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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called microbiome therapy (also known as Fecal Microbiota Transplantation or Microbiome Restoration Therapy) to determine if it can safely and effectively reduce dangerous gut bacteria that resist regular antibiotics. This approach aims to prevent infections that require strong antibiotics with serious side effects. The treatment involves taking capsules made from healthy bacteria to combat these resistant bacteria. Individuals diagnosed with antibiotic-resistant bacteria in their gut who can stop taking antibiotics and probiotics for the trial may be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that treatments like fecal microbiota transplant (FMT) are generally safe for people. Studies have found that FMT can help reduce antibiotic-resistant bacteria in the gut, which is crucial because these bacteria can lead to difficult-to-treat infections.

One study found that FMT is safe, with most patients not experiencing serious side effects. Another study reported that over 80% of patients had positive results, indicating the treatment worked well without causing harm.

In summary, research supports the safety of treatments like FMT. They are well-tolerated and show promise in reducing harmful bacteria while remaining safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for antibiotic-resistant bacterial colonization involve using stronger antibiotics or combinations of antibiotics, which can unfortunately lead to more resistance over time. Unlike these standard approaches, the microbiome therapeutic under study is derived from healthy donor microbiomes and is delivered in a novel way—via swallowed capsules. This treatment aims to restore the natural balance of bacteria in the gut, potentially preventing harmful bacteria from taking hold without relying on more antibiotics. Researchers are excited because this approach could offer a sustainable and natural method to combat antibiotic resistance, addressing a growing global health challenge.

What evidence suggests that microbiome therapy might be an effective treatment for antibiotic-resistant bacterial colonization?

Research shows that microbiome therapy, particularly fecal microbiota transplantation (FMT), may help reduce antibiotic-resistant bacteria in the gut. Studies have found that FMT effectively removes harmful bacteria, such as those causing repeat Clostridioides difficile infections. This method also lowers other resistant bacteria in the intestines. By introducing healthy bacteria to the gut, the therapy can outcompete and decrease the number of resistant bacteria. In this trial, participants will receive either the microbiome therapeutic or a placebo. Early findings suggest that microbiome therapy could be a useful tool in managing antibiotic-resistant bacteria. ^{1 3 6 7 8}

Who Is on the Research Team?

Michael Woodworth, MD, MSc

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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) 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6667716/

The Role of Fecal Microbiota Transplantation in Reducing ... This review summarizes clinical outcomes data for fecal microbiota transplantation (FMT) for antibiotic-resistant organism (ARO) decolonization.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2836786

Microbiota Transplantation Among Patients Receiving ... Although not powered to test these outcomes, this study found potential reductions in bacteremia, intestinal pathogen domination, and antibiotic ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2452231720300026

Fecal microbiota transplantation for antibiotic resistant ... Overall, the use of FMT is a promising perspective for intestinal decolonization, but it requires greater standardization.

4. genomemedicine.biomedcentral.com genomemedicine.biomedcentral.com/articles/10.1186/s13073-021-00843-9

Microbiota restoration reduces antibiotic-resistant bacteria gut ... Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota ...

5. withpower.com withpower.com/trial/phase-2-multi-drug-resistant-organism-4-2023-85d26

Microbiome Therapy for Antibiotic-Resistant Bacterial ... Research shows that Fecal Microbiota Transplantation (FMT) is effective in treating recurrent Clostridium difficile infections and has potential benefits for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7888090/

Microbiota restoration reduces antibiotic-resistant bacteria ... Antibiotic treatment increases the risk of Clostridioides difficile infection (CDI) by decreasing colonization resistance mediated by commensal ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0163445325000982

Faecal microbiota transplant to ERadicate gastrointestinal ... FMT is safe and acceptable to participants colonised with MDRO. •. FMT increases microbiome diversity, enhancing colonisation resistance. •. MDRO decolonisation ...

8. journals.lww.com journals.lww.com/annals-of-medicine-and-surgery/abstract/9900/fecal_microbiota_transplantation_as_a_therapeutic.3219.aspx

Fecal microbiota transplantation as a therapeutic modality... Clinical trials consistently report success rates exceeding 80%, markedly surpassing outcomes with antibiotics. Innovations in delivery methods, ...