This study, a Randomized controlled trial of Autologous microbiome reconstitution to prevent Colonization by antibiotic rEsistant bacteria (RACE), seeks to investigate the safety, feasibility and the role of autologous fecal microbiota transplantation (FMT) for the prevention of antibiotic resistant bacteria (ARB) through microbiome restoration.
Full Title of Study: “Randomized Controlled Trial of Autologous Microbiome Reconstitution to Prevent Colonization by Antibiotic rEsistant Bacteria”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Prevention
- Masking: Triple (Participant, Care Provider, Investigator)
- Study Primary Completion Date: December 19, 2018
- Biological: Autologous fecal microbiota transplant
- Fecal Microbiota Transplant (FMT) FMT is the process by which processed donor microbiota material is transplanted into recipients, by either upper or lower gastrointestinal delivery. The aim is to reconstitute the normal intestinal microbial flora in recipients. FMT can be administered by either enema or capsule depending on eligibility criteria. In this study, the fecal microbiota preparation will be made from the participant’s own stool (autologous FMT).
- Other: Placebo
- Placebo FMT material delivered via enema.
Arms, Groups and Cohorts
- Experimental: Treatment (autologous fecal microbiota preparation)
- Autologous treatment preparation: Patient stool will be collected and processed into an auto-fecal microbiota preparation (FMP) formulation. In this treatment arm, the auto-FMP will be administered to the participant following an infectious episode requiring antibiotics. V-A Auto-FMP Enema (125 mL): Route of Administration: Enema nozzle will be inserted into rectum and contents expelled into the distal colon. Target dwell time is 1 hour. Participants will lie in the left lateral decubitas position but if mobility permits will rotate to supine and right lateral decubitus position. Dosing Regimen: 125mL x 1 dose
- Placebo Comparator: Placebo
- Participants randomized to the placebo arm will receive a placebo FMT via enema. The placebo enema preparation interventional enema in appearance. The placebo enema preparation will be comprised of Sodium Chloride (0.9%, USP), Glycerol (12.5%, USP), and 8-12 drops brown food coloring (<1%), to prevent unmasking of the trial arms.
Clinical Trial Outcome Measures
- Safety (short-term) defined as absence of NIH Grade ≥2 adverse events including IND safety reporting criteria
- Time Frame: 7 days
- Safety (short-term) at day 7 defined as absence of NIH Grade ≥2 adverse events including IND safety reporting criteria
- Microbiome Disruption Index (MDI)
- Time Frame: Day 0, Day 3, Day 7, and Day 28
- Microbiome disruption indices (16S rRNA sequencing): MDI-community and MDI-species at baseline (pre-infection on the date of stool collection), post-antibiotics on the intervention/placebo date (Day 0, Day 3, Day 7, and Day 28). MDI will be applied to pre- and post-intervention communities in comparison to baseline and reference communities.
- ARB Colonization
- Time Frame: Day 0, Day 3, Day 7, and Day 28
- Rate of ARB clearance among patients with ARB colonization
- ARB-associated clinical infectionDay 3, Day 7, Day 28, and Month 6.
- Time Frame: Day 3, Day 7, Day 28, and Month 6
- Composite endpoint for presence of any ARB-associated clinical infection
- Safety (intermediate and long-term) defined as NIH Grade ≥2 adverse events.
- Time Frame: Day 28 and Month 6
- Safety (intermediate at Day 28 and long-term at Month 6) defined as NIH Grade ≥2 adverse events.
Participating in This Clinical Trial
Inclusion criteria for study enrollment
1. Long-term care residents in Boston
2. Adults (18 years or older)
Inclusion criteria for randomization
1) Infection requiring antimicrobial treatment at the discretion of the treating physician
Exclusion criteria for study enrollment
1. Oral or intravenous antibiotic exposure within the previous 6 weeks of stool collection date. -Topical antibiotics will be permitted
2. Gastrointestinal (GI) symptoms such as (but not limited to) vomiting or diarrhea 30 days prior to stool collection
3. Participant or substitute decision maker unable to provide informed consent
4. Active gastrointestinal infection at stool collection
5. Fever at the time of stool collection
6. Patients with allergies to following ingredients Generally Recognized as Safe: glycerol and sodium chloride
7. Life expectancy <6 months
8. Unable to adhere to protocol requirements
9. Any condition that the physician investigators deems unsafe, including other conditions or medications that the investigator determines puts the participant at greater risk from FMT
10. Stool culture positive for common enteric pathogens (Salmonella spp., Shigella spp., Campylobacter spp.)
11. Recent travel (last six months) to high risk regions based on the International SOS Medical Risk Rating system
12. Recent exposure (last six months) to unsafe drinking water
Exclusion criteria for randomization
- History of gastrointestinal (GI) symptoms such as (but not limited to) vomiting or diarrhea 30 days post collection of enrollment stool.
- Stool testing positive for common enteric pathogens
- Colonized with CRE (assessed by PCR assay on stool collected at biobanking phase)
- Colonized with VRE (assessed by PCR assay on stool collected at biobanking phase)
- Colonized with ESBL (assessed by PCR assay on stool collected at biobanking phase)
- Colonized with CDI (assessed by EIA assay on stool collected at biobanking phase)
- Treatment with antibiotics which are active against MRSA (i.e. vancomycin or linezolid) prior to randomization to FMT intervention or placebo.
- Any condition that the physician investigators deems unsafe
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: N/A
Are Healthy Volunteers Accepted: Accepts Healthy Volunteers
- Lead Sponsor
- Microbiome Health Research Institute
- Boston Medical Center
- Provider of Information About this Clinical Study
- Overall Official(s)
- Zain Kassam, MD, Principal Investigator, Microbiome Health Research Institute, (d/b/a OpenBiome)
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