single variation in genetic material (DNA), a single environmental factor, or a single malfunction in immune cells, there are genetic alterations, environmental exposures and immunologic factors that make the development of MS more likely. Obtaining information about who is at risk for MS will be beneficial in the future if the investigators can identify effective ways to prevent or slow down the progression of this disease.

Detailed Description

MS is an autoimmune disease in which the immune system (white bloods cells that normally fight infection) becomes misdirected and attacks healthy tissue. In patients with MS, the misdirected white blood cells attack myelin, a lining that insulates the nerves found in the brain and spinal cord. This results in inflammation and damage in the myelin. Loss of this protective lining disrupts nerve impulses and causes abnormal function in the nervous system.

This large research study will ultimately enroll 5000 subjects who are at risk of developing MS.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Saliva Sample (required), Blood Sample (optional), Stool Sample (optional) Biospecimen collection is done remotely by mailing kits to subjects. Coded samples are stored at Columbia University Medical Center (CUMC).

• Sampling Method: Probability Sample
• Study Population: This large research study will ultimately enroll over 10000 subjects who are at risk of developing MS. The study will last 20 years. We will recruit subjects from all over the United States, as everything is done via mail, email, or/and phone.
• Condition: Multiple Sclerosis
• Intervention: Not Provided

Study Groups/Cohorts

• Received anti-TNFa therapy
  Received anti-TNFa therapy
• First-degree relative of MS patients

  First-degree relative (child, parent or sibling) of a diagnosed MS patient

  A subgroup will be asked to undergo magnetic resonance imaging (MRI). Participants may be asked to donate a stool sample for gut flora analysis and a blood sample for ribonucleic acid (RNA) sequencing.

• Referred by the Partners MS Center
  Referred by the Partners MS Center

• Publications *: Xia Z, Steele SU, Bakshi A, Clarkson SR, White CC, Schindler MK, Nair G, Dewey BE, Price LR, Ohayon J, Chibnik LB, Cortese IC, De Jager PL, Reich DS. Assessment of Early Evidence of Multiple Sclerosis in a Prospective Study of Asymptomatic High-Risk Family Members. JAMA Neurol. 2017 Mar 1;74(3):293-300. doi: 10.1001/jamaneurol.2016.5056.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 12, 2011): 5000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2040
• Estimated Primary Completion Date: October 2040 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• First Degree Relatives of Patients with MS, or
• Patients who have received anti-TNFa therapy as treatment for inflammatory diseases other than MS such as Crohn's disease, psoriasis and rheumatoid arthritis, or
• Patients that have been referred for an evaluation of first presentation of neurologic symptoms but do not have a diagnosis of MS
• Live in the United States

Exclusion Criteria:

• Does not match any of the inclusion criteria

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Fatoumata B. Diallo, BS; 212-304-1548; fd2292@cumc.columbia.edu

Contact: Kaho Onomichi; 212-305-9155; ko2418@cumc.columbia.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01353547
• Other Study ID Numbers: AAAR4456
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Columbia University
• Original Responsible Party: Philip De Jager, MD PhD, Brigham and Womens Hospital
• Current Study Sponsor: Columbia University
• Original Study Sponsor: Brigham and Women's Hospital

Collaborators

• University of Pittsburgh
• Brigham and Women's Hospital

Investigators

• Study Director: Zongqi Xia, MD, PhD; University of Pittsburgh

• PRS Account: Columbia University
• Verification Date: September 2022