Clinical trial NCT06329453: Intestinal Immunity in Neurologic Disease
Official title: Intestinal Immunity in Neurologic Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Parkinson Disease
REM Sleep Behavior Disorder
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2024-03-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Characterization of immune cells from the gastrointestinal mucosa
timeFrame: Through study completion, an average of 5 years
Secondary outcomes:
measure: Evaluate spatial transcriptomics of intestinal tissue
timeFrame: Through study completion, an average of 5 years
measure: Characterize the microbiome at different anatomic sites within the gastrointestinal tract
timeFrame: Through study completion, an average of 5 years
Other outcomes:
Locations:
city: North Haven
country: United States
facility: Yale MS Clinic
state: Connecticut
Study officials:
affiliation: Yale University
name: Erin Longbrake
role: PRINCIPAL_INVESTIGATOR
References: