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

Ulcerative Colitis Clinical Trial

— COMMIT  

Official title:

An Early Combined Microbiota and Metabolic Signature in Ulcerative Colitis Patients Predict the Clinical Success of Anti-inflammatory Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05702879
• Other study ID #: 2022-02008
• Status: Recruiting
• Start date: September 6, 2023
• Est. completion date: January 31, 2025

Study information

• Verified date: November 2023
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Benjamin Misselwitz, Prof.
• Phone: 31 664 0430
• Email: benjamin.misselwitz[@]dbmr.unibe.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: January 31, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Ozanimod
Start of standard therapy
• TNF Inhibitor
Start of standard therapy
• Steroids
Start of standard therapy
• Vedolizumab
Start of standard therapy
• Ustekinumab
Start of standard therapy

Locations

Country	Name	City	State
Switzerland	University Hospital Bern Inselspital	Bern

Sponsors (2)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern	Bristol-Myers Squibb

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Predicting clinical remission	Assessment of the microbiota/metabolic signature predicting clinical remission (SSCAI <2.5)	8 weeks
Secondary	Predicting clinical remission	Assessment of the microbiota/metabolic signature predicting clinical remission (SSCAI <2.5)	12 weeks
Secondary	Predicting clinical remission	Assessment of the microbiota/metabolic signature predicting clinical remission (SSCAI <2.5)	6 months
Secondary	Predicting clinical remission	Assessment of the microbiota/metabolic signature predicting clinical remission (SSCAI <2.5)	12 months
Secondary	Predicting calprotectin reduction	Assessment of the microbiota/metabolic signature predicting a reduction in fecal calprotectin levels	2 weeks
Secondary	Predicting calprotectin reduction	Assessment of the microbiota/metabolic signature predicting a reduction in fecal calprotectin levels	8 weeks
Secondary	Predicting calprotectin reduction	Assessment of the microbiota/metabolic signature predicting a reduction in fecal calprotectin levels	12 weeks
Secondary	Predicting calprotectin reduction	Assessment of the microbiota/metabolic signature predicting a reduction in fecal calprotectin levels	6 months
Secondary	Predicting calprotectin reduction	Assessment of the microbiota/metabolic signature predicting a reduction in fecal calprotectin levels	12 months
Secondary	Differential microbiota response to therapy: Ozanimod	Sensitivity analysis in the subgroup treated with Ozanimod in regards to differential signatures in the prediction signature	12 months
Secondary	Differential microbiota response to therapy: TNF-inhibitors	Sensitivity analysis in the subgroup treated with TNF-inhibitors in regards to differential signatures in the prediction signature	12 months
Secondary	Differential microbiota response to therapy: Vedolizumab	Sensitivity analysis in the subgroup treated with Vedolizumab in regards to differential signatures in the prediction signature	12 months
Secondary	Differential microbiota response to therapy: Ustekinumab	Sensitivity analysis in the subgroup treated with Ustekinumab in regards to differential signatures in the prediction signature	12 months
Secondary	Differential microbiota response to therapy: Steroids	Sensitivity analysis in the subgroup treated with Steroids in regards to differential signatures in the prediction signature	12 months
Secondary	Signature differences between ulcerative colitis and healthy controls	Comparison of microbiota/metabolic signatures between ulcerative colitis patients and controls using clustering and differential abundance analysis	12 months
Secondary	Metagenomic substrain assessment	Identification of substrains in patient samples using metagenomic sequencing and follow up their persistence/loss over time	12 months
Secondary	Fatigue assessment	Fatigue severity measured by the fatigue severity scale over time and assessed for reduction after therapy start	12 months
Secondary	Adverse effects	Assessment regarding potential adverse effects in relation medical therapy by screening questionnaires	12 months