Microbiome Therapy for Antibiotic-Resistant Bacterial Colonization

(FAIR Trial)

Recruiting at 4 trial locations

Overseen By Amanda Strudwick, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Systemic antibiotics, GI motility drugs

Disqualifiers: Pregnancy, Uncontrolled illness, Compromised immunity, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 14 days per cycle

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to better understand the effectiveness and safety of microbiome therapies (MT) as a treatment for patients with Multidrug Resistant Organism (MDRO) colonization after an infection. Limited data from prior studies suggest that MT may be an effective treatment to reduce intestinal MDRO colonization Although shedding of MDROs from patients to their surrounding environment is a recognized pathway of transmission, the potential effect of MT on the transmission of MDRO to other patients in the hospital environment is unclear. This study will test the safety and efficacy of MT for this use in hospitalized patients. This study will also help design larger studies. The MT may help reduce MDROs that colonize the gut. By reducing colonization before infections happen, this could help doctors avoid using "last resort" antibiotics that can have serious side effects like kidney damage. The reduction in MDROs after MT was originally identified in patients treated with MT for recurrent Clostridioides difficile (often called "C. diff") diarrhea. It has been shown that a type of MT called fecal microbiota transplant (FMT) can eliminate both C. difficile and other resistant bacteria.

Do I have to stop taking my current medications for the trial?

Yes, you will need to stop taking systemic antibiotics and probiotics at least one day before the study starts and for as long as medically possible during the study.

What data supports the effectiveness of the treatment Microbiome Therapeutic, Fecal Microbiota Transplantation (FMT), Microbiome Restoration Therapy for antibiotic-resistant bacterial colonization?

Research shows that Fecal Microbiota Transplantation (FMT) is effective in treating recurrent Clostridium difficile infections and has potential benefits for patients with multidrug-resistant bacterial infections by altering the gut microbiome and reducing antibiotic resistance genes. ^{1 2 3 4 5}

Is microbiome therapy generally safe for humans?

Fecal microbiota transplantation (FMT), a type of microbiome therapy, is considered safe and effective for treating recurrent Clostridium difficile infections. However, there are some adverse events (unwanted side effects) associated with its use, and more research is needed to confirm its safety for other conditions. ^{3 6 7 8 9}

How does the treatment Microbiome Therapeutic differ from other treatments for antibiotic-resistant bacterial colonization?

Microbiome Therapeutic, also known as Fecal Microbiota Transplantation (FMT), is unique because it involves transferring healthy gut bacteria from a donor to a patient, which can help restore the balance of bacteria in the gut and reduce antibiotic resistance genes. Unlike traditional antibiotics, which kill bacteria, FMT aims to replenish and balance the gut microbiome, potentially reducing the presence of antibiotic-resistant bacteria. ^{1 2 4 10 11}

Research Team

Michael Woodworth, MD, MSc

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adults over 18 who are colonized with certain drug-resistant bacteria but not currently ill from them. They must stop taking antibiotics, probiotics, and PPIs before the study starts and agree to use birth control. People can't join if they're very sick (like heart failure), pregnant, on strong immune system drugs, have a short life expectancy, or have other serious health issues.

Inclusion Criteria

I am a man and will use birth control if my partner can have children.

I can follow the study rules and can swallow pills.

I am willing to stop taking antibiotics, probiotics, other gut health treatments, and acid reducers before the study starts.

Exclusion Criteria

Have any other intercurrent acute illness that in the opinion of the investigator will preclude the subject from entering the study

Have a life expectancy of 24 weeks or less

I have not been part of a study involving new treatments or devices in the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive microbiome therapy or placebo for MDRO colonization in a randomized, controlled setting

14 days per cycle

Day 0, Day 7, Day 14 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Day 0, Day 14 of last cycle, 28 weeks post-treatment

Treatment Details

Interventions

• Microbiome Therapeutic

Trial Overview The trial tests microbiome therapy (MT) against a placebo to see if it reduces gut colonization by multi-drug resistant organisms in hospitalized patients. This could prevent infections and reduce the need for powerful antibiotics that can harm kidneys.

Participant Groups

Group I: microbiome therapeutic Experimental Treatment 1 Intervention

The study intervention is manufactured from a healthy screened donor as an investigational product (IP) and delivered via swallowed capsule after room reset of the patient's hospital room.

Group II: Placebo Placebo Group 1 Intervention

The control arm will remain in routine contact precautions per standard of care, take placebo capsules, and have a room reset.

