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

• ClinicalTrials.gov Identifier: NCT06043531
• Recruitment Status: Recruiting
• First Posted: September 21, 2023
• Last Update Posted: March 6, 2024
• Sponsor: Virginia Commonwealth University
• Information provided by (Responsible Party): Virginia Commonwealth University

Tracking Information

• First Submitted Date: September 12, 2023
• First Posted Date: September 21, 2023
• Last Update Posted Date: March 6, 2024
• Actual Study Start Date: January 18, 2024
• Estimated Primary Completion Date: September 15, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 12, 2023)

Serum TMAO [ Time Frame: Change from baseline at four weeks ]

Serum TMAO levels will be assessed by nuclear magnetic resonance (NMR)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 4, 2023)

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

Original Secondary Outcome Measures (submitted: September 12, 2023)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Targeting Trimethylamine N-Oxide for Cardiovascular Health In Liver Transplant Recipients
• Official Title: Targeting Trimethylamine N-Oxide for Cardiovascular Health In Liver Transplant Recipients
• 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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Liver Transplant

Intervention

Other: Experimental: EVOO

Subjects will consume 50g of cold pressed EVOO per day for 28 days.

Other Name: Dietary EVOO

Study Arms

• Experimental: EVOO supplementation
  50g/day, dietary supplementation Extra Virgin Olive Oil (EVOO)
  Intervention: Other: Experimental: EVOO
• No Intervention: Standard of Care
  Standard of care control

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 12, 2023): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 15, 2025
• Estimated Primary Completion Date: September 15, 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Patrice Wiecek; (804) 827-1815; wiecekpj@vcu.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06043531
• Other Study ID Numbers: HM20027920
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Virginia Commonwealth University
• Original Responsible Party: Same as current
• Current Study Sponsor: Virginia Commonwealth University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Danielle Kirkman; Virginia Commonwealth University

• PRS Account: Virginia Commonwealth University
• Verification Date: March 2024