A Trial of Encapsulated Fecal Microbiota for Vancomycin Resistant Enterococcus Decolonization

• ClinicalTrials.gov Identifier: NCT03063437
• Recruitment Status: Completed
• First Posted: February 24, 2017
• Results First Posted: February 5, 2020
• Last Update Posted: April 13, 2020
• Sponsor: Microbiome Health Research Institute
• Collaborators: University of Wisconsin, Madison; Indiana University
• Information provided by (Responsible Party): Microbiome Health Research Institute

Study Description

Brief Summary:

The objective of this study is to provide preliminary insight into the safety and efficacy of fecal microbiota transplantation (FMT) for the eradication of gastrointestinal carriage of vancomycin-resistant Enterococcus.

Condition or disease	Intervention/treatment	Phase
Antibiotic Resistant Strain	Biological: Encapsulated fecal microbiota preparation; Biological: Encapsulated placebo	Phase 2

Detailed Description:

Note: The Protocol and Statistical Analysis Plan document contains modifications from what is on file at the FDA to reflect redactions and formatting requirements for public posting on ClinicalTrials.gov.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase II Randomized, Double Blind, Placebo-controlled, Parallel Group Trial of Encapsulated Fecal Microbiota Transplantation for Vancomycin Resistant Enterococcus Decolonization
• Actual Study Start Date: August 17, 2017
• Actual Primary Completion Date: September 19, 2018
• Actual Study Completion Date: February 26, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active: Encapsulated Fecal Microbiota Preparation; Single dose of oral, encapsulated fecal microbiota preparation (30 capsules per dose) with follow-up at 3 days, 10 days, 28 days, and 6 months.	Biological: Encapsulated fecal microbiota preparation; 30 capsules
Placebo Comparator: Placebo: Encapsulated Placebo; Single dose of oral, placebo capsule (30 capsules per dose) with follow-up at 3 days, 10 days, and 28 days, and 6 months.	Biological: Encapsulated placebo; 30 capsules

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With VRE Decolonization [ Time Frame: Day 10 (±3 days) after randomization ]
   VRE decolonization is defined by absence of VRE on stool culture using standard clinical laboratory techniques at Day 10 (± 3 days) after randomization.
2. Percentage of Participants With an Adverse Event (AE); Severe Adverse Event (SAE); and Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI) [ Time Frame: Day 10 (±3 days) after randomization ]
   Percentage of participants with an adverse event (AE); severe adverse event (SAE); and newly acquired transmissible infectious diseases which are considered adverse events of special interest (AESI) through Day 10 (± 3 days) after randomization.

Secondary Outcome Measures :

1. Percentage of Participants With VRE Infection [ Time Frame: Week 4 (±5 days) after randomization ]
   Percentage of participants with VRE infection, defined as an associated bacteremia, urinary tract infection, or wound-related infection.
2. Percentage of Participants With ARB Colonization on Day 10 Following Fecal Microbiota Transplantation (FMT) [ Time Frame: Day 10 (± 3 days) after randomization ]
   Percentage of participants with other antibiotic resistant bacteria (ARB) colonization
3. Percentage of Participants With ARB Infection 4 Weeks Following FMT [ Time Frame: Week 4 (±5 days) after randomization ]
   Percentage of participants with composite ARB infection
4. Number of Days Between FMT and VRE Colonization and Infection Occurs [ Time Frame: Up to 6 months after randomization ]
   Time (in days) from randomization until the study day when VRE colonization and infection occurs
5. VRE Decolonization Among Immunocompromised Patients [ Time Frame: Day 10 (± 3 days) after randomization ]
   Percentage of participants with VRE decolonization among immunocompromised patients
6. Adverse Events Within 4 Weeks Following FMT [ Time Frame: Week 4 (±5 days) after randomization ]
   Percentage of participants with an adverse event (AE)
7. Serious Adverse Events Within 4 Weeks Following FMT [ Time Frame: Week 4 (±5 days) after randomization ]
   Percentage of participants with a serious adverse event (SAE)
8. Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI) [ Time Frame: Week 4 (±5 days) after randomization ]
   Percentage of participants with newly acquired transmissible infectious diseases which are considered adverse events of special interest (AESI)
9. Serious Adverse Events Within 6 Months Following FMT [ Time Frame: Month 6 (±14 days) phone safety assessment after randomization ]
   Percentage of participants with a Serious Adverse Event (SAE)

Other Outcome Measures:

1. Microbiome Disruption [ Time Frame: Day 3, day 10, week 4 after randomization. ]
   To evaluate the microbiome disruption index (MDI) by 16s rRNA sequencing): MDI-community and MDI-species
2. Engraftment Dynamics [ Time Frame: 6 months following FMT ]
   To evaluate the trends in VRE type/strain-level engraftment using whole genome sequencing among those colonized

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Adults 18 years or older at the time of enrollment.
• Able to provide signed and dated informed consent.
• Identified as VRE-positive by a stool culture within last 14 days.
• Women of childbearing potential in sexual relationships with men must use an acceptable method of contraception§ from 30 days prior to enrollment until 4 weeks after completing study treatment.

