RACE: Autologous Fecal Microbiota Transplantation to Prevent Antibiotic Resistant Bacteria Colonization
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (autologous fecal microbiota preparation) Participants randomized into the treatment arm will receive a single dose of autologous fecal microbiota preparation (auto-FMP) via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. Route of Administration: Enema Dosing Regimen: 125mL x 1 dose |
Biological: Autologous fecal microbiota transplant (Auto-FMP Enema)
FMT is the process by which processed donor microbiota material is transplanted into recipients. The aim is to reconstitute the normal intestinal microbial flora in recipients. In this study, the fecal microbiota preparation will be made from the participant's own stool and processed into an auto-FMP enema formulation.
|
| Placebo Comparator: Placebo Participants randomized to the placebo arm will receive a single dose of placebo FMT via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. |
Other: Placebo Enema Preparation
The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events (NIH Grade ≥2) at Day 7 After Randomization [Day 7 after randomization]
Number of participants with NIH Grade ≥2 adverse events at Day 7 after randomization.
Secondary Outcome Measures
- Number of Patients With Clearance of Antibiotic Resistant Bacteria (ARB) [Day 28 after randomization]
Number of patients with clearance of ARB among patients colonized at Day 28 by Polymerase Chain Reaction (PCR) assay or culture-based assay. ARBs are: Carbapenem-resistant Enterobacteriaceae (CRE) by PCR or culture assay, Extended spectrum beta-lactamase (ESBL)-producing organisms by PCR or culture assay, Vancomycin-resistant enterococci (VRE) by PCR or culture assay, or Clostridium difficile by PCR
- Number of Participants Who Develop Any ARB-associated Infections [Day 3, Day 7, Day 28, Month 6]
Number of participants who develop any ARB-associated infections following autologous FMT at Day 3, Day 7, Day 28, and Month 6
- Number of Participants With NIH Grade ≥2 AEs at Day 28 and Month 6 [Day 28, Month 6]
Number of participants with NIH Grade ≥2 adverse events (intermediate at Day 28 and long-term at Month 6) following autologous FMT.
Other Outcome Measures
- Microbiome Disruption Indices (MDI) (16S rRNA Sequencing) [Day 0, Day 3, Day 7, Day 28]
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)
Eligibility Criteria
Criteria
Inclusion criteria for study enrollment
-
Long-term care residents associated with Boston University-Boston Medical Center nursing home consortium
-
Adults (18 years or older)
Inclusion criteria for randomization
- Infection requiring antimicrobial treatment at the discretion of the treating physician
Exclusion criteria for study enrollment
-
Pregnant. Participants of childbearing age will undergo urine pregnancy testing
-
Participant or substitute decision maker unable to provide informed consent
-
Allergies to following ingredients generally recognized as safe: glycerol and sodium chloride
-
Current enrollment in hospice
-
Colostomy
-
Unable to adhere to protocol requirements
-
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
-
Recent travel (last six months) to high risk regions based on the International SOS Medical Risk Rating system
-
Recent exposure (last six months) to unsafe drinking water
Exclusion criteria for stool collection
Enrollment stool sample will be tested for ARBs and processed into autologous FMT treatment (if of qualifying size). Sample will not be collected if any of the following are true:
-
Oral or intravenous antibiotic exposure within the previous 6 weeks of stool collection date (topical antibiotics will be permitted)
-
Active gastrointestinal infection at stool collection
-
Fever at the time of stool collection
-
Currently ill or complaining of any of the following signs or symptoms of illness: fever, diarrhea, blood stools and/or vomiting
-
Participants with a history of gastrointestinal (GI) illness within the past 30 days prior to enrollment stool collection, that at the discretion of the site investigator could reasonably be caused by one of the following pathogens: 1) Vibrio spp. 2) Norovirus 3) Rotovirus 4) Adenovirus 5) Shiga toxin
Exclusion criteria for randomization
-
Colonized with CRE (assessed by PCR or culture assay during enrollment phase)
-
Colonized with VRE (assessed by PCR or culture assay during enrollment phase)
-
Colonized with ESBL (assessed by PCR or culture assay during enrollment phase)
-
Colonized with CDI (assessed by EIA assay on stool collected at enrollment phase)
-
Treatment with antibiotics which are active against MRSA (i.e. vancomycin or linezolid) prior to randomization to FMT intervention or placebo.
