Pilot Study Using Oral Capsule FMT to Decolonize GI CRE

NCT03527056 — Early Phase 1, Withdrawn, University of California, Los Angeles

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

Registry	NCT03527056
Status	Withdrawn - Investigator left the institution
Phase	Early Phase 1
Study type	Interventional; non randomized, parallel, masking: none, treatment
Sponsor	University of California, Los Angeles (Other); collaborators: OpenBiome, Finch Research and Development LLC.
Conditions	Enterobacteriaceae Infections, Fecal Microbiota Transplantation
Interventions	Fecal Microbiota Transplantation (Biological)
Dates	start 2019-06-01 (estimated), primary completion 2019-09-24, completion 2019-09-24, first posted 2018-05-16, last updated 2019-10-23

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
Oral capsule fecal transplantation	Experimental	Biological: Fecal Microbiota 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.
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.

Fecal Microbiota Transplantation (Biological), also known as FMT, Fecal Transplant: 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.

+Outcome measures

Primary outcomes

Proportion of participants with CRE decolonization at day 10 (+/- 3 days) after fecal transplant [10 days]: 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.
Proportion of participants with an adverse event through day 10 (+/- 3 days) after FMT [10 days]: 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).

Secondary outcomes

Proportion of participants with CRE decolonization at month 1 (+/-5 days) after FMT [1 month]: 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.
Proportion of participants with CRE infection at day 10 (+/-3 days) and month 1 (+/-5 days) after FMT [1 month]: 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.
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]: 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).
Proportion of participants with a severe adverse event at month 6 (+/-14 days) after FMT. [6 months]: Telephone calls are made to participants 6 months after FMT to assess for severe adverse event.
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]: Stool samples collected at baseline before FMT, day 10 after FMT, 1 month after FMT will be sent for 16s sequencing.

+Eligibility

Sex: All, ages: 18 Years to any, accepts healthy volunteers

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

+Investigators

Zachary Rubin, MD, Principal investigator, University of California, Los Angeles