Pilot Study Using Oral Capsule FMT to Decolonize GI CRE

NCT03527056 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: 16-001946
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Enterobacteriaceae Infections; Fecal Microbiota Transplantation

Keywords

CRE

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Proportion of participants with CRE decolonization at month 1 (+/-5 days) after FMT

  1 month

• Proportion of participants with CRE infection at day 10 (+/-3 days) and month 1 (+/-5 days) after FMT

  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.

  1 month

• Proportion of participants with a severe adverse event at month 6 (+/-14 days) after FMT.

  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

  1 month

Study Arms (2)

Oral capsule fecal transplantation

EXPERIMENTAL

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

Observation

NO INTERVENTION

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.

Interventions

Fecal Microbiota Transplantation BIOLOGICAL

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.

Also known as: FMT, Fecal Transplant

Oral capsule fecal transplantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Outpatient
• Have intestinal carriage of CRE

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• OpenBiome: collaborator
• Finch Research and Development LLC.: collaborator

MeSH Terms

Conditions

Enterobacteriaceae Infections

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Zachary Rubin, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2018
• First Posted: May 16, 2018
• Study Start: June 1, 2019
• Primary Completion: September 24, 2019
• Study Completion: September 24, 2019
• Last Updated: October 23, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share