Biomarker-based Multidisciplinary Team (Bio-MDT) Approach to Personalized Microbial-targeted Treatment of Pouchitis and Crohn's Disease

Study Overview
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Brief Summary
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Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) currently affecting over 5 million patients globally, mostly young adults. These conditions are often debilitating, disabling and may markedly affect patient's quality of life. Despite important advances in research, the pathogenesis of IBD remains obscure, the incidence-rising, the condition - incurable, and drugs have a modest effect. The common denominator may be environmental factors, specifically diet and the microbiome, which remain a fundamental unmet need in IBD care as high quality randomized trials and mechanistic research are limited. Up to a quarter of patients with UC may undergo complete large bowel resection due to disease complications. In order to preserve bowel continuity, this surgery includes a restorative part with creation of a reservoir (pouch) from normal small bowel instead of the resected rectum. The majority of these patients develop small intestinal inflammation in the previously normal small bowel creating the pouch (pouchitis). Based on our results from previous studies, we hypothesized that personalized antibiotics and dietary interventions will modify microbial composition and result in significantly improved outcomes, specifically resolution of inflammation and prolonged remission rates in patients with a pouch. Aims: Compare the effect of two antibiotic treatments on clinical, inflammatory and microbiological outcomes of patients with pouch inflammation. Evaluate the effect of combined microbiome-targeted antibiotic and dietary intervention as treatment and prevention strategy in patients after pouch surgery. Evaluate the effect of a microbiome-targeted dietary intervention as prevention strategy in patients after pouch surgery. Identify predictors for response to specific antibiotic and dietary interventions.

Detailed Description
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All patients will undergo comprehensive screening by the bio-MDT. Aim 1: Antibiotic treatment- (patients with active disease) will be randomized to receive a prescription for one of two antibiotic regimens. Ciprofloxacin + metronidazole Doxycycline+ metronidazole Aim 2: Combination therapy ( Antibiotics+diet) After arm 1 recruitment completion, a favorable antibiotic regimen will be determined and recommended in arm 2, in which, patients with active disease will be randomized to Favorable antibiotics + Mediterranean diet (MED) Favorable antibiotics + The Specific Carbohydrate Diet (SCD) Aim 3: Nutritional prevention- Patients in clinical remission will be recruited to a dietary prevention study and be allocated to one of three groups: Mediterranean diet (MED) Control- based on the American Dietetic Association recommendations for patients with IBD. Personalized nutrition group- based on prior results from study- NCT02858557 Comprehensive assessment including nutritional, clinical, inflammatory and microbial parameters will be performed at baseline and at weeks 2,3,4,8,26, 52.

Official Title
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Biomarker-based Multidisciplinary Team Approach to Personalized Microbial-targeted Treatment of Pouchitis and Crohn's Disease

Conditions
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Inflammatory Bowel Diseases

Intervention / Treatment
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* Other: Arm 1- Antibiotics treatment
* Other: Arm 2- Antibiotics treatment
* Other: Arm 1- Combination therapy (Antibiotics + diet)
* Other: Arm 2- Combination therapy (Antibiotics + diet)
* Other: Arm 1- Nutritional prevention
* Other: Arm 2- Nutritional prevention
* Other: Arm 3- Nutritional prevention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients are able and willing to sign an informed consent Patients with UC who underwent pouch surgery and have a functioning pouch Disease activity (PDAI and PGA) according to study arm 1-3 inclusion Exclusion Criteria: Patients with ileostomy Significant comorbidity that precludes the patient from participating according to the physicians' judgment Non-Hebrew readers Pregnant and lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Antibiotic treatment<br>Patients with active disease will be randomized and will receive a prescription for one of two antibiotic regimens. Ciprofloxacin 500 mg 2/d + metronidazole 500 mg 2/d for two weeks Doxycycline 100 mg 2/d + metronidazole 500 mg 2/d for two weeks | Other: Arm 1- Antibiotics treatment<br>* Patients with active disease will be randomized and will receive a prescription antibiotic regimens<br>* Other names: Ciprofloxacin 500 mg 2/d + metronidazole 500 mg 2/d for two weeks;Other: Arm 2- Antibiotics treatment<br>* Patients with active disease will be randomized and will receive a prescription antibiotic regimens<br>* Other names: Doxycycline 100 mg 2/d + metronidazole 500 mg 2/d for two weeks;|
| Other: Combination therapy (Antibiotics + diet)<br>Favorable antibiotics (according to aim 1) for two weeks + Mediterranean diet (MED) for 8 weeks. Favorable antibiotics (according to aim 1) for two weeks + specific carbohydrate diet (SCD) for 8 weeks. | Other: Arm 1- Combination therapy (Antibiotics + diet)<br>* Patients with active disease receiving a prescription for the antibiotic regimen defined as favorable in the antibiotics according to aim 1 , and randomized into one of two dietary interventions: Mediterranean diet (MED) or the specific carbohydrate diet (SCD).<br>* Other names: Favorable antibiotics (according to aim 1) for two weeks + Mediterranean diet (MED) for 8 weeks.;Other: Arm 2- Combination therapy (Antibiotics + diet)<br>* Patients with active disease receiving a prescription for the antibiotic regimen defined as favorable in the antibiotics according to aim 1 , and randomized into one of two dietary interventions: Mediterranean diet (MED) or the specific carbohydrate diet (SCD).<br>* Other names: Favorable antibiotics (according to aim 1) for two weeks + specific carbohydrate diet (SCD) for 8 weeks.;|
| Other: Nutritional prevention<br>Patients in clinical remission will be recruited to a dietary prevention study. Mediterranean diet Control- based on the American Dietetic Association recommendations for patients with IBD Personalized nutrition group- based on prior results from study- NCT02858557 | Other: Arm 1- Nutritional prevention<br>* Patients in clinical remission will be recruited to a dietary prevention study<br>* Other names: Mediterranean diet;Other: Arm 2- Nutritional prevention<br>* Patients in clinical remission will be recruited to a dietary prevention study<br>* Other names: Control- based on the American Dietetic Association recommendations for patients with IBD;Other: Arm 3- Nutritional prevention<br>* Patients in clinical remission will be recruited to a dietary prevention study<br>* Other names: Personalized nutrition group- based on prior results from study- NCT02858557;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time interval to response | Decrease in PGA and PDAI | One year | 
| Time interval to remission | PGA=0 and PDAI<7 | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBD