Regulation of Mucosal Healing in Inflammatory Bowel Disease

Terrence A Barrett

Status: Enrolling

Conditions: Inflammatory Bowel Diseases

Treatments: Procedure: Serial Biopsy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04504136

IMDDN-20-MUCOSALHEALING

2R01DK095662-10A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups

Healthy Controls

Experimental group

Description:

Participants in this group will be healthy (not diagnosed with inflammatory bowel disease).

Treatment:

Procedure: Serial Biopsy

Inflammatory Bowel Disease

Experimental group

Description:

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.

Treatment:

Procedure: Serial Biopsy

Rheumatoid/Psoriatic Arthritis

Experimental group

Description:

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.

Treatment:

Procedure: Serial Biopsy