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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Crohn's disease Patients | 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. |
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| Controls | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Baseline blood sample | Diagnostic Test | Blood sample for cytokine measurements and genetics. |
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| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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Patients who are scheduled for a colonoscopy at the Vanderbilt Endoscopy Laboratory as part of their routine care and who do not meet any of the pre-defined exclusion criteria will be considered for participation in the study as control subjects. Patients who are part of the Vanderbilt IBD practice who initiate therapy on an anti-TNF, ustekinumab, or vedolizumab as part of their routine care will be considered for participation in the study as subjects.
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| Name | Affiliation | Role |
|---|---|---|
| Elizabeth Scoville, MD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Inflammatory Bowel Disease Clinic, Vanderbilt University Medical Center | Nashville | Tennessee | 37212 | United States | ||
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Any remaining serum or tissue samples may be evaluated for other markers of IBD or stored for future studies.
| Baseline intestinal biopsies | Diagnostic Test | 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. |
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| Crohn's disease activity index (CDAI) | Other | 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. |
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| Post treatment blood sample | Diagnostic Test | Blood sample for cytokine measurements after patients have been on therapy for at least 6 weeks but no more than 52 weeks. |
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| Post treatment intestinal biopsies | Diagnostic Test | 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. |
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| Baseline stool sample | Diagnostic Test | Stool sample for inflammatory markers or microbiome analysis. |
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| Post treatment stool sample | Diagnostic Test | Stool sample for inflammatory markers or microbiome analysis. |
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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 |
| Vanderbilt University Medical Center Endoscopy Laboratory |
| Nashville |
| Tennessee |
| 37232 |
| United States |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| ID | Term |
|---|---|
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
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