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

NCT04082559 | Unknown

• 1 other identifier: 0129-19-RMC
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

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. 1.Compare the effect of two antibiotic treatments on clinical, inflammatory and microbiological outcomes of patients with pouch inflammation.
2. 2.Evaluate the effect of combined microbiome-targeted antibiotic and dietary intervention as treatment and prevention strategy in patients after pouch surgery.
3. 3.Evaluate the effect of a microbiome-targeted dietary intervention as prevention strategy in patients after pouch surgery.
4. 4.Identify predictors for response to specific antibiotic and dietary interventions.

Conditions

Inflammatory Bowel Diseases

Keywords

IBD

Outcome Measures

Primary Outcomes (2)

• Time interval to response

  Decrease in PGA and PDAI

  One year

• Time interval to remission

  PGA=0 and PDAI\<7

  One year

Study Arms (3)

Antibiotic treatment

OTHER

Patients 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

Other: Arm 1- Antibiotics treatment; Other: Arm 2- Antibiotics treatment

Combination therapy (Antibiotics + diet)

OTHER

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.

Other: Arm 1- Combination therapy (Antibiotics + diet); Other: Arm 2- Combination therapy (Antibiotics + diet)

Nutritional prevention

OTHER

Patients 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

Other: Arm 1- Nutritional prevention; Other: Arm 2- Nutritional prevention; Other: Arm 3- Nutritional prevention

Interventions

Arm 1- Antibiotics treatment OTHER

Patients with active disease will be randomized and will receive a prescription antibiotic regimens

Also known as: Ciprofloxacin 500 mg 2/d + metronidazole 500 mg 2/d for two weeks

Antibiotic treatment

Arm 2- Antibiotics treatment OTHER

Patients with active disease will be randomized and will receive a prescription antibiotic regimens

Also known as: Doxycycline 100 mg 2/d + metronidazole 500 mg 2/d for two weeks

Antibiotic treatment

Arm 1- Combination therapy (Antibiotics + diet) OTHER

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).

Also known as: Favorable antibiotics (according to aim 1) for two weeks + Mediterranean diet (MED) for 8 weeks.

Combination therapy (Antibiotics + diet)

Arm 2- Combination therapy (Antibiotics + diet) OTHER

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).

Also known as: Favorable antibiotics (according to aim 1) for two weeks + specific carbohydrate diet (SCD) for 8 weeks.

Combination therapy (Antibiotics + diet)

Arm 1- Nutritional prevention OTHER

Patients in clinical remission will be recruited to a dietary prevention study

Also known as: Mediterranean diet

Nutritional prevention

Arm 2- Nutritional prevention OTHER

Patients in clinical remission will be recruited to a dietary prevention study

Also known as: Control- based on the American Dietetic Association recommendations for patients with IBD

Nutritional prevention

Arm 3- Nutritional prevention OTHER

Patients in clinical remission will be recruited to a dietary prevention study

Also known as: Personalized nutrition group- based on prior results from study- NCT02858557

Nutritional prevention

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are able and willing to sign an informed consent
• Patients with UC who underwent pouch surgery and have a functioning pouch

You may not qualify if:

• Patients with ileostomy
• Significant comorbidity that precludes the patient from participating according to the physicians' judgment
• Non-Hebrew readers
• Pregnant and lactating women

Sponsors & Collaborators

• Rabin Medical Center: lead
• The Leona M. and Harry B. Helmsley Charitable Trust: collaborator
• Tel Aviv University: collaborator

Study Sites (1)

Rabin Medical Center

Petah Tikva, Israel

RECRUITING

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

Ciprofloxacin; Metronidazole; Doxycycline; Anti-Bacterial Agents; Diet; WW Domain-Containing Oxidoreductase; Diet, Mediterranean

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins; Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Therapeutics

Central Study Contacts

Iris Dotan, Prof

CONTACT

+97237525015; irisdo@clalit.org.il

Lihi Godny, BSc

CONTACT

+97237525015; lihigodny@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of The Gastroenterology Division

Study Record Dates

• First Submitted: August 28, 2019
• First Posted: September 9, 2019
• Study Start: June 11, 2019
• Primary Completion: June 11, 2021
• Study Completion: June 11, 2023
• Last Updated: October 8, 2020

Record last verified: 2020-10

Locations

IL (1)