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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether fecal microbial transplants (FMT) can treat unexplained atherosclerosis, a condition where arteries clog with plaque without clear causes. Researchers aim to determine if altering gut bacteria can reduce harmful substances in the blood that might lead to heart problems. Participants will receive either capsules containing stool from healthy donors or a placebo. Individuals with severe plaque buildup in their arteries, not due to common risk factors, may be suitable for this study. As a Phase 1 trial, this research focuses on understanding how FMT works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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.

Is there any evidence suggesting that fecal microbial transplant is likely to be safe for humans?

Research has shown that fecal microbial transplants (FMT) have been safely used in many cases, particularly for treating recurrent Clostridium difficile infections. Studies indicate that FMT is usually well-tolerated, with most individuals experiencing only mild side effects like stomach upset or diarrhea.

However, some reports have noted more serious side effects, such as infections or negative immune responses. These are less common but important to consider. In Crohn's disease, FMT has shown promise without major safety concerns.

This trial is in an early stage, focusing primarily on assessing the treatment's safety for participants. While FMT has been successful with other conditions, its use for atherosclerosis remains under investigation. Researchers will closely monitor participants to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fecal Microbial Transplant (FMT) is unique because it uses stool from healthy donors to potentially transform the gut microbiome of patients with atherosclerosis. Unlike traditional treatments that focus on lowering cholesterol or blood pressure, FMT targets the gut bacteria, which might play a role in inflammation and plaque buildup in arteries. Researchers are excited about FMT because it offers a novel approach by addressing the underlying gut health, which could lead to new ways of managing or even preventing atherosclerosis.

What evidence suggests that fecal microbial transplant might be an effective treatment for atherosclerosis?

Research has shown that fecal microbial transplants (FMT), which participants in this trial may receive, might help treat atherosclerosis. In animal studies, FMT showed promise in reducing symptoms of this condition. This effect may occur because FMT can alter gut bacteria, which in turn lowers harmful substances in the blood, such as trimethylamine N-oxide (TMAO), linked to atherosclerosis. Although few human studies have explored FMT for atherosclerosis, FMT has already been used successfully for other issues, such as recurring Clostridium difficile infections. These findings suggest that FMT could help manage unexplained atherosclerosis by altering gut bacteria. ^{1 3 5 6 7}

Who Is on the Research Team?

J. David Spence, M.D.

Principal Investigator

Western University, Canada

Chrysi Bogiatzi, M.D.

Principal Investigator

Division of Neurology, Western University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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 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) 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]

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) 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 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) 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]

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 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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4895930/

Fecal Microbiota Transplantation: Current Applications ...

Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107:1079–1087. doi ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11143861/

Fecal microbiota transplantation and next-generation therapies

Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn's disease. Inflam Bowel Dis 2015; 21(3): 556–563.

3.

e-ce.org

e-ce.org/journal/view.php?number=7984

Fecal microbiota transplantation: present and future

Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol 2012;107 ...

4.

nature.com

nature.com/articles/s12276-022-00728-w

Fecal microbiota transplantation ameliorates ...

These interesting results indicate that CTRP9-KO mice are an effective animal model for atherosclerosis studies, and the transfer of fecal ...

5.

frontiersin.org

frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2019.00002/full

The Super-Donor Phenomenon in Fecal Microbiota ...

Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn's disease. Inflamm. Bowel Dis. 21, 556–563. doi ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4836576/

Fecal Microbiota Transplantation: A Review of Emerging ...

American Journal of Gastroenterology Lecture: Intestinal microbiota and the role of fecal microbiota transplant (FMT) in treatment of C difficile infection.

7.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1471489218301553

The dirty aspects of fecal microbiota transplantation

Baxter et al. Adverse events in faecal microbiota transplant: a review of the literature. J Hosp Infect. (2016).