Fecal Microbiota Transplantation for Gastrointestinal Disorders After HCT

Overseen By Gabriela Maron, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Cytomegalovirus, Epstein Barr Virus, Pregnancy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4-6 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The study participant is being asked to take part in this clinical trial, a type of research study, because the participant has Gastrointestinal (GI) symptoms following a Hematopoietic Cell Transplant (HCT). Primary Objective * To determine the safety and feasibility of FMT for treating a GvHD of the gut following HCT. * To determine the safety and feasibility of FMT for treating HCT induced gut dysfunction. Secondary Objectives * To assess the potential efficacy of FMT for treating a GvHD of the gut following HCT. * To assess the potential efficacy of FMT for treating HCT induced gut dysfunction.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on medications that the investigator believes could increase your risk or affect the study results, you might need to stop them.

What data supports the effectiveness of the treatment Fecal microbiota transplantation (FMT) for gastrointestinal disorders after HCT?

FMT is effective for treating recurrent Clostridium difficile infections and shows promise for other gastrointestinal diseases like inflammatory bowel disease, where it helps restore healthy gut bacteria. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) safe for humans?

Fecal microbiota transplantation (FMT) is generally considered safe and well-tolerated, even in high-risk patients, with most short-term risks being mild and related to delivery methods. However, long-term safety data is limited, and serious adverse events have been associated with FMT products from stool banks that do not screen for multi-drug resistant organisms. ^{5 6 7 8 9}

How is fecal microbiota transplantation different from other treatments for gastrointestinal disorders after HCT?

Fecal microbiota transplantation (FMT) is unique because it involves transferring stool from a healthy donor to restore a balanced gut microbiome, which is different from traditional drug treatments that often target symptoms rather than the underlying microbiome imbalance. This approach is particularly novel as it uses living organisms to potentially cure diseases linked to an altered microbiome. ^{3 10 11 12 13}

Research Team

Gabriela Maron, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for children under 22 who've had a bone marrow transplant at least 30 days ago and are now having serious gut problems that steroids can't fix or keep coming back when trying to stop steroid treatment. They shouldn't be pregnant, have had previous FMT, recent belly surgery, devices in their abdomen (except certain feeding tubes), or be on dialysis.

Inclusion Criteria

I had a stem cell transplant from a donor more than 30 days ago.

I have been diagnosed with gastroparesis by a GI specialist.

Willing and able to provide informed assent/consent

Exclusion Criteria

I am currently pregnant or nursing.

I am currently receiving radiation therapy to my abdomen.

I am at high risk for abdominal infection due to devices inside me, dialysis, or fluid buildup.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fecal Microbiota Transplantation (FMT) on or after Day +30 post-HCT, with a possible second FMT at least 14 days later if symptoms have partially improved or not changed

4-6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and response to treatment

30 days

Long-term follow-up

Participants are monitored for long-term outcomes, including steroid reduction and overall response

1 year

Treatment Details

Interventions

• Fecal microbiota transplant (FMT)

Trial Overview The study tests if putting healthy stool from donors into the child's intestines is safe and could work for treating stubborn gut issues after a bone marrow transplant. It looks at how well kids handle this treatment and if it helps with their symptoms.

Participant Groups

Group I: Stratum B Experimental Treatment 1 Intervention

GI Dysfunction

Group II: Stratum A Experimental Treatment 1 Intervention

Diagnosed with GvHD

Fecal microbiota transplant (FMT) is already approved in United States, European Union, Canada, China for the following indications:

Approved in United States as Fecal microbiota transplantation for:

• Recurrent Clostridioides difficile infection (RCDI)
• Graft-versus-host disease (GvHD) of the gut following hematopoietic cell transplant (HCT)
• HCT-induced gut dysfunction

Approved in European Union as Fecal microbiota transplantation for:

• Recurrent Clostridioides difficile infection (RCDI)
• Ulcerative colitis
• Graft-versus-host disease (GvHD) of the gut following hematopoietic cell transplant (HCT)

Approved in Canada as Fecal microbiota transplantation for:

• Recurrent Clostridioides difficile infection (RCDI)
• Graft-versus-host disease (GvHD) of the gut following hematopoietic cell transplant (HCT)

Approved in China as Fecal microbiota transplantation for:

• Recurrent Clostridioides difficile infection (RCDI)
• Ulcerative colitis
• Graft-versus-host disease (GvHD) of the gut following hematopoietic cell transplant (HCT)
• Autism spectrum disorder (ASD)

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Findings from Research

Fecal microbiota transplantation (FMT) is a cost-effective treatment for recurrent Clostridium difficile infection (rCDI), with all economic evaluations showing it to be more cost-effective than other standard treatments at a threshold of ≤$50,000 per quality-adjusted life year (QALY).

The systematic review included 9 high-quality economic evaluations, primarily focusing on rCDI and inflammatory bowel disease (IBD), indicating that while FMT is effective for rCDI, further studies are needed to explore its economic impact for other conditions like IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of economic evaluation in fecal microbiota transplantation. Stalder, T., Kapel, N., Diaz, S., et al.[2021]

Faecal microbiota transplantation (FMT) has shown significant benefits in treating ulcerative colitis, with four randomized controlled trials indicating its effectiveness compared to placebo.

Research is ongoing to optimize donor and patient selection for FMT, and complementary strategies like pre-antibiotics are being explored to enhance treatment efficacy, although data for Crohn's disease and pouchitis are still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of faecal microbiota transplantation in the treatment of inflammatory bowel disease. Haifer, C., Leong, RW., Paramsothy, S.[2021]

Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infections, highlighting its established role in restoring gut health.

There is growing interest in exploring FMT's potential benefits for other gastrointestinal diseases linked to dysbiosis, suggesting it may have broader therapeutic applications beyond just C. difficile infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplant, its usefulness beyond Clostridioides difficile in gastrointestinal diseases. Núñez F, P., Quera, R., Bay, C., et al.[2022]

Faecal microbiota transplantation (FMT) has a high cure rate of 95.6% for Clostridium difficile infections (CDI), indicating its efficacy as a treatment for this condition.

The study revealed significant variability in donor screening and characteristics, with less than 50% of studies screening for transmittable pathogens, highlighting the need for standardized protocols in FMT procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: review of donor features, procedures and outcomes in 168 clinical studies of faecal microbiota transplantation. Lai, CY., Sung, J., Cheng, F., et al.[2020]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for dysbiosis in children, with a primary clinical remission rate of 72.9% observed after the procedure.

While most adverse events (AEs) were self-limiting and occurred shortly after FMT, the long-term efficacy of FMT decreased over time, suggesting that multiple FMTs may be necessary for recurrent conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study. Zou, B., Liu, SX., Li, XS., et al.[2022]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (CDI), with a 90% resolution of diarrhea reported in 867 patients across 33 studies, and a 94% resolution after repeated FMT in a randomized controlled trial with 16 participants.

FMT shows promise in treating ulcerative colitis, with remission rates varying from 0% to 68% in 106 patients, while its efficacy in Crohn's disease, chronic constipation, pouchitis, and irritable bowel syndrome remains inconclusive due to limited data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. Rossen, NG., MacDonald, JK., de Vries, EM., et al.[2022]

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) 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]

Fecal microbiota transplantation (FMT) is a therapeutic procedure that involves transferring fecal matter from a healthy donor to treat diseases, particularly recurrent Clostridium difficile infections.

Recent research highlights the importance of the human microbiome, showing that the complex mixture of microorganisms in our bodies plays a crucial role in overall health and disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. Aroniadis, OC., Brandt, LJ.[2022]

Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridium difficile infection (RCDI), helping to restore a balanced intestinal flora.

While FMT shows promise for treating other gastrointestinal and non-gastrointestinal disorders, more research is needed to fully understand the role of intestinal microbiota in health and to establish controlled trials for broader clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation: past, present and future. Aroniadis, OC., Brandt, LJ.[2020]

Fecal microbiota transplantation (FMT) is primarily effective for treating recurrent Clostridium difficile infections by restoring a healthy microbiome in the colon.

Currently, there is not enough evidence to support the use of FMT for other gastrointestinal or nongastrointestinal diseases, although research is ongoing in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation. Vindigni, SM., Surawicz, CM.[2020]

Fecal microbiota transplantation (FMT) has a total adverse event (AE) incidence rate of 28.5%, with abdominal discomfort being the most common AE reported in 19 studies, highlighting the need for careful monitoring during the procedure.

Serious adverse events (SAEs) occurred in 9.2% of patients, with a notable incidence of death (3.5%) and infections (2.5%), indicating that while FMT can be beneficial, it carries significant risks that require further investigation through high-quality randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. Wang, S., Xu, M., Wang, W., et al.[2023]

References

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

A systematic review of economic evaluation in fecal microbiota transplantation. [2021]

2. England pubmed.ncbi.nlm.nih.gov

The role of faecal microbiota transplantation in the treatment of inflammatory bowel disease. [2021]

3. Spain pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplant, its usefulness beyond Clostridioides difficile in gastrointestinal diseases. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: review of donor features, procedures and outcomes in 168 clinical studies of faecal microbiota transplantation. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study. [2022]

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

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Fecal Microbiota Transplantation: Is It Safe? [2021]

9. China pubmed.ncbi.nlm.nih.gov

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

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

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. [2022]

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

Fecal microbiota transplantation: past, present and future. [2020]

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

Fecal Microbiota Transplantation. [2020]

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

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. [2023]