-
Stool culture positive for common enteric pathogens (Salmonella spp., Shigella spp., Campylobacter spp.)
-
Participants who develop a GI illness with symptoms such as (but not limited to) vomiting or diarrhea within 30 days after collection of enrollment stool will be evaluated by the site investigator. If the site investigator determines that the symptoms were most likely caused by 1) Vibrio spp., 2) Norovirus, 3) Rotavirus, 4) Adenovirus, or 5) Shiga toxin, the enrollment stool will be sent out to test for these organisms. If the culture is positive for any of these organisms, the participant will be excluded from randomization
-
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
-
Participants who become severely immunocompromised, as defined by the investigator or treating physician, will be excluded prior to receiving intervention
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Boston University - Boston Medical Center nursing home consortium | Boston | Massachusetts | United States | 02118 |
Sponsors and Collaborators
- Microbiome Health Research Institute
- Boston Medical Center
Investigators
- Principal Investigator: Majdi Osman, MD, MPH, Microbiome Health Research Institute, (d/b/a OpenBiome)
Study Documents (Full-Text)
More Information
Publications
None provided.- 200201691946
Study Results
Participant Flow
| Recruitment Details | We enrolled 78 patients across four nursing homes from July 10, 2017 to June 30, 2018. Of these 78, a total of 33 individuals were able to provide a stool sample of sufficient quantity to undergo procedures required for preparation of autologous FMT. As specified in the protocol, only participants that had stool processed into autologous FMT and subsequently received a course of antibiotics will undergo randomization. Out of the 33 eligible participants, a total of 7 were ultimately randomized |
|---|---|
| Pre-assignment Detail | Of the 7 randomized participants, 3 participants withdrew prior to administration of FMT. A total of 26 enrolled participants were withdrawn or discontinued prior to randomization for reasons including: enrollment in hospice care, passing away from age-related comorbidities, withdrawal of consent, and non-compliance. The remaining 45 enrolled participants were removed at study closure since they did not meet criteria for randomization at the time of closure. |
| Arm/Group Title | Treatment (Autologous Fecal Microbiota Preparation) | Placebo |
|---|---|---|
| Arm/Group Description | Participants randomized into the treatment arm will receive a single dose of autologous fecal microbiota preparation (auto-FMP) via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. Route of Administration: Enema Dosing Regimen: 125mL x 1 dose Autologous fecal microbiota transplant (Auto-FMP Enema): FMT is the process by which processed donor microbiota material is transplanted into recipients. The aim is to reconstitute the normal intestinal microbial flora in recipients. In this study, the fecal microbiota preparation will be made from the participant's own stool and processed into an auto-FMP enema formulation. | Participants randomized to the placebo arm will receive a single dose of placebo FMT via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. Placebo Enema Preparation: The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. |
| Period Title: Overall Study | ||
| STARTED | 4 | 3 |
| COMPLETED | 4 | 0 |
| NOT COMPLETED | 0 | 3 |
Baseline Characteristics
| Arm/Group Title | Treatment (Autologous Fecal Microbiota Preparation) | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Participants randomized into the treatment arm will receive a single dose of autologous fecal microbiota preparation (auto-FMP) via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. Route of Administration: Enema Dosing Regimen: 125mL x 1 dose Autologous fecal microbiota transplant (Auto-FMP Enema): FMT is the process by which processed donor microbiota material is transplanted into recipients. The aim is to reconstitute the normal intestinal microbial flora in recipients. In this study, the fecal microbiota preparation will be made from the participant's own stool and processed into an auto-FMP enema formulation. | Participants randomized to the placebo arm will receive a single dose of placebo FMT via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. Placebo Enema Preparation: The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. | Total of all reporting groups |
| Overall Participants | 4 | 3 | 7 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
4
100%
|
3
100%
|
7
100%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
1
25%
|
2
66.7%
|
3
42.9%
|
| Male |
3
75%
|
1
33.3%
|
4
57.1%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
50%
|
2
66.7%
|
4
57.1%
|
| White |
2
50%
|
1
33.3%
|
3
42.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
4
100%
|
3
100%
|
7
100%
|
Outcome Measures
| Title | Number of Participants With Adverse Events (NIH Grade ≥2) at Day 7 After Randomization |
|---|---|
| Description | Number of participants with NIH Grade ≥2 adverse events at Day 7 after randomization. |