Microbiome Therapeutic is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fecal Microbiota Transplantation (FMT) for:

• Recurrent Clostridioides difficile infection
• Decolonization of multidrug-resistant organisms (MDROs)

Approved in European Union as Fecal Microbiota Transplantation (FMT) for:

• Recurrent Clostridioides difficile infection
• Decolonization of MDROs

Approved in Canada as Fecal Microbiota Transplantation (FMT) for:

• Recurrent Clostridioides difficile infection
• Decolonization of MDROs

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+

Findings from Research

Fecal microbiome transplants (FMT) have shown potential in reducing antibiotic resistance gene (ARG) carriage in the gut, particularly after treatments for recurrent C. difficile infections and antibiotic use, based on several studies.

However, the research is still in its early stages, with mixed results regarding the impact of FMT on the gut resistome, highlighting the need for larger studies and better understanding of individual responses before FMT can be reliably used to manage ARGs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-edged sword: impact of fecal microbiome transplants on the gut resistome. Hallowell, HA., Gao, AL., Suez, J.[2022]

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 microbial transplant (FMT) has shown high efficacy in treating recurrent Clostridium difficile infections, indicating its potential as a powerful therapeutic option for gastrointestinal microbiome issues.

Research is expanding to explore FMT for a variety of other diseases linked to microbiome disturbances, highlighting the growing interest in this treatment approach beyond just gastrointestinal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbial therapy: promises and pitfalls. Merenstein, D., El-Nachef, N., Lynch, SV.[2021]

Fecal microbiota transplantation (FMT) has proven to be highly effective in treating Clostridium difficile infection (CDI) and its recurrent forms, showcasing its therapeutic potential.

There is growing interest in using FMT for other health issues linked to the microbiota, such as antibiotic-resistant infections and inflammatory bowel disease, highlighting its potential to restore healthy microbiota and combat antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbial transplantation as a therapeutic option in patients colonized with antibiotic resistant organisms. Laffin, M., Millan, B., Madsen, KL.[2018]

Fecal microbiota transplantation (FMT) is a therapeutic procedure that involves transferring fecal matter from a healthy donor to treat diseases, particularly recurrent Clostridium difficile infections.

Recent research highlights the importance of the human microbiome, showing that the complex mixture of microorganisms in our bodies plays a crucial role in overall health and disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. Aroniadis, OC., Brandt, LJ.[2022]

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) is a safe and effective treatment for Clostridioides difficile infection, and emerging evidence suggests it may also benefit various other conditions like irritable bowel syndrome and inflammatory bowel disease.

The review highlights the expanding applications of FMT beyond gastrointestinal issues, including its potential roles in treating liver disorders, metabolic disorders, and even neurological conditions, while also discussing regulatory aspects and future directions for FMT research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders. Ianiro, G., Segal, JP., Mullish, BH., et al.[2021]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent Clostridium difficile infections, and research is expanding to explore its potential for treating other conditions related to chronic inflammation and autoimmunity.

Current studies on FMT for conditions like ulcerative colitis and metabolic syndrome show promise, but many lack rigorous methodology, highlighting the need for more standardized and well-designed trials to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation : current status and prospects]. Gilbert, B., Schrenzel, J.[2019]

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]

In a study of 186 patients with IBS, fecal microbiota transplantation (FMT) administered to the small intestine (duodenum) showed a significantly higher long-term response rate compared to administration to the large intestine (colon) after 12 months.

Repeating the FMT procedure in the small intestine resulted in greater improvements in symptoms and quality of life than a single FMT, indicating that multiple treatments may enhance the benefits of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors affecting the outcome of fecal microbiota transplantation for patients with irritable bowel syndrome. El-Salhy, M., Gilja, OH., Hatlebakk, JG.[2023]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridioides difficile infection (CDI), achieving resolution rates close to 100%, making it a crucial therapy for this serious condition.

FMT is being explored as a promising treatment for other gastrointestinal disorders, such as inflammatory bowel disease, irritable bowel syndrome, and colon cancer, due to its ability to manipulate the gut microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer. Borody, TJ., Eslick, GD., Clancy, RL.[2020]

References

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

Double-edged sword: impact of fecal microbiome transplants on the gut resistome. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Fecal microbial therapy: promises and pitfalls. [2021]

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

Fecal microbial transplantation as a therapeutic option in patients colonized with antibiotic resistant organisms. [2018]

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

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. [2022]

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

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation : current status and prospects]. [2019]

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

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

10. England pubmed.ncbi.nlm.nih.gov

Factors affecting the outcome of fecal microbiota transplantation for patients with irritable bowel syndrome. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer. [2020]