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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Anticipated): 170
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lihi Godny, BSc; Phone Number: +97237525015; Email: lihigodny@gmail.com

Study Locations

• Israel
  • Petah Tikva, Israel
    • Recruiting
    • Rabin Medical Center
    • Contact: Lihi Godny, BSc; Phone Number: +97237525015; Email: lihigodny@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Collaborators: Tel Aviv University; The Leona M. and Harry B. Helmsley Charitable Trust

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 11, 2019
• Primary Completion (ANTICIPATED): June 11, 2021
• Study Completion (ANTICIPATED): June 11, 2023

Study Registration Dates

• First Submitted: August 28, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (ACTUAL): September 9, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: IBD
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enteritis; Ileitis; Ileal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Pouchitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antitubercular Agents; Antimalarials; Cytochrome P-450 CYP1A2 Inhibitors; Complement Inactivating Agents; Metronidazole; Anti-Bacterial Agents; Antibiotics, Antitubercular; Doxycycline; Ciprofloxacin; Complement Factor H
• Other Study ID Numbers: 0129-19-RMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No