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The Colonic Microbiome and Mucosal Immunity in Inflammatory Bowel Disease and Ankylosing Spondylitis

Active, not recruiting
Conditions
Inflammatory Bowel Diseases (IBD)
Ankylosing Spondylitis (AS)
Interventions
Procedure: Pinch biopsies
Procedure: Flexible sigmoidoscopy
Registration Number
NCT02389075
Lead Sponsor
University of Colorado, Denver
Brief Summary

This study plans to learn more about the relationship between systemic autoimmune disease, such as inflammatory bowel disease and ankylosing spondyloarthritis, bacteria in the colon, and the changes in colon tissue.

Detailed Description

Changes in human gut bacteria has been shown in patients with autoimmune diseases, such as inflammatory bowel diseases (IBD). The gut flora in ankylosing spondylitis (AS), an arthritis that can occur with IBD, has not been well studied. The immune cells in the colon directly interface with bacteria and may be influenced by them. The interactions between the colon immune system, bacteria and autoimmunity hasn't been studied. The study goal is to specifically study the link between bacteria, the colonic immune system, and the autoimmune diseases of AS and IBD. This will be done by collecting clinical data by questionnaires, blood samples, colonic tissue during endoscopy, and microbiome data in subjects with IBD, AS, and controls.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
129
Inclusion Criteria
  • Established IBD (either Crohn's disease or ulcerative colitis)
  • Suspected to have IBD by a gastroenterologist and undergoing diagnostic endoscopy and biopsy. Diagnosis will be confirmed on biopsy and patients who are negative will be considered for controls based on the pathology found.
Read More
Exclusion Criteria
  • Pregnancy
  • Use of antibiotics within the past 14 days
  • Current diagnosis of colon cancer
  • Diagnosis of celiac disease
  • Diagnosis of any other rheumatologic disease such as RA, SLE, etc.
  • Chemotherapy or radiation therapy for any malignancy within the past year
  • Daily use of aspirin or NSAIDs with inability to hold the drug 7 days before and after the procedure
  • Current use of anticoagulation (LMWH, warfarin,etc.)
  • A diagnosis of HIV
  • Clostridium difficile within the past 3 months
  • Evidence of inflammatory spinal or axial arthritis or disease based on chart review such as inflammation seen on radiographs or a diagnosis of sacroiliitis

AS:

Inclusion Criteria:

  • Diagnosed with an axial spondyloarthritis (SpA) by a rheumatologist -
  • Meet the Assessment of SpondyloArthritis international Society (ASAS) axial spondyloarthritis (SpA) criteria

Exclusion criteria:

  • Pregnancy
  • Use of antibiotics within the past 14 days
  • Current diagnosis of colon cancer
  • Diagnosis of celiac disease
  • Diagnosis of any other rheumatologic disease such as RA, SLE, etc.
  • Chemotherapy or radiation therapy for any malignancy within the past year
  • Daily use of aspirin or NSAIDs with inability to hold the drug 7 days before and after the procedure
  • Current use of anticoagulation (LMWH,warfarin,etc.)
  • A diagnosis of HIV
  • Clostridium difficile within the past 3 months
  • A known history of idiopathic macroscopic or microscopic colitis
Read More

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Healthy ControlsPinch biopsiesSubjects without any major autoimmune diseases or pathologies undergoing routine colonoscopy. They will be asked to fill out questionnaires, give blood, perform a rectal swab, and have pinch biopsies taken during endoscopy.
Ankylosing SpondylitisPinch biopsiesSubjects with a diagnosis of ankylosing spondylitis undergoing routine colonoscopy or willing to undergo a flexible sigmoidoscopy for research purposes only. They will be asked to fill out questionnaires, give blood, perform a rectal swab, and have pinch biopsies taken during endoscopy.
Ankylosing SpondylitisFlexible sigmoidoscopySubjects with a diagnosis of ankylosing spondylitis undergoing routine colonoscopy or willing to undergo a flexible sigmoidoscopy for research purposes only. They will be asked to fill out questionnaires, give blood, perform a rectal swab, and have pinch biopsies taken during endoscopy.
Inflammatory Bowel DiseasePinch biopsiesSubjects with a diagnosis of inflammatory bowel disease undergoing routine colonoscopy. They will be asked to fill out questionnaires, give blood, perform a rectal swab, and have pinch biopsies taken during endoscopy.
Primary Outcome Measures
NameTimeMethod
IEL characteristics in IBD, AS, and healthy controls1 hour after colonoscopy

The primary goal for this measure will be to demonstrate characteristics of IEL (intraepithelial lymphocytes) subtypes of healthy individuals and compare those with AS or IBD. IEL characteristics will be based on cell marker outcomes using flow cytometry for CD3, CD4, CD8α, CD8β, CD44, CD45, CD62L, CD69, CD103, TCRαβ, and TCRγδ.

Secondary Outcome Measures
NameTimeMethod
Microbiome Differences in IBD, AS, and healthy controls1 hour after colonoscopy

The primary hypothesis is that the microbiome population will differ between controls, IBD, and AS; outcomes for this hypothesis will include relative abundance (RA) of individual bacterial species and the Shannon Index for community diversity.

Microbiome changes are reflected in IELs1 hour after colonoscopy

The primary hypothesis is that dysbiosis will be reflected in the IEL populations in AS and IBD by having a different predominant phenotype (as seen by cell markers) compared to healthy controls; the investigators will evaluate the IEL outcomes determined to be significantly different among AS, IBD, and healthy controls as identified in Outcome 1 (Primary Outcome).

Trial Locations

Locations (1)

University of Colorado

🇺🇸

Denver, Colorado, United States

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