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

Not Applicable
Conditions
Inflammatory Bowel Diseases
Interventions
Other: Arm 1- Combination therapy (Antibiotics + diet)
Other: Arm 1- Antibiotics treatment
Other: Arm 1- Nutritional prevention
Other: Arm 2- Antibiotics treatment
Other: Arm 2- Combination therapy (Antibiotics + diet)
Other: Arm 2- Nutritional prevention
Other: Arm 3- Nutritional prevention
Registration Number
NCT04082559
Lead Sponsor
Rabin Medical Center
Brief Summary

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:

1. Compare the effect of two antibiotic treatments on clinical, inflammatory and microbiological outcomes of patients with pouch inflammation.

2. Evaluate the effect of combined microbiome-targeted antibiotic and dietary intervention as treatment and prevention strategy in patients after pouch surgery.

3. Evaluate the effect of a microbiome-targeted dietary intervention as prevention strategy in patients after pouch surgery.

4. Identify predictors for response to specific antibiotic and dietary interventions.

Detailed Description

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.

1. Ciprofloxacin + metronidazole

2. 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

1. Favorable antibiotics + Mediterranean diet (MED)

2. 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:

1. Mediterranean diet (MED)

2. Control- based on the American Dietetic Association recommendations for patients with IBD.

3. 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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
170
Inclusion Criteria
  1. Patients are able and willing to sign an informed consent
  2. Patients with UC who underwent pouch surgery and have a functioning pouch
  3. Disease activity (PDAI and PGA) according to study arm 1-3 inclusion
Exclusion Criteria
  1. Patients with ileostomy
  2. Significant comorbidity that precludes the patient from participating according to the physicians' judgment
  3. Non-Hebrew readers
  4. Pregnant and lactating women

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Combination therapy (Antibiotics + diet)Arm 1- Combination therapy (Antibiotics + diet)1. Favorable antibiotics (according to aim 1) for two weeks + Mediterranean diet (MED) for 8 weeks. 2. Favorable antibiotics (according to aim 1) for two weeks + specific carbohydrate diet (SCD) for 8 weeks.
Antibiotic treatmentArm 1- Antibiotics treatmentPatients with active disease will be randomized and will receive a prescription for one of two antibiotic regimens. 1. Ciprofloxacin 500 mg 2/d + metronidazole 500 mg 2/d for two weeks 2. Doxycycline 100 mg 2/d + metronidazole 500 mg 2/d for two weeks
Antibiotic treatmentArm 2- Antibiotics treatmentPatients with active disease will be randomized and will receive a prescription for one of two antibiotic regimens. 1. Ciprofloxacin 500 mg 2/d + metronidazole 500 mg 2/d for two weeks 2. Doxycycline 100 mg 2/d + metronidazole 500 mg 2/d for two weeks
Nutritional preventionArm 3- Nutritional preventionPatients in clinical remission will be recruited to a dietary prevention study. 1. Mediterranean diet 2. Control- based on the American Dietetic Association recommendations for patients with IBD 3. Personalized nutrition group- based on prior results from study- NCT02858557
Combination therapy (Antibiotics + diet)Arm 2- Combination therapy (Antibiotics + diet)1. Favorable antibiotics (according to aim 1) for two weeks + Mediterranean diet (MED) for 8 weeks. 2. Favorable antibiotics (according to aim 1) for two weeks + specific carbohydrate diet (SCD) for 8 weeks.
Nutritional preventionArm 1- Nutritional preventionPatients in clinical remission will be recruited to a dietary prevention study. 1. Mediterranean diet 2. Control- based on the American Dietetic Association recommendations for patients with IBD 3. Personalized nutrition group- based on prior results from study- NCT02858557
Nutritional preventionArm 2- Nutritional preventionPatients in clinical remission will be recruited to a dietary prevention study. 1. Mediterranean diet 2. Control- based on the American Dietetic Association recommendations for patients with IBD 3. Personalized nutrition group- based on prior results from study- NCT02858557
Primary Outcome Measures
NameTimeMethod
Time interval to remissionOne year

PGA=0 and PDAI\<7

Time interval to responseOne year

Decrease in PGA and PDAI

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Rabin Medical Center

🇮🇱

Petah Tikva, Israel

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