Fecal Microbiota Transplant for Chronic Pouchitis

Overseen By Maia Kayal

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Maia Kayal

Must be taking: Antibiotics

Must not be taking: Biologics, Immunomodulators, Steroids, others

Disqualifiers: Pregnancy, Breastfeeding, Fever, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if fecal microbiota transplant (FMT) is safe and effective for treating chronic pouchitis, a condition causing inflammation and discomfort in individuals who have undergone surgery for ulcerative colitis. FMT involves transplanting healthy bacteria from a donor's stool to restore gut balance. The trial seeks participants with pouchitis that does not improve with antibiotics or recurs frequently. As an Early Phase 1 trial, the study focuses on understanding how FMT 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 requires that you stop taking certain medications, such as biologics, immunomodulators, steroids, or any investigational drugs, to participate.

Is there any evidence suggesting that fecal microbiota transplant is likely to be safe for humans?

Research has shown that Fecal Microbiota Transplant (FMT) is generally safe for treating long-term pouchitis. In studies, patients have tolerated FMT well, though some experienced mild side effects such as stomach discomfort or diarrhea. No serious safety issues emerged. However, the treatment's effectiveness can vary among individuals. These factors are important to consider when deciding to join a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for chronic pouchitis, which typically include antibiotics, probiotics, and anti-inflammatory medications, Fecal Microbiota Transplant (FMT) offers a unique approach. FMT works by restoring the balance of beneficial bacteria in the gut, directly targeting the microbiome rather than just alleviating symptoms. This approach is exciting for researchers because it aims to address the root cause of the inflammation and dysbiosis associated with chronic pouchitis, potentially leading to more effective and longer-lasting results.

What evidence suggests that fecal microbiota transplant might be an effective treatment for chronic pouchitis?

Research has shown mixed results for using fecal microbiota transplant (FMT) to treat chronic pouchitis. Some studies suggest FMT can help, but many patients experience mild side effects. Other research indicates that FMT might not work well with certain treatment methods. While FMT effectively stops recurring C. difficile infections, its success with chronic pouchitis is less clear. Overall, some patients have benefited, but the effectiveness of FMT for chronic pouchitis remains uncertain. ^{2 3 4 5 6}

Who Is on the Research Team?

Maia Kayal

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults with chronic pouchitis who rely on antibiotics to stay in remission and have tried stopping antibiotics at least twice, leading to flare-ups. It's not for those with certain pouch strictures, Crohn's-like inflammation, allergies to specific antibiotics used here, pregnant or breastfeeding women, or patients currently on biologics, immunomodulators, steroids or other trials.

Inclusion Criteria

I am 18 or older with UC and had surgery to create a pouch in my lower belly.

I need ongoing antibiotics for pouchitis and have had flare-ups when trying to stop them.

I have active pouchitis and have tried at least 4 antibiotic treatments in the past year.

Exclusion Criteria

I currently have a fever over 100.4F or show signs of being sick.

I am currently taking immunomodulators, steroids, or experimental drugs.

Allergy to vancomycin, metronidazole, or ingredients present in the FMT

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fecal microbiota transplant (FMT) for the treatment of chronic pouchitis

8 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fecal Microbiota Transplant (FMT)

Trial Overview The study is testing the safety and effectiveness of fecal microbiota transplant (FMT) as a treatment option for people suffering from chronic pouchitis. Participants will receive FMT to see if it can help maintain their condition without the need for continuous antibiotic use.

How Is the Trial Designed?

Group I: Fecal Microbiota Transplant (FMT) Experimental Treatment 1 Intervention

Single arm of 16-18 subjects, all of whom will receive the interventional FMT.

Fecal Microbiota Transplant (FMT) is already approved in United States for the following indications:

Approved in United States as Fecal Microbiota Transplant for:

• Recurrent Clostridioides difficile infection (CDI)

Who Is Running the Clinical Trial?

Maia Kayal

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

In a study involving 8 patients with chronic pouchitis, faecal microbiota transplantation (FMT) led to variable changes in the composition of gut microbiota, indicating potential shifts towards a healthier microbiota.

