Pilot Study Using Oral Capsule FMT to Decolonize GI CRE

Pilot Study Using Oral Capsule Fecal Microbiota Transplant To Decolonize Gastrointestinal Carbapenem-Resistant Enterobacteriaceae (CRE)

Carbapenem-Resistant Enterobacteriaceae (CRE) are bacteria that have become resistant to carbapenems by producing enzymes that break down carbapenems. The prevalence of CRE continues to rise globally but the treatment options are extremely limited. In case series, isolation of CRE from any site, whether there is clinical infection or not, has been associated with all-cause hospital mortality ranging from 29% to 52%. There are no known methods for reliably decolonizing gastrointestinal (GI) CRE. In rare case reports, fecal microbiota transplant (FMT) has successfully eradicated gastrointestinal colonization of CRE, but there has been no larger study further investigating this. FMT via oral capsules is the least invasive method and has demonstrated efficacy and short-term safety in treating patients with recurrent Clostridium difficile infections. Therefore, the investigators propose this pilot study to determine the effectiveness of oral capsule fecal transplantation in the decolonization of gastrointestinal CRE.

Study Overview

• Status: Withdrawn
• Conditions: Enterobacteriaceae Infections; Fecal Microbiota Transplantation
• Intervention / Treatment: Biological: Fecal Microbiota Transplantation

• Study Type: Interventional
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatient
• Have intestinal carriage of CRE

Exclusion Criteria:

• Pregnant
• Peripheral WBC >12 x 10^9/L and/or temperature >38 degrees Celsius
• Swallowing dysfunction or known chronic aspiration
• Delayed gastric emptying
• History of intestinal obstruction
• Active CRE infection
• Acute exacerbation of underlying comorbid condition
• Severely immunocompromised patients
• Inflammatory bowel disease
• Allergies to ingredients Generally Recognized as Safe
• Adverse event attributable to previous FMT
• Concomitant antibiotic use or antibiotic use 48 hours before FMT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral capsule fecal transplantation; Enrolled patients who have screened positive for CRE in the stool will receive fecal transplant via OpenBiome oral capsules. The patient is given 90 minutes to swallow all capsules and does not require any anesthesia or sedation. Stool samples to test for CRE will be taken 10 days and 30 days after the fecal transplant.	Biological: Fecal Microbiota Transplantation; This is a parallel arm study. All participants in the experimental arm will receive a single fecal transplantation via oral capsules to determine effectiveness and safety in decolonizing gastrointestinal CRE.; Other Names: FMT; Fecal Transplant
No Intervention: Observation; Enrolled patients who have screened positive for CRE in the stool will have stool samples to test for CRE taken 10 days and 30 days after initial enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with CRE decolonization at day 10 (+/- 3 days) after fecal transplant	CRE decolonization is defined by absence of CRE on stool culture using standard clinical laboratory techniques. Stool samples will be collected 10 days after FMT.	10 days
Proportion of participants with an adverse event through day 10 (+/- 3 days) after FMT	Telephone calls are made to participants 10 days after FMT to assess for adverse event, severe adverse event, and adverse events of special interest (newly acquired transmissible infectious diseases).	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with CRE decolonization at month 1 (+/-5 days) after FMT	CRE decolonization is defined by absence of CRE on stool culture using standard clinical laboratory techniques. Stool samples will be collected 30 days after FMT.	1 month
Proportion of participants with CRE infection at day 10 (+/-3 days) and month 1 (+/-5 days) after FMT	CRE infection will be defined as an associated bacteremia, urinary tract infection, wound-related infection or other clinical infection deemed to be CRE associated at the discretion of the treating physician.	1 month
Proportion of participants with an adverse event, severe adverse event, or adverse events of special interest through month 1 (+/-5 days) after FMT.	Telephone calls are made to participants 1 month after FMT to assess for adverse event, severe adverse event, and adverse events of special interest (newly acquired transmissible infectious diseases).	1 month
Proportion of participants with a severe adverse event at month 6 (+/-14 days) after FMT.	Telephone calls are made to participants 6 months after FMT to assess for severe adverse event.	6 months
Proportion of participants with microbial engraftment assessed by microbiome disruption index (MDI) (MDI-community and MDI-species) measured by 16s ribosomal RNA at time of enrollment, day 10 (+/-3 days) and month 1 (+/-5 days) after FMT	Stool samples collected at baseline before FMT, day 10 after FMT, 1 month after FMT will be sent for 16s sequencing.	1 month

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: OpenBiome; Finch Research and Development LLC.
• Investigators: Principal Investigator: Zachary Rubin, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2019
• Primary Completion (Actual): September 24, 2019
• Study Completion (Actual): September 24, 2019

Study Registration Dates

• First Submitted: May 4, 2018
• First Submitted That Met QC Criteria: May 4, 2018
• First Posted (Actual): May 16, 2018

Study Record Updates

• Last Update Posted (Actual): October 23, 2019
• Last Update Submitted That Met QC Criteria: October 21, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: CRE
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections
• Other Study ID Numbers: 16-001946

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