Microbiota Capsules vs Fecal Transplants for C. Difficile Infection

Overseen By Sari Feldman, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Icahn School of Medicine at Mount Sinai

Must be taking: CDI antibiotics

Must not be taking: Non-anti-CDI antibiotics

Disqualifiers: Pregnancy, Gastroenteritis, IBD, others

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

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that you cannot participate if you need continued non-anti-CDI antibiotic therapy or use drugs that alter gut motility. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of this treatment for C. difficile infection?

Research shows that fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridium difficile infection, especially when standard antibiotics fail. Studies have demonstrated its success in both traditional and capsule forms, with promising results in restoring healthy gut bacteria. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) safe for humans?

FMT is generally considered safe and well-tolerated, especially for treating recurrent Clostridioides difficile infections. Most short-term risks are mild, but long-term effects are not well-studied. Serious adverse events have been linked to inadequate donor screening, highlighting the importance of strict protocols. ^{6 7 8 9 10}

How is the treatment for C. difficile infection using microbiota capsules different from other treatments?

Microbiota capsules for treating C. difficile infection are unique because they involve taking oral capsules filled with healthy bacteria from donor stool, which is a simpler and less invasive alternative to traditional fecal transplants that require procedures like colonoscopy or enemas. ^{1 2 3 4 11}

What is the purpose of this trial?

Investigating four different treatment of MTC or FMT

Research Team

Ari Grinspan

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for adults over 18 who've had at least two episodes of a specific infection called recurrent Clostridioides Difficile Infection (RCDI) in the last six months. Participants must have had diarrhea as part of this condition and tested positive for the infection recently. They should have responded to standard antibiotics before joining.

Inclusion Criteria

Documented positive stool test by local laboratory for toxigenic C. difficile (toxin EIA or PCR-based testing) for the current CDI episode within 60 days prior to randomization

I have had more than one Clostridium difficile infection episode.

I have completed a standard antibiotic treatment for my recent CDI episode.

Exclusion Criteria

Women with reproductive potential should use a reliable method of birth control

I have had a fecal microbiota transplant in the last year.

I am currently hospitalized but can be an outpatient for my colonoscopy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either MTC01 or FMT treatment via colonoscopy

8 weeks

1 visit (in-person) for colonoscopy

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Regular follow-up visits

Treatment Details

Interventions

• Fecal Microbiota Transplantation (FMT)
• MTC 01

Trial Overview The study is comparing four different treatments using either MTC 01 or Fecal Microbiota Transplantation (FMT). These are therapies aimed at restoring healthy bacteria in the gut to combat RCDI.

Participant Groups

Group I: Low Dose MTC 01 Experimental Treatment 1 Intervention

Low Dose MTC 01 is 10 x 10 CFU slurry to be administered via colonoscopy

Group II: High Dose MTC 01 Experimental Treatment 1 Intervention

High dose MTC 01 is 10 x 11 CFU slurry to be administered via colonoscopy

Group III: High Dose Fecal Microbiota Transplantation (FMT) Experimental Treatment 1 Intervention

Low dose FMT is 10 x 10 CFU slurry to be administered via colonoscopy

Group IV: Low dose Fecal Microbiota Transplantation (FMT) Active Control 1 Intervention

High dose FMT is 10 x 11 CFU slurry to be administered via colonoscopy

Fecal Microbiota Transplantation (FMT) is already approved in European Union, United States for the following indications:

Approved in European Union as Fecal Microbiota Transplantation for:

• Recurrent Clostridium difficile infection

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent Clostridium difficile infection

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

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) using targeted colonic release capsules (FMTcr) showed a slightly higher clinical cure rate for recurrent Clostridium difficile infection (rCDI) at 80.6% compared to 75% for gastric release capsules (FMTgr), although the difference was not statistically significant.

Both FMT formulations were found to be safe with no serious adverse events, but FMTcr was more effective in increasing gut microbial diversity, suggesting better microbial engraftment patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose. Allegretti, JR., Fischer, M., Sagi, SV., et al.[2020]

Fecal microbiota transplantation (FMT) was found to be a safe and effective treatment for recurrent Clostridium difficile infection (R-CDI) in a study of 13 patients, achieving an overall resolution rate of 91.7%.

The novel approach of administering FMT via oral capsules resulted in a 100% resolution rate, suggesting that this method could facilitate wider use of FMT in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for recurrent Clostridium difficile infection: Experience, protocol, and results. Reigadas, E., Olmedo, M., Valerio, M., et al.[2020]

In a study of 180 patients aged 7-95 with recurrent C. difficile infection, oral administration of frozen fecal capsules led to an 82% resolution rate after one treatment, increasing to 91% with two treatments.

The procedure was generally safe, with only three adverse events classified as Grade 2 or above, indicating that frozen encapsulated fecal microbiota transplantation is a promising treatment for recurrent CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection. Youngster, I., Mahabamunuge, J., Systrom, HK., et al.[2022]

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) 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 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) 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.[2022]

In a long-term follow-up study of 84 patients (45 receiving faecal microbiota transplantation (FMT) and 39 receiving antibiotics), FMT was found to be a safe and effective treatment for recurrent C. difficile infection, with no significant differences in severe disease incidence between the two groups over an average of 3.8 years.

Patients who received FMT reported significantly faster improvements in bowel habits and better mental health compared to those treated with antibiotics, indicating that FMT may offer additional benefits beyond just treating the infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-term effects of faecal microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent Clostridium difficile infection. Jalanka, J., Hillamaa, A., Satokari, R., et al.[2022]

Fecal microbiota transplantation (FMT) via colonoscopy has the highest cure rate for recurrent Clostridioides difficile infections (CDI) at 94.8%, compared to 92.1% for capsules, 87.2% for enemas, and 78.1% for nasogastric tube (NGT) administration, based on a review of 26 studies involving 1309 patients.

Both colonoscopy and capsule methods of FMT show comparable efficacy in treating CDI, indicating that capsules can be a viable alternative to the more invasive colonoscopy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation (FMT) with Colonoscopy Is Superior to Enema and Nasogastric Tube While Comparable to Capsule for the Treatment of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis. Ramai, D., Zakhia, K., Fields, PJ., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection. [2018]

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

Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose. [2020]

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

Fecal microbiota transplantation for recurrent Clostridium difficile infection: Experience, protocol, and results. [2020]

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

Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection. [2022]

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

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

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

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

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

Fecal Microbiota Transplantation: Is It Safe? [2021]

8. Spain 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. [2021]

9. Spain 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. [2022]

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

The long-term effects of faecal microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent Clostridium difficile infection. [2022]

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

Fecal Microbiota Transplantation (FMT) with Colonoscopy Is Superior to Enema and Nasogastric Tube While Comparable to Capsule for the Treatment of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis. [2021]