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

Insel Gruppe AG, University Hospital Bern240 enrolled

Overview

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.

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 Type

OBSERVATIONAL

Enrollment

240

Conditions

Ulcerative Colitis

Interventions

OzanimodDRUG

Start of standard therapy

TNF InhibitorDRUG

Start of standard therapy

SteroidsDRUG

Start of standard therapy

Vedolizumab

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria ulcerative colitis: 1. Signed informed consent 2. Age 18-80 years 3. General ability to understand and follow study procedures, fluency in German, French, or English 4. Diagnosis of ulcerative colitis since ≥3 months 5. Confirmed flare of ulcerative colitis with partial SCCAI score ≥5 points and at least one biomarker supporting intestinal inflammation 6. Planned start with ozanimod, steroids (prednisone ≥20mg/d or equivalent), or a biological (vedolizumab, infliximab, adalimumab, golimumab, ustekinumab) Exclusion criteria ulcerative colitis 1. Confirmed cytomegalovirus (CMV) reactivation within the previous 2 weeks (tested as part of standard medical practice at the discretion of the responsible physician) 2. C. difficile related diarrhea, or other confirmed infectious diarrhea in the last 4 weeks (tested as part of standard medical practice at the discretion of the responsible physician) 3. Diagnosis of Crohn's disease 4. Current pouch or ileostomy/ colostomy 5. Severe medical, surgical, or psychiatric comorbidities interfering with study procedures Inclusion criteria controls 1. Signed informed consent 2. Age 18-80 years 3. General ability to understand and follow study procedures, fluency in German, French, or English 4. No current or past diagnosis of inflammatory bowel disease (IBD) 5. No current medical complaints typic for IBD e.g. * Diarrhea, severe constipation, abdominal pain, blood in stool, weight loss * Slight symptoms (without impact onto daily activities) are permitted 6. No other current relevant gastrointestinal disease or condition plausibly interfering with microbiota assessment according to the discretion of the study physician Exclusion criteria controls 1. Confirmed cytomegalovirus (CMV) reactivation within the previous 2 weeks 2. C. difficile related diarrhea, or other confirmed infectious diarrhea in the last 4 weeks 3. Diagnosis of Crohn's disease, ulcerative colitis 4. Current pouch or ileostomy/ colostomy 5. Severe medical, surgical, or psychiatric comorbidities interfering with study procedures

Locations (1)

University Hospital Bern Inselspital

Bern, Switzerland

RECRUITING

Outcomes

Primary Outcomes

Development of a predictive score regarding success of anti-inflammatory therapy after start of a new treatment in ulcerative colitis

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.

Time frame: 4 months

Secondary Outcomes

Predicting clinical remission

Assessment of the microbiota/metabolic signature predicting clinical remission (SSCAI \<2.5)

Time frame: 8 weeks

Predicting clinical remission

Assessment of the microbiota/metabolic signature predicting clinical remission (SSCAI \<2.5)

Time frame: 12 weeks

Predicting clinical remission

Assessment of the microbiota/metabolic signature predicting clinical remission (SSCAI \<2.5)

Time frame: 6 months

Predicting clinical remission

Assessment of the microbiota/metabolic signature predicting clinical remission (SSCAI \<2.5)

Time frame: 12 months

Predicting calprotectin reduction

Assessment of the microbiota/metabolic signature predicting a reduction in fecal calprotectin levels

Time frame: 2 weeks

Predicting calprotectin reduction

Assessment of the microbiota/metabolic signature predicting a reduction in fecal calprotectin levels

Central Contacts

Benjamin Misselwitz, Prof.

CONTACT

31 664 0430 benjamin.misselwitz@dbmr.unibe.ch

Jacqueline Wyss, Dr.

CONTACT

764411617 jacqueline.wyss@dbmr.unibe.ch

Data from ClinicalTrials.gov

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