Clinical trial NCT04504136: Regulation of Mucosal Healing in Inflammatory Bowel Disease
Official title: Regulation of Mucosal Healing in Inflammatory Bowel Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Inflammatory Bowel Diseases
Keywords: mucosal
rheumatoid arthritis
psoriatic arthritis
ulcer
colitis
Crohn's
mitochondria
biopsy
wound
biologic
anti-TNF
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-08-07
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Change in mitochondrial DNA copy number
timeFrame: 35 days
measure: Change in expression levels of cMyc
timeFrame: 35 days
measure: Change in expression levels of PGC-1 alpha
timeFrame: 35 days
measure: Change in expression levels of Ki67
timeFrame: 35 days
measure: Number of visible ulcers
timeFrame: 1 day (at follow-up visit)
Secondary outcomes:
measure: Change in Mayo Endoscopic Score
timeFrame: 35 days
measure: Change in Segmental SES-CD Score
timeFrame: 35 days
Other outcomes:
measure: Fecal calprotectin levels
timeFrame: 35 days
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Terrence Barrett, MD
role: PRINCIPAL_INVESTIGATOR
References: