Auto Fecal Microbial Transplant Post Helicobacter Pylori Antibiotic Therapy

Fecal Auto-transplantation for Enteric Microbial Rehabilitation Post 14 Day Antibiotics Therapy Against Helicobacter Pylori Infection

Current guidelines mandate Helicobacter pylori (H. Pylori) eradication with 2-3 antibiotics for 14 days ,This may result in multiple side effects and in eradication of important bacterial species to human health, exposing humans to multiple disease conditions.

Preservation of fecal microbiome prior to antibiotic therapy and auto-transplantation of the microbes post H. pylori eradication, will enable avoiding eradication of beneficial microbial populations and perhaps protect from consequent disease conditions.

Study Overview

• Status: Recruiting
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Other: Placebo capsules; Biological: Fecal Microbial Transplant (FMT); Biological: Auto Fecal Microbial Transplant (FMT) via enema

Detailed Description

This is a pilot study. Prior to antibiotics therapy for their baseline H.Pylori infection, patients will be asked to deliver at least 50 grams of fresh stool to the Tel Aviv Medical Center (TLVMC) Bacteriotherapy Clinic. All patients will receive therapy to eradicate H. Pylori according to current guidelines (14 days) and physician's discretion, and will be tested to validate H. pylori eradication, at least 21 days post therapy (according to guidelines: Kyoto/ ACG/ Maastricht). For patients that H. pylori was not eradicated- a second line therapy will be administered according to guidelines, and stool will be retrieved at an additional time point, before FMT and after successful H. pylori eradication.

Patients will be allocated into one of three groups:

1. Intervention group- patients will undergo Auto-FMT through capsules.
2. Intervention group-patients will undergo Auto-FMT through enema.
3. Control Group-patients will receive FMT through placebo capsules.

Patients in Intervention group will undergo an additional breath test for H. Pylori, 14-28 days post FMT, to exclude H. pylori-self infection, by the FMT. This concern is related to the capsules therapy, although the fecal filtrate is double packaged in two capsules (one inside another) which are designed to dissolve only in the duodenum at a basic pH.

If patients are found to be re-infected, they will undergo an additional antibiotics course and post eradication will receive FMT through an enema according to the above specified protocol.

FMT capsules will be generated at the laboratory of the Gastrointestinal department at the Tel Aviv Medical Center. The same procedure for FMT generation will be used in this study as in other studies of the IBD unit and in the clinical Bacteriotherapy setting.

FMT administration:

1. FMT through capsules (FMT/placebo)- patients will evacuate the bowel with 1 liter of Meroken solution 12 hours prior to the procedure and will fast from food for 12 hours prior to the procedure. Patients will swallow 30 frozen capsules on two consecutive days.
2. FMT through enema- patients will evacuate the bowel prior to the procedure and will fast for 3 hours prior to the procedure . Patients will receive 80 ml of enema. Enemas will be administered with the assistance of the study nurse. Patients will be asked to hold the enema content for at least 15 minutes.

At the post-FMT visit and follow -up visits, patients will be examined by a physician who will record clinical symptoms (abdominal pain, nausea, vomiting, weight change), adverse events (fever, abdominal pain, bloating, changes in bowel habits) and general well-being (quality of life and patient reported outcomes questionnaires).

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Nitsan Maharshak, MD; Phone Number: 97227360384; Email: nitsanm@tlvmc.gov.il
• Study Contact Backup: Name: Rony Izhar, PHD; Phone Number: 97237772613; Email: ronyi@tlvmc.gov.il

Study Locations

• Israel
  • Tel Aviv, Israel
    • Recruiting
    • Dep. of Gastroenterology, Tel Aviv Sourasky Medical Center
    • Principal Investigator: Nitsan Maharshak, MD
    • Sub-Investigator: Naomi Fliss Isakov, PhD
    • Contact: Nitsan Maharshak, MD; Phone Number: 972-3-6947305; Email: nitsanm@tlvmc.gov.il
    • Sub-Investigator: Nathaniel Aviv Cohen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-70 years old
• Positive H. pylori on either breath test or gastric biopsy
• Patient is intended to receive antibiotics therapy for H. pylori eradication

