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| Name | Class |
|---|---|
| American Heart Association | OTHER |
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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.
To evaluate the effect of the PCSK9 inhibitor evolocumab on coronary and systemic endothelial function, systemic biomarkers of endothelial function and of inflammation, and echocardiographic measures of left ventricular diastolic and systolic properties in subjects who are HIV+. Potential participants will be asked to undergo a screening MRI exam. Those who have evidence of coronary endothelial dysfunction on the MRI exam will receive evolocumab 420 mg sq (the dose that is approved for treatment of hypercholesterolemia) following the screening exam and again at one month. Repeat MRI and ultrasound measures of coronary and systemic endothelial function, as well as serum markers of endothelial function and inflammation, and echocardiographic measures of diastolic and systolic left ventricular function will be obtained at one and six weeks following the first administration of evolocumab.
The investigators will test the hypotheses that PCSK9 inhibition improves endothelial function measured non-invasively on MRI and systemic markers of inflammation at one week (+/- 3 days) and six weeks after initiation of the PCSK9 antibody.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Evolocumab | Experimental | All enrolled patients will receive evolocumab sq once a month for a total of two doses |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Evolocumab | Drug | Evolocumab sq once a month for a total of two doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Coronary Endothelial Function as Assessed by Percent Coronary Artery Area Change With Isometric Handgrip Exercise | Coronary endothelial function will be assessed by the percent change in cross sectional coronary artery area (measured on MRI) from rest to isometric handgrip stress exercise at week 1 and week 6. The percent change from week 1 to week 6 is presented below. | 1 week and 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| LDL Cholesterol Level | LDL cholesterol level: mg/dL. | At 6 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Allison Hays, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University | Baltimore | Maryland | 21205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32674634 | Derived | Leucker TM, Gerstenblith G, Schar M, Brown TT, Jones SR, Afework Y, Weiss RG, Hays AG. Evolocumab, a PCSK9-Monoclonal Antibody, Rapidly Reverses Coronary Artery Endothelial Dysfunction in People Living With HIV and People With Dyslipidemia. J Am Heart Assoc. 2020 Jul 21;9(14):e016263. doi: 10.1161/JAHA.120.016263. Epub 2020 Jul 17. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Evolocumab | All enrolled patients (people living with HIV) who received evolocumab sq once a month for a total of two doses |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Evolocumab Group | Patients (people living with HIV) who received Evolocumab sq once a month for total of 2 doses |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Coronary Endothelial Function as Assessed by Percent Coronary Artery Area Change With Isometric Handgrip Exercise | Coronary endothelial function will be assessed by the percent change in cross sectional coronary artery area (measured on MRI) from rest to isometric handgrip stress exercise at week 1 and week 6. The percent change from week 1 to week 6 is presented below. | Posted | Mean | Standard Deviation | percent change in coronary artery area | 1 week and 6 weeks |
|
|
Up to 10 weeks from start of study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Evolocumab | All enrolled patients who received evolocumab sq once a month for a total of two doses. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Allison Hays | Johns Hopkins University | 443-287-6827 | ahays2@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 25, 2017 | Jul 8, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C577155 | evolocumab |
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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.
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| Participants |
| No |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
|
|
| Secondary | LDL Cholesterol Level | LDL cholesterol level: mg/dL. | Posted | Mean | Standard Deviation | mg/dL | At 6 weeks |
|
|
|
| 0 |
| 19 |
| 0 |
| 19 |
| 0 |
| 19 |
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| D015229 |
| Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |