Metabolic and Metagenomic Effects of Intestinal Microbiome Repopulation in Unexplained Atherosclerosis

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-02

Study Completion Date

2025-07-30

Brief Summary

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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.

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Detailed Description

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100 patients with Unexplained Atherosclerosis, and 5 donors with the protected phenotype will be recruited; there will be extensive microbial, viral and parasitic screening of the donors. Recipients will be randomized to receive capsules of stool from the donors, or cellulose placebo. Recipients will take cloxacillin 500 mg 4 times daily for 5 days before the FMT, and will undergo purging with an electrolyte solution, (PegLyte) the day before the FMT. Metagenomic analysis of the recipient stool will be performed before FMT, 6 weeks later and after 12 months.Plasma levels of toxic intestinal metabolites will be measured before FMT, at 6 weeks and 12 months after FMT; the levels to be measured will be TMAO, P-cresylsulfate, Hippuric acid. Indoxyl sulfate, P-cresyl glucuronide. Phenyl acetyl glutamine, and Phenyl sulfate.

The investigators will analyze the metagenomic changes in the intestinal microbiome of recipients that are associated with decline in the plasma levels of the metabolic products of the intestinal microbiome to identify candidate bacteria for an "ecosystem therapeutic for atherosclerosis. Based on previous experience of designing such a therapeutic for clostridium difficile, it is anticipated that \~ 40 bacterial species would be needed.

Conditions

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Atherosclerosis Intestinal Microbiome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized controlled trial

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Patients and persons involved in the followup and assessment of the participants will be blinded to the randomized assignment.

Study Groups

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Placebo

Cellulose capsules, cloxacillin, electrolyte purgative (Peglyte)

Group Type PLACEBO_COMPARATOR

Fecal microbial transplant

Intervention Type BIOLOGICAL

Fecal microbial transplant

Active

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

Group Type ACTIVE_COMPARATOR

Fecal microbial transplant

Intervention Type BIOLOGICAL

Fecal microbial transplant

Interventions

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Fecal microbial transplant

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Severe atherosclerosis, with total plaque area in the top quartile (\>119 mm2), not explained by traditional risk factors in linear regression (residual score \>= 2)

Exclusion Criteria

* Excluded will be patients unwilling/unable to provide informed consent, unwilling to ingest the stool capsules at baseline, patients with moderate to severe renal failure (eGFR\<50), immunosuppressed patients, and patients with cancer, unstable angina, planned carotid revascularization or other conditions that might be expected to reduce their survival to \< 1 year (including age \>80).

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No