Intestinal Immunity in Neurologic Disease

Multiple Sclerosis Clinical Trial

Official title:

Intestinal Immunity in Neurologic Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06329453
• Other study ID #: 2000033081
• Status: Recruiting
• Start date: August 2, 2022
• Est. completion date: August 31, 2027

Study information

• Verified date: March 2024
• Source: Yale University
• Contact: Cynthia Marques
• Phone: 2032876100
• Email: cynthia.marques[@]yale.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: August 31, 2027
• Est. primary completion date: August 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Mental Disorders
• Multiple Sclerosis
• Nervous System Diseases
• Parkinson Disease
• REM Sleep Behavior Disorder

Intervention

Procedure:
• Colon Tissue Biopsy
Colonoscopy and colon tissue biopsy.

Locations

Country	Name	City	State
United States	Yale MS Clinic	North Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Evaluate spatial transcriptomics of intestinal tissue	Spatial transcriptomics will be performed on gut mucosal biopsies	Through study completion, an average of 5 years
Secondary	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