Effect of Evolocumab on Coronary Endothelial Function

• Status: Completed
• Trial end date: 2019-11-30
• Target enrollment: 0
• Participant gender: All

Summary

The investigators propose a pilot study using (1) MRI to assess coronary artery endothelial function, (2) brachial ultrasound to assess systemic endothelial function, (3) serum markers of inflammation and of endothelial cell function and (4) echocardiographic measures of left ventricular diastolic and systolic properties, before and following initiation of PCSK9 antibody in HIV positive subjects.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johns Hopkins University
• Collaborator: American Heart Association
• Treatments: Antibodies, Monoclonal; Evolocumab

Criteria

Inclusion Criteria:

• Participants of either gender who are >21 years of age (no upper age limit)

• HIV (Human Immunodeficiency Virus) positive and taking stable Anti-Retroviral Therapy (ART), no change in regimen in last 3 months)

• Undetectable HIV viral load (plasma HIV RNA concentration, RNA=Ribonucleic Adic)

• Abnormal coronary endothelial function on MRI (Magnetic Resonance Imaging) at baseline (<5% change in coronary cross sectional area during isometric handgrip exercise as compared to resting value).

• Lipids at screening visit: Fasting LDL-C >70 mg/dL (LDL-C=Low Density Lipoprotein Cholesterol); fasting TG<500 mg/dL (TG=Triglycerides)

• Permission of treating physician

Exclusion Criteria:

• Patients unable to understand the risks, benefits, and alternatives of participation and give meaningful consent.

• Patients with contraindications to MRI such as implanted metallic objects (pre-existing cardiac pacemakers, cerebral clips),

• History of a recent cardiovascular or cerebrovascular events or procedure (e.g. myocardial infarction, stroke, transient ischemic attack, angioplasty, Coronary artery bypass surgery) during the past 90 days.

• Subjects with prior exposure to evolocumab or another PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitor.

• Pregnant women or breastfeeding women. Women of childbearing potential (even if using oral contraceptive agents) or intention to breastfeed.

• History of alcoholism or drug addiction according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria within 12 months prior to screening. Use of any recreational drugs within 6 months prior to screening.

• Renal impairment defined by estimated glomerular filtration rate <45 ml/min.

• Moderate-severe hepatic disease (elevation in hepatic transaminases >3x upper limit of normal, ULN) or direct bilirubin >3.0 X ULN at screening.

• Cluster of differentiation 4 (CD4)<200 cell/mm3

• Congestive heart failure, New York Heart Association functional class III or greater, or left ventricular ejection fraction measured by imaging known to be <30%. (Imaging not required for study inclusion).

• History of allergic or anaphylactic reaction to any therapeutic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibodies

• Active phase hepatitis. Stable patients with hepatitis B or C infection >3 years before randomization are eligible.