Intestinal Immunity in Neurologic Disease

The purpose of this study is to ascertain the functional profiles of the immune cells within the gastrointestinal tract and to determine how these cells contribute to autoimmune and neurologic diseases.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Parkinson Disease; REM Sleep Behavior Disorder
• Intervention / Treatment: Procedure: Colon Tissue Biopsy

Detailed Description

Immune cells and microbes within the GI tract likely play an important role for neurologic disease pathogenesis, including MS and Parkinson's disease. Nevertheless, these immune cells have never been studied in detail using modern single cell technologies. Moreover, most of the human microbiome work done in this space to date has utilized fecal samples, but different anatomic niches within the gut may have greater importance for disease. This study will provide seminal information about how the relationships between gut immunity and neurologic/autoimmune diseases and may be paradigm shifting in regards to how the pathogenesis of some neurologic diseases is viewed.

This is an observational cohort study. Individuals undergoing colonoscopy (+/- upper endoscopy) as a part of standard of care or who consent to have a colonoscopy (+/- upper endoscopy) will be recruited to provide tissue biopsies obtained from the gastrointestinal mucosa. The rationale for including those who are not yet due to have a screening colonoscopy is that for many neurologic diseases (like MS), the disease onset is in adolescence or early adulthood, and the disease is diagnosed in young adults. These individuals would not yet be due to have screening colonoscopies, and yet changes in immune cells within the intestines may be a critical part of disease pathogenesis. This is what the investigators are exploring with this study.

The investigators will need to recruit age matched healthy controls because many features of the immune system change with age; as people get older, the immune system becomes less inflammatory ("immune senescence") and thus it is essential to have age-matched tissues for comparison.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Cynthia Marques; Phone Number: 2032876100; Email: cynthia.marques@yale.edu
• Study Contact Backup: Name: Dimitri Duvilaire; Phone Number: 2032876100; Email: dimitri.duvilaire@yale.edu

Study Locations

• United States
  • Connecticut
    • North Haven, Connecticut, United States, 06473
      • Recruiting
      • Yale MS Clinic
      • Principal Investigator: Erin Longbrake, MD
      • Contact: Cynthia Marques; Phone Number: 203-287-6100; Email: cynthia.marques@yale.edu
      • Contact: Dimitri Duvilaire; Phone Number: 2032876100; Email: dimitri.duvilaire@yale.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Study participants will be individuals who are having screening colonoscopies (+/- upper endoscopies) and those who are willing to have these procedure/s performed for research, and who are willing to donate tissue for research. Healthy individuals, individuals with neurologic diseases, and individuals with known or suspected autoimmune diseases will all be candidates to participate

Description

Inclusion Criteria:

• Age 18 and up

ONE of the following:

• Recommended to under a screening colonoscopy (+/- upper endoscopy) as part of standard of care. This includes healthy individuals as well as those with neurologic and/or autoimmune diseases. OR
• Willing to undergo research colonoscopy (+/- upper endoscopy) for research

Exclusion Criteria:

• Currently pregnant. Women of childbearing potential would perform a point of care urine pregnancy test prior to colonoscopy/endoscopy.
• Known or suspected, chronic inflammatory gastrointestinal disease (e.g. inflammatory bowel disease)
• Known, acute or chronic infections
• Systemic antibiotic (PO or IV) use within 3 months of colonoscopy
• Systemic corticosteroid use (equivalent of prednisone 10 mg per day or higher for >5 days) within 2 weeks of colonoscopy
• Malignancy, diagnosed or treated within the last 5 years
• Probiotic use within 2 weeks of procedure
• History of major GI surgery (e.g. colon resection, gastric bypass)
• Bleeding disorder, or on anticoagulant medication
• Other medical condition that, in the judgement of the investigator, would lead to higher-than-expected risks of biopsy
• Allergy to MAC anesthesia or other drugs used pursuant to standard of care for biospecimen collection

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Individuals	Procedure: Colon Tissue Biopsy; Colonoscopy and colon tissue biopsy.
Individuals with neurologic diseases	Procedure: Colon Tissue Biopsy; Colonoscopy and colon tissue biopsy.
Individuals with known or suspected autoimmune diseases	Procedure: Colon Tissue Biopsy; Colonoscopy and colon tissue biopsy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of immune cells from the gastrointestinal mucosa	Gastrointestinal mucosa cells will be characterized using sRNA measured through high-throughput sequencing with quantitative polymerase chain reaction (qPCR) validation.	Through study completion, an average of 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate spatial transcriptomics of intestinal tissue	Spatial transcriptomics will be performed on gut mucosal biopsies	Through study completion, an average of 5 years
Characterize the microbiome at different anatomic sites within the gastrointestinal tract	16S and/or shotgun metagenomic sequencing will be utilized to assess the composition of gut microbiome	Through study completion, an average of 5 years

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Erin Longbrake, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2022
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: January 29, 2024
• First Submitted That Met QC Criteria: March 22, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Sleep Wake Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parasomnias; REM Sleep Parasomnias; Multiple Sclerosis; Parkinson Disease; Mental Disorders; Nervous System Diseases; REM Sleep Behavior Disorder
• Other Study ID Numbers: 2000033081

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