Fecal Microbiota Transplant for Small Intestinal Bacterial Overgrowth

Overseen By Fariha Chowdhury, BASc, MSc, PhD(c)

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: McMaster Children's Hospital

Must not be taking: Antibiotics, Probiotics, Antacids, Antimotility

Disqualifiers: Under 3 years old, 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: 4

Duration: 1 week

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of the study is to assess feasibility, and clinical efficacy of a novel Fecal Microbiota Transplantation protocol for the treatment of pediatric small intestinal bacterial overgrowth (SIBO).

Will I have to stop taking my current medications?

You will need to stop taking antibiotics at least 1 week before the trial starts. You cannot start any new treatments, including antibiotics, probiotics, or antacids, until Week 8 unless it's necessary for your health.

What data supports the effectiveness of the treatment Fecal Microbiota Transplant for Small Intestinal Bacterial Overgrowth?

Research shows that Fecal Microbiota Transplant (FMT) is effective for treating Clostridium difficile infections, which are also related to gut bacteria imbalances. This suggests potential benefits for other conditions involving gut bacteria, like Small Intestinal Bacterial Overgrowth. ^{1 2 3 4 5}

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 delivery methods. However, long-term safety data is limited, and serious adverse events have been associated with inadequate screening for multi-drug resistant organisms in some cases. ^{5 6 7 8 9}

How is Fecal Microbiota Transplant (FMT) different from other treatments for Small Intestinal Bacterial Overgrowth?

FMT is unique because it involves transferring healthy donor feces into a patient's gut to restore a balanced microbiome, unlike traditional treatments that may use antibiotics to kill bacteria. This approach aims to directly modify the gut environment, potentially offering a novel way to address the root cause of bacterial overgrowth. ^{2 10 11 12 13}

Research Team

Nikhil Pai, MD

Principal Investigator

McMaster University | McMaster Children's Hospital

Eligibility Criteria

This trial is for children and teenagers aged 3-18 who have been diagnosed with Small Intestinal Bacterial Overgrowth (SIBO) confirmed by a lactose breath test. Participants must show symptoms of SIBO and agree to stop taking antibiotics at least one week before the Fecal Microbiota Transplant (FMT).

Inclusion Criteria

I will stop taking antibiotics 1 week before my fecal microbiota transplantation.

I have been diagnosed with SIBO through a breath test and show symptoms.

Exclusion Criteria

I am older than 3 years.

I won't start new treatments like antibiotics until after Week 8, unless necessary for my health.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single Fecal Microbiota Transplant (FMT) infusion via enteral feeding tubes or elective upper endoscopy

1 week

1 visit (in-person)

Short-term Follow-up

Participants are monitored for clinical efficacy and safety, with outcomes measured at one and four weeks post-FMT

4 weeks

2 visits (in-person)

Long-term Follow-up

Participants are monitored for long-term clinical efficacy, including durability of remission and recurrence of symptoms, with outcomes measured at eight weeks post-FMT

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Fecal Microbiota Transplant

Trial Overview The study is testing the feasibility and effectiveness of a new treatment protocol using Fecal Microbiota Transplant (FMT) to manage pediatric SIBO.

Participant Groups

Group I: Fecal Microbiota Transpant Experimental Treatment 1 Intervention

Participants will receive a Fecal Microbiota transplant Infusion via participants' existing enteral feeding tubes or via elective upper endoscopy (with infusion into the duodenum). Most patients with SBS at MCH and HSC have an existing enteral feeding tube (gastrostomy or jejunostomy tube).

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

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent and refractory Clostridioides difficile infection

Approved in European Union as Faecal Microbiota Transplantation for:

• Recurrent and refractory Clostridioides difficile infection

Approved in Canada as Fecal Microbiota Transplantation for:

• Recurrent and refractory Clostridioides difficile infection

Who Is Running the Clinical Trial?

McMaster Children's Hospital

Lead Sponsor

Trials

43

Recruited

19,900+

The Hospital for Sick Children

Collaborator

Trials

724

Recruited

6,969,000+

Findings from Research

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]

Faecal microbiota transplantation (FMT) has proven effective for treating recurrent Clostridium difficile infections, with established protocols and donor stool banks in Denmark.

However, FMT is not recommended for routine use in treating inflammatory bowel disease or irritable bowel syndrome due to insufficient clinical trial data supporting its efficacy for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Faecal microbiota transplantation for the treatment of bowel disease]. Rode, AA., Chehri, M., Petersen, AM., et al.[2019]

Faecal microbiota transplantation (FMT) was found to be highly effective in treating recurrent Clostridioides difficile infection (CDI), with an 84.6% success rate in a study of 13 patients, all of whom experienced symptom resolution within 48 hours.

The procedure was deemed safe, as no significant short or long-term complications were reported during a follow-up period averaging 25.66 months, demonstrating its feasibility even in elderly patients with multiple health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal Microbiota Transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice. Ferre Aracil, C., El Hajra Martínez, I., Vera Mendoza, MS., et al.[2023]

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 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 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 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 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 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]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for Clostridioides difficile infection, and emerging evidence suggests it may also benefit various other conditions like irritable bowel syndrome and inflammatory bowel disease.

The review highlights the expanding applications of FMT beyond gastrointestinal issues, including its potential roles in treating liver disorders, metabolic disorders, and even neurological conditions, while also discussing regulatory aspects and future directions for FMT research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders. Ianiro, G., Segal, JP., Mullish, BH., et al.[2021]

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]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridioides difficile infection (CDI), achieving resolution rates close to 100%, making it a crucial therapy for this serious condition.

FMT is being explored as a promising treatment for other gastrointestinal disorders, such as inflammatory bowel disease, irritable bowel syndrome, and colon cancer, due to its ability to manipulate the gut microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer. Borody, TJ., Eslick, GD., Clancy, RL.[2020]

In a pilot study involving nine patients with collagenous colitis, fecal microbiota transfer (FMT) showed some improvement in symptoms, particularly in reducing diarrhea and enhancing quality of life, although it did not significantly reduce the number of watery stools overall.

FMT was safe, with no serious adverse events reported, and it appeared to activate the mucosal immune system, as indicated by an increase in lamina propria lymphocytes, suggesting potential benefits for a specific subset of patients with collagenous colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal microbiota transfer in patients with microscopic colitis - a pilot study in collagenous colitis. Holster, S., Rode, J., Bohr, J., et al.[2021]

References

1. 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]

2. Denmark pubmed.ncbi.nlm.nih.gov

[Faecal microbiota transplantation for the treatment of bowel disease]. [2019]

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

Faecal Microbiota Transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice. [2023]

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

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

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. China pubmed.ncbi.nlm.nih.gov

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

7. Greece pubmed.ncbi.nlm.nih.gov

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

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

Fecal Microbiota Transplantation: Is It Safe? [2021]

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

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

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

Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders. [2021]

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

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

12. England pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Faecal microbiota transfer in patients with microscopic colitis - a pilot study in collagenous colitis. [2021]