Inflammatory Bowel Diseases
Conditions
Keywords
Cytokines, Pharmacogenetics
Brief 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.
Interventions
DIAGNOSTIC_TESTBaseline blood sample
Blood sample for cytokine measurements and genetics.
DIAGNOSTIC_TESTBaseline 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.
OTHERCrohn'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_TESTPost 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.
DIAGNOSTIC_TESTPost 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.
DIAGNOSTIC_TESTBaseline stool sample
Stool sample for inflammatory markers or microbiome analysis.
DIAGNOSTIC_TESTPost treatment stool sample
Stool sample for inflammatory markers or microbiome analysis.
Sponsors
Vanderbilt University Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare longitudinal cytokine measurements in treatment responders versus nonresponders. | 52 weeks | The investigators will classify Crohn's disease subjects as primary responders or primary non-responders to anti-TNF-α, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare serum and tissue pro-inflammatory cytokines in CD patients and healthy subjects. | 26 weeks | The investigators will compare serum and tissue cytokine/chemokine levels to see if Crohn's disease patients express a difference versus control. |
| To assess whether gene variants are associated with treatment response. | 52 weeks | 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. |
Countries
United States
Outcome results
None listed