Fecal Microbiota Transplant for Auto-Brewery Syndrome

Overseen By Elizabeth Hohmann, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Massachusetts General Hospital

Must not be taking: Antifungals, Warfarin, Immunosuppressants

Disqualifiers: Pregnancy, Severe immunodeficiency, Ulcerative colitis, Crohn's disease, Type I diabetes, others

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

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

Compensation: Varies

Number of Visits: 10

Duration: 1 week

8 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to study fecal microbiota transplantation(FMT) by oral capsule in people already diagnosed with auto-brewery syndrome (ABS, also known as gut fermentation syndrome). The main question it aims to answer: Is FMT safe and feasible in this syndrome? Participants will 1. have a "gut cleanout" with oral antibiotics and a colon cleanse, similar to that administered before colonoscopy 2. receive five oral doses of fecal transplant capsules over a week 3. be followed for six months for safety and research samples

Will I have to stop taking my current medications?

Participants must stop taking antifungals and any other complementary therapies for auto-brewery syndrome if they are currently using them. The protocol does not specify other medications, but certain medications like warfarin and suppressive antibacterial agents may affect eligibility.

What data supports the effectiveness of the treatment Fecal Microbiota Transplantation for Auto-Brewery Syndrome?

Fecal Microbiota Transplantation (FMT) is well-documented to be effective for treating recurrent Clostridium difficile infections, and there is some evidence suggesting it can help with ulcerative colitis. While these conditions are different from Auto-Brewery Syndrome, the success in altering gut bacteria in these cases may suggest potential benefits for other gut-related issues. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) generally safe for humans?

FMT is generally considered safe and well-tolerated, even in high-risk patients, with most short-term risks being mild and related to delivery methods. Long-term side effects are not well-established, but no significant harm has been found to date. However, serious adverse events have been associated with FMT products from stool banks that do not screen for multi-drug resistant organisms. ^{6 7 8 9 10}

How does the treatment Fecal Microbiota Transplantation (FMT) differ from other treatments for Auto-Brewery Syndrome?

FMT is unique because it involves transferring stool from a healthy donor to a patient to restore a balanced gut microbiome, which is different from traditional treatments that might focus on medication or dietary changes. This approach is novel for Auto-Brewery Syndrome, as there are no standard treatments for this condition, and FMT is being explored for its potential to address underlying gut microbiota imbalances. ^{1 11 12 13 14}

Research Team

Elizabeth Hohmann, MD

Principal Investigator

MGH

Eligibility Criteria

This trial is for adults aged 18-70 with Auto-Brewery Syndrome (ABS) who've had symptoms for at least a year, including alcohol production in the gut. They must have experienced multiple ABS flares and be able to travel to Boston. Excluded are those unable to swallow large capsules, pregnant women, people with severe illnesses or immune deficiencies, certain medication users, and individuals not fully vaccinated against COVID.

Inclusion Criteria

Active ABS including at least 3 flares by either serum or breath alcohol levels in the past year (blood or breath samples)

My microbiome can produce alcohol outside my body.

I can travel to Boston for assessments and understand there's some reimbursement.

Exclusion Criteria

Severe food allergy or intolerance (donors are omnivores and do not maintain dietary restrictions)

Allergy to erythromycin, neomycin, or rifaximin

I often feel nauseous or vomit, or I frequently inhale food into my lungs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Gut Cleanout

Participants undergo a gut cleanout with oral antibiotics and a colon cleanse

1 week

1 visit (in-person)

Treatment

Participants receive five oral doses of fecal transplant capsules over a week

1 week

Daily monitoring for 7 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Intermittent visits at 2 weeks, 2 months, and 6 months

Treatment Details

Interventions

• Fecal Microbiota Transplantation

Trial Overview The study tests fecal microbiota transplantation (FMT) via oral capsules after a 'gut cleanout' process. Participants will take five doses over one week and then be monitored for six months. The research aims to determine if FMT is safe and can help manage ABS by altering gut bacteria.

Participant Groups

Group I: Active FMT Experimental Treatment 1 Intervention

Active FMT (5 doses) over 7 days. Each dose contains 15 capsules.

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

Approved in United States as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Approved in European Union as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)
• Other gastrointestinal disorders

Approved in Canada as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Findings from Research

Faecal microbiota transplantation (FMT) has proven effective for treating recurrent Clostridium difficile infections, with established protocols and donor stool banks in Denmark.

However, FMT is not recommended for routine use in treating inflammatory bowel disease or irritable bowel syndrome due to insufficient clinical trial data supporting its efficacy for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Faecal microbiota transplantation for the treatment of bowel disease]. Rode, AA., Chehri, M., Petersen, AM., et al.[2019]

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) was performed on 26 patients with recurrent Clostridium difficile infection, showing a 92% success rate in preventing further diarrhea or CDI relapse over a follow-up period of up to 30 months.

The procedure was found to be simple and safe, with most patients remaining free of significant diarrhea after the treatment, highlighting FMT as a promising alternative to prolonged antibiotic courses for managing recurrent CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. Kelly, CR., de Leon, L., Jasutkar, N.[2022]

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 effective in treating recurrent Clostridium difficile infections, as demonstrated in a case study of a woman who was successfully treated with this method.

The case raises concerns about potential side effects, such as new-onset obesity, when using stool from overweight donors, suggesting the need for further research on the impact of donor characteristics on FMT outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight gain after fecal microbiota transplantation. Alang, N., Kelly, CR.[2022]

Fecal microbiota transplantation (FMT) is recommended for treating recurrent Clostridium difficile infections and has shown benefits for various gastrointestinal disorders, but safety data is still limited due to the rapid adoption of the technique without extensive long-term studies.

Capsulized FMT therapy offers a promising solution for long-term maintenance and reduces the need for invasive procedures, indicating a shift towards safer and more tolerable methods of delivering FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. Li, N., Tian, H.[2020]

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]

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) showed significant long-term efficacy in reducing IBS symptoms, with response rates of 69.1% and 77.8% for the 30g and 60g treatment groups, respectively, at 2 years, and 64.9% and 71.8% at 3 years, compared to only 26.3% in the placebo group.

No long-term adverse events were reported, indicating that FMT is a safe intervention for IBS, with improvements in quality of life and a decrease in dysbiosis index observed in the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. El-Salhy, M., Winkel, R., Casen, C., et al.[2022]

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]

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) 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 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]

In 2018, OpenBiome, a large stool bank, processed 4,271 fecal microbiota transplants (FMT) from 7,536 donations, indicating a robust system for providing FMT material to treat recurrent Clostridioides difficile infections.

The median time from donation to shipment of FMT preparations was 8.9 months, highlighting the need for improved efficiency in the stool banking process to enhance patient access to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stool Banking for Fecal Microbiota Transplantation: Methods and Operations at a Large Stool Bank. Chen, J., Zaman, A., Ramakrishna, B., et al.[2021]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

[Faecal microbiota transplantation for the treatment of bowel disease]. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis]. [2022]

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

Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. [2022]

4. 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]

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

Weight gain after fecal microbiota transplantation. [2022]

6. China pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. [2020]

7. Greece pubmed.ncbi.nlm.nih.gov

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

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

Fecal Microbiota Transplantation: Is It Safe? [2021]

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

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. [2022]

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

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

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

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

12. Switzerland pubmed.ncbi.nlm.nih.gov

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

13. England pubmed.ncbi.nlm.nih.gov

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

14. Switzerland pubmed.ncbi.nlm.nih.gov

Stool Banking for Fecal Microbiota Transplantation: Methods and Operations at a Large Stool Bank. [2021]