Fecal Microbiota Transplant for Clostridium Infections

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Antianaerobic antibiotics

Disqualifiers: Severe colitis, IBD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a fecal microbiota transplant, using a participant's own stored stool, can prevent future Clostridium difficile infections (CDI). Researchers will compare two groups: one receiving the transplant and the other receiving standard care. The trial targets individuals about to undergo a bone marrow transplant and will monitor participants for a year to check for CDI and other infections. Those who have struggled with CDI in the past and are planning a bone marrow transplant might find this trial suitable. As a Phase 2 trial, it focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on prolonged antibiotic treatment that affects the gut. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that fecal microbiota transplantation (FMT) is generally safe and well-tolerated. Studies have found that FMT effectively prevents the return of Clostridioides difficile infection (CDI), which is the primary goal of this treatment.

FMT is usually easy for patients to handle, with mild side effects like stomach discomfort or diarrhea that typically resolve quickly. Importantly, FMT has been used successfully for other conditions, indicating it is generally safe for humans.

This trial uses autologous FMT, meaning the patient's own stored feces are used. The overall safety data for FMT in various situations is reassuring, suggesting this treatment is a good option for preventing CDI. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Clostridium difficile infections (CDI) rely on antibiotics like vancomycin or metronidazole. However, Autologous Fecal Microbiota Transplantation (Auto-FMT) offers a unique approach by using a patient's own stored feces to restore healthy gut bacteria. This method aims to rebalance the gut microbiome more naturally and may reduce the recurrence of CDI, a common issue with antibiotics. Researchers are excited about Auto-FMT because it could provide a personalized treatment option, potentially improving outcomes and minimizing side effects compared to standard antibiotic therapies.

What evidence suggests that fecal microbiota transplantation might be an effective treatment for Clostridium infections?

Research has shown that fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infections (CDI). In this trial, participants may undergo FMT using their stored pre-transplantation feces. Studies have found that FMT significantly reduces the likelihood of CDI returning by restoring the natural balance of gut bacteria, which helps control harmful bacteria like C. difficile. Recent reviews and analyses confirm FMT's effectiveness, although its success can depend on the method and frequency of administration. Clinical guidelines recommend this approach for adults with recurring CDI, highlighting its promise as a treatment option. ^{2 3 6 7 8}

Who Is on the Research Team?

Ying Taur, MD, MPH

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults (18+) who are scheduled to receive an allogeneic hematopoietic stem cell transplantation (allo-HSCT). It's not suitable for those with severe colitis, a history of inflammatory bowel disease, or those needing long-term antibiotics that affect the gut.

Inclusion Criteria

I am scheduled for a stem cell transplant from a donor.

Exclusion Criteria

I am on long-term antibiotics that affect my gut, as decided by my doctor.

I have severe bowel inflammation or a history of IBD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant Preparation

Feces are collected and stored from all participating subjects prior to the initiation of conditioning regimens, analyzed by deep 16S rRNA gene sequencing, and tested by assay for intestinal pathogens.

Varies

Treatment

Subjects undergo fecal microbiota transplantation with the subject's stored pre-transplantation feces within a 28-day window following engraftment.

28 days

Follow-up

Subjects are monitored for development of CDI, infections, and graft-versus-host disease. Fecal specimens are collected serially and analyzed for microbial diversity and composition.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Fecal Microbiota Transplantation (Auto-FMT)

Trial Overview The study is testing whether fecal microbiota transplantation (FMT) can prevent Clostridium Difficile Infection in patients after allo-HSCT. Some participants will get FMT while others won't and will just receive routine care.

How Is the Trial Designed?

Group I: Fecal microbiota transplantation with pre-transplant feces Experimental Treatment 1 Intervention

Prior to transplant hospitalization, store feces for testing and possible future use. Patients undergo fecal microbiota transplantation with the subject's stored pre-transplantation feces. The post-engraftment Bacteroidetes testing, randomization, and fecal microbiota transplantation procedure should all be performed within a 28-day window, beginning on the first day of engraftment. In the event that engraftment occurs prior to day +7, the 28-day window will start on day +7. Subjects from both arms will be followed for one year after transplantation for development of CDI, which will be treated by their BMT clinicians per the standards of care at MSKCC. Subjects from both arms will also be assessed for infections and graft-versus-host disease. During the follow-up period, fecal specimens will be collected serially, if feasible, until one year post randomization and analyzed for microbial diversity and composition.

Group II: No FMT, routine management Active Control 1 Intervention

Subjects from both arms will be followed for one year after randomization for development of CDI, which will be treated by their primary BMT clinician per the standards of care at MSKCC. Subjects from both arms will also be assessed by their BMT clinicians for infections and graft-versus-host disease. During the follow-up period, fecal specimens will be collected serially if feasible until one year post randomization and analyzed for microbial diversity and composition.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

A survey of 135 physicians revealed that only 20% had treated a patient with fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection, indicating limited adoption of this effective therapy despite its safety and efficacy.

Many physicians believe that patients would find FMT unappealing and have concerns about the clinical appropriateness of the treatment, leading to a significant gap between physician attitudes and potential patient acceptance of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physician attitudes toward the use of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection. Zipursky, JS., Sidorsky, TI., Freedman, CA., et al.[2021]

Fecal microbiota transplantation (FMT) has a reported adverse event (AE) rate of 39.3%, primarily involving mild and self-limiting issues like abdominal pain and diarrhea, based on a meta-analysis of 9 high-quality studies involving 756 FMTs.

