Cholesterol and Inflammation Lowering Via Bempedoic Acid, an ACL-inhibiting Regimen in HIV Trial (CLEAR HIV Trial)
Priscilla Hsue, MD
Summary
This is a randomized placebo-controlled study in treated and suppressed HIV-infected individuals aged ≥40 years with either known CVD or 1 CVD risk factor to study the effect of Bempedoic acid (BA) on safety, arterial inflammation as assessed by FDG-PET/CT, lipids, inflammation, immune activation, cardiometabolic indices, and non-calcified plaque (NCP) in the coronary arteries (assessed by coronary CT angiography, CCTA). This trial will be enrolled at UCSF and UCLA. Collaborators at Massachusetts General Hospital (MGH) will serve as the core facility for imaging.
Description
Persons living with HIV infection (PLWH) have a 2-fold higher risk of myocardial infarction and are twice as likely to develop cardiovascular disease accounting for a significant global burden of disease. While the mechanism underlying this excess risk remains poorly understood, studies demonstrate that atherosclerosis in the setting of HIV is distinct and characterized by heightened arterial inflammation as assessed by FDG-PET/CT. HIV and antiretroviral medication can worsen cardiometabolic parameters. Thus a therapeutic strategy that can lower lipids, inflammation, and improve glycemic param…
Eligibility
- Age range
- 40+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Documented HIV infection * On continuous antiretroviral therapy and virologically suppressed HIV infection for ≥12 weeks prior to study entry * CD4 T-cell count ≥ 200 cells/mm3 * Male or female between the ages ≥ 40 years of age * LDL-C ≥ 50 mg/dL * Documented cardiovascular disease as defined by: 1. Prior myocardial infarction, 2. Prior cerebrovascular disease, 3. Prior peripheral arterial disease, 4. History of percutaneous coronary intervention, 5. History of coronary artery bypass graft OR 6. Angiographic evidence of \>50% stenosis in at least one coronary artery\] O…
Interventions
- DrugBempedoic acid
Bempedoic Acid is an oral first-in-class small molecular adenosine triphosphate (ATP)-citrate lyase (ACL) inhibitor which lowers LDL-C by inhibition of cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Inhibition of ACL by bempedoyl-CoA results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via upregulation of LDL receptors and concomitant suppression of hepatic fatty acid biosynthesis. BA has been studied in \>4300 individuals and is currently being studied in \>14,000 individuals in CLEAR Outcomes (NCT02993406).
- OtherPlacebo
Placebo
Locations (3)
- UCLA Center for Clinical AIDS Research and Education (CARE)Los Angeles, California
- San Francisco General HospitalSan Francisco, California
- UT Health HoustonHouston, Texas