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Principal Investigator: Jeremiah James Faith
Organization: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Fiscal Year: 2024
Award: $324,480
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
PROJECT SUMMARY
The treatment of recurrent Clostridioides difficile infection (rCDI) by fecal microbiota transplantation (FMT) is
the defining success amongst therapeutics aimed to manipulate the microbiome with cure rates typically
exceeding 80% of recipients. This success has facilitated numerous clinical trials yielding important insights
that have advanced clinical care including the quantification of the durable stability of frozen fecal slurries that
enabled stool biobanks, the studies of fecal slurry administration that compared efficacies across
administration routes of oral, colonoscopic, and nasogastric, and the application of FMT in other conditions
including ulcerative colitis where it appears to have modest efficacy. However, the use of complex fecal slurries
as a therapy is a challenge due to our inability to completely determine the safety of a product that varies with
each FMT donor, including some that have transmitted opportunistic pathogens that led to serious adverse
events. The scaling of FMT is also a challenge, as the drug material is sourced from individual human
donations that are finite in supply and labor intensive to process into the final product. We propose to
administer live biotherapeutic products (LBP) as an alternative to FMT. We have isolated the strains for this
LBP from known-successful FMT donors allowing us to compare (Aim 1) the clinical response and (Aim 2) the
microbial engraftment of the FMT with that of the LBP. The LBP was specifically designed to contain prevalent
human gut microbes that have engrafted in a majority of recipients and that are not associated with severe
adverse events in prior FMT studies. The results from this pilot and feasibility clinical trial (60 subjects, N=30
FMT and N=30 LBP) will provide important safety data, clinical insights, and basic science results to advance
the potential of LBPs as novel therapeutics.
Terms: <Acceleration><Adverse Experience><Adverse event><After Care><After-Treatment><Aftercare><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Bacteria><Basic Research><Basic Science><Biological Response Modifier Therapy><Biological Therapy><C diff><C difficile><C. diff><C. difficile><COVID-19 transmission><COVID-19 virus transmission><Cessation of life><Clinical><Clinical Trials><Clostridioides difficile><Clostridium difficile><Collection><Communities><Complex><Coupled><Data><Death><Dependence><Diarrhea><Donor person><Drugs><E coli><E. coli><E. coli produce shiga toxin><EHEC><EPEC><Engraftment><Enterohemorrhagic E. coli><Enterohemorrhagic Escherichia coli><Enterohemorrhagic strain of E. coli><Enterohemorrhagic strain of Escherichia coli><Escherichia coli><Escherichia coli EHEC><Extended-spectrum beta-lactamase><Extended-spectrum β-lactamase><Feces><Freezing><GI microbiota><Gastrointestinal microbiota><Healthcare><Human><In Vitro><Individual><Infection><Investigation><Laboratories><Medication><Miscellaneous Antibiotic><Modern Man><Oral><Organism><Patients><Pharmaceutical Preparations><Process><Randomized><Randomized, Controlled Trials><Recurrence><Recurrent><Relapse><Reporting><Risk><Route><SARS-CoV-2 transmission><Safety><Selection Criteria><Serious Adverse Event><Severe Adverse Event><Shiga toxigenic E. coli><Shiga toxigenic Escherichia coli><Shiga toxin containing E. coli><Shiga toxin containing Escherichia coli><Shiga toxin producing E. coli><Shiga toxin secreting E. coli><Shiga toxin secreting Escherichia coli><Shiga toxin-producing Escherichia coli><Single-Blind Study><Single-blind><Source><Therapeutic><Translations><Transmission><Transplant Recipients><Transplantation><Ulcerated Colitis><Ulcerative Colitis><Vancomycin><active comparator><active comparison control><anti-microbial><antimicrobial><biobank><biological therapeutic><biological treatment><biologically based therapeutics><biorepository><biotherapeutics><biotherapy><clinical applicability><clinical application><clinical care><comparable efficacy><comparative efficacy><compare efficacy><coronavirus disease 2019 transmission><coronavirus disease 2019 virus transmission><cost effective><death risk><density><design><designing><drug/agent><enteric microbial community><enteric microbiota><enteropathogenic E coli><enteropathogenic E. coli><enteropathogenic E.coli><enteropathogenic Escherichia coli><fecal microbial transplantation><fecal microbiome transplantation><fecal microbiota transplant><fecal microbiota transplantation><fecal sample><fecal transplant><fecal transplantation><fitness><gastrointestinal microbial flora><gut commensal><gut community><gut flora><gut microbe community><gut microbes><gut microbial community><gut microbial composition><gut microbial consortia><gut microbial species><gut microbiota><gut microbiotic><gut microflora><health care><improved><in vitro Model><in vivo><individual response><individualized response><insight><intestinal flora><intestinal microbes><intestinal microbiota><intestinal microflora><intestinal tract microflora><living system><manufacture><manufacturing process><microbial><microbiome><mortality risk><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><open label><open label study><opportunistic pathogen><pathogen><post treatment><prevent relapse><programs><randomisation><randomization><randomized control trial><randomly assigned><relapse prediction><relapse prevention><response><restoration><serious adverse experience><serious adverse reaction><severe acute respiratory syndrome coronavirus 2 transmission><stool><stool sample><stool specimen><success><translation><transmission process><transmitted COVID-19><transmitted SARS-CoV-2><transmitted coronavirus disease 2019><transmitted severe acute respiratory syndrome coronavirus 2><transplant><transplant donor><transplant patient><transplant therapy><transplant treatment><transplantation therapy><transplantation treatment><viral transmission><virus transmission>