Cholesterol and Inflammation Lowering Via Bempedoic Acid, an ACL-inhibiting Regimen in HIV Trial (CLEAR HIV Trial)

Phase

Condition

Hiv Infections

Inflammation

Atherosclerosis

Treatment

Placebo

Bempedoic acid

Clinical Study ID

NCT05488431

1.0

Ages > 40
All Genders

Study 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.

Eligibility Criteria

Inclusion

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 ≥ 70 mg/dL
Documented cardiovascular disease as defined by: 1. Prior myocardial infarction, 2.Prior cerebrovascular disease, 3. Prior peripheral arterial disease, 4. History ofpercutaneous coronary intervention, 5. History of coronary artery bypass graft OR 6.Angiographic evidence of >50% stenosis in at least one coronary artery] OR 1 CVDrisk factor (T2DM, current smoking, hypertension, dyslipidemia, hsCRP≥2mg/L, familyhistory)
TBR of >1.6 of the MDS of the carotid/aorta at baseline. This baseline arterial TBRcutoff excludes the rare individual that lacks appreciable arterial inflammation. Itis notable that while 5-10% of uninfected individuals will have lower TBRs, it israre that an HIV infected individual will fall below this range.
Female subjects must either be of non-childbearing potential (defined aspost-menopausal or amenorrhea > 12 months) or agree to use two forms ofcontraception (one hormonal and one barrier) throughout the study and for at leastone month following study completion and have a negative pregnancy test at screeningand prior to the first dose of drug.
Males must use at least one method of contraception throughout the study.

Exclusion

Exclusion Criteria:

Pregnant/nursing women (as there is no data on bempedoic acid in this setting)
Diabetes requiring insulin (as insulin treatment alters the uptake of 18FDG)
Uncontrolled HTN as defined by baseline blood pressure reading of ≥160 mmHg systolicOR ≥100 mmHg diastolic (exclusion criteria in other studies with BA)
AST/ALT or alkaline phosphatase >2x ULN
Triglycerides >500 mg/dL at screening
Cancer within the last 5 years with exception of squamous cell carcinoma and basalcell carcinoma
Individuals on simvastatin >20mg or pravastatin >40mg. All other dosages and statinswill be permitted with close monitoring for myopathies including assessment of CKlevels
Nephrotic syndrome or eGFR <30 mL/min/1.73m2
Cytopenias which include 1) WBC <3.5 x103/uL 2) Platelet <120 x103/uL 3) ANC <1.5x103/uL, and absolute lymphocytes <0.8 x 103/uL
Anemia as fined by Hgb <10 g/dL
Acute systemic infection within 30 days

Study Design

Placebo

March 01, 2023

March 01, 2028

Study 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 parameters may be even more advantageous in HIV. Bempedoic acid (BA, an inhibitor of ATP citrate lyase), is safely tolerated, significantly lowers LDL-C and inflammatory markers (on top of statin therapy), and is FDA approved for individuals with heterozygous familial hypercholesterolemia or with established ASCVD who require additional LDL-C lowering. Additionally, BA has a protective effect on glycemic parameters and may reduce adiposity. Given the key role of lipids and inflammation in atherosclerosis in HIV, the purpose of this proof-of-concept mechanistic trial is to evaluate the impact of BA on the biology of HIV-associated atherosclerosis. This is a randomized placebo controlled study of effectively treated PLWH aged 40 years and older with either known CVD or 1 CVD risk factor to study the effect of BA on arterial inflammation (assessed by FDG-PET/CT), lipid levels, biomarkers of inflammatory/immune activation, cardiometabolic indices, and non-calcified plaque in the coronary arteries (assessed by CCTA). This multicenter trial will include PLWH enrolled at UCSF and UCLA. Long term collaborators at MGH will serve as the core facility for the imaging end-points. There are three specific aims for the: Cholesterol and inflammation Lowering via BEmpedoic Acid, an ACL-inhibiting Regimen in HIV Trial (CLEAR HIV Trial): Aim 1: To determine whether BA can safely reduce arterial inflammation including carotid plaque as assessed by FDG-PET/CT; Aim 2: To determine whether BA improves cardiometabolic measures (lipid, inflammatory, glycemic and adipose parameters) among PLWH. Exploratory objectives will be to assess BA's effect (vs. placebo) on glycemic as well as adipose tissue measures (HbA1c, HOMA IR, and adipose tissue volumes); Aim 3: To evaluate the impact of BA on non-calcified coronary plaque volume as measured by coronary CT angiography (CCTA).

Connect with a study center

San Francisco General Hospital
San Francisco, California 94110
United States
Active - Recruiting

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