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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Liver Transplant

Intervention / Treatment
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* Other: Experimental: EVOO


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 |