Fecal Microbial Transplant for Atherosclerosis

Overseen By Leslie Paddock, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Western University, Canada

Disqualifiers: Renal failure, Immunosuppressed, Cancer, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with unexplained atherosclerosis (severe atherosclerosis not explained by traditional risk factors) will receive fecal microbial transplants (FMT) from patients with a Protected phenotype (patients who have high levels of risk factors but little or no carotid atherosclerosis). The objective is to determine what changes in the intestinal microbiome are associated with a decline in plasma levels of toxic metabolites of the itnestinal microbiome such as trimethylamine N-oxide (TMAO) and p-cresylsulfate. The intention is to develop an ecosystem therapeutic of cultured bacteria to treat atherosclerosis.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Fecal Microbial Transplant for Atherosclerosis?

Fecal Microbial Transplant (FMT) has shown effectiveness in treating recurrent Clostridium difficile infections, with cure rates up to 90%. It is also being explored for other conditions like inflammatory bowel disease and metabolic disorders, although results are more variable. This suggests potential for broader applications, including atherosclerosis, but more research is needed. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) 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. However, long-term side effects are not well-established, and serious adverse events have been linked to inadequate donor screening for drug-resistant organisms. ^{6 7 8 9 10}

How is fecal microbial transplant different from other treatments for atherosclerosis?

Fecal microbial transplant is unique because it involves transferring healthy gut bacteria from a donor to a patient, aiming to restore a balanced microbiome, which is different from traditional treatments that typically focus on managing symptoms or risk factors of atherosclerosis. This approach is novel as it targets the gut microbiome, which is not a standard focus in atherosclerosis treatment. ^{1 2 11 12 13}

Research Team

J. David Spence, M.D.

Principal Investigator

Western University, Canada

Chrysi Bogiatzi, M.D.

Principal Investigator

Division of Neurology, Western University

Eligibility Criteria

This trial is for people with severe atherosclerosis, where plaque buildup in arteries isn't due to usual risk factors. Participants should have a high amount of plaque (top 25%) and not fit the typical profile for heart disease as assessed by doctors.

Inclusion Criteria

I have severe artery blockage not caused by common risk factors.

Exclusion Criteria

My kidney function is low (eGFR<50).

I have cancer.

Immunosuppressed patients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Preparation

Participants take cloxacillin and undergo purging with an electrolyte solution before FMT

1 week

Treatment

Participants receive fecal microbial transplants (FMT) or placebo

6 weeks

1 visit (in-person) for FMT administration

Follow-up

Participants are monitored for changes in plasma levels of metabolites and metagenomic changes

12 months

2 visits (in-person) at 6 weeks and 12 months

Treatment Details

Interventions

• Fecal Microbial Transplant

Trial Overview The study tests if fecal microbial transplants from individuals resistant to artery plaque can improve gut bacteria in those with unexplained atherosclerosis, potentially lowering harmful metabolites like TMAO.

Participant Groups

Group I: Active Active Control 1 Intervention

Capsules of stool from Protected donors, cloxacillin, electrolyte purgative (Peglyte)

Group II: Placebo Placebo Group 1 Intervention

Cellulose capsules, cloxacillin, electrolyte purgative (Peglyte)

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

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent Clostridium difficile infection

Approved in European Union as Fecal Microbiota Transplantation for:

• Recurrent Clostridium difficile infection

Approved in Canada as Fecal Microbiota Transplantation for:

• Recurrent Clostridium difficile infection

Who Is Running the Clinical Trial?

Western University, Canada

Lead Sponsor

Trials

270

Recruited

62,500+

European Bioinformatics Institute

Collaborator

Trials

2

Recruited

200+

Findings from Research

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 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 microbial transplantation (FMT) involves transferring healthy gut microbiota from a donor to a patient and has been shown to be effective for treating recurrent Clostridium difficile infections (RCDI), with approval in several countries including Israel.

FMT may also hold potential for treating other conditions like obesity, diabetes, and inflammatory bowel diseases, highlighting the importance of gut microbiota in overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of fecal microbial transplantations for disease states in Israel]. Maharshak, N.[2020]

Fecal microbiota transplantation (FMT) is recognized as an effective treatment for recurrent Clostridium difficile infection (CDI), particularly in elderly patients (age ≥ 65 years), and is recommended for severe or complicated cases to reduce mortality and the need for colectomy.

Current evidence supports the safety and efficacy of FMT in older adults, suggesting it may be beneficial to administer FMT earlier in the treatment process to prevent serious complications associated with CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Present Status of Fecal Microbiota Transplantation and Its Value in the Elderly. Cheng, YW., Fischer, M.[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 and considered safe for treating recurrent Clostridium difficile infections, even in patients with complex medical conditions like tetraplegia.

In this case, a self-advancing nasal jejunal feeding tube was successfully used for a minimally invasive FMT, but the patient experienced persistent arterial hypertension post-procedure, suggesting a potential new side effect and a possible link between the intestinal microbiome and blood pressure regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive fecal microbiota transplantation for recurrent Clostridium difficile infection in a patient presenting with hypertensive disorder post interventionem. Goeser, F., Schlabe, S., Ruiner, CE., et al.[2020]

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) 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 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) is gaining attention not only for treating chronic gastrointestinal infections and inflammatory bowel diseases but also for its potential in addressing cardiometabolic and autoimmune conditions, suggesting a broader therapeutic role for the intestinal microbiota.

Current research highlights the relationship between the intestinal microbiome and various diseases, including obesity and insulin resistance, indicating that specific microbial strains may eventually be used for diagnosis and treatment of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of fecal microbiota transplantation. Smits, LP., Bouter, KE., de Vos, WM., et al.[2022]

Fecal microbiota transplantation (FMT) is an effective treatment for restoring healthy gut bacteria in patients with disrupted intestinal microbiota, particularly in conditions like Clostridium difficile infection.

The review emphasizes the importance of careful donor selection and proper processing and storage of fecal material to ensure the safety and efficacy of the transplantation procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. Iakupova, AA., Abdulkhakov, SR., Safin, AG., et al.[2022]

Fecal microbiota transplantation (FMT) and mixed probiotics (VSL#3) were both found to be effective in achieving clinical remission and response in patients with active ulcerative colitis, significantly outperforming placebo treatments in a systematic review of seven randomized trials.

Both FMT and VSL#3 showed no significant increase in adverse events compared to placebo, indicating they are safe treatment options; however, VSL#3 appeared to be safer as it did not report any serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the efficacy and safety of fecal microbiota transplantation and probiotic VSL#3 for active ulcerative colitis: A systematic review and meta-analysis. Dang, X., Xu, M., Liu, D., et al.[2020]

References

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

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

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

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

3. Israel pubmed.ncbi.nlm.nih.gov

[Use of fecal microbial transplantations for disease states in Israel]. [2020]

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

The Present Status of Fecal Microbiota Transplantation and Its Value in the Elderly. [2021]

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

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

6. Germany pubmed.ncbi.nlm.nih.gov

Non-invasive fecal microbiota transplantation for recurrent Clostridium difficile infection in a patient presenting with hypertensive disorder post interventionem. [2020]

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

Fecal Microbiota Transplantation: Is It Safe? [2021]

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

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

9. Greece pubmed.ncbi.nlm.nih.gov

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

10. China pubmed.ncbi.nlm.nih.gov

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

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

Therapeutic potential of fecal microbiota transplantation. [2022]

12. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. [2022]

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

Assessing the efficacy and safety of fecal microbiota transplantation and probiotic VSL#3 for active ulcerative colitis: A systematic review and meta-analysis. [2020]