Ulcerative Colitis
Conditions
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.
Interventions
DRUGOzanimod
Start of standard therapy
DRUGTNF Inhibitor
Start of standard therapy
DRUGSteroids
Start of standard therapy
DRUGVedolizumab
Start of standard therapy
DRUGUstekinumab
Start of standard therapy
Sponsors
Bristol-Myers Squibb
Insel Gruppe AG, University Hospital Bern
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Predicting calprotectin reduction | 2 weeks | Assessment of the microbiota/metabolic signature predicting a reduction in fecal calprotectin levels |
| 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 |
| 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 |
| 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: Ustekinumab | 12 months | Sensitivity analysis in the subgroup treated with Ustekinumab in regards to differential signatures in the prediction signature |
| Predicting clinical remission | 8 weeks | Assessment of the microbiota/metabolic signature predicting clinical remission (SSCAI \<2.5) |
| 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 |
| 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 |
| Adverse effects | 12 months | Assessment regarding potential adverse effects in relation medical therapy by screening questionnaires |
| 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 |
Countries
Switzerland
Contacts
Primary ContactBenjamin Misselwitz, Prof.
Backup ContactJacqueline Wyss, Dr.
Outcome results
None listed