Cytokines and Genes in Therapeutic Response in Crohn's Disease

Study Overview
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Brief Summary
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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.

Official Title
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Cytokines and Genes in Therapeutic Response in Crohn's Disease

Conditions
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Inflammatory Bowel Diseases

Intervention / Treatment
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* Diagnostic Test: Baseline blood sample
* Diagnostic Test: Baseline intestinal biopsies
* Other: Crohn's disease activity index (CDAI)
* Diagnostic Test: Post treatment blood sample
* Diagnostic Test: Post treatment intestinal biopsies
* Diagnostic Test: Baseline stool sample
* Diagnostic Test: Post treatment stool sample


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Crohn's disease Patients<br>Patients that are seen in the Inflammatory Bowel Disease clinic with CD confirmed by endoscopy or radiology assessment who are initiating either an anti-tumor necrosis factor (TNF)-α agent (infliximab, adalimumab, certolizumab, or infliximab biosimilar), ustekinumab, or vedolizumab as part of their routine clinical care will be asked to provide blood samples, stool samples, and intestinal biopsies from standard of care colonoscopy at baseline and post therapy of at least 6 weeks duration but not more than 52 weeks. | Diagnostic Test: Baseline blood sample<br>* Blood sample for cytokine measurements and genetics.<br>Diagnostic Test: Baseline intestinal biopsies<br>* 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.<br>Other: Crohn's disease activity index (CDAI)<br>* 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.<br>Diagnostic Test: Post treatment blood sample<br>* Blood sample for cytokine measurements after patients have been on therapy for at least 6 weeks but no more than 52 weeks.<br>Diagnostic Test: Post treatment intestinal biopsies<br>* 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.<br>Diagnostic Test: Baseline stool sample<br>* Stool sample for inflammatory markers or microbiome analysis.<br>Diagnostic Test: Post treatment stool sample<br>* Stool sample for inflammatory markers or microbiome analysis.<br>|
| Controls<br>Healthy adults without IBD undergoing colonoscopy for colorectal cancer screening or other non-IBD related indication will be asked to provide blood samples, stool samples and intestinal biopsies from standard of care colonoscopy. | Diagnostic Test: Baseline blood sample<br>* Blood sample for cytokine measurements and genetics.<br>Diagnostic Test: Baseline intestinal biopsies<br>* 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.<br>Diagnostic Test: Baseline stool sample<br>* Stool sample for inflammatory markers or microbiome analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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-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. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytokines, Pharmacogenetics