Inflammatory Bowel Disease(IBD), Treatment Response

Terminated

• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis

• Registration Number: NCT05350644
• Lead Sponsor: University of Southern Denmark

Brief Summary

Inflammatory bowel diseases (IBD) is treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF), i.e. TNF inhibitors. Up to one third of the patients do, however, not respond to biologics and little is known of the biological mechanism as a prognostic factor (possibly enabling personalised medicine). The aim of this project is to identify biomarkers that support individualized forecasting of optimized treatment outcome on these costly drugs.

This prospective cohort study will enroll IBD patients assigned for biologic treatment. At baseline (Pre-treatment), biopsies and blood is taken from each patient. Follow-up will be conducted at week 14-16 after treatment initiation (according to the current Danish standards). Evaluation of a successful treatment outcome response will - for each disease - be based on most frequently used primary endpoints; the major outcome of the analyses will be to detect differences in treatment outcome between patients with the cell expression.

The overarching goal of this project is to improve the lives of patients suffering from IBD, by providing evidence to potential biomarkers that would be likely to improve the clinical outcome.

The study is approved by the local Ethics Committee (S-20160124) and the local Data Agency (2008-58-035). The study findings will be disseminated in peer-reviewed journals, via patient associations, and presented at national and international conferences.

Detailed Description

Inflammatory bowel diseases \[IBD\] (of which Crohn's disease (CD) and ulcerative colitis (UC) are the two most prevailed entities) is a disease of the immune system that are managed with biological agents targeting the pro-inflammatory cytokine tumour necrosis factor-α (TNF), i.e. TNF inhibitors.

Design: In this prospective cohort study disease activity prior to and after (14-16 weeks) initiation of biologic treatment will be assessed. The endpoint is the treatment outcome defined as A: Responder according to the specific criteria described below (incl. drug-continuation) or B: Non-responder (incl. drug-discontinuation due to unacceptable side effects). Whether a patient will discontinue therapy is assumed to be based on a certain degree of shared decision making between the patient and physician supported by principles from national guidelines for each patient as recommended in the respective national guidelines and laboratory data.

Setting: All patients assigned for initiation of biologic treatment at the Department of Medical Gastroenterology, Odense University Hospital from 1st of February 2022 and until 31th of December 2022 or until a minimum of 20 patients with IBD is achieved.

Clinical data consist of personal data, data on health and disease and disease activity scores. Information registered by clinicians and technicians will be transferred from paper format to electronic format using either double entry of data or automated forms processing.

Sample size considerations: We will include a limited set of patient biopsies from 20 UC patients and analyze the changes in responders versus non-responders for identifying potential predictive pathways and biomarkers. Such a strategy has recently been proven valuable for identification of biomarkers predictive of treatment response in CD with a similar number of samples as in our study All data analysis will be done in R, transparently reporting the source code used to analyze the data.

Project organization: The project is organized with a Clinical Research Group and an Analytical Research Group. The clinical group includes specialists from the medical, gastroenterological, departments that are sampling the cohort. The analytical group will perform the analyses on the biological material.

Study Timeline

• Study Start: 2022-02-08
• Study First Submitted: 2022-04-22
• Study First Submitted QC: 2022-04-22
• Study First Posted: 2022-04-28
• Status Verified: 2022-05
• Primary Completion: 2023-06-30
• Study Completion: 2024-06-30
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• diagnosed with inflammatory bowel disease
• initiation of targeted therapy
• able to read and understand Danish

Exclusion Criteria

• Patients with cancer
• Not mentally able to reply the questionnaire

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Clinical response to therapy depending on condition	week 14-16	The predefined primary endpoint will be the proportion of patients with clinical response to therapy at first clinical follow-up.; * Crohn's disease: Harvey Bradshaw Index (HBI) 4 or less (clinical remission) to \<16 (non-remission); * Ulcerative colitis: Mayo Clinic Score of 2 or less (with no individual subscore of \>1) (remission) to \<12 (non-remission)

Trial Locations

Locations (1)

Odense University Hospital; 🇩🇰 Odense, Denmark