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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for individuals with recurrent C. difficile infections, a bacterial infection causing severe diarrhea. The researchers aim to compare the effectiveness of fecal microbiota transplantation (FMT) and a new treatment called MTC 01, a microbiota capsule. Participants will receive one of four treatments: high or low doses of either FMT or MTC 01. Candidates may qualify if they have experienced at least two episodes of C. difficile infection in the past six months and are dealing with frequent diarrhea. As a Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants the chance to receive a potentially groundbreaking new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fecal microbiota transplantation (FMT) effectively treats recurring Clostridioides difficile infection (CDI). Studies indicate it is generally safe, with most patients experiencing few serious side effects. Some people might have mild symptoms like stomach upset or diarrhea, but these usually resolve quickly.

MTC 01, a newer treatment, is being tested against FMT. As this is an early trial, little is known about its safety. However, since this is a Phase 1 study, the main focus is on safety and observing participants' responses to the treatment. Researchers will closely monitor participants for any side effects.

In summary, while FMT has a strong safety record, MTC 01 remains under evaluation. Researchers will carefully monitor participants to ensure their safety during the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach to tackling C. difficile infections. Unlike standard fecal microbiota transplantation (FMT), which involves transplanting stool from a healthy donor, the treatments being studied involve microbiota capsules like MTC 01. MTC 01 is delivered via colonoscopy and comes in both high-dose and low-dose forms, potentially offering a more controlled and precise way to restore healthy gut bacteria. These capsules could provide a more standardized, less invasive alternative to traditional FMT, which can have variability in donor material and delivery methods. This innovative approach might lead to more consistent outcomes and improved patient experiences.

What evidence suggests that this trial's treatments could be effective for C. Difficile Infection?

Research shows that Fecal Microbiota Transplantation (FMT) effectively treats people with recurrent Clostridioides difficile infections (CDI). Studies indicate that FMT restores a healthy balance of gut bacteria, significantly reducing the chance of infection recurrence. It works well whether administered through a colonoscopy or as oral capsules. In this trial, participants will receive either FMT or MTC 01, a newer treatment tested against FMT. Although less research exists on MTC 01, it is under study for its potential to offer similar benefits by altering gut bacteria to combat infections. Overall, FMT remains the proven option for treating recurring CDI, while MTC 01 serves as a new alternative explored in this trial. ^{1 2 5 6 7}

Who Is on the Research Team?

Ari Grinspan

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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) 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]

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]

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]

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) 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) 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]

Citations

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2. sciencedirect.com sciencedirect.com/science/article/pii/S1542356524005147

Real-world Effectiveness of Fecal Microbiota ... Clostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI ...

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A Randomized Controlled Trial of Efficacy and Safety ... ... Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection ... Fecal Microbiota Transplantation* / adverse effects ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00234-2/fulltext

Clinical management of Clostridioides difficile infection ... Faecal microbiota transplantation (FMT) is a well-established treatment with high cumulative effectiveness for Clostridioides difficile ...

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Fecal microbiota transplantation: Current evidence and ... Fecal microbiota transplantation (FMT), a well-established procedure, is recognized for effectively treating recurrent Clostridioides difficile infection.

7. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2836642

Fecal Transplant Appears Noninferior to Antibiotics for ... Treating Clostridioides difficile infection (CDI) with fecal microbiota transplantation (FMT) provides similar long-term outcomes compared with standard oral ...