Effect of Evolocumab on Coronary Endothelial Function
Condition: Human Immunodeficiency Virus; Coronary Artery Disease
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Coronary Artery Disease
Intervention: Evolocumab
Intervention description: Evolocumab sq once a month for a total of two doses
Intervention MeSH terms: Evolocumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Pilot clinical trial to study HIV+ patients with baseline coronary endothelial dysfunction and assess changes in that function from the baseline measure to 1 and 6 weeks following initiation of therapy with evolocumab so as to test the hypotheses that PCSK9 inhibition with evolocumab improves coronary endothelial function (CEF) measured directly and non-invasively with MRI at 1 week and 6 weeks after initiation of evolocumab.
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No

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.
    

Eligibility 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.