Clinical trial NCT03063437: A Trial of Encapsulated Fecal Microbiota for Vancomycin Resistant Enterococcus Decolonization
Official title: Phase II Randomized, Double Blind, Placebo-controlled, Parallel Group Trial of Encapsulated Fecal Microbiota Transplantation for Vancomycin Resistant Enterococcus Decolonization
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Antibiotic Resistant Strain
Keywords: vancomycin resistant enterococcus
VRE
decolonization
VRE colonization
fecal microbiota transplantation
FMT
FMT capsule
capsule
antimicrobial resistance
antibiotic resistance
MDRO
multidrug-resistant organism
OpenBiome
Lead sponsor: Microbiome Health Research Institute
Sponsor class: OTHER
Collaborators: name: University of Wisconsin, Madison
name: Indiana University
First posted: 2017-02-24
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With VRE Decolonization
timeFrame: Day 10 (±3 days) after randomization
measure: 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)
timeFrame: Day 10 (±3 days) after randomization
Secondary outcomes:
measure: Percentage of Participants With VRE Infection
timeFrame: Week 4 (±5 days) after randomization
measure: Percentage of Participants With ARB Colonization on Day 10 Following Fecal Microbiota Transplantation (FMT)
timeFrame: Day 10 (± 3 days) after randomization
measure: Percentage of Participants With ARB Infection 4 Weeks Following FMT
timeFrame: Week 4 (±5 days) after randomization
measure: Number of Days Between FMT and VRE Colonization and Infection Occurs
timeFrame: Up to 6 months after randomization
measure: VRE Decolonization Among Immunocompromised Patients
timeFrame: Day 10 (± 3 days) after randomization
measure: Adverse Events Within 4 Weeks Following FMT
timeFrame: Week 4 (±5 days) after randomization
measure: Serious Adverse Events Within 4 Weeks Following FMT
timeFrame: Week 4 (±5 days) after randomization
measure: Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI)
timeFrame: Week 4 (±5 days) after randomization
measure: Serious Adverse Events Within 6 Months Following FMT
timeFrame: Month 6 (±14 days) phone safety assessment after randomization
Other outcomes:
measure: Microbiome Disruption
timeFrame: Day 3, day 10, week 4 after randomization.
measure: Engraftment Dynamics
timeFrame: 6 months following FMT
Locations:
city: Indianapolis
country: United States
facility: IU Health University Hospital
state: Indiana
city: Madison
country: United States
facility: University of Wisconsin University Hospital
state: Wisconsin
Study officials:
affiliation: Microbiome Health Research Institute d/b/a OpenBiome
name: Majdi Osman, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: