Microbiota Therapy for Superbugs

Recruiting at 4 trial locations

Overseen By Deepti Suchindran, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Systemic antibiotics

Disqualifiers: Pregnancy, Congestive heart failure, Cancer, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 11

Duration: 4 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new microbiota therapy to determine if it can reduce superbugs (germs that resist many medicines) in the body. Researchers aim to assess whether this treatment, called Allogeneic Microbiota in Glycerol (9%) (AMG), is safe and effective compared to patient observation alone. Participants will either receive the microbiota therapy or join the observation group. This trial may suit individuals diagnosed with a multi-drug resistant organism (MDRO) who can manage without antibiotics for a period. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

Participants must stop taking antibiotics, probiotics, and other microbiota restoration therapies by the day before the trial starts and cannot resume them until after Day 28.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using Allogeneic Microbiota in Glycerol (AMG) is effective and generally safe. Studies report that it successfully reduces harmful bacteria in 60-90% of cases without causing serious side effects, indicating that most patients tolerate the treatment well. In trials with similar treatments, such as fecal microbiota transplants, the procedure proved safe for patients with difficult infections.

Although no treatment is completely risk-free, current evidence suggests that AMG is a promising option for reducing drug-resistant bacteria in the body. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for infections caused by multidrug-resistant organisms (MDROs) rely on antibiotics, which can sometimes be ineffective due to resistance. But allogeneic microbiota in glycerol (AMG) works differently. This therapy uses beneficial bacteria from healthy donors to restore balance in the patient's gut microbiome, potentially outcompeting the superbugs without directly relying on antibiotics. Researchers are excited because this approach could offer a novel way to combat superbugs, reducing the reliance on traditional antibiotics and possibly preventing further resistance development.

What evidence suggests that microbiota therapy might be an effective treatment for MDRO colonization?

Research has shown that treatments like Allogeneic Microbiota in Glycerol (AMG), which participants in this trial may receive, can reduce the presence of superbugs—bacteria resistant to many antibiotics. Studies have found that this treatment successfully lowers these harmful bacteria in 60-90% of cases, decreasing the number of dangerous bacteria in the body. Additionally, patients receiving similar microbiota treatments often experience better health outcomes, including higher survival rates, compared to those who do not receive the treatment. Overall, AMG has proven effective in reducing superbugs and is considered safe. ^{1 2 3 5 6}

Who Is on the Research Team?

Michael Woodworth, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for individuals who are colonized with multi-drug resistant organisms (MDRO), commonly known as 'superbugs'. Participants should not have any other ongoing infections or conditions that could interfere with the study.

Inclusion Criteria

Agree to refrain from receptive anal intercourse until the last biological specimen (stool sample or peri-rectal swab) is collected (Day 28)

I agree to use effective birth control or abstain from sex during the study.

I can understand and sign the consent form myself, or have someone legally authorized to do so on my behalf.

Exclusion Criteria

Are pregnant, breastfeeding, lactating, or planning a pregnancy during study duration (through 4 weeks after the last dose of investigational product, or MT), if POCBP

Have a compromised immune system, defined as: AIDS with CD4+ T-cell count <200 and detectable HIV viral load on most recent assay, Absolute neutrophil count (ANC) <1,000 neutrophils / mL on day of enrollment, Active malignancy requiring intensive induction chemotherapy, radiotherapy, or biologic treatment within 2 months prior to enrollment, History of hematopoietic cell transplantation, either allogeneic or autologous in the last 1 year, Have a history of significant food allergy that led to anaphylaxis or hospitalization, Have a life expectancy of 24 weeks or less

Have any condition that, in the opinion of the investigator, might interfere with study objectives or limit compliance with study requirements, including but not limited to: Known active intravenous drug or alcohol abuse, Uncontrolled psychiatric illness, Social situations (e.g. incarceration), Received an interventional agent (drug, device, or procedure) within 28 days prior to enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Prevalence screening activities

Treatment

Participants receive microbiota therapy (MT) or are assigned to observation, with repeat sampling at Days 7, 14, 21, and 28

4 weeks

5 visits (in-person) at Days 0, 7, 14, 21, 28

Follow-up

Participants are monitored for safety and effectiveness after treatment, with data collection on adverse events and changes in medications

6 months

Monthly follow-up for 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Microbiota in Glycerol (9%) (AMG)

Trial Overview

The REACT study is testing a microbiota therapy called AMG, which aims to reduce colonization by superbugs. It's an open-label and cluster randomized trial, meaning both researchers and participants know what treatment is being given, and groups of participants are randomly assigned to different treatments in turns.

How Is the Trial Designed?

Group I: Group 1: microbiota therapy (MT) Experimental Treatment 1 Intervention

Group 1 will offer Microbiome therapeutic (MT) to all MDRO-positive patients (i.e., intervention condition).

Group II: Group 2: Observation Active Control 1 Intervention

Group 2 will be assigned to observation.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Centers for Disease Control and Prevention

Collaborator

Trials

902

Recruited

25,020,000+

Published Research Related to This Trial

In a randomized controlled trial involving 11 renal transplant recipients, fecal microbiota transplantation (FMT) successfully led to MDRO decolonization, with 8 out of 9 participants becoming MDRO culture negative after treatment.

The study identified key beneficial bacteria and metabolites that may help in eradicating MDROs, suggesting that FMT could leverage strain competition among gut bacteria to reduce multidrug-resistant organism colonization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement. Woodworth, MH., Conrad, RE., Haldopoulos, M., et al.[2023]

Fecal microbiota transplantation (FMT) has been successfully used to inhibit the colonization of multidrug-resistant bacteria, specifically Klebsiella pneumoniae and Escherichia coli, in immunocompromised patients.

This approach represents a novel strategy to combat gut dysbiosis and the associated risks of MDR infections, highlighting the potential of FMT in restoring healthy gut microbiota.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation Inhibits Multidrug-Resistant Gut Pathogens: Preliminary Report Performed in an Immunocompromised Host. Biliński, J., Grzesiowski, P., Muszyński, J., et al.[2018]

In a phase 2a study involving 24 patients with steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGvHD), the pooled allogeneic faecal microbiota MaaT013 showed a 38% overall response rate at day 28, indicating potential efficacy in this challenging condition.

MaaT013 was found to be safe, although there were some infectious complications, including cases of sepsis; however, the treatment was associated with increased microbial richness and beneficial bacteria in responding patients, suggesting a positive impact on gut health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled allogeneic faecal microbiota MaaT013 for steroid-resistant gastrointestinal acute graft-versus-host disease: a single-arm, multicentre phase 2 trial. Malard, F., Loschi, M., Huynh, A., et al.[2023]

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]

In a clinical trial involving 25 patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), autologous fecal microbiota transplantation (auto-FMT) significantly improved gut microbiota diversity compared to a control group, suggesting a promising method to restore beneficial gut bacteria after antibiotic treatment.

The study indicates that auto-FMT can effectively reestablish the intestinal microbiota composition to pre-treatment levels, highlighting its potential as a therapeutic intervention to mitigate the negative effects of antibiotic-induced microbiota depletion in allo-HSCT patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant. Taur, Y., Coyte, K., Schluter, J., et al.[2022]

Adoptive T cell therapy (ACT) effectiveness in tumor-bearing mice is significantly influenced by the gut microbiome, with specific bacteria playing a crucial role in the host's immune response.

Treatment with vancomycin not only slowed tumor growth but also increased systemic CD8α+ dendritic cells and IL-12 levels, suggesting that modifying the gut microbiota could enhance the efficacy of ACT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12. Uribe-Herranz, M., Bittinger, K., Rafail, S., et al.[2022]

Fecal microbiota transplantation (FMT) is effective for treating recurrent Clostridioides difficile infection (rCDI) by correcting microbial imbalances, but its efficacy for other diseases is moderate due to the resilience of the host's microbiota.

Pre-treatment with broad-spectrum antibiotics before FMT did not enhance the overall engraftment of donor microbiota in recipient mice, although it did improve the establishment of specific beneficial bacteria like Bifidobacterium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minor Effect of Antibiotic Pre-treatment on the Engraftment of Donor Microbiota in Fecal Transplantation in Mice. Freitag, TL., Hartikainen, A., Jouhten, H., et al.[2020]

The study successfully amplified the microbial diversity from fresh fecal samples using an in vitro gut-simulating system, which can enhance the sharing and reproducibility of gut microbiota research.

Dimethylsulfoxide (DMSO) was found to be the most effective cryoprotective agent for preserving the viability and functionality of gut microbes over 3 to 6 months, improving the safety of fecal microbiota transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional amplification and preservation of human gut microbiota. Gaci, N., Chaudhary, PP., Tottey, W., et al.[2020]

Microbiota transplants can introduce a significant number of antibiotic resistance (AR) genes into recipients, as shown by a study examining fecal microbiota from various sources, including donors and recipients, highlighting potential health risks.

