Clinical trial NCT06043531: Targeting Trimethylamine N-Oxide for Cardiovascular Health In Liver Transplant Recipients
Official title: Targeting Trimethylamine N-Oxide for Cardiovascular Health In Liver Transplant Recipients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Liver Transplant
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2023-09-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Serum TMAO
timeFrame: Change from baseline at four weeks
Secondary outcomes:
measure: Conduit artery endothelial function changes
timeFrame: Change from baseline at four weeks
measure: Microvascular function change
timeFrame: Change from baseline at four weeks
measure: Arterial hemodynamics changes
timeFrame: Change from baseline at four weeks
measure: Diastolic Function change
timeFrame: Change from baseline at four weeks
measure: Frailty outcome hanges
timeFrame: Change from baseline at four weeks
measure: Quality of life changes
timeFrame: Change from baseline at four weeks
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Danielle Kirkman
role: PRINCIPAL_INVESTIGATOR
References: