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

Completed

• Conditions: Inflammatory Bowel Disease
• Interventions: Biological: Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab

• Registration Number: NCT03043677
• Lead Sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04-01
• Study First Submitted: 2017-02-02
• Study First Submitted QC: 2017-02-03
• Study First Posted: 2017-02-06
• Primary Completion: 2017-12-31
• Study Completion: 2018-05-30
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-21
• Last Update Posted: 2019-02-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Inflamed ulcerative colitis	Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab	-
inflamed Crohn´s disease	Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab	-
Non-inflamed	Ex-vivo stimulation of cells with infliximab, golimumab, adalimumab, vedolizumab and ustekinumab	-

Primary Outcome Measures

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