Fecal Microbiota Transplantation for Clostridioides difficile Colitis
Trial Summary
What is the purpose of this trial?
The study is on indefinite HOLD due to the loss of funding that occurred during the pandemic emergency. Subsequently, a key collaborator left our institution, and as a near-term result, the protocol awaits reactivation. Three patient subjects were enrolled, all 3 patients/subjects were cured of the infection, and there were no adverse events or sequelae observed or reported. The aim of the study continues to confirm and extend the work of Trede and Rask-Madsen (Lancet 1989;1:1156-1160) that administration of a defined fecal microbiota will lead to rapid and sustained resolution of C. difficile-associated chronic relapsing diarrhea. FDA required 4 non-geriatric qualified patients to be studied before including the elderly. However, C. difficile-associated chronic relapsing diarrheal illness is predominantly a disease of the elderly, so this requirement GREATLY impeded timely enrollment. No protocol deviations have occurred. The current rationale behind FMT for CDI is that the introduction of microbes from a healthy donor should allow for the restoration of a normal microbial community in the diseased host with consequent suppression of C. difficile colonization and disease pathogenesis. The first modern use of FMT was reported in a 1958 case series of 4 patients with pseudomembranous enterocolitis. The first case of confirmed CDI treated with FMT was reported in 1983; treatment was curative. Until 1989, retention enemas were the most common technique for FMT. Alternative methods for delivering FMT have included fecal infusion via duodenal tube (1991), rectal tube (1994), and colonoscopy (1998). FMT for recurrent CDI has been used successfully, whether administered by nasogastric tube, rectal administration by colonoscopy, or rectal tube, including self-administration at home by enema. FMT has proven to be remarkably effective and remarkably safe without any significant problems (see below and attached reviews and meta-analyses). Increasing interest is emerging regarding the changes in the intestinal microbiota associated with CDI. In 2008 Chang et al. constructed small (\< 200 sequences per subject) 16S rRNA gene libraries from the stools of 4 patients with first-time CDI and 3 patients with recurrent CDI. Based on 16S rRNA gene classification, they found that the fecal microbiomes of patients with an initial episode of CDI were similar at the phylum level to healthy subjects (i.e., the majority of sequences belonged to dominant fecal phyla Bacteroidetes and Firmicutes), while a major reduction or loss of Bacteroidetes was observed in patients with recurrent CDI. The loss of the Bacteroidetes was accompanied by the expansion of other phyla, including Proteobacteria and Verrucomicrobia, which are normally minor constituents of the fecal microbiota. Khoruts et al. (2010) compared the microbiota of a patient with recurrent CDI before and after FMT by using terminal-restriction fragment length polymorphism and clone-based 16S rRNA gene sequencing. Before transplantation, the patient's microbiota was deficient in members of Bacteroides and instead was composed of atypical fecal genera such as Veillonella, Clostridium, Lactobacillus, Streptococcus, and unclassified bacteria similar to Erysipelothrix. Two weeks after the infusion of donor fecal suspension, the bacterial composition of her feces approached normal and was dominated by Bacteroides sp. strains. In 1989, Tvede and Rask-Madsen used a combination of nine normal fecal organisms to treat 6 patients with chronic relapsing C. difficile diarrhea. These investigators cultivated 10 strains of bacteria, including Enterococcus (Streptococcus) faecalis (1108-2), Clostridium inoculum (A27-24), Clostridium ramosum (A3I-3), Bacteroides ovatus (A40-4), Bacteroides vulgatus (A33-14), Bacteroides thetaiotaomicron (A33-12), Escherichia coli (1109), E. coli (1108-1), Clostridium bifermentans (A27-6), and Blautia producta (Peptostreptococcus productus) (1108-2) in broth for 48 h to a concentration of approximately 10 to the 9th power bacteria/mL. Two mL from each bacterial culture were admixed with 180 mL saline that had been pretreated in an anaerobic chamber for 24 h; the bacterial suspension was then instilled rectally. This procedure was followed promptly by a decline of C. difficile to undetectable levels by culture and the loss of detectable toxin from the stools. Normal bowel function was restored within 24 hours, and abdominal symptoms disappeared. Stool cultures and toxin assays for C. difficile remained negative during a year of follow-up. It is especially important to note that feces from none of the 6 patients contained Bacteroides sp.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you are on major immunosuppressive drugs or require ongoing antimicrobial therapy, you may not be eligible to participate.
What data supports the effectiveness of the treatment Defined Fecal Microbiota Transplantation for Clostridioides difficile Colitis?
Research shows that fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection, with cure rates over 90% reported from multiple centers. This treatment works by restoring the balance of bacteria in the gut, which helps to stop the infection from coming back.12345
Is fecal microbiota transplantation (FMT) safe for humans?
FMT is generally considered safe and well-tolerated, even in high-risk patients, with most short-term risks being mild and related to the delivery method. However, long-term side effects are not well-established, and there have been serious adverse events linked to inadequate screening for multi-drug resistant organisms in some FMT products.16789
How is fecal microbiota transplantation different from other treatments for Clostridioides difficile colitis?
Fecal microbiota transplantation (FMT) is unique because it involves transferring stool from a healthy donor to a patient to restore the natural balance of bacteria in the gut, which is disrupted in Clostridioides difficile colitis. Unlike antibiotics, which can sometimes worsen the imbalance, FMT directly replenishes beneficial bacteria, leading to high cure rates of over 90% for recurrent infections.1241011
Research Team
David Y Graham, MD
Principal Investigator
Baylor College of Medicine
Antone R Opekun, MS, PA-C
Principal Investigator
Baylor College of Medicine
Eligibility Criteria
This trial is for VA patients with confirmed C. difficile infection (CDI) that persists or returns after standard treatment. They must be able to give informed consent and not have severe kidney issues, active serious cancer, HIV/AIDS, be bedridden, on high-dose steroids or other strong immune-suppressing drugs, have advanced liver disease, need certain concurrent antibiotics, or have a life expectancy under one year.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Pre-treatment
Participants are pretreated with 4 days of oral vancomycin to reduce the C. difficile load
Treatment
Defined fecal microbiota transplantation is administered into the small intestine
Initial Follow-up
Participants are monitored daily in the hospital and contacted daily by phone after discharge for 14 days
Extended Follow-up
Participants are contacted at 30 days, monthly for 3 months, then every 3 months for one year to monitor symptoms and collect stool samples
Treatment Details
Interventions
- Defined Fecal Microbiota Transplantation
Find a Clinic Near You
Who Is Running the Clinical Trial?
Baylor College of Medicine
Lead Sponsor
Michael E. DeBakey VA Medical Center
Collaborator