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

NCT05702879 | Unknown

• 1 other identifier: 2022-02008
• Study Type: observational
• Target: 240
• Locations: 1 country
• Sites: 1

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.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• 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.

  4 months

Secondary Outcomes (18)

• Predicting clinical remission

  8 weeks

• Predicting clinical remission

  12 weeks

• Predicting clinical remission

  6 months

• Predicting clinical remission

  12 months

• Predicting calprotectin reduction

  2 weeks

Study Arms (2)

Ulcerative colitis patients

Patients with a flare of ulcerative colitis who meet the inclusion criteria. 120 patients will be included.

Drug: Ozanimod; Drug: TNF Inhibitor; Drug: Steroids; Drug: Vedolizumab; Drug: Ustekinumab

Controls

For each patient, enrollment of a healthy control individual who shares the same living conditions (e.g., spouse or roommate) is attempted

Interventions

Ozanimod DRUG

Start of standard therapy

Ulcerative colitis patients

TNF Inhibitor DRUG

Start of standard therapy

Also known as: infliximab, adalimumab, etanercept, golimumab, and certolizumab.

Ulcerative colitis patients

Steroids DRUG

Start of standard therapy

Also known as: Prednisolon

Ulcerative colitis patients

Vedolizumab DRUG

Start of standard therapy

Ulcerative colitis patients

Ustekinumab DRUG

Start of standard therapy

Ulcerative colitis patients

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients/ participants fulfilling inclusion criteria to one of the following groups will be included: 1. Patients with a flare of ulcerative colitis who meet the inclusion criteria (see above). Inclusion of 120 patients is planned. 2. Healthy controls. For each patient, a healthy control individual who shares the same living conditions (e.g., spouse or roommate) is attempted. Enrolment of controls will not be enforced but enrolment of ≥100 controls for 120 patients is expected.

You may qualify if:

• Signed informed consent
• Age 18-80 years
• General ability to understand and follow study procedures, fluency in German, French, or English
• Diagnosis of ulcerative colitis since ≥3 months
• Confirmed flare of ulcerative colitis with partial SCCAI score ≥5 points and at least one biomarker supporting intestinal inflammation
• Planned start with ozanimod, steroids (prednisone ≥20mg/d or equivalent), or a biological (vedolizumab, infliximab, adalimumab, golimumab, ustekinumab)

You may not qualify if:

• Confirmed cytomegalovirus (CMV) reactivation within the previous 2 weeks (tested as part of standard medical practice at the discretion of the responsible physician)
• 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)
• Diagnosis of Crohn's disease
• Current pouch or ileostomy/ colostomy
• Severe medical, surgical, or psychiatric comorbidities interfering with study procedures
• Signed informed consent
• Age 18-80 years
• General ability to understand and follow study procedures, fluency in German, French, or English
• No current or past diagnosis of inflammatory bowel disease (IBD)
• 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
• No other current relevant gastrointestinal disease or condition plausibly interfering with microbiota assessment according to the discretion of the study physician
• Confirmed cytomegalovirus (CMV) reactivation within the previous 2 weeks
• C. difficile related diarrhea, or other confirmed infectious diarrhea in the last 4 weeks

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University Hospital Bern Inselspital

Bern, 3013, Switzerland

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Stool samples collected by patients and healthy controls

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

ozanimod; Tumor Necrosis Factor Inhibitors; Infliximab; Adalimumab; Etanercept; golimumab; Certolizumab Pegol; Steroids; vedolizumab; Ustekinumab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Anti-Inflammatory Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Constant Regions; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Benjamin Misselwitz, Prof.

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin Misselwitz, Prof.

CONTACT

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

Jacqueline Wyss, Dr.

CONTACT

764411617; jacqueline.wyss@dbmr.unibe.ch

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: January 27, 2023
• Study Start: September 6, 2023
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: December 6, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: With publication of results
• Access Criteria: Acess to analytic code will be detailed in the final publication

Locations

CH (1)