Summary

Eligibility
for people ages 40 years and up (full criteria)
Location
at San Francisco, California
Dates
study started
estimated completion
Principal Investigator
by Priscilla Hsue, MD
Headshot of Priscilla Hsue
Priscilla Hsue

Description

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, UCLA, and University of Utah; collaborators at Massachusetts General Hospital (MGH) will serve as the core facility for imaging.

Details

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, UCLA, and Univ. of Utah. 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).

Keywords

Dyslipidemias Cardiovascular Diseases HIV Infections Atherosclerosis Inflammation 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid Bempedoic acid Bempedoic acid (BA)

Eligibility

You can join if…

Open to people ages 40 years and up

  • 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 ≥ 100 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] OR 1 CVD risk factor (T2DM, current smoking, hypertension, dyslipidemia, hsCRP≥2mg/L, family history)
  • TBR of >1.6 of the MDS of the carotid/aorta at baseline. This baseline arterial TBR cutoff excludes the rare individual that lacks appreciable arterial inflammation. It is notable that while 5-10% of uninfected individuals will have lower TBRs, it is rare that an HIV infected individual will fall below this range.
  • Female subjects must either be of non-childbearing potential (defined as post-menopausal or amenorrhea > 12 months) or agree to use two forms of contraception (one hormonal and one barrier) throughout the study and for at least one month following study completion and have a negative pregnancy test at screening and prior to the first dose of drug.
  • Males must use at least one method of contraception throughout the study.

You CAN'T join if...

  • 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 systolic OR ≥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 basal cell carcinoma
  • Individuals on simvastatin >20mg or pravastatin >40mg. All other dosages and statins will be permitted with close monitoring for myopathies including assessment of CK levels
  • 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 <1.5 x103/uL, and absolute lymphocytes <0.8 x 103/uL
  • Anemia as fined by Hgb <10 g/dL
  • Acute systemic infection within 30 days

Location

  • San Francisco General Hospital
    San Francisco California 94110 United States

Lead Scientist at UCSF

  • Priscilla Hsue, MD
    Professional Experience: Dr. Hsue trained in Internal Medicine in the Molecular Medicine Training Program at UC San Francisco and in Cardiovascular Medicine at UC San Francisco. She served as Chief Cardiology Fellow during this time. She has been on the faculty in the Department of Medicine at San Francisco General Hospital since 2002.

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Priscilla Hsue, MD
ID
NCT05488431
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 121 study participants
Last Updated