Exclusion Criteria:

• Severe systemic disease that may impact the microbiome. For example: heart disease, type two diabetes, chronic liver or kidney failure
• Antibiotics therapy during the prior 2 months to enrollment
• Planned to receive antibiotics within the upcoming 2 months (surgery etc) for reasons other than H. Pylori
• Inability to complete the study protocol (swallow capsules or to hold enema content for at least 15 minutes)
• Pregnancy
• Inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo FMT capsules; Glycerol and saline solution will be pipetted into commercially available acid-resistant hypromellose capsules (DRCaps, Capsugel) (650 μL), which will be closed and then secondarily sealed. Capsules will be stored frozen at -80°C (-112°F). Patients will swallow 30 frozen capsules on two consecutive days. Capsules look exactly the same as FMT capsules	Other: Placebo capsules; Patients will evacuate the bowel with 1 liter of Meroken solution 12 hours prior to the procedure and will fast from food for 12 hours prior to the procedure. Patients will swallow 30 frozen placebo-capsules on two consecutive days.
Experimental: FMT capsules; Fecal matter solution (feces, glycerol and saline solution) will be pipetted into commercially available acid-resistant hypromellose capsules (DRCaps, Capsugel) (650 μL), which will be closed and then secondarily sealed. Capsules will be stored frozen at -80°C (-112°F). Patients will swallow 30 frozen capsules on two consecutive days.	Biological: Fecal Microbial Transplant (FMT); FMT through capsules- patients will evacuate the bowel with 1 liter of Meroken solution 12 hours prior to the procedure and will fast from food for 12 hours prior to the procedure. Patients will swallow 30 frozen capsules on two consecutive days.
Active Comparator: FMT enemas; patients will evacuate the bowel prior to the procedure and will fast for 3 hours prior to the procedure . Patients will receive 80 ml of enema/ Fecal matter solution (feces(25 gr of stool , glycerol and saline solution) will be stored at 50 ml tubes frozen at -80°C (-112°F).	Biological: Auto Fecal Microbial Transplant (FMT) via enema; 3.FMT through enema- patients will evacuate the bowel prior to the procedure and will fast for 3 hours prior to the procedure . Patients will receive 80 ml of enema. Enemas will be administered with the assistance of the study nurse. Patients will be asked to hold the enema content for at least 15 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing restoration of the fecal microbiota after 14 day of H. pylori antibiotic regimen	A change of <10% of fecal microbial diversity before antibiotics and after FMT	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects rate of auto-FMT delivered through capsules	Side effects will be recorded at every visit and will be compared between the groups	4 months
Side effects rate of auto-FMT delivered through enema	Side effects will be recorded at every visit and will be compared between the groups	4 months
H pylori re-infection rate after auto-FMT procedure	4 week after each auto-transplantation a breath test for H. Pylori will be performed to evaluate whether auto-FMT results in re-infection. Re-infection is expected to be lower than 10%	4 weeks
Fecal microbial diversity change in auto-FMT delivered through capsules 18 weeks post FMT compared to 4 weeks post FMT	The microbial composition and diversity analysis at week 18 will be compared to microbial composition analysis at week 4 in patients receiving FMT through capsules and is expected to be higher than 10% in the intervention group	18 weeks
Fecal microbial diversity change in auto-FMT delivered through enema 18 weeks post FMT compared to 4 weeks post FMT	The microbial composition and diversity analysis at week 18 will be compared to microbial composition analysis at week 4 in patients receiving FMT through enema and is expected to be higher than 10% in the intervention group	18 weeks

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Collaborators: Weizmann Institute of Science

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2018
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: April 7, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Actual): July 8, 2024
• Last Update Submitted That Met QC Criteria: July 3, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Helicobacter Infections
• Other Study ID Numbers: 0278-18TLV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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