Fecal Transplant for Antibiotic-Related Gut Disruption

(aFMT-babies Trial)

Overseen By Anna Dulencin, PhD

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Rutgers, The State University of New Jersey

Disqualifiers: Recent antibiotics, Immunological condition

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Antibiotics are lifesaving therapeutic drugs which have been used by adults, children, and infants alike for decades. There is an increase in global use of antibiotics over the course of lifetime and earlier in lifetime, with some countries recording as high as 12 courses a year in children younger than two. While antibiotics are successful in eradicating many pathogenic bacteria, research has demonstrated significant effect on beneficial gut microbiota, including long-lasting shift in the dynamics, composition, richness, and maturity of the intestinal flora. Microbiota alterations during early life, including through antibiotics use as well as birth via C-section, constitute a developmental perturbation, which increases the risk of modern diseases of immune and metabolic dysfunction. Strong epidemiological evidence suggests associations between early stressors of the microbiota and a number of common diseases, such as obesity, asthma, allergies, celiac disease, and Type 1 Diabetes. Furthermore, excess antibiotic exposure is associated with the development of neurological and psychiatric disorders. Currently, no strategies exist to restore the microbiome other than reliance on spontaneous repair mechanism, which often takes months in a healthy individual barring further antibiotic exposure. Contrary to popular belief, ingestion of probiotics, particularly after antibiotics, has been demonstrated to slow down the repair as it introduces an exogenous and massive amounts of only a few types of bacterial strains into a finely-tuned ecosystem of hundreds of different strains. It is hypothesized that by preserving the child's microbiome prior to antibiotic therapy and reintroducing it afterwards through an autologous fecal matter transplant (FMT) will assist in a quick, effective, and host-specific microbiome recolonization to the levels and patterns to those prior to antibiotics. This would in turn reduce the overall loss of microbiome diversity over the child's lifespan, essentially providing a 'reset' option to the child's most unadulterated version of microbiome. This approach utilizes delivering the sample by mixing it in maternal milk or formula and feeding it to the child through a bottle, which can be performed anywhere without any discomfort for the child.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications, but children who have used antibiotics in the last 3 months cannot join the study.

What data supports the effectiveness of the treatment Autologous Fecal Transplant for antibiotic-related gut disruption?

Fecal microbiota transplantation (FMT) has been shown to be effective in treating recurrent Clostridium difficile infections, which are often related to antibiotic use. This success suggests that similar treatments, like autologous FMT, could help restore gut health after antibiotic-related disruptions. ^{1 2 3 4 5}

Is fecal transplant safe for humans?

Fecal microbiota transplantation (FMT) is generally considered safe and well-tolerated, especially for treating recurrent Clostridioides difficile infections. Most short-term risks are mild, but long-term side effects are not well-established. Serious adverse events have been linked to inadequate donor screening, so strict protocols are important to ensure safety. ^{6 7 8 9 10}

How is autologous fecal transplant different from other treatments for antibiotic-related gut disruption?

Autologous fecal transplant (Auto-FMT) uses a person's own stool collected during a healthy state to restore gut bacteria after disruption, reducing the risk of infection from donor stool used in other fecal transplants. This approach is unique because it eliminates the variability and potential risks associated with using stool from different donors. ^{1 3 5 11 12}

Research Team

Maria Gloria Dominguez-Bello, PhD

Principal Investigator

Rutgers Department of Biochemistry & Microbiology

Eligibility Criteria

This trial is for infants who have been prescribed antibiotics, which can disrupt their gut bacteria. The study aims to help these young patients by using a treatment that involves giving back their own stored fecal matter after antibiotic use to restore the balance of good bacteria in their intestines.

Inclusion Criteria

My child is between 1 month and 4 years old and healthy.

Exclusion Criteria

My child has not taken antibiotics in the last 3 months.

Documented immunological condition from the child's pediatrician

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Sample Collection

Caregivers collect monthly fecal samples while the child is healthy and right before an antibiotic treatment.

Varies

Monthly sample collection

Antibiotic Treatment

Children receive antibiotics as prescribed by their pediatrician for a non-gastrointestinal condition.

Varies

Autologous Fecal Matter Transplant (aFMT)

One day after the last dose of antibiotics, the child receives an autologous fecal matter transplant by drinking 2 ounces of inoculum mixed with milk.