Transplants using rural Amish microbiota resulted in a higher prevalence of AR genes in gnotobiotic pigs compared to urban microbiota, indicating that the source of microbiota can influence the risk of AR gene amplification, especially in newborns with naïve gut microbiota.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Microbiota Transplant on Resistome of Gut Microbiota in Gnotobiotic Piglets and Human Subjects. Liu, H., Wang, HH.[2020]

Fecal microbiota transplantation (FMT) effectively decolonized multidrug-resistant organisms (MDRO), specifically carbapenem-resistant Enterobacteriaceae (CRE), in three patients, leading to significant changes in their gut microbiome.

The study revealed that FMT resulted in a notable increase in Klebsiella phages, which correlated with a decrease in Klebsiella bacteria, suggesting that phages may play a crucial role in eliminating these harmful bacteria after FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal Evaluation of Gut Bacteriomes and Viromes after Fecal Microbiota Transplantation for Eradication of Carbapenem-Resistant Enterobacteriaceae. Liu, Q., Zuo, T., Lu, W., et al.[2022]

A new method for humanizing conventional mice using fecal microbiota transplantation (FMT) after bowel cleansing successfully transferred human bacteria, demonstrating the potential for studying liver diseases in relation to intestinal microbiota.

The optimal frequency for FMT was found to be once a week, as more frequent FMTs disrupted the stability of the microbiota, while this strategy allowed for better engraftment and diversity of beneficial bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of human microbiota into conventional mice durably reshapes the gut microbiota. Wrzosek, L., Ciocan, D., Borentain, P., et al.[2019]

In a study involving 34 patients with recurrent Clostridium difficile infection, the specific donor material used to prepare the microbiota-based drug RBX2660 did not significantly impact treatment outcomes.

This suggests that the efficacy of RBX2660 is consistent across different donor materials, indicating a robust mechanism of action for the drug in treating recurrent CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the donor matter? Donor vs patient effects in the outcome of a next-generation microbiota-based drug trial for recurrent Clostridium difficile infection. Ray, A., Jones, C.[2022]

In a study of 37 patients with Clostridioides difficile infection (CDI), oral fecal microbiota transplantation (FMT) resulted in a sustained cure rate of 89%, demonstrating its efficacy for both primary and recurrent CDI without any safety concerns.

FMT led to significant changes in the gut microbiome, with increased bacterial diversity and specific shifts in bacterial populations associated with treatment success, indicating that the composition of gut bacteria plays a crucial role in the effectiveness of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Bacterial and Fungal Dynamics following Oral Lyophilized Fecal Microbiota Transplantation in Clostridioides difficile Infection. Haifer, C., Paramsothy, S., Borody, TJ., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8430254/

Fecal Microbiota Transplant Mitigates Adverse Outcomes ...

At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% versus 61.9% respectively, p=0.012), and higher non ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05780801

Study Details | NCT05780801 | Sentinel Cohort REACT

MT like Allogeneic Microbiota in Glycerol (AMG) has been shown to have ~ 60-90% efficacy for decolonization and an acceptable safety profile but has not been ...

3.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2836786

Microbiota Transplantation Among Patients Receiving ...

This nonrandomized clinical trial examines the safety and acceptability of fecal microbiota transplantation in long-term acute care hospital ...

4.

frontiersin.org

frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.684659/pdf

Fecal Microbiota Transplant Mitigates Adverse Outcomes ...

Collectively, these data suggest that negative clinical outcomes, including mortality associated with MDRO colonization, may be ameliorated by ...

5.

researchgate.net

researchgate.net/publication/354162563_Fecal_Microbiota_Transplant_Mitigates_Adverse_Outcomes_Seen_in_Patients_Colonized_With_Multidrug-Resistant_Organisms_Undergoing_Allogeneic_Hematopoietic_Cell_Transplantation

(PDF) Fecal Microbiota Transplant Mitigates Adverse ...

At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% versus 61.9% respectively, p=0.012), and higher non ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12290730/

Microbiota Transplantation Among Patients Receiving Long ...

This nonrandomized clinical trial examines the safety and acceptability of fecal microbiota transplantation in long-term acute care hospital ...