Regulation of Mucosal Healing in Inflammatory Bowel Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Procedure: Serial Biopsy

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Syed Adeel Hassan, MBBS/MD; Phone Number: 312-340-4925; Email: syed.hassan@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky
      • Contact: Syed Adeel Hassan, MBBS/MD; Phone Number: 312-340-4925; Email: syed.hassan@uky.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mitochondrial DNA copy number	Mitochondrial DNA copy number will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.	35 days
Change in expression levels of cMyc	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.	35 days
Change in expression levels of PGC-1 alpha	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.	35 days
Change in expression levels of Ki67	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.	35 days
Number of visible ulcers	The number of visible ulcers will be assessed during the follow-up endoscopy for healthy patients and rheumatoid/psoriatic arthritis patients only.	1 day (at follow-up visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mayo Endoscopic Score	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.	35 days
Change in Segmental SES-CD Score	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.	35 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal calprotectin levels	Levels of fecal calprotectin (ug/g) will be measured from stool samples collected from patients at any time during the study protocol.	35 days

Collaborators and Investigators

• Sponsor: Terrence A Barrett
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Terrence Barrett, MD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2021
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: August 4, 2020
• First Submitted That Met QC Criteria: August 4, 2020
• First Posted (Actual): August 7, 2020

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; mitochondria; anti-TNF; psoriatic arthritis; wound; biopsy; mucosal; colitis; ulcer; Crohn's; biologic
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: IMDDN-20-MUCOSALHEALING; 2R01DK095662-10A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No