Fecal Microbiota Transplantation for Clostridioides difficile Colitis

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must be taking: Metronidazole, Vancomycin

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Liver cirrhosis, Active malignancy, HIV, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called fecal microbiota transplantation (FMT) to help people with a difficult intestinal infection caused by Clostridioides difficile, which often leads to chronic, recurring diarrhea. The goal is to introduce healthy bacteria from a donor into the gut to restore balance and stop the infection. The trial seeks veterans with confirmed C. difficile infections that have not improved after standard treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on major immunosuppressive drugs or require ongoing antimicrobial therapy, you may not be eligible to participate.

What prior data suggests that this fecal microbiota transplantation is safe for treating Clostridioides difficile colitis?

Research has shown that fecal microbiota transplantation (FMT) is generally safe and effective for treating Clostridioides difficile infections. Past studies have demonstrated high success rates, with some showing rates as high as 90.9%. Importantly, these studies found that FMT did not cause significant harmful side effects, indicating that most people did not experience serious problems.

In this study, three patients received FMT, and all were cured of their infections without negative side effects. This outcome suggests that FMT can be a safe option for those dealing with recurring C. difficile infections. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for Clostridioides difficile colitis rely on antibiotics like vancomycin or metronidazole to kill harmful bacteria. But Fecal Microbiota Transplantation (FMT) works differently by replenishing the gut with healthy bacteria. Researchers are excited about FMT because it directly restores the natural balance of microbes in the intestines, which can be disrupted by antibiotics. This approach not only targets the root cause of recurrent infections but also offers a natural and potentially more effective alternative to traditional antibiotics. By using a catheter to deliver the microbiota directly into the small intestine, FMT has the potential to act quickly and may reduce the risk of further antibiotic resistance.

What evidence suggests that defined fecal microbiota transplantation is effective for Clostridioides difficile colitis?

Research has shown that fecal microbiota transplantation (FMT), which participants in this trial will receive, effectively treats recurrent Clostridioides difficile infections (CDI). One study found that about 75% of patients improved after just one FMT treatment, with the success rate increasing to over 87% with additional treatments. FMT introduces healthy bacteria to the gut, restoring balance and reducing harmful bacteria like C. difficile. Past research, including a study from 1989, found that a specific mix of healthy bacteria led to quick recovery and long-lasting symptom relief. Overall, FMT is considered a safe and effective method for addressing recurrent CDI. ^{1 2 6 7 8}

Who Is on the Research Team?

David Y Graham, MD

Principal Investigator

Baylor College of Medicine

Antone R Opekun, MS, PA-C

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for VA patients with confirmed C. difficile infection (CDI) that persists or returns after standard treatment. They must be able to give informed consent and not have severe kidney issues, active serious cancer, HIV/AIDS, be bedridden, on high-dose steroids or other strong immune-suppressing drugs, have advanced liver disease, need certain concurrent antibiotics, or have a life expectancy under one year.

Inclusion Criteria

Patients must give informed consent and sign approved consent form by Baylor IRB

Presence of fever, leukocytosis, and low serum albumin not necessary for diagnosis

I am a veteran diagnosed with CDI and treated with metronidazole or vancomycin.

Exclusion Criteria

Condition suggesting life span will not be >1 yr

Contraindication for ultra-slim endoscopy

My kidney function is severely impaired.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants are pretreated with 4 days of oral vancomycin to reduce the C. difficile load

4 days

Treatment

Defined fecal microbiota transplantation is administered into the small intestine

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored daily in the hospital and contacted daily by phone after discharge for 14 days

2 weeks

Daily contact

Extended Follow-up

Participants are contacted at 30 days, monthly for 3 months, then every 3 months for one year to monitor symptoms and collect stool samples

12 months

Regular contact and sample collection

What Are the Treatments Tested in This Trial?

Interventions

• Defined Fecal Microbiota Transplantation

Trial Overview The study tests fecal microbiota transplantation (FMT), which involves transferring stool from a healthy donor to the patient's intestine to restore normal gut bacteria balance. This could suppress C. difficile growth and alleviate chronic diarrhea associated with CDI.

How Is the Trial Designed?

Group I: microbiota transplantation Experimental Treatment 1 Intervention

Two hundred mL of the bacterial suspension (microbiota transplantation) will be instilled into the small intestine via a catheter introduced through the biopsy channel of the endoscope and the flushed with 25 mL of sterile pre-reduced 0.9% saline. After removal of the endoscope, after recovery, patients will be allowed to resume a normal diet and physical activities.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Michael E. DeBakey VA Medical Center

Collaborator

Trials

68

Recruited

17,200+

Published Research Related to This Trial

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 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 become a key treatment for Clostridium difficile infection, but its efficacy and safety in patients with underlying inflammatory bowel disease (IBD) are not well established, particularly regarding the risk of IBD flare-ups.

Emerging evidence suggests that FMT may also be beneficial for treating IBD itself, with promising results from randomized trials in ulcerative colitis, although the variability in study outcomes means more research is needed to clarify its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Landscape and Lessons from Fecal Microbiota Transplantation for Inflammatory Bowel Disease: Past, Present, and Future. Allegretti, J., Eysenbach, LM., El-Nachef, N., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10966711/

Beneficial effects of fecal microbiota transplantation in ... SUMMARY. Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI).

2. cghjournal.org cghjournal.org/article/S1542-3565(25)00646-9/abstract

Effectiveness and Safety of Fecal Microbiota ... The clinical resolution rate after a single FMT was 75.3% (95% confidence interval [CI], 71.7%–78.6%), increasing to 87.4% (95% CI, 84.8%–89.6%) ...

3. cidrap.umn.edu cidrap.umn.edu/clostridium-difficile/study-highlights-optimal-strategies-fecal-transplantation-c-diff-patients

Study highlights optimal strategies for fecal transplantation ... Among the included patients, 699 (60%) were cured of CDAD after 8 weeks following their first FMT treatment. The cure rate among the different ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34864789/

Outcomes of Fecal Microbiota Transplantation for C. difficile ... FMT appears to be a highly effective therapy for preventing recurrent CDI in patients with IBD. Patients who fail a single FMT may benefit from multiple FMTs.

5. frontiersin.org frontiersin.org/journals/microbiomes/articles/10.3389/frmbi.2024.1409967/full

Recent advances in fecal microbiota transplantation for ... Fecal microbiota transplantation (FMT) is highly effective in preventing and treating CDIs. It is an emerging therapeutic approach that restores ...

6. cureus.com cureus.com/articles/398525-microbiota-based-therapies-for-recurrent-clostridium-difficile-infection-a-systematic-review-of-their-efficacy-and-safety

Microbiota-Based Therapies for Recurrent Clostridium ... In our analysis, the clinical cure rate with donor FMT was 90.9%, as reported in Kelly et al. (2016) [18], while Cammarota et al. (2015) [5] ...

7. hopkinsmedicine.org hopkinsmedicine.org/health/treatment-tests-and-therapies/fecal-transplant

Fecal Transplant Research shows that fecal transplant can restore healthy bacteria in the lower intestine, which can help control C. diff and keep it from coming back. In some ...

8. ferringusa.com ferringusa.com/?press=ferring-presents-new-real-world-rebyota-fecal-microbiota-live-jslm-data-underscoring-effectiveness-and-significant-improvements-in-patient-quality-of-life

Ferring Presents New Real-World REBYOTA® (fecal ... These analyses highlight the effectiveness and safety of REBYOTA in preventing recurrent Clostridioides difficile infection (rCDI) in real-world ...