1 day

Follow-up

Caregivers continue collecting samples once a week for a month followed by once a month for five months to monitor microbiome recovery.

6 months

Weekly sample collection for 1 month, then monthly for 5 months

Treatment Details

Interventions

• Autologous Fecal Transplant (Microbiome Restoration)

Trial Overview The intervention being studied is autologous fecal matter transplant (FMT). This means taking a sample of an infant's stool before they start antibiotics and then reintroducing it into their system afterwards, with the goal of quickly rebuilding a healthy gut microbiome.

Participant Groups

Group I: Intervention Arm Experimental Treatment 1 Intervention

Caregivers of the participants in the intervention arm will collect monthly fecal samples while the child is healthy and right before an antibiotic treatment which has been prescribed by the pediatrician for a non-gastrointestinal condition. One day after the last dose of antibiotics, the caregiver will collect another fecal sample and then the child will orally drink 2 ounces of the autologous fecal matter transplant inoculum prepared by the research team by mixing the child's own most recent sample prior to falling ill and mixed with milk. The caregivers then continue collecting samples once a week for a month followed by once a month for five months.

Group II: Control Active Control 1 Intervention

Participants do not partake in the autologous fecal matter transplant that will be used to re-seed the child's gut with his or her own personalized microbiome composition which was preserved prior to antibiotics use.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Findings from Research

Capsulized autologous faecal microbiota transplantation (FMT) was found to be safe and well tolerated in a study of 24 healthy volunteers, with no serious side effects reported during the treatment.

While both the FMT and placebo groups showed improvements in general and intestinal health after antibiotic treatment, there was no significant difference in the time it took for participants to normalize their intestinal habits, indicating that FMT did not provide additional benefits over placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial. Stefansson, M., Bladh, O., Flink, O., 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) has proven to be highly effective in treating recurrent and refractory Clostridioides difficile infections (CDI), leading to a surge in research on gut microbiota therapies.

The future of microbiome-based treatments is expected to focus on developing oral formulations with known ingredients, clear mechanisms of action, and strong safety profiles, expanding the potential applications of FMT beyond CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond. Kumar, V., Fischer, M.[2020]

Fecal microbiota transplantation (FMT) was performed on an 87-year-old male with recurrent cholangitis and multidrug-resistant (MDR) bacteria, showing safety and no complications across three procedures.

After FMT, there was a notable decrease in hospital admissions and a change in the microbial resistance profile of bacteria in blood cultures, suggesting that FMT may effectively manipulate gut microbiota and reduce MDR bacteremias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplant in a Patient Infected with Multidrug-Resistant Bacteria: A Case Report. Gouveia, C., Palos, C., Pereira, P., 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]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (CDI), with a 90% resolution of diarrhea reported in 867 patients across 33 studies, and a 94% resolution after repeated FMT in a randomized controlled trial with 16 participants.

FMT shows promise in treating ulcerative colitis, with remission rates varying from 0% to 68% in 106 patients, while its efficacy in Crohn's disease, chronic constipation, pouchitis, and irritable bowel syndrome remains inconclusive due to limited data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. Rossen, NG., MacDonald, JK., de Vries, EM., et al.[2022]

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]

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]

Autologous fecal microbiota transplantation (a-FMT) uses a person's own feces collected during a healthy state to restore gut microbiota, potentially offering a safer alternative to heterologous fecal microbiota transplantation (h-FMT), which carries risks of infectious exposure from donor stool.

While h-FMT has shown high cure rates (up to 90%) for recurrent Clostridioides difficile infection, its effectiveness for inflammatory bowel disease (IBD) is variable, with response rates between 24% and 50%, highlighting the complexity of IBD as a microbiome-driven disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease. Basson, AR., Zhou, Y., Seo, B., et al.[2021]

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]

References

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

Technical Aspects of Fecal Microbial Transplantation (FMT). [2018]

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

Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial. [2023]

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

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

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

Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplant in a Patient Infected with Multidrug-Resistant Bacteria: A Case Report. [2022]

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

Fecal Microbiota Transplantation: Is It Safe? [2021]

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

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. [2022]

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. Greece pubmed.ncbi.nlm.nih.gov

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies. [2022]

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

Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease. [2021]

12. 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]