nravelling intestinal fibrosis in ulcerative colitis: INTERACT study

Phase 1

Conditions: lcerative colitis
Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: CTIS2023-507907-73-00

Lead Sponsor: Amsterdam UMC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 10

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria: - Adults =18 years with confirmed diagnosis of ulcerative colitis - Active disease confirmed by endoscopy (endoscopic Mayo score = 2) - Indication to start treatment with filgotinib AND one of the following: - Active disease confirmed by intestinal ultrasound (BWT > 3 mm in atleast one bowel segment and atleast one other pathological IUS parameter) or - Increased CRP (>5 mg/L) and/or fecal calprotectin levels (>250 mg/kg)

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study: - Pregnancy - Unable to provide informed consent - Colorectal carcinoma or high grade dysplasia

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objectives are: (i) to identify candidate fibrotic cellular pathways in UC patients treated with a JAK inhibitor filgotinib), and (ii) to detect and monitor in vivo fibrosis in UC patients using FAPi-PET/CT imaging.;Secondary Objective: Detection of in vivo intestinal fibrosis by means of measuring 68Ga-FAPi uptake, both visually as semi-quantitatively, in UC patients using FAPi-PET/CT imaging at baseline and 24 weeks after treatment initiation with filgotinib, To determine to what extent 68Ga-FAPi bowel uptake in UC patients corresponds to (phospohorylated and total) STAT protein (i.e. down-stream JAK targets) and gene expression, To determine to what extent 68Ga-FAPi bowel uptake in UC patients corresponds to clinical and endoscopic changes after 24 weeks of treatment with filgotinib;Primary end point(s): Identified pathways obtained via pathway analysis (single-cell RNA sequencing). Changes in these identified pathways (in gene and protein expression at week 24 compared to week 0)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Binding of [68Ga]Ga-FAPi-46 will be measured using the standardized uptake value (SUV) and target to background ratios will aid in scoring and quantifying tracer uptake. Semi-quantitative uptake above local background will be corrected and uncorrected for tracer plasma concentration based on pharmacokinetic analysis. SUV quantified from the FAPi-PET/CT-scan participants will be compared to non-affected intestinal regions. FAPi PET uptake expressed as SUV. Percentage of SUV decrease at week 24.;Secondary end point(s):Changes in gene and protein expression levels expressed as percentages in mucosal biopsies at week 0 and at week 24 (increased/ decreased an to what degree this corresponds to the SUV.;Secondary end point(s):Changes in FAPi PET uptake and correlation to clinical (SCCAI score) and endoscopic (Mayo score) changes.