Regulation of Mucosal Healing in Inflammatory Bowel Disease
- Conditions
- Inflammatory Bowel Diseases
- Interventions
- Procedure: Serial Biopsy
- Registration Number
- NCT04504136
- Lead Sponsor
- Terrence A Barrett
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Healthy Controls Serial Biopsy Participants in this group will be healthy (not diagnosed with inflammatory bowel disease). Rheumatoid/Psoriatic Arthritis Serial Biopsy 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. Inflammatory Bowel Disease Serial Biopsy 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.
- Primary Outcome Measures
Name Time Method Change in expression levels of Ki67 35 days Relative expression of Ki67 alpha (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.
Change in mitochondrial DNA copy number 35 days Mitochondrial DNA copy number will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.
Change in expression levels of cMyc 35 days Relative expression of cMyc (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.
Change in expression levels of PGC-1 alpha 35 days Relative expression of PGC-1 alpha (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.
Number of visible ulcers 1 day (at follow-up visit) The number of visible ulcers will be assessed during the follow-up endoscopy for healthy patients and rheumatoid/psoriatic arthritis patients only.
- Secondary Outcome Measures
Name Time Method Change in Mayo Endoscopic Score 35 days The Mayo Endoscopic Score will be calculated at baseline and at follow-up in patients with ulcerative colitis only. The Mayo Endoscopic score is evaluated for the macroscopically most severely inflamed segment: 0 for normal or inactive disease; 1 for erythema, decreased vascular pattern, mild friability; 2 for marked erythema, absent vascular pattern, friability, erosions; 3 ulcerations or spontaneous bleeding. Segmental scores range from 0-3; higher scores indicate more severe disease.
Change in Segmental SES-CD Score 35 days The Simple Endoscopic Score (SES) will be calculated at baseline and follow-up in patients with Crohn's disease (CD) only. The SES-CD score incorporates ulcer size, narrowing, and the area affected by disease or ulceration. Scores range from 0-12; lower scores indicate remission while higher scores indicate severe endoscopic activity.
Trial Locations
- Locations (1)
University of Kentucky
🇺🇸Lexington, Kentucky, United States