Regulation of Mucosal Healing in Inflammatory Bowel Disease

Purpose

The objective of the current study is to compare non-healing colonic ulcers in patients with inflammatory bowel disease (IBD) with iatrogenic colonic ulcers (biopsy sites) in healthy control patients and patients with rheumatoid or psoriatic arthritis. Patients will be biopsied at baseline and again at a follow-up visit in a "biopsy of the biopsy" approach. These biopsies will be used to reveal patterns about gene expression and mitochondrial function during ulcer healing.

Condition

  • Inflammatory Bowel Diseases

Eligibility

Eligible Ages
Between 18 Years and 90 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

(Group 1): - Diagnosed ulcerative colitis or Crohn's disease - Biologic failure or naive to biologic treatment - Eligible to be treated with anti-TNF therapy Inclusion Criteria (Group 2): - Diagnosed rheumatoid or psoriatic arthritis - Receiving anti-TNF antibody therapy at the time of enrollment Inclusion Criteria (Group 3): - Endoscopically unremarkable colonic mucosa - Absence of inflammatory bowel disease

Exclusion Criteria

  • Classified in an anesthesia risk group, ASA Class =4 - History of bleeding diathesis or coagulopathy - Stroke or transient neurological attack with the last 6 months - Pregnant - Receiving anticoagulants or anti-platelet medications other than low-dose aspirin - Receiving steroid therapy or metformin - HIV positive - Incarceration - History of total proctocolectomy - History of system chemotherapy within 18 months - Uncontrolled intercurrent illness

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Basic Science
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Healthy Controls 		Participants in this group will be healthy (not diagnosed with inflammatory bowel disease).
  • Procedure: Serial Biopsy
    During the initial colonoscopy, 16-20 biopsies will be collected in addition to standard of care biopsies, and biopsy sites will be tattoed. Patients will return for a follow-up colonoscopy 4-35 days later. An additional 16-20 biopsies will be collected in a "biopsy of the biopsy" approach.
Experimental
Inflammatory Bowel Disease 		Participants in this group will have been diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and have either failed treatment with biologics or be naive to biologic therapy.
  • Procedure: Serial Biopsy
    During the initial colonoscopy, 16-20 biopsies will be collected in addition to standard of care biopsies, and biopsy sites will be tattoed. Patients will return for a follow-up colonoscopy 4-35 days later. An additional 16-20 biopsies will be collected in a "biopsy of the biopsy" approach.
Experimental
Rheumatoid/Psoriatic Arthritis 		Participants in this group will have been diagnosed with rheumatoid (RA) or psoriatic arthritis (PsA) and will be receiving anti-TNF antibody therapy at the time of enrollment.
  • Procedure: Serial Biopsy
    During the initial colonoscopy, 16-20 biopsies will be collected in addition to standard of care biopsies, and biopsy sites will be tattoed. Patients will return for a follow-up colonoscopy 4-35 days later. An additional 16-20 biopsies will be collected in a "biopsy of the biopsy" approach.

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky
Lexington, Kentucky 40536
Contact:
Syed Adeel Hassan, MBBS/MD
312-340-4925
syed.hassan@uky.edu

More Details

NCT ID
NCT04504136
Status
Recruiting
Sponsor
Terrence A Barrett

Study Contact

Syed Adeel Hassan, MBBS/MD
312-340-4925
syed.hassan@uky.edu

Detailed Description

Induction of mucosal healing in inflammatory bowel disease (IBD) is associated with reduced hospitalizations, surgeries, and reduced cancer risk. However, previous studies have shown that 54-69% of ulcerative colitis (UC) patients fail to heal ulcers after several weeks of treatment, and roughly half do not maintain remission at one year. The single most important factor in preventing severe medical consequences, like colon removal surgery or cancer, is treatment to completely heal the top layer of the intestine as quickly as possible. Healing is a complex process and the dysfunction observed in colitis can only be fully understood by comparison to healing in non-IBD patients. This is a prospective trial involving three groups of patients: 1) IBD patients with active disease, newly treated with anti-TNF therapy (biologic failure or naïve); 2) non-IBD patients with rheumatoid/psoriatic arthritis who are receiving anti-TNF therapy, and 3) healthy control patients. Biopsies will be collected at baseline during standard of care endoscopy and at a follow-up research endoscopy. This study will probe mechanisms of ulcer healing by analyzing gene expression patterns and mitochondrial function.