• Males must agree to avoid impregnation of women during and for four weeks after completing study treatment through use of an acceptable method of contraception*.

  • Includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 30 days prior to study enrollment), intercourse with men who underwent vasectomy.

    • Includes, but is not limited to, barrier with additional spermicidal foam or jelly and vasectomy.

Exclusion Criteria:

• Female patient who are pregnant, lactating or planning on becoming pregnant during study. Female patients of childbearing potential will undergo a pregnancy test, and be excluded from the study if positive.
• Inability (e.g. dysphagia) to or unwilling to swallow capsules.
• Active antibiotic resistant bacteria (ARB) or gastrointestinal infection at time of enrollment.
• Patient received antibiotics in the last 48 hours. Patients will be eligible to enroll if antibiotic therapy is discontinued for at minimum 48 hours prior to randomization. Does not include antibiotics used for prophylaxis or topical antibiotics.
• Requires continued antibiotic use or anticipates antibiotic use in the upcoming 4 weeks. Does not include antibiotics used for prophylaxis or topical antibiotics.
• Unwilling to withhold probiotics for a minimum of 48 hours prior to providing a screening stool sample.
• Known or suspected toxic megacolon and/or known small bowel ileus.
• Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment. This does not include appendectomy or cholecystectomy.
• History of total colectomy or bariatric surgery.
• Admitted to or expected to an intensive care unit for medical reasons (not just boarding). Patients residing in a nursing home, long-term care facility or rehabilitation center may be enrolled.
• Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for active malignancy. Patients on maintenance chemotherapy may be enrolled only after consultation with medical monitor.
• Unable or unwilling to comply with protocol requirements.
• Expected life expectancy < 6 months
• Previous FMT or microbiome-based products at any time excluding this study.
• Patients with a history of severe anaphylactic or anaphylactoid food allergy.
• Solid organ transplant recipients ≤ 90 days post-transplant or on active treatment for rejection.
• Neutropenia (≤500 neutrophils/mL) or other severe immunosuppression. Anti-TNF will be permitted. Patients on monoclonal antibodies to B and T cells. glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine, methotrexate), calcineurin inhibitors (tacrolimus, cyclosporine) and mycophenolate mofetil may be enrolled only after consultation with the medical monitor.
• If at risk for CMV/EBV associated disease (at investigator's discretion, e.g. immunocompromised), negative IgG testing for cytomegalovirus (CMV) or Epstein Barr Virus (EBV).
• A condition that would jeopardize the safety or rights of the subject, would make it unlikely for the subject to complete the study, or would confound the results of the study.

Contacts and Locations

Locations

United States, Indiana

IU Health University Hospital

Indianapolis, Indiana, United States, 46202

United States, Wisconsin

University of Wisconsin University Hospital

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Microbiome Health Research Institute

University of Wisconsin, Madison

Indiana University

Investigators

• Principal Investigator: Majdi Osman, MD, MPH; Microbiome Health Research Institute d/b/a OpenBiome

  Study Documents (Full-Text)

Documents provided by Microbiome Health Research Institute:

Study Protocol and Statistical Analysis Plan  [PDF] September 9, 2019

More Information

• Responsible Party: Microbiome Health Research Institute
• ClinicalTrials.gov Identifier: NCT03063437
• Other Study ID Numbers: 200-2016-91948
• First Posted: February 24, 2017
• Results First Posted: February 5, 2020
• Last Update Posted: April 13, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Microbiome Health Research Institute:

vancomycin resistant enterococcus; VRE; decolonization; VRE colonization; fecal microbiota transplantation; FMT; FMT capsule; capsule; antimicrobial resistance; antibiotic resistance; MDRO; multidrug-resistant organism; OpenBiome

Additional relevant MeSH terms:

Sprains and Strains; Wounds and Injuries