| Time Frame | Day 7 after randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| All three (3) participants assigned to placebo arm withdrew post-randomization but pre-treatment administration. One (1) participant was outside of treatment window following antibiotic exposure and therefore no longer eligible to receive the treatment. Two (2) participants withdrew consent prior to administration of the intervention. |
| Arm/Group Title | Treatment (Autologous Fecal Microbiota Preparation) | Placebo |
|---|---|---|
| Arm/Group Description | Participants randomized into the treatment arm will receive a single dose of autologous fecal microbiota preparation (auto-FMP) via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. Route of Administration: Enema Dosing Regimen: 125mL x 1 dose Autologous fecal microbiota transplant (Auto-FMP Enema): FMT is the process by which processed donor microbiota material is transplanted into recipients. The aim is to reconstitute the normal intestinal microbial flora in recipients. In this study, the fecal microbiota preparation will be made from the participant's own stool and processed into an auto-FMP enema formulation. | Participants randomized to the placebo arm will receive a single dose of placebo FMT via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. Placebo Enema Preparation: The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. |
| Measure Participants | 4 | 0 |
| Count of Participants [Participants] |
4
100%
|
0
0%
|
| Title | Number of Patients With Clearance of Antibiotic Resistant Bacteria (ARB) |
|---|---|
| Description | Number of patients with clearance of ARB among patients colonized at Day 28 by Polymerase Chain Reaction (PCR) assay or culture-based assay. ARBs are: Carbapenem-resistant Enterobacteriaceae (CRE) by PCR or culture assay, Extended spectrum beta-lactamase (ESBL)-producing organisms by PCR or culture assay, Vancomycin-resistant enterococci (VRE) by PCR or culture assay, or Clostridium difficile by PCR |
| Time Frame | Day 28 after randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| All three (3) participants assigned to placebo arm withdrew post-randomization but pre-treatment administration. One (1) participant was outside of treatment window following antibiotic exposure and therefore no longer eligible to receive the treatment. Two (2) participants withdrew consent prior to administration of the intervention. |
| Arm/Group Title | Treatment (Autologous Fecal Microbiota Preparation) | Placebo |
|---|---|---|
| Arm/Group Description | Participants randomized into the treatment arm will receive a single dose of autologous fecal microbiota preparation (auto-FMP) via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. Route of Administration: Enema Dosing Regimen: 125mL x 1 dose Autologous fecal microbiota transplant (Auto-FMP Enema): FMT is the process by which processed donor microbiota material is transplanted into recipients. The aim is to reconstitute the normal intestinal microbial flora in recipients. In this study, the fecal microbiota preparation will be made from the participant's own stool and processed into an auto-FMP enema formulation. | Participants randomized to the placebo arm will receive a single dose of placebo FMT via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. Placebo Enema Preparation: The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. |
| Measure Participants | 4 | 0 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Number of Participants Who Develop Any ARB-associated Infections |
|---|---|
| Description | Number of participants who develop any ARB-associated infections following autologous FMT at Day 3, Day 7, Day 28, and Month 6 |
| Time Frame | Day 3, Day 7, Day 28, Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All three (3) participants assigned to placebo arm withdrew post-randomization but pre-treatment administration. One (1) participant was outside of treatment window following antibiotic exposure and therefore no longer eligible to receive the treatment. Two (2) participants withdrew consent prior to administration of the intervention. |
| Arm/Group Title | Treatment (Autologous Fecal Microbiota Preparation) | Placebo |
|---|---|---|
| Arm/Group Description | Participants randomized into the treatment arm will receive a single dose of autologous fecal microbiota preparation (auto-FMP) via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. Route of Administration: Enema Dosing Regimen: 125mL x 1 dose Autologous fecal microbiota transplant (Auto-FMP Enema): FMT is the process by which processed donor microbiota material is transplanted into recipients. The aim is to reconstitute the normal intestinal microbial flora in recipients. In this study, the fecal microbiota preparation will be made from the participant's own stool and processed into an auto-FMP enema formulation. | Participants randomized to the placebo arm will receive a single dose of placebo FMT via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. Placebo Enema Preparation: The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. |
