Regulation of Mucosal Healing in Inflammatory Bowel Disease

Overview

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.

Interventions

• 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.

Primary outcome measures

• Change in mitochondrial DNA copy number [Time frame: 35 days]
• Change in expression levels of cMyc [Time frame: 35 days]
• Change in expression levels of PGC-1 alpha [Time frame: 35 days]
• Change in expression levels of Ki67 [Time frame: 35 days]
• Number of visible ulcers [Time frame: 1 day (at follow-up visit)]

Secondary outcome measures (2)

• Change in Mayo Endoscopic Score [Time frame: 35 days]
• Change in Segmental SES-CD Score [Time frame: 35 days]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• University of Kentucky — Lexington

Identifiers

NCT: NCT04504136 · IMDDN-20-MUCOSALHEALING · 2R01DK095662-10A1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