Fecal Microbiota Transplant for Clostridium Difficile and IBD

Overseen By Melissa Kennedy, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Hospital of Philadelphia

Must not be taking: Antibiotics, Corticosteroids

Disqualifiers: Severe IBD, Pregnancy, Anaphylactic allergy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Fecal Microbiota Transplant (FMT) for children who frequently suffer from the gut infection C. Difficile, with or without Inflammatory Bowel Disease (IBD). The main goal is to determine if FMT is safe and effective in improving their condition by altering gut bacteria. The trial includes two groups: one for children with only C. Difficile and another for those with both C. Difficile and IBD. Children with repeated C. Difficile infections or moderate to severe symptoms may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, ongoing or anticipated antibiotic use for non-CDI indications is an exclusion criterion, so you may need to stop those. Please consult with the study team for more details.

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 does exclude patients who are on high doses of corticosteroids or those using antibiotics for reasons other than C. difficile. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that Fecal Microbiota Transplant is likely to be safe for pediatric patients?

Research has shown that Fecal Microbiota Transplant (FMT) is a recognized treatment for recurring Clostridioides difficile infections. Studies have found that FMT is usually well-tolerated in adults, with most experiencing no serious side effects. Although less information exists for children, early results suggest similar safety.

FMT restores gut balance using healthy bacteria from a donor's stool. Current research considers it effective and safe for treating C. difficile infections. For individuals with both C. difficile and Inflammatory Bowel Disease (IBD), FMT remains under study, but there is hope it could help manage symptoms by adjusting gut bacteria.

In summary, FMT is generally safe for treating C. difficile, and ongoing studies are examining its safety for those with IBD. Always consult healthcare providers for personal advice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Fecal Microbiota Transplant (FMT) is unique because it introduces beneficial gut bacteria directly from a healthy donor to restore balance in the recipient's gut microbiome. Unlike standard treatments for recurrent Clostridium Difficile infections, such as antibiotics that can disrupt gut flora even more, FMT aims to repopulate the gut with healthy bacteria, potentially offering a more sustainable solution. Researchers are particularly excited about its application in patients with Inflammatory Bowel Disease (IBD) because it may address underlying microbiome imbalances that traditional treatments, like anti-inflammatory drugs, don't target. This innovative approach could lead to more effective and long-lasting relief for patients suffering from these challenging conditions.

What evidence suggests that Fecal Microbiota Transplant might be an effective treatment for recurrent C. Difficile and IBD?

Research has shown that Fecal Microbiota Transplant (FMT) effectively treats recurrent infections of the bacteria C. difficile. Studies indicate that FMT can prevent C. difficile diarrhea from returning in over 90% of cases. In this trial, one group of participants with recurrent C. difficile will receive FMT, while another group with both C. difficile and Inflammatory Bowel Disease (IBD) will also receive FMT. For patients with both C. difficile and IBD, FMT has been shown to reduce recurrence and improve gut health by increasing the variety of beneficial bacteria. This method transfers healthy bacteria from a donor to the patient, restoring a balanced gut environment. Overall, FMT is considered a promising treatment for these conditions. ^{2 3 6 7 8}

Who Is on the Research Team?

Judith Kelsen, MD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for kids and young adults aged 3-21 with recurrent C. difficile or moderate to severe cases, who may also have Inflammatory Bowel Disease (IBD). They must pass a medical interview and physical exam, not be pregnant if female of childbearing age, and not have other intestinal infections or allergies to certain safe ingredients.

Inclusion Criteria

Signed informed consent form, and assent (if applicable)

I have been diagnosed with Inflammatory Bowel Disease through tests.

I have had C. difficile infection more than once or it is severe.

Exclusion Criteria

Any other condition for which the treating physician thinks the treatment may pose a health risk

Predicted death within time period of follow-up

I am taking high doses of steroids.

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) to treat recurrent C. Difficile with or without Inflammatory Bowel Disease

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after FMT treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fecal Microbiota Transplant

Trial Overview The study tests Fecal Microbiota Transplant (FMT) in children with C. difficile, observing its safety and effectiveness alone or when combined with IBD. It also examines changes in gut bacteria through advanced sequencing before and after the transplant.

How Is the Trial Designed?

Group I: C. Difficile without IBD Experimental Treatment 1 Intervention

Fecal Microbiota transplant in pediatric patients with recurrent C. Difficile

Group II: C. Difficile with IBD Experimental Treatment 1 Intervention

Fecal Microbiota transplant in pediatric patients with recurrent C. Difficile with Inflammatory Bowel Disease

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

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent and refractory Clostridioides difficile infection

Approved in European Union as Faecal Microbiota Transplantation for:

• Recurrent and refractory Clostridioides difficile infection

Approved in Canada as Fecal Microbiota Transplantation for:

• Recurrent and refractory Clostridioides difficile infection

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Judith Kelsen

Lead Sponsor

Trials

1

Recruited

250+

Published Research Related to This Trial

Fecal microbiota transplantation (FMT) has shown a high success rate of 80-98% in treating severe and recurrent Clostridium difficile infections (CDI), particularly when administered via colonoscopy, which was the method used for most patients in the studies reviewed.

FMT works by restoring the normal microbiome of the colon, and evidence increasingly supports its effectiveness as a treatment option for CDI, although challenges such as patient perceptions and the need for standardized protocols remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal microbiota transplantation for Clostridium difficile infection. Dodin, M., Katz, DE.[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]

In a review of 12 published studies on fecal microbiota transplantation (FMT) for inflammatory bowel disease (IBD), only one study suggested a significant donor effect, while the majority showed no statistically significant differences in efficacy based on donor material.