| Measure Participants | 4 | 0 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Number of Participants With NIH Grade ≥2 AEs at Day 28 and Month 6 |
|---|---|
| Description | Number of participants with NIH Grade ≥2 adverse events (intermediate at Day 28 and long-term at Month 6) following autologous FMT. |
| Time Frame | Day 28, Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All three (3) participants assigned to placebo arm withdrew post-randomization but pre-treatment administration. One (1) participant was outside of treatment window following antibiotic exposure and therefore no longer eligible to receive the treatment. Two (2) participants withdrew consent prior to administration of the intervention. Note: the 1 participant who experienced Grade ≥2 adverse events experienced a total of two (2) adverse events by Month 6. |
| Arm/Group Title | Treatment (Autologous Fecal Microbiota Preparation) | Placebo |
|---|---|---|
| Arm/Group Description | Participants randomized into the treatment arm will receive a single dose of autologous fecal microbiota preparation (auto-FMP) via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. Route of Administration: Enema Dosing Regimen: 125mL x 1 dose Autologous fecal microbiota transplant (Auto-FMP Enema): FMT is the process by which processed donor microbiota material is transplanted into recipients. The aim is to reconstitute the normal intestinal microbial flora in recipients. In this study, the fecal microbiota preparation will be made from the participant's own stool and processed into an auto-FMP enema formulation. | Participants randomized to the placebo arm will receive a single dose of placebo FMT via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. Placebo Enema Preparation: The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. |
| Measure Participants | 4 | 0 |
| Count of Participants [Participants] |
1
25%
|
0
0%
|
| Title | Microbiome Disruption Indices (MDI) (16S rRNA Sequencing) |
|---|---|
| Description | 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) |
| Time Frame | Day 0, Day 3, Day 7, Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | Adverse events were collected for 6 months after randomization. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | For the placebo arm: All three (3) participants assigned to placebo arm withdrew post-randomization but pre-treatment administration. One (1) participant was outside of treatment window following antibiotic exposure and therefore no longer eligible to receive the treatment. Two (2) participants withdrew consent prior to administration of the intervention. | |||
| Arm/Group Title | Treatment (Autologous Fecal Microbiota Preparation) | Placebo | ||
| Arm/Group Description | Participants randomized into the treatment arm will receive a single dose of autologous fecal microbiota preparation (auto-FMP) via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. Route of Administration: Enema Dosing Regimen: 125mL x 1 dose Autologous fecal microbiota transplant (Auto-FMP Enema): FMT is the process by which processed donor microbiota material is transplanted into recipients. The aim is to reconstitute the normal intestinal microbial flora in recipients. In this study, the fecal microbiota preparation will be made from the participant's own stool and processed into an auto-FMP enema formulation. | Participants randomized to the placebo arm will receive a single dose of placebo FMT via enema following an infectious episode requiring antibiotics, with follow-up at day 3, 7, 28, and 6 months. The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. Placebo Enema Preparation: The placebo enema preparation will be identical in appearance but will not contain human feces to prevent unmasking of the trial arms. | ||
All Cause Mortality |
||||
| Treatment (Autologous Fecal Microbiota Preparation) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 0/0 (NaN) | ||
Serious Adverse Events |
||||
| Treatment (Autologous Fecal Microbiota Preparation) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 0/0 (NaN) | ||
| Gastrointestinal disorders | ||||
| Nausea | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| General disorders | ||||
| Death | 2/4 (50%) | 2 | 0/0 (NaN) | 0 |
| Pyrexia | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Infections and infestations | ||||
| Pneumonia | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Sepsis | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Neoplasm malignant | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Renal and urinary disorders | ||||
| Urinary tract infection | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Pneumonia aspiration | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Treatment (Autologous Fecal Microbiota Preparation) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 0/0 (NaN) | ||
| Gastrointestinal disorders | ||||
| Diarrhea | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Vascular disorders | ||||
| Hemorrhoids | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Majdi Osman, MD, MPH |
|---|---|
| Organization | Microbiome Health Research Institute |
| Phone | 617-575-2201 |
| majdi@openbiome.org |
- 200201691946