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

Not Applicable

Recruiting

• Conditions: Liver Transplant

• Registration Number: NCT06043531
• Lead Sponsor: Virginia Commonwealth University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2023-09-12
• Study First Submitted QC: 2023-09-12
• Study First Posted: 2023-09-21
• Study Start: 2024-01-18
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-06
• Last Update Posted: 2025-03-07
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Serum TMAO	Change from baseline at four weeks	Serum TMAO levels will be assessed by nuclear magnetic resonance (NMR)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States