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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests fecal microbiota transplantation (FMT) to determine its effectiveness in removing tough-to-treat gut bacteria in children. It targets infections caused by ESC-R Enterobacteriaceae, a type of bacteria resistant to regular antibiotics. The trial aims to assess the safety and effectiveness of FMT for children who have experienced at least one of these infections. Children and teens who have had such an infection and can attend study visits may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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.

What prior data suggests that this protocol is safe for pediatric patients?

Research has shown that fecal microbiota transplantation (FMT) is generally safe and well-tolerated, even for patients at higher risk. Most short-term risks are mild and relate to the method of administration. Previous studies have safely used FMT to treat various conditions, including digestive issues like Crohn's disease and repeated infections.

Although individual experiences may vary, the overall evidence suggests that FMT offers a promising option with manageable risks for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Fecal Microbiota Transplantation (FMT) is unique because it uses healthy donor stool to restore the balance of good bacteria in the gut, a new approach compared to traditional antibiotics for drug-resistant infections. While antibiotics often struggle with resistant bacteria and can disrupt the gut microbiome, FMT introduces a diverse range of beneficial microbes that can outcompete harmful bacteria and help rebuild the gut's natural defenses. Researchers are excited about FMT because it offers a novel way to tackle infections that don't respond to usual treatments, potentially offering relief in a much shorter timeframe.

What evidence suggests that fecal microbiota transplantation is effective for drug-resistant infections?

Research shows that fecal microbiota transplantation (FMT), which participants in this trial will receive, could help fight infections unresponsive to antibiotics. Studies have found that FMT can reduce the number of antibiotic-resistant genes in patients, crucial for combating tough bacteria like ESC-R Enterobacteriaceae. One review even mentioned cases where FMT successfully removed these resistant bacteria. By transferring healthy bacteria from a donor to a patient, FMT helps restore gut balance, potentially eliminating harmful, resistant bacteria. Although more research is needed, early results suggest FMT could be a useful method against these difficult infections. ^{4 6 7 8 9}

Who Is on the Research Team?

Danielle M Zerr, MD, MPH

Principal Investigator

Seattle Children's Hospital

Are You a Good Fit for This Trial?

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

You are allergic to omeprazole or polyethylene glycol.

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

I have a bleeding disorder.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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 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 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) 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]

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]

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) 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) 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6667716/

The Role of Fecal Microbiota Transplantation in Reducing ... This review summarizes clinical outcomes data for fecal microbiota transplantation (FMT) for antibiotic-resistant organism (ARO) decolonization.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0163445325000982

Faecal microbiota transplant to ERadicate gastrointestinal ... Burguiere, T.A. Tompkins, et al. Fecal microbial transplants reduce antibiotic-resistant genes in patients with recurrent Clostridium difficile infection.

3. asm.org asm.org/articles/2024/february/fecal-microbiota-transplants-past-present-future

Fecal Microbiota Transplants (FMT): Past, Present and Future Fecal microbiota transplants (FMTs) involve transferring stool from a donor to a recipient for therapeutic purposes. When did FMTs start?

4. academic.oup.com academic.oup.com/cid/article/80/1/52/7756590

A Randomized Controlled Trial of Efficacy and Safety of Fecal ... We conducted a randomized double-blind clinical trial of the efficacy and safety of fecal microbiota transplant (FMT) for reducing recurrent Clostridioides.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910437

Drug-Resistant E. coli Bacteremia Transmitted by Fecal ... A systematic review of the efficacy and safety of fecal microbiota transplant for Clostridium difficile infection in immunocompromised patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8039753/

Fecal Microbiota Transplantation: Is It Safe? - PMC FMT is generally considered safe and well-tolerated - even in high-risk patients. Most short-term risks are mild and known to be associated with delivery ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04014413

Safety and Efficacy of Fecal Microbiota Transplantation Randomized controlled trial has been conducted in a number of disorders and shown positive results, including alcoholic hepatitis, Crohn's disease (CD), ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2949928324000087

Review Fecal microbiota transplantation in clinical practice The data included here mainly include patients exhibiting gastrointestinal symptoms [2]. The effectiveness rate of FMT treatment in this context was 48.3%, ...

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

Safety and efficacy of fecal microbiota transplantation (FMT ... Subsequent case studies have shown high success rates of using FMT in treating various diseases, including non-infectious diseases. The earliest documented ...