Fecal Microbiota Transplant for Irritable Bowel Syndrome

Overseen By Jonah Pedelty, MS

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Madhusudan (Madhu) Grover, MBBS

Must not be taking: Immunosuppressants, Antibiotics, NSAIDs, others

Disqualifiers: Immune deficiency, Active cancer, Severe psychiatric disorder, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

43 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to learn the efficacy and safety of fecal microbiota transplantation (FMT) using stool from a donor with low proteolytic activity and containing the bacteria Alistipes putredinis in patients with irritable bowel syndrome (IBS) and high proteolytic activity. Proteolytic activity is the breakdown of proteins into smaller polypeptides or amino acids.

Will I have to stop taking my current medications?

The trial requires that you stop taking new probiotics, antibiotics, and NSAIDs (non-steroidal anti-inflammatory drugs) at least 4 weeks before joining. You also cannot use treatments that affect bowel movement, except for loperamide.

What data supports the effectiveness of the treatment Fecal Microbiota Transplantation for Irritable Bowel Syndrome?

Research suggests that Fecal Microbiota Transplantation (FMT) can be a promising treatment for irritable bowel syndrome (IBS) by restoring the balance of gut bacteria, which is often disrupted in IBS patients. Studies have shown that FMT can improve symptoms and quality of life, although the effectiveness may vary based on factors like the number of FMT infusions and patient characteristics. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) safe for humans?

Research indicates that fecal microbiota transplantation (FMT) is generally safe for humans, including those with irritable bowel syndrome (IBS), based on studies that have assessed its safety over periods ranging from 3 months to 3 years. ^{4 6 7 8 9}

How is fecal microbiota transplantation (FMT) different from other treatments for irritable bowel syndrome (IBS)?

FMT is unique because it involves transferring healthy bacteria from a donor's stool to a patient's gut to restore balance in gut bacteria, which is different from traditional IBS treatments that often focus on managing symptoms with medication or diet changes. ^{1 2 3 4 7}

Research Team

Madhusudan Grover, MBBS

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for individuals with post-infection irritable bowel syndrome (PI-IBS) who experience moderate to severe symptoms. They must be able to undergo a colonoscopy and not have constipation-dominant IBS. People with recent abdominal surgery, bleeding disorders, low neutrophil count, active cancer, certain GI diseases, or those pregnant or on immune-suppressing drugs cannot participate.

Inclusion Criteria

I do not have constipation-predominant IBS.

I can safely have and agree to a colonoscopy.

My IBS symptoms are moderate to severe.

Exclusion Criteria

Absolute neutrophil count (ANC) <500 IU/ml

I cannot undergo a colonoscopy with sedation due to severe bowel or medical conditions.

Pregnant or lactating

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fecal microbiota transplantation (FMT) using stool from a donor or their own stool

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Autologous Fecal Microbiota Transplantation
• Donor Fecal Microbiota Transplantation

Trial Overview The study tests the effectiveness of fecal microbiota transplantation (FMT). Participants will receive stool from a donor with specific bacteria thought to help PI-IBS symptoms versus their own stool. The goal is to see if this can reduce protein breakdown in the gut linked to IBS.

Participant Groups

Group I: Donor Fecal Microbiota Transplantation Group Experimental Treatment 1 Intervention

Subjects will receive a fecal microbiota transplantation (FMT) using stool from a donor

Group II: Autologous Fecal Microbiota Transplantation Group Placebo Group 1 Intervention

Subjects will receive a fecal microbiota transplantation (FMT) using their own stool

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

Approved in European Union as Fecal Microbiota Transplantation for:

• Recurrent Clostridioides difficile infection
• Research use for IBS

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent Clostridioides difficile infection
• Research use for IBS

Approved in Canada as Fecal Microbiota Transplantation for:

• Recurrent Clostridioides difficile infection
• Research use for IBS

Who Is Running the Clinical Trial?

Madhusudan (Madhu) Grover, MBBS

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

In a study of 164 IBS patients, there was no overall sex difference in the response to fecal microbiota transplantation (FMT) for moderate-to-severe IBS symptoms, indicating that both males and females can benefit similarly from this treatment.

However, female patients with diarrhea-predominant IBS (IBS-D) showed a significantly better response to FMT, with greater symptom reduction compared to males at both 1 month and 3 months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responses to faecal microbiota transplantation in female and male patients with irritable bowel syndrome. El-Salhy, M., Casen, C., Valeur, J., et al.[2021]

In a study of 17 IBS patients, allogenic fecal microbiota transfer (FMT) significantly reduced IBS symptoms compared to baseline, while autologous FMT did not show a significant change in symptoms.

