Metabolic and Metagenomic Effects of Intestinal Microbiome Repopulation in Unexplained Atherosclerosis

May 27, 2020 updated by: Western University, Canada

Metabolic and Metagenomic Effects of Repopulation of the Intestinal Microbiome in Patients With Severe Unexplained Atherosclerosis

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.

Study Overview

Status

Unknown

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Cellulose capsules, cloxacillin, electrolyte purgative (Peglyte)
Fecal microbial transplant
ACTIVE_COMPARATOR: Active
Capsules of stool from Protected donors, cloxacillin, electrolyte purgative (Peglyte)
Fecal microbial transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in plasma levels of metabolites of the intestinal microbiome
Time Frame: 6 weeks and 12 months
The primary outcome is changes in plasma levels of trimethylamine N-oxide and p-cresylsulfate
6 weeks and 12 months
Metagenomic changes of the intestinal microbiome
Time Frame: 6 weeks and 12 months
Metagenomic changes in the stool of transplant recipients will be analyzed to determine what changes in the intestinal bacteria are associated with changes in the plasma levels of the intestinal metabolites.
6 weeks and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: J. David Spence, M.D., University of Western Ontario, Canada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

June 2, 2020

Primary Completion (ANTICIPATED)

April 30, 2022

Study Completion (ANTICIPATED)

April 30, 2022

Study Registration Dates

First Submitted

February 24, 2020

First Submitted That Met QC Criteria

May 27, 2020

First Posted (ACTUAL)

June 1, 2020

Study Record Updates

Last Update Posted (ACTUAL)

June 1, 2020

Last Update Submitted That Met QC Criteria

May 27, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • 115450

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data might be made available with approval of the ethics committee

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Atherosclerosis

Clinical Trials on Fecal microbial transplant

3
Subscribe