Genes and Environment in Multiple Sclerosis (GEMS)

Integrating Genetic and Environmental Risk Scores Into an Algorithm to Predict Multiple Sclerosis Susceptibility

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis

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
• Enrollment (Anticipated): 5000

Contacts and Locations

• Study Contact: Name: Kaho Onomichi; Phone Number: 212-305-9155; Email: ko2418@cumc.columbia.edu
• Study Contact Backup: Name: Fatoumata B. Diallo, BS; Phone Number: 212-304-1548; Email: fd2292@cumc.columbia.edu

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 15213
      • Recruiting
      • National Institute of Neurological Disorders and Stroke
      • Principal Investigator: Daniel S Reich, MD, PhD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Terminated
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Terminated
      • Brigham and Women's Hospital
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Center
      • Contact: Fatoumata Diallo, BS; Phone Number: 212-305-1485; Email: mscenter_neuro@cumc.columbia.edu
      • Contact: Kaho Onomichi, MS; Phone Number: 212-305-9155
      • Principal Investigator: Philip L De Jager, MD, PhD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
      • Principal Investigator: Zongqi Xia, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of subjects who are diagnosed with MS	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.	20 years

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: University of Pittsburgh; Brigham and Women's Hospital
• Investigators: Study Director: Zongqi Xia, MD, PhD, University of Pittsburgh

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Anticipated): October 1, 2040
• Study Completion (Anticipated): October 1, 2040

Study Registration Dates

• First Submitted: May 11, 2011
• First Submitted That Met QC Criteria: May 12, 2011
• First Posted (Estimate): May 13, 2011

Study Record Updates

• Last Update Posted (Actual): September 19, 2022
• Last Update Submitted That Met QC Criteria: September 16, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: genomic analysis; online surveys; biological specimen collection
• 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: AAAR4456

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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