Both types of FMT led to shifts in gut microbiota composition, but there was no clear superiority of allogenic over autologous FMT, suggesting that the process of FMT itself may influence outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study. Holster, S., Lindqvist, CM., Repsilber, D., et al.[2020]

A meta-analysis of seven randomized controlled trials involving 489 IBS patients found that fecal microbiota transplantation (FMT) did not significantly improve overall IBS symptoms compared to placebo, indicating limited efficacy of FMT in general.

However, FMT delivered through invasive methods (like gastroscopy or colonoscopy) showed a significant improvement in IBS symptoms, while oral capsule delivery had a negative impact, suggesting that the method of administration is crucial for the effectiveness of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials. Zhao, HJ., Zhang, XJ., Zhang, NN., et al.[2022]

A novel six-month fecal microbiota transplantation (FMT) protocol showed significant efficacy in reducing IBS symptoms, with up to 75% of participants maintaining symptom improvement at week-52 after treatment.

The treatment was found to be safe, with only 28% of participants experiencing mild and transient adverse events, while also improving quality of life for 64% of respondents by the end of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-Antibiotic Treatment Followed by Prolonged Repeated Faecal Microbiota Transplantation Improves Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome: An Observational Australian Clinical Experience. Hamblin, H., Gunaratne, AW., Clancy, A., et al.[2022]

In a study of 17 Japanese patients with refractory irritable bowel syndrome (IBS), 58.8% showed significant improvement in IBS severity after fecal microbiota transplantation (FMT), with an average decrease of 115.58 points in the IBS severity index over 12 weeks.

The treatment was well-tolerated, with only mild side effects reported, and improvements in IBS symptoms were associated with increased microbiome diversity and closer similarity to the donor microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan. Hamazaki, M., Sawada, T., Yamamura, T., et al.[2022]

Fecal microbiota transplantation (FMT) showed significant long-term efficacy in reducing IBS symptoms, with response rates of 69.1% and 77.8% for the 30g and 60g treatment groups, respectively, at 2 years, and 64.9% and 71.8% at 3 years, compared to only 26.3% in the placebo group.

No long-term adverse events were reported, indicating that FMT is a safe intervention for IBS, with improvements in quality of life and a decrease in dysbiosis index observed in the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. El-Salhy, M., Winkel, R., Casen, C., et al.[2022]

A single stool fecal microbiota transplantation (FMT) significantly improves symptoms in patients with irritable bowel syndrome (IBS), showing reductions in IBS severity scores at multiple time points (1, 3, 6, 24, and 36 months) compared to placebo.

FMT is considered safe, as it does not increase the risk of serious adverse events, and the quality of evidence supporting its efficacy is moderate, although capsule FMT did not show positive effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Wang, M., Xie, X., Zhao, S., et al.[2023]

A systematic review of 8 randomized trials involving 472 IBS patients found that fecal microbiota transfer (FMT) did not significantly improve overall IBS symptom severity compared to placebo, indicating limited efficacy of FMT for IBS treatment.

While the oral route of FMT showed some initial improvement in response rates, this did not translate into a significant reduction in symptom severity, and the benefits appeared to diminish over time, suggesting that alternative bacterial-based treatments may be more effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of fecal microbiota transplant in irritable bowel syndrome: An update based on meta-analysis of randomized control trials. Abdelghafar, YA., AbdelQadir, YH., Motawea, KR., et al.[2022]

In a follow-up study of 77 IBS patients who previously responded to fecal microbiota transplantation (FMT), 86.5% of those receiving 30-g and 87.5% of those receiving 60-g FMT maintained their positive response after 1 year.

Improvements in abdominal symptoms and quality of life continued to increase over the year, alongside significant changes in the fecal bacterial profile and levels of short-chain fatty acids, indicating the long-term efficacy and safety of FMT for IBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome. El-Salhy, M., Kristoffersen, AB., Valeur, J., et al.[2022]

References

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

Responses to faecal microbiota transplantation in female and male patients with irritable bowel syndrome. [2021]

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

The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials. [2022]

4. Egypt pubmed.ncbi.nlm.nih.gov

Pre-Antibiotic Treatment Followed by Prolonged Repeated Faecal Microbiota Transplantation Improves Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome: An Observational Australian Clinical Experience. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan. [2022]

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

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. [2023]

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

Efficacy and safety of fecal microbiota transplant in irritable bowel syndrome: An update based on meta-analysis of randomized control trials. [2022]

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

Long-term effects of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome. [2022]