Inflammatory Bowel Disease(IBD), Treatment Response

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

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.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis
• Intervention / Treatment: Other: Primary exposure variable; Other: Other (exploratory) exposure variables

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 Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Vibeke Andersen, Prof; Phone Number: 004521157790; Email: vandersen@health.sdu.dk
• Study Contact Backup: Name: Zainab Hikmat, MSc; Phone Number: 004520181720; Email: zainab.hikmat@rsyd.dk

Study Locations

• Denmark
  • Aabenraa, Denmark, 6200
    • Withdrawn
    • Hospital of Southern Jutland
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Kjeldsen; Email: Jens.Kjeldsen@rsyd.dk
  • Odense, Denmark, 5230
    • Withdrawn
    • University of Southern Denmark

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

targeted therapy and able to read and understand Danish.

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Southern Denmark
• Collaborators: Odense University Hospital; University of Kiel; Hospital of Southern Jutland; Colitis-Crohn Foreningen
• Investigators: Principal Investigator: Vibeke Andersen, Prof, University of Southern Denmark

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2022
• Primary Completion (Anticipated): March 31, 2023
• Study Completion (Anticipated): January 14, 2024

Study Registration Dates

• First Submitted: April 22, 2022
• First Submitted That Met QC Criteria: April 22, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 24, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Biomarkers; Treatment outcome; Transcriptomics
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Intestinal Diseases
• Other Study ID Numbers: BELIEVE-IBD-SCT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No