Despite the lack of strong evidence for donor effects, the study highlights that the existing data cannot completely rule out their potential clinical importance, indicating a need for larger, well-designed trials to explore this further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-Evaluating the Evidence for Faecal Microbiota Transplantation 'Super-Donors' in Inflammatory Bowel Disease. Olesen, SW., Gerardin, Y.[2021]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for Clostridioides difficile infection (CDI) in patients who also have inflammatory bowel disease (IBD).

There is ongoing research into the potential of FMT as a treatment for IBD itself, given the link between gut microbiome alterations and conditions like ulcerative colitis and Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FMT: What's Next? A Narrative Review of Fecal Microbiota Transplantation in Clostridioides difficile Infection and Inflammatory Bowel Disease. Patwa, SA., Ward, C., Kelly, CR.[2022]

Fecal microbiota transplantation (FMT) has a reported adverse event (AE) rate of 39.3%, primarily involving mild and self-limiting issues like abdominal pain and diarrhea, based on a meta-analysis of 9 high-quality studies involving 756 FMTs.

Serious adverse events (SAE) were relatively rare at 5.3%, with the most common being Clostridium difficile infection, indicating that while FMT is generally safe, monitoring and standardized reporting are essential for understanding its long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies. Michailidis, L., Currier, AC., Le, M., et al.[2022]

In a follow-up survey of 137 patients who received fecal microbiota transplant (FMT) for recurrent Clostridium difficile infection (RCDI), 82% reported no recurrence of CDI at a median follow-up of 22 months, indicating FMT's long-term efficacy.

Despite the high success rate, 33% of patients reported new medical conditions or symptoms post-FMT, but 95% expressed willingness to undergo the procedure again, highlighting patient satisfaction with FMT as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durability and Long-term Clinical Outcomes of Fecal Microbiota Transplant Treatment in Patients With Recurrent Clostridium difficile Infection. Mamo, Y., Woodworth, MH., Wang, T., 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]

Faecal microbiota transplantation (FMT) shows an initial cure rate of 81% and an overall cure rate of 89% for Clostridium difficile infection (CDI) in patients with inflammatory bowel disease (IBD), based on a systematic review of nine cohort studies involving 346 patients.

The recurrence rate of CDI after FMT in these patients is 19%, and there is no significant difference in cure rates between patients with IBD and those without, indicating that FMT is an effective treatment option for CDI in IBD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Faecal Microbiota Transplantation for Treatment of Clostridium difficile Infection in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Cohort Studies. Chen, T., Zhou, Q., Zhang, D., et al.[2022]

In a survey of 262 ulcerative colitis patients, 56.1% expressed willingness to undergo fecal microbiota transplantation (FMT) as a treatment option, motivated primarily by the effectiveness of the procedure and the failure of other therapies.

Concerns about FMT included the potential transmission of infectious agents and contamination of the stool graft, highlighting the need for safe implementation practices in this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis]. Roggenbrod, S., Schuler, C., Haller, B., et al.[2022]

Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD), with an overall pooled cure rate of 88% after single and multiple FMTs based on a systematic review of 457 adult patients.

While FMT is effective, there is a 26.8% rate of IBD flare-ups following the procedure, indicating that while it helps with CDI, monitoring for IBD symptoms is important after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Fecal Microbiota Transplantation for C. difficile Infection in Inflammatory Bowel Disease : A Systematic Review and Meta-analysis. Tariq, R., Syed, T., Yadav, D., et al.[2023]

Faecal microbiota transplantation (FMT) was found to be highly effective in treating recurrent Clostridioides difficile infection (CDI), with an 84.6% success rate in a study of 13 patients, all of whom experienced symptom resolution within 48 hours.

The procedure was deemed safe, as no significant short or long-term complications were reported during a follow-up period averaging 25.66 months, demonstrating its feasibility even in elderly patients with multiple health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal Microbiota Transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice. Ferre Aracil, C., El Hajra Martínez, I., Vera Mendoza, MS., et al.[2023]

Citations

1. ccjm.org ccjm.org/content/92/7/421

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

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8034505/

Fecal Microbiota Transplantation Is Highly Effective in Real ... A systematic review of the efficacy and safety of fecal microbiota transplant for Clostridium difficile infection in immunocompromised patients. Can J ...

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

Real-world Effectiveness of Fecal Microbiota ... The primary outcome was cure of C. difficile-associated diarrhea (CDAD) 8 weeks after the last FMT treatment. Secondary outcomes included CDAD cure 1 and 8 ...

4. academic.oup.com academic.oup.com/cid/article/80/1/52/7756590

A Randomized Controlled Trial of Efficacy and Safety of Fecal ... We conducted a randomized double-blind clinical trial of the efficacy and safety of fecal microbiota transplant (FMT) for reducing recurrent Clostridioides.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6453848/

Fecal Microbiota Transplantation: An Update on Clinical ... FMT has been successfully used to treat recurrent Clostridium difficile infection (rCDI). The short-term success of FMT in rCDI has led to investigations of its ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7757860/

Efficacy and safety of fecal microbiota transplantation for the ... Preliminary data suggest that FMT is a potentially safe, well-tolerated and efficacious treatment for certain conditions other than CDI, with evidence for ...

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

Fecal Transplant FMT is mainly used to treat persistent infections with C. diff. The procedure works by taking healthy bacteria (microbiota) from the feces of a carefully ...

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

AGA Clinical Practice Guideline on Fecal Microbiota ... This guideline to provide recommendations on the use of fecal microbiota–based therapies in adults with recurrent Clostridioides difficile infection.