Clinical trial NCT05702879: Combined Microbiota and Metabolic Signature in Ulcerative Colitis Predicts Anti-Inflammatory Therapy Success
Official title: An Early Combined Microbiota and Metabolic Signature in Ulcerative Colitis Patients Predict the Clinical Success of Anti-inflammatory Therapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ulcerative Colitis
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2023-01-27
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Development of a predictive score regarding success of anti-inflammatory therapy after start of a new treatment in ulcerative colitis
timeFrame: 4 months
Secondary outcomes:
measure: Predicting clinical remission
timeFrame: 8 weeks
measure: Predicting clinical remission
timeFrame: 12 weeks
measure: Predicting clinical remission
timeFrame: 6 months
measure: Predicting clinical remission
timeFrame: 12 months
measure: Predicting calprotectin reduction
timeFrame: 2 weeks
measure: Predicting calprotectin reduction
timeFrame: 8 weeks
measure: Predicting calprotectin reduction
timeFrame: 12 weeks
measure: Predicting calprotectin reduction
timeFrame: 6 months
measure: Predicting calprotectin reduction
timeFrame: 12 months
measure: Differential microbiota response to therapy: Ozanimod
timeFrame: 12 months
measure: Differential microbiota response to therapy: TNF-inhibitors
timeFrame: 12 months
measure: Differential microbiota response to therapy: Vedolizumab
timeFrame: 12 months
measure: Differential microbiota response to therapy: Ustekinumab
timeFrame: 12 months
measure: Differential microbiota response to therapy: Steroids
timeFrame: 12 months
measure: Signature differences between ulcerative colitis and healthy controls
timeFrame: 12 months
measure: Metagenomic substrain assessment
timeFrame: 12 months
measure: Fatigue assessment
timeFrame: 12 months
measure: Adverse effects
timeFrame: 12 months
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: University Hospital Bern Inselspital
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Benjamin Misselwitz, Prof.
role: PRINCIPAL_INVESTIGATOR
References: