Targeting Trimethylamine N-Oxide for Cardiovascular Health In Liver Transplant Recipients

Despite medical and surgical advances, long-term survival in liver transplant (LT) recipients is compromised by an increased risk of cardiovascular disease (CVD) after transplant, the mechanisms of which are still not fully understood. TMAO is an attractive therapeutic target to improve vascular health and diastolic function toward preventing CVD in LT patients. Therefore, the purpose of this study is to better understand the role of TMAO in cardiovascular dysfunction patients with chronic kidney disease.

Study Overview

• Status: Completed
• Conditions: Liver Transplant
• Intervention / Treatment: Other: Experimental: EVOO

Detailed Description

Despite medical and surgical advances, long-term survival in liver transplant (LT) recipients is compromised by an increased risk of cardiovascular disease (CVD) after transplant, the mechanisms of which are still not fully understood. Following LT, patients have an increased incidence of atherosclerotic CVD. Notably, atherosclerotic CVD is an established risk factor for diastolic dysfunction and incident heart failure with preserved ejection fraction (HFpEF). There is a critical need to better understand the biological mechanisms of LT related vascular dysfunction and establish targeted interventions that will reduce the risk of CVD in this patient population. In the general population, there is strong epidemiological evidence linking high TMAO levels with atherosclerotic CVD and heart failure, and that it can modulated rapidly by diet within two weeks. Therefore, the purpose of this study is to better understand the role of TMAO in cardiovascular dysfunction patients with chronic kidney disease.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged > 18 years
• Speak and understand English
• Have received and LT

Exclusion Criteria:

• Acute cellular or chronic rejection within 3 months
• Post-LT liver or non-liver related malignancy
• Active viral hepatitis (B or C) or autoimmune hepatitis
• Untreated biliary strictures or vascular complications (e.g. hepatic artery thrombosis)
• Poorly controlled diabetes (HbA1c >8.5%)
• Relapse of alcohol use after LT
• Follow a vegetarian or vegan diet
• Current pregnancy
• Unable to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EVOO supplementation; 50g/day, dietary supplementation Extra Virgin Olive Oil (EVOO)	Other: Experimental: EVOO; Subjects will consume 50g of cold pressed EVOO per day for 28 days.; Other Names: Dietary EVOO
No Intervention: Standard of Care; Standard of care control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum TMAO	Serum TMAO levels will be assessed by nuclear magnetic resonance (NMR)	Change from baseline at four weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conduit artery endothelial function changes	Conduit artery endothelial function assessed by flow mediated dilation	Change from baseline at four weeks
Microvascular function change	Skin blood flow response to local heating measured by laser doppler flowmetry	Change from baseline at four weeks
Arterial hemodynamics changes	Arterial hemodynamics derived from radial artery tonometry recordings	Change from baseline at four weeks
Diastolic Function change	Diastolic function at rest by echocardiography and during isometric handgrip exercise	Change from baseline at four weeks
Frailty outcome hanges	Frailty outcomes assessed according to Fried criteria	Change from baseline at four weeks
Quality of life changes	Quality of Life assessed by SF-36	Change from baseline at four weeks

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Danielle Kirkman, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2024
• Primary Completion (Actual): October 25, 2024
• Study Completion (Actual): October 25, 2024

Study Registration Dates

• First Submitted: September 12, 2023
• First Submitted That Met QC Criteria: September 12, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: HM20027920

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No