Inflammatory Bowel Disease(IBD), Treatment Response

Ulcerative Colitis Clinical Trial

Official title:

Predicting Response to Medical Treatment of Inflammatory Bowel Disease (IBD) Using Single Cell Transcriptomic on Intestinal Biopsies: a Prospective Cohort Study of Personalized Medicine

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05350644
• Other study ID #: BELIEVE-IBD-SCT
• Status: Recruiting
• Start date: February 8, 2022
• Est. completion date: January 14, 2024

Study information

• Verified date: May 2022
• Source: University of Southern Denmark
• Contact: Vibeke Andersen, Prof
• Phone: 004521157790
• Email: vandersen[@]health.sdu.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 14, 2024
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Ulcerative Colitis

Intervention

Other:
• Primary exposure variable
Specific activated CD8+ T-cell transcriptome signature in biopsies is associated with better treatment outcome Specific activated CD8+ T-cell transcriptome signature in blood is associated with better treatment outcome
• Other (exploratory) exposure variables
Specific transcriptomic signatures in intestinal biopsies and peripheral blood mononuclear cells (PBMCs) of IBD patients can work as a predictive biomarker for the tumor necrosis factor inhibitors (TNFi) treatment response

Locations

Country	Name	City	State
Denmark	Hospital of Southern Jutland	Aabenraa
Denmark	Odense University Hospital	Odense
Denmark	University of Southern Denmark	Odense

Sponsors (5)

Lead Sponsor	Collaborator
University of Southern Denmark	Colitis-Crohn Foreningen, Hospital of Southern Jutland, Odense University Hospital, University of Kiel

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1. Clinical response to therapy depending on condition	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)	week 14-16