Fecal Microbiota Transplantation for Drug-Resistant Infections

Overseen By Amanda Adler

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Seattle Children's Hospital

Must not be taking: Immunosuppressants, Omeprazole

Disqualifiers: Malignancy, Immunocompromised, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 1 day

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This protocol will evaluate fecal microbiota transplantation (FMT) as a strategy to eradicate intestinal colonization of extended-spectrum resistant (ESC-R) Enterobacteriaceae in pediatric patients. FMT will be performed on subjects with a history of at least one infection due to ESC-R Enterobacteriaceae. This protocol aims to determine the feasibility, safety, tolerability, and potential efficacy of FMT in pediatric patients with a history of ESC-R Enterobacteriaceae.

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 using systemic immunosuppressive agents, you would not be eligible to participate.

Is fecal microbiota transplantation (FMT) safe for humans?

FMT is generally considered safe and well-tolerated, especially for treating recurrent Clostridioides difficile infections, but there are some risks associated with the delivery methods and donor screening. Short-term risks are usually mild, and while long-term effects are not well-established, serious adverse events have been linked to inadequate screening for drug-resistant organisms in donor stool. ^{1 2 3 4 5}

How is fecal microbiota transplantation different from other treatments for drug-resistant infections?

Fecal microbiota transplantation (FMT) is unique because it involves transferring stool from a healthy donor to a patient to restore the balance of bacteria in the gut, which can help fight drug-resistant infections. Unlike traditional antibiotics, FMT aims to change the gut environment to reduce harmful bacteria, offering a novel approach for infections that don't respond to standard treatments. ^{6 7 8 9 10}

Research Team

Danielle M Zerr, MD, MPH

Principal Investigator

Seattle Children's Hospital

Eligibility Criteria

This trial is for children and teens aged 7 to 21 who've had an infection caused by drug-resistant bacteria called ESC-R Enterobacteriaceae. They must be able to handle a nasogastric tube, not have allergies to certain medications, and attend all study visits. Pregnant individuals or those with specific gastrointestinal diseases, frequent vomiting, or on systemic immunosuppressants cannot join.

Inclusion Criteria

I have had an infection caused by bacteria resistant to certain antibiotics.

I am willing and able to sign a consent form.

I am between 7 and 21 years old.

Exclusion Criteria

I have never had cancer before and my immune system is not compromised.

You are allergic to omeprazole or polyethylene glycol.

I have a bleeding disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Fecal Microbiota Transplantation (FMT) is administered via nasogastric tube

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, tolerability, and efficacy of FMT

12 months

6 visits (in-person) at 2 days, 2 weeks, 4 weeks, 8 weeks, 6 months, and 12 months post-FMT

Long-term follow-up (optional)

Participants may opt into long-term follow-up to monitor for safety and efficacy

5 years

Treatment Details

Interventions

• Fecal Microbiota Transplantation

Trial Overview The trial tests fecal microbiota transplantation (FMT) in pediatric patients previously infected by resistant bacteria. It aims to see if FMT can remove these bacteria from the gut safely and effectively while checking how well kids tolerate this treatment.

Participant Groups

Group I: Fecal Microbiota Transplantation Experimental Treatment 1 Intervention

Subjects will receive 50mL of prepared stool fecal via nasogastric tube

Fecal Microbiota Transplantation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Approved in European Union as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)
• Other gastrointestinal disorders

Approved in Canada as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Findings from Research

Fecal microbiota transplantation (FMT) is a generally safe and well-tolerated procedure for treating recurrent Clostridioides difficile infections, even in high-risk patients, with most short-term risks being mild and related to delivery methods.

Recent concerns have emerged regarding serious adverse events linked to FMT products from stool banks that do not screen for multi-drug resistant organisms, highlighting the need for improved safety protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? Park, SY., Seo, GS.[2021]

Fecal microbiota transplantation (FMT) is recommended for treating recurrent Clostridium difficile infections and has shown benefits for various gastrointestinal disorders, but safety data is still limited due to the rapid adoption of the technique without extensive long-term studies.

Capsulized FMT therapy offers a promising solution for long-term maintenance and reduces the need for invasive procedures, indicating a shift towards safer and more tolerable methods of delivering FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. Li, N., Tian, H.[2020]

Faecal microbiota transplantation (FMT) is being established as a safe second-line treatment for recurrent Clostridium difficile infections, with a comprehensive framework developed to ensure donor screening and clinical application comply with the European Tissue Act.

The framework includes rigorous donor recruitment and screening processes, laboratory protocols for processing faecal samples, and a structured follow-up system to monitor patient outcomes, ensuring safety and traceability in FMT procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal microbiota transplantation: establishment of a clinical application framework. Jørgensen, SMD., Hansen, MM., Erikstrup, C., et al.[2022]

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) 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 microbiota transplantation (FMT) was performed on an 87-year-old male with recurrent cholangitis and multidrug-resistant (MDR) bacteria, showing safety and no complications across three procedures.

After FMT, there was a notable decrease in hospital admissions and a change in the microbial resistance profile of bacteria in blood cultures, suggesting that FMT may effectively manipulate gut microbiota and reduce MDR bacteremias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplant in a Patient Infected with Multidrug-Resistant Bacteria: A Case Report. Gouveia, C., Palos, C., Pereira, P., et al.[2022]

Fecal microbiota transplantation (FMT) successfully treated a case of relapsing Clostridium difficile colitis and also eliminated colonization of several multidrug-resistant organisms (MDROs).

This suggests that FMT may provide additional benefits beyond treating C. difficile, potentially helping to eradicate other harmful bacteria, warranting further research into its broader applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation and successful resolution of multidrug-resistant-organism colonization. Crum-Cianflone, NF., Sullivan, E., Ballon-Landa, G.[2020]

Fecal microbiota transplantation (FMT) is effective for treating recurrent Clostridioides difficile infection (CDI), but 16.3% of patients experienced treatment failure, with significant predictors including advanced age, severe CDI, and use of non-CDI antibiotics around the time of FMT.

Improving bowel preparation and antibiotic management before and after FMT can enhance treatment success, and patients with certain risk factors should be informed about their likelihood of FMT failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of Fecal Microbiota Transplant Failure in Clostridioides difficile Infection : An Updated Meta-analysis. Beran, A., Sharma, S., Ghazaleh, S., et al.[2023]

Fecal microbiota transplantation (FMT) has proven to be highly effective in treating recurrent and refractory Clostridioides difficile infections (CDI), leading to a surge in research on gut microbiota therapies.

The future of microbiome-based treatments is expected to focus on developing oral formulations with known ingredients, clear mechanisms of action, and strong safety profiles, expanding the potential applications of FMT beyond CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond. Kumar, V., Fischer, M.[2020]

Fecal microbiota transplantation (FMT) effectively normalizes the gut microbiota in patients with recurrent Clostridium difficile infection, showing significant changes within just one day after the procedure.

While the microbiota composition initially resembles that of the donor, it diverges over time, indicating that the gut microbiome is dynamic and requires ongoing monitoring to evaluate the long-term success of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection. Weingarden, A., González, A., Vázquez-Baeza, Y., et al.[2018]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? [2021]

2. China pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Faecal microbiota transplantation: establishment of a clinical application framework. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies. [2022]

5. Spain 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. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplant in a Patient Infected with Multidrug-Resistant Bacteria: A Case Report. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation and successful resolution of multidrug-resistant-organism colonization. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Predictors of Fecal Microbiota Transplant Failure in Clostridioides difficile Infection : An Updated Meta-analysis. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection. [2018]