Serious adverse events (SAE) were relatively rare at 5.3%, with the most common being Clostridium difficile infection, indicating that while FMT is generally safe, monitoring and standardized reporting are essential for understanding its long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies. Michailidis, L., Currier, AC., Le, M., et al.[2022]

Fecal microbiota transplantation (FMT) using targeted colonic release capsules (FMTcr) showed a slightly higher clinical cure rate for recurrent Clostridium difficile infection (rCDI) at 80.6% compared to 75% for gastric release capsules (FMTgr), although the difference was not statistically significant.

Both FMT formulations were found to be safe with no serious adverse events, but FMTcr was more effective in increasing gut microbial diversity, suggesting better microbial engraftment patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose. Allegretti, JR., Fischer, M., Sagi, SV., et al.[2020]

Capsulized autologous faecal microbiota transplantation (FMT) was found to be safe and well tolerated in a study of 24 healthy volunteers, with no serious side effects reported during the treatment.

While both the FMT and placebo groups showed improvements in general and intestinal health after antibiotic treatment, there was no significant difference in the time it took for participants to normalize their intestinal habits, indicating that FMT did not provide additional benefits over placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial. Stefansson, M., Bladh, O., Flink, O., et al.[2023]

In a study of 9 patients with severe and complicated Clostridium difficile infection (CDI) who were at risk of needing colectomy, fecal microbiota transplant (FMT) resulted in a 78% cure rate after just one treatment, demonstrating its efficacy as an alternative therapy.

Following FMT, 88.88% of patients were able to avoid colectomy during their hospital stay, indicating that FMT could be a valuable bowel-saving intervention in critical cases of CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of fecal microbiota transplant in 9 critically ill patients with severe and complicated Clostridium difficile infection with impending colectomy. Alukal, J., Dutta, SK., Surapaneni, BK., et al.[2020]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent Clostridioides difficile infections, highlighting its importance in clinical practice.

The selection of fecal microbiota donors is crucial for ensuring the safety of recipients, prompting the establishment of protocols and recommendations by a multidisciplinary group in Cataluña to minimize risks associated with the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations for stool donor selection for fecal microbiota transplant. Consensus document endorsed by the Catalan Society of Digestology, Catalan Society of Infectious diseases and Clinical microbiology and the GEMBIOTA group from Spanish Society of Infectious Diseases and Clinical Microbiology. Aira, A., Arajol, C., Casals-Pascual, C., et al.[2021]

Fecal microbial transplantation (FMT) is an effective treatment for recurrent Clostridium difficile colitis, with various delivery methods such as oral ingestion, colonoscopy, and enemas tailored to patient needs.

Careful selection of donors and patients is essential to ensure safety and efficacy, as FMT is being explored for potential treatment of other conditions beyond just C. difficile infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical Aspects of Fecal Microbial Transplantation (FMT). Bhutiani, N., Schucht, JE., Miller, KR., et al.[2018]

Fecal microbiota transplantation (FMT) has shown a high success rate of 80-98% in treating severe and recurrent Clostridium difficile infections (CDI), particularly when administered via colonoscopy, which was the method used for most patients in the studies reviewed.

FMT works by restoring the normal microbiome of the colon, and evidence increasingly supports its effectiveness as a treatment option for CDI, although challenges such as patient perceptions and the need for standardized protocols remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal microbiota transplantation for Clostridium difficile infection. Dodin, M., Katz, DE.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7308243/

Autologous fecal microbiota transplantation for the treatment ... Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Ann ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1931312823001245

Beneficial effects of fecal microbiota transplantation in ... Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI).

3. gastrojournal.org gastrojournal.org/article/S0016-5085(24)00041-6/fulltext

AGA Clinical Practice Guideline on Fecal Microbiota ... This guideline to provide recommendations on the use of fecal microbiota–based therapies in adults with recurrent Clostridioides difficile infection.

4. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30386-2/fulltext

An updated systematic review and meta-analysis High-quality evidence supports FMT is effective for recurrent CDI, but its effect varies with the delivery method and the number of administrations.

5. frontiersin.org frontiersin.org/journals/microbiomes/articles/10.3389/frmbi.2024.1409967/full

Recent advances in fecal microbiota transplantation for ... This review summarizes the recent progress in FMT for CDI-associated diarrhea after renal transplantation.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7757860/

Efficacy and safety of fecal microbiota transplantation for the ... Preliminary data suggest that FMT is a potentially safe, well-tolerated and efficacious treatment for certain conditions other than CDI, with evidence for ...

7. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1439176/full

Safety and efficacy of fecal microbiota transplantation (FMT ... This study aims to comprehensively review the current literature on FMT as a modern procedure for treating various diseases.

8. cureus.com cureus.com/articles/398525-microbiota-based-therapies-for-recurrent-clostridium-difficile-infection-a-systematic-review-of-their-efficacy-and-safety.pdf?email=

A Systematic Review of Their Efficacy and Safety Research question: What are the safety and efficacy outcomes of fecal microbiota transplantation in patients with recurrent Clostridium ...