Targeting Trimethylamine N-Oxide for Cardiovascular Health In Liver Transplant Recipients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 Design
Arms and Interventions
| 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:
|
| No Intervention: Standard of Care Standard of care control |
Outcome Measures
Primary Outcome Measures
- Serum TMAO [Change from baseline at four weeks]
Serum TMAO levels will be assessed by nuclear magnetic resonance (NMR)
Secondary Outcome Measures
- Conduit artery endothelial function [Change from baseline at four weeks]
Conduit artery endothelial function assessed by flow mediated dilation
- Microvascular function [Change from baseline at four weeks]
Skin blood flow response to local heating measured by laser doppler flowmetry
- Arterial hemodynamics [Change from baseline at four weeks]
Arterial hemodynamics derived from radial artery tonometry recordings
- Diastolic Function [Change from baseline at four weeks]
Diastolic function at rest by echocardiography and during isometric handgrip exercise
- Frailty [Change from baseline at four weeks]
Frailty outcomes assessed according to Fried criteria
- Quality of life [Change from baseline at four weeks]
Quality of Life assessed by SF-36
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Aged > 18 years
-
Speak and understand English
-
Have received and LT
Exclusion Criteria:
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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)
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Poorly controlled diabetes (HbA1c >8.5%)
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Relapse of alcohol use after LT
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Follow a vegetarian or vegan diet
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Current pregnancy
-
Unable to provide informed consent
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Virginia Commonwealth University
Investigators
- Principal Investigator: Danielle Kirkman, Virginia Commonwealth University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HM20027920