Regulation of Mucosal Healing in Inflammatory Bowel Disease

Inflammatory Bowel Diseases Clinical Trial

Official title:

Regulation of Mucosal Healing in Inflammatory Bowel Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04504136
• Other study ID #: IMDDN-20-MUCOSALHEALING
• Secondary ID: 2R01DK095662-10A
• Status: Recruiting
• Phase: N/A
• Start date: April 30, 2021
• Est. completion date: May 1, 2025

Study information

• Verified date: November 2023
• Source: University of Kentucky
• Contact: Syed Adeel Hassan, MBBS/MD
• Phone: 312-340-4925
• Email: syed.hassan[@]uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

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.

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Terrence A Barrett	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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