Cytokines and Genes in Therapeutic Response in Crohn's Disease

Inflammatory Bowel Diseases Clinical Trial

Official title:

Cytokines and Genes in Therapeutic Response in Crohn's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03266471
• Other study ID #: 171198
• Status: Completed
• Start date: October 13, 2017
• Est. completion date: May 3, 2022

Study information

• Verified date: May 2022
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Inflammatory bowel disease (IBD), consisting of two major forms, Crohn's disease (CD) and ulcerative colitis (UC), affects more than 1.6 million people in the United States alone. Though the precise mechanisms underlying the inflammation and immune responses in IBD are still being investigated, various inflammatory mediators, including pro-inflammatory cytokines, and genes have been implicated in the disease process. At present, there are no reliable mechanisms to predict response to individual IBD medications. The investigators seek to evaluate whether inflammatory cytokines change longitudinally during treatment with anti-cytokine agents in both treatment primary responders and primary non-responders. In addition, the investigators will be evaluating the pharmacogenetics of treatment response to these agents.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: May 3, 2022
• Est. primary completion date: May 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients that are seen in the Inflammatory Bowel Disease clinic with Crohn's disease who are initiating either treatment as part of their routine clinical care.

• Healthy adults without IBD undergoing colonoscopy for colorectal cancer screening or other non-IBD related indication.

Exclusion Criteria:

• pregnant

• have a known coagulopathy or bleeding disorder

• have known renal or hepatic impairment

• have a history of organ transplantation

• CD patients who are being seen in consultation and do not plan to receive longitudinal care through initiation their new therapy at the Vanderbilt IBD center will be excluded.

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Diseases

Intervention

Diagnostic Test:
• Baseline blood sample
Blood sample for cytokine measurements and genetics.
• Baseline intestinal biopsies
Up to 20 additional biopsies will be obtained at the time of standard of care colonoscopy. It is not felt that additional biopsies substantially increases the risk of a colonoscopy. Cytokine measurements will be performed on the tissue collected.

Other:
• Crohn's disease activity index (CDAI)
To determine response, a Crohn's Disease Activity Index (CDAI) score will be obtained at time point 1 and time point 2 in all enrolled CD patients. The CDAI is a well validated symptom index for CD which assesses 8 factors including stool frequency, abdominal pain, general well being, CD complications, HCT, and deviation from ideal body weight.

Diagnostic Test:
• Post treatment blood sample
Blood sample for cytokine measurements after patients have been on therapy for at least 6 weeks but no more than 52 weeks.
• Post treatment intestinal biopsies
Up to 20 additional biopsies will be obtained at the time of standard of care colonoscopy at least 6 weeks but no more than 52 weeks after initiation of therapy. It is not felt that additional biopsies substantially increases the risk of a colonoscopy. Cytokine measurements will be performed on the tissue collected.
• Baseline stool sample
Stool sample for inflammatory markers or microbiome analysis.
• Post treatment stool sample
Stool sample for inflammatory markers or microbiome analysis.

Locations

Country	Name	City	State
United States	Inflammatory Bowel Disease Clinic, Vanderbilt University Medical Center	Nashville	Tennessee
United States	Vanderbilt University Medical Center Endoscopy Laboratory	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare longitudinal cytokine measurements in treatment responders versus nonresponders.	The investigators will classify Crohn's disease subjects as primary responders or primary non-responders to anti-TNF-a, ustekinumab, or vedolizumab therapy based on clinical, endoscopic, and/or histologic data. The investigators will compare serum and tissue cytokines in CD subjects at before and after treatment initiation.	52 weeks
Secondary	Compare serum and tissue pro-inflammatory cytokines in CD patients and healthy subjects.	The investigators will compare serum and tissue cytokine/chemokine levels to see if Crohn's disease patients express a difference versus control.	26 weeks
Secondary	To assess whether gene variants are associated with treatment response.	The investigators will collect a one time whole blood sample from subjects starting a new anti-cytokine agent (infliximab, infliximab biosimilar, adalimumab, certolizumab, ustekinumab, or vedolizumab) and extract DNA and genotype. The investigators will look for associations between genotype and treatment response.	52 weeks