Combined Microbiota and Metabolic Signature in Ulcerative Colitis Predicts Anti-Inflammatory Therapy Success

Recruiting

• Conditions: Ulcerative Colitis
• Interventions: Drug: Ozanimod; Drug: TNF Inhibitor; Drug: Steroids; Drug: Vedolizumab; Drug: Ustekinumab

• Registration Number: NCT05702879
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

Brief Summary

The primary goal of the study is to develop an early (within 4 weeks) combined microbiota/metabolic signature predicting clinical response upon anti-inflammatory treatment in UC patients.

Detailed Description

The investigators perform a longitudinal prospective multi-center study for ulcerative colitis (UC) patients with a flare at/and after the time of starting a new treatment and healthy household controls. They will perform intense longitudinal bio-sampling and deep clinical characterization.

With this information the aim is to develop a predictive signature regarding the success of a new ly started anti-inflammatory therapy after an UC flare.

Study Timeline

• Study First Submitted: 2023-01-18
• Study First Submitted QC: 2023-01-26
• Study First Posted: 2023-01-27
• Study Start: 2023-09-06
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-29
• Last Update Posted: 2023-12-06
• Primary Completion: 2025-01-31
• Study Completion: 2025-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ulcerative colitis patients	TNF Inhibitor	Patients with a flare of ulcerative colitis who meet the inclusion criteria. 120 patients will be included.
Ulcerative colitis patients	Ozanimod	Patients with a flare of ulcerative colitis who meet the inclusion criteria. 120 patients will be included.
Ulcerative colitis patients	Steroids	Patients with a flare of ulcerative colitis who meet the inclusion criteria. 120 patients will be included.
Ulcerative colitis patients	Vedolizumab	Patients with a flare of ulcerative colitis who meet the inclusion criteria. 120 patients will be included.
Ulcerative colitis patients	Ustekinumab	Patients with a flare of ulcerative colitis who meet the inclusion criteria. 120 patients will be included.

Primary Outcome Measures

Name	Time	Method
Development of a predictive score regarding success of anti-inflammatory therapy after start of a new treatment in ulcerative colitis	4 months	The predictive microbiota signature will be developed using machine learning, considering clinical data, microbiota descriptors, and metabolic changes from day 0 to week 4 (see analysis). Clinical response will be defined as a decrease in the simple clinical colitis activity index (SCCAI) score by ≥3 points 25or to a level of ≤2.5 points 26 at 8 weeks after the start of anti-inflammatory treatment.

Secondary Outcome Measures

Name	Time	Method
Predicting clinical remission	12 months	Assessment of the microbiota/metabolic signature predicting clinical remission (SSCAI \<2.5)
Differential microbiota response to therapy: TNF-inhibitors	12 months	Sensitivity analysis in the subgroup treated with TNF-inhibitors in regards to differential signatures in the prediction signature
Signature differences between ulcerative colitis and healthy controls	12 months	Comparison of microbiota/metabolic signatures between ulcerative colitis patients and controls using clustering and differential abundance analysis
Predicting calprotectin reduction	12 months	Assessment of the microbiota/metabolic signature predicting a reduction in fecal calprotectin levels
Differential microbiota response to therapy: Ustekinumab	12 months	Sensitivity analysis in the subgroup treated with Ustekinumab in regards to differential signatures in the prediction signature
Adverse effects	12 months	Assessment regarding potential adverse effects in relation medical therapy by screening questionnaires
Differential microbiota response to therapy: Vedolizumab	12 months	Sensitivity analysis in the subgroup treated with Vedolizumab in regards to differential signatures in the prediction signature
Differential microbiota response to therapy: Steroids	12 months	Sensitivity analysis in the subgroup treated with Steroids in regards to differential signatures in the prediction signature
Metagenomic substrain assessment	12 months	Identification of substrains in patient samples using metagenomic sequencing and follow up their persistence/loss over time
Fatigue assessment	12 months	Fatigue severity measured by the fatigue severity scale over time and assessed for reduction after therapy start
Differential microbiota response to therapy: Ozanimod	12 months	Sensitivity analysis in the subgroup treated with Ozanimod in regards to differential signatures in the prediction signature

Trial Locations

Locations (1)

University Hospital Bern Inselspital; 🇨🇭 Bern, Switzerland