Cytokines and Genes in Therapeutic Response in Crohn's Disease

Completed

• Conditions: Inflammatory Bowel Diseases
• Interventions: 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

• Registration Number: NCT03266471
• Lead Sponsor: Vanderbilt University Medical Center

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-08-28
• Study First Submitted QC: 2017-08-28
• Study First Posted: 2017-08-30
• Study Start: 2017-10-13
• Status Verified: 2022-05
• Primary Completion: 2022-05-03
• Study Completion: 2022-05-03
• Last Update Submitted: 2023-04-13
• Last Update Posted: 2023-04-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 96

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.

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Crohn's disease Patients	Post treatment blood sample	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.
Crohn's disease Patients	Baseline intestinal biopsies	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.
Crohn's disease Patients	Post treatment intestinal biopsies	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.
Crohn's disease Patients	Baseline stool sample	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.
Crohn's disease Patients	Post treatment stool sample	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.
Crohn's disease Patients	Crohn's disease activity index (CDAI)	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.
Controls	Baseline blood sample	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.
Controls	Baseline intestinal biopsies	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.
Crohn's disease Patients	Baseline blood sample	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.
Controls	Baseline stool sample	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (2)

Vanderbilt University Medical Center Endoscopy Laboratory; 🇺🇸 Nashville, Tennessee, United States

Inflammatory Bowel Disease Clinic, Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States