Despite these changes, FMT did not result in significant improvements in metabolic, immunological responses, or clinical outcomes, suggesting that the current method of FMT administration may need further optimization for effective treatment of pouchitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis. Landy, J., Walker, AW., Li, JV., et al.[2023]

A systematic review of 129 studies involving 4241 patients found that 19% of fecal microbiota transplantation (FMT) procedures reported adverse events, with the most common being mild issues like diarrhea (10%) and abdominal discomfort (7%).

Serious adverse events (SAEs) occurred in 1.4% of patients, primarily in those with mucosal barrier injury, highlighting the need for improved FMT methodologies to enhance safety, especially for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020. Marcella, C., Cui, B., Kelly, CR., et al.[2021]

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 transplant (FMT) appears to be safe for patients with chronic pouchitis, as indicated by the four studies reviewed, but its efficacy is limited, with only a few patients achieving sustained clinical remission.

Out of the studies, only one showed a significant clinical response, with 75% of patients in that study reaching remission, while the overall results suggest that more research is needed to better understand the effectiveness of FMT for both acute and chronic pouchitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Fecal Microbiota Transplant for the Management of Pouchitis. Kayal, M., Lambin, T., Pinotti, R., et al.[2023]

A systematic review of nine studies involving 69 patients with chronic pouchitis found that fecal microbiota transplantation (FMT) resulted in clinical response in 31.8% and clinical remission in 22.7% of patients, indicating some potential efficacy.

Despite these findings, the overall quality of the studies was low, with only one randomized controlled trial showing no beneficial effect of FMT, highlighting the need for more rigorous research to establish the effectiveness of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation in the Treatment of Chronic Pouchitis: A Systematic Review. Cold, F., Kousgaard, SJ., Halkjaer, SI., et al.[2020]

In a pilot study involving nine patients with chronic pouchitis, fecal microbiota transplantation (FMT) led to significant clinical improvement in symptoms for four patients, with three maintaining remission for up to six months.

FMT treatment resulted in a notable increase in gut microbial diversity and successful engraftment of donor microbiota in six patients, suggesting a potential mechanism for its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical results and microbiota changes after faecal microbiota transplantation for chronic pouchitis: a pilot study. Kousgaard, SJ., Michaelsen, TY., Nielsen, HL., et al.[2021]

Faecal microbiota transplantation (FMT) showed a clinical response rate of 42.6% and a remission rate of 29.8% in treating chronic pouchitis, based on a systematic review of 9 studies involving 103 patients.

The treatment was well tolerated with minor, self-limiting adverse events reported, indicating a good safety profile, but the evidence is limited and calls for more rigorous studies to better assess FMT's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal microbiota transplantation (FMT) in the treatment of chronic refractory pouchitis: A systematic review and meta-analysis. Zaman, S., Akingboye, A., Mohamedahmed, AYY., et al.[2023]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11676736/

Fecal Microbiota Transplantation for Chronic Pouchitis Although FMT is an effective treatment for chronic pouchitis, there is still a high rate of mild adverse events.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772572323000675

Safety and Efficacy of Fecal Microbiota Transplant in ... In patients with chronic pouchitis, FMT is safe though there are mixed results in terms of its long-term efficacy.

3. academic.oup.com academic.oup.com/ecco-jcc/article/18/1/144/7224460

Faecal Microbiota Transplantation [FMT] in the Treatment of ... The aim of this systematic review and meta-analysis is to assess the efficacy and safety of faecal microbiota transplantation [FMT] in the treatment of chronic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8528148/

Fecal Microbiota Transplantation in Chronic Pouchitis Our clinical results suggest that FMT is not effective in the treatment of chronic pouchitis with the treatment protocol that was used in this study. We ...

5. gastrojournal.org gastrojournal.org/article/S0016-5085(24)00041-6/fulltext

AGA Clinical Practice Guideline on Fecal Microbiota ... Conclusions. Fecal microbiota–based therapies are effective therapy to prevent recurrent C difficile in select patients. Conventional fecal microbiota ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7565999/

Fecal Microbiota Transplantation in the Treatment of Chronic ... This systematic review is the first to collect data on clinical outcomes from all published studies treating chronic pouchitis patients with FMT. A ...