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

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.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Disease
• Intervention / Treatment: Biological: Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab

• Study Type: Observational
• Enrollment (Actual): 45

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

healthy controls and patients with active inflammatory bowel disease (ulcerative colitis and Crohn´s disease).

Description

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:

1. Age less than 18 years
2. Chronic disease or any other advanced clinically significant pathology, uncontrolled by investigator judgment.
3. Should be with medication, this will be unchanged in the 3 months prior to colonoscopy.
4. Alcohol or drugs.
5. Pregnancy or lactation
6. 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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Non-inflamed	Biological: Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab; 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.
Inflamed ulcerative colitis	Biological: Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab; 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.
inflamed Crohn´s disease	Biological: Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2016
• Primary Completion (ACTUAL): December 31, 2017
• Study Completion (ACTUAL): May 30, 2018

Study Registration Dates

• First Submitted: February 2, 2017
• First Submitted That Met QC Criteria: February 3, 2017
• First Posted (ESTIMATE): February 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 25, 2019
• Last Update Submitted That Met QC Criteria: February 21, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Tumor Necrosis Factor Inhibitors; Adalimumab; Vedolizumab; Infliximab; Golimumab; Ustekinumab
• Other Study ID Numbers: JPG-VED-2016-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No