Ex-vivo Modulatory Effect of Biological Drugs for Inflammatory Bowel Disease on the Mucosa and on Peripheral Blood Mononuclear Cells

Study Overview
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Brief Summary
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To characterize circulating DC subsets from healthy controls and IBD patients and to assess, following an ex vivo challenge, the effect of anti-TNF (infliximab, adalimumab and golimumab), anti-p40 -IL-12/IL-23- (ustekinumab) and anti-α4β7 (vedolizumab) immunomodulators on both the GI production of soluble immune mediators and the mucosal capacity to alter the recruitment capacity of circulating DC subsets. It is expected that such approach will provide further information on the action mechanisms of such therapies on IBD patients, allowing a better understanding of the pathophysiology of this disease and the identification of tissue-specific therapeutic targets, thus avoiding collateral problems associated with systemic immunomodulation.

Official Title
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Ex-vivo Modulatory Effect of Biological Drugs for Inflammatory Bowel Disease on the Mucosa and on Peripheral Blood Mononuclear Cells

Conditions
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Inflammatory Bowel Disease

Intervention / Treatment
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* Biological: Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with active IBD, and endoscopic and histological diagnosis of CD or UC that attend a colonoscopy with sedation performed by medical criteria. Patients without an IBD diagnosis, or other types of inflammatory, allergic, malignant or autoimmune diseases, prior to their inclusion in this project. All patients will attend a colonoscopy with sedation at medical judgment with biopsy indication for histopathological study as in cases of diarrhea but also due to changes in the bowel transit, rectal bleeding or screening for gastrointestinal diseases. Patients will be paired in age and gender with the IBD groups. All patients will have no signs of macroscopic or microscopic inflammation hence excluding the presence of microscopic colitis. Exclusion Criteria: Age less than 18 years Chronic disease or any other advanced clinically significant pathology, uncontrolled by investigator judgment. Should be with medication, this will be unchanged in the 3 months prior to colonoscopy. Alcohol or drugs. Pregnancy or lactation Do not sign the informed consent form (see Ethical Issues) In any case NO colonoscopies exclusively targeted for sampling for this project will be made

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non-inflamed<br> | Biological: Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab<br>* Ex-vivo conditioning of lamina propria and peripheral blood mononuclear cells. Here, we will address whether the current available biological therapies for IBD patients (infliximab, golimumab, adalimumab, vedolizumab and ustekinumab) elicit a differential effect on the mucosal capacity to recruit circulating leukocytes on an ex-vivo approach using transwell culture systems.<br>|
| Inflamed ulcerative colitis<br> | Biological: Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab<br>* Ex-vivo conditioning of lamina propria and peripheral blood mononuclear cells. Here, we will address whether the current available biological therapies for IBD patients (infliximab, golimumab, adalimumab, vedolizumab and ustekinumab) elicit a differential effect on the mucosal capacity to recruit circulating leukocytes on an ex-vivo approach using transwell culture systems.<br>|
| inflamed Crohn´s disease<br> | Biological: Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab<br>* Ex-vivo conditioning of lamina propria and peripheral blood mononuclear cells. Here, we will address whether the current available biological therapies for IBD patients (infliximab, golimumab, adalimumab, vedolizumab and ustekinumab) elicit a differential effect on the mucosal capacity to recruit circulating leukocytes on an ex-vivo approach using transwell culture systems.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of biological drugs on the secretion of gut-chemoattractants by the intestinal mucosa | To assess, ex-vivo, the capacity of the IBD mucosa to recruit subsets of circulating leukocytes following mucosal conditioning with biological drugs. | 18 months |