Metabolic and Metagenomic Effects of Intestinal Microbiome Repopulation in Unexplained Atherosclerosis

NCT04410003 | Recruiting Phase 1 DMC

• 1 other identifier: 115450
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atherosclerosis; Intestinal Microbiome

Outcome Measures

Primary Outcomes (2)

• Changes in plasma levels of metabolites of the intestinal microbiome

  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

  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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Cellulose capsules, cloxacillin, electrolyte purgative (Peglyte)

Biological: Fecal microbial transplant

Active

ACTIVE COMPARATOR

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

Biological: Fecal microbial transplant

Interventions

Fecal microbial transplant BIOLOGICAL

Fecal microbial transplant

Active; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Western University, Canada: lead
• European Bioinformatics Institute: collaborator

Study Sites (1)

Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute

London, Ontario, N6G 2V4, Canada

RECRUITING

Related Publications (1)

• Bogiatzi C, Gloor G, Allen-Vercoe E, Reid G, Wong RG, Urquhart BL, Dinculescu V, Ruetz KN, Velenosi TJ, Pignanelli M, Spence JD. Metabolic products of the intestinal microbiome and extremes of atherosclerosis. Atherosclerosis. 2018 Jun;273:91-97. doi: 10.1016/j.atherosclerosis.2018.04.015. Epub 2018 Apr 17.

  PMID: 29702430 BACKGROUND

MeSH Terms

Conditions

Atherosclerosis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• J. David Spence, M.D.

  Western University, Canada

  PRINCIPAL INVESTIGATOR

• Chrysi Bogiatzi, M.D.

  Division of Neurology, Western University

  STUDY DIRECTOR

Central Study Contacts

J. David Spence, M.D.

CONTACT

1-519-931-5731; dspence@robarts.ca

Leslie Paddock, R.N.

CONTACT

1-519-931-5731; leslie.paddock@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients and persons involved in the followup and assessment of the participants will be blinded to the randomized assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: February 24, 2020
• First Posted: June 1, 2020
• Study Start: June 2, 2020
• Primary Completion: July 1, 2025
• Study Completion: July 30, 2025
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)