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Cytokines and Genes in Therapeutic Response in Crohn's Disease

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ClinicalTrials.gov Identifier: NCT03266471
Recruitment Status : Enrolling by invitation
First Posted : August 30, 2017
Last Update Posted : December 20, 2018
Sponsor:
Information provided by (Responsible Party):
Elizabeth Scoville, 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.

Condition or disease Intervention/treatment
Inflammatory Bowel Diseases 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

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Study Type : Observational
Estimated Enrollment : 185 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Cytokines and Genes in Therapeutic Response in Crohn's Disease
Actual Study Start Date : October 13, 2017
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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 and intestinal biopsies from standard of care colonoscopy at baseline and post therapy of at least 12 weeks duration but not more than 52 weeks.
Diagnostic Test: Baseline blood sample
Blood sample for cytokine measurements and genetics.

Diagnostic Test: 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 12 weeks but no more than 52 weeks.

Diagnostic Test: Post treatment intestinal biopsies
Up to 20 additional biopsies will be obtained at the time of standard of care colonoscopy at least 12 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.

Controls
Healthy adults without IBD undergoing colonoscopy for colorectal cancer screening or other non-IBD related indication will be asked to provide blood samples and intestinal biopsies from standard of care colonoscopy.
Diagnostic Test: Baseline blood sample
Blood sample for cytokine measurements and genetics.

Diagnostic Test: 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.




Primary Outcome Measures :
  1. Compare longitudinal cytokine measurements in treatment responders versus nonresponders. [ Time Frame: 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 :
  1. Compare serum and tissue pro-inflammatory cytokines in CD patients and healthy subjects. [ Time Frame: 26 weeks ]
    The investigators will compare serum and tissue cytokine/chemokine levels to see if Crohn's disease patients express a difference versus control.

  2. To assess whether gene variants are associated with treatment response. [ Time Frame: 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.


Biospecimen Retention:   Samples With DNA
Any remaining serum or tissue samples may be evaluated for other markers of IBD or stored for future studies.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
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.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03266471


Locations
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United States, Tennessee
Inflammatory Bowel Disease Clinic, Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37212
Vanderbilt University Medical Center Endoscopy Laboratory
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University Medical Center
Investigators
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Principal Investigator: Elizabeth Scoville, MD Vanderbilt University Medical Center

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Responsible Party: Elizabeth Scoville, Principal Investigator, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT03266471     History of Changes
Other Study ID Numbers: 171198
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: December 20, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Elizabeth Scoville, Vanderbilt University Medical Center:
Cytokines
Pharmacogenetics

Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases