Clinical trial

In Vitro Demonstration of Direct Platelet-Related Effects of PCSK9 Enzyme

Opening soon · Not applicable · 0 countries · Registry ID NCT06675994

Opening soonNot applicableObservational

What this study is about

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has evolved as a pivotal enzyme in lipid metabolism and therapeutic target for hypercholesterolemia and atherosclerotic cardiovascular disease (CVD). Furthermore, research from in-vitro and in-vivo animal models suggest that the inhibition of PCSK9 expression may suppress platelet activation, and systemic inflammation thereby reducing thrombotic risk. Taken together, these data support the lower rates of myocardial infarction, stroke, and coronary revascularization in subjects with increased CVD risk in clinical trials with alirocumab (Praluent) and evolocumab (Repatha) as compared to placebo. The main aim of this single center, exploratory in-vitro evaluation is to investigate the direct role of PCSK9 on platelet activation and aggregation using blood collected from a diverse population of antiplatelet naïve healthy volunteers (n=40) and subjects with CVD risk factors (n=40) between the 18-50 years of age. All procedures including consenting, collection of clinical data, and lab processing will occur at the Sinai Center for Thrombosis Research. The results of this study will provide a better understanding of cardioprotective effects of PCSK9 inhibition beyond lipid lowering.

A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.

Basic eligibility

Age18 Years to 50 Years

SexAll

Healthy volunteersAccepted

ConditionHealthy, Hypercholesterolemia, Hypertension, Overweight, Prediabetes, Diabetes, Family History of Coronary Artery Disease, Family History of Peripheral Artery Disease, Family History of Cerebrovascular Disease

Full registry criteria

Inclusion Criteria: * Healthy subjects (n=40): 18-50 years old male and female subjects without any conditions or taking any agents or food supplements that may influence platelet function as determined by the study principal investigator. * Subjects with CV risk factors (n=40): 18-50 years old male and female subjects with at least three of the following CV risk factors: History of hypercholesterolemia, hypertension, overweight, current smoker, prediabetes or diabetes who are only on metformin and insulin, and family history of coronary artery, peripheral artery, or cerebrovascular disease. Overweight is defined as subjects with BMI ≥25 kg/m2 (https://www.heart.org/en/healthy-living/healthy-eating/losing-weight/bmi-in-adults). Diabetes is defined as haemoglobin (Hb)A1c ≥6.5%, prediabetes =5.7%-6.4%) (https://diabetes.org/about-diabetes/diagnosis) Exclusion Criteria: * Subjects with Diabetes mellitus, who are on GLP-1 agonists or SGLT2 inhibitors. * Subjects on high dose statin therapy or PCSK9 therapy. * Prior coronary of cerebrovascular event requiring intervention. * Use of any antiplatelet or anticoagulant therapy within 14 days of enrollment. * Subjects with a history of chronic kidney disease, liver disease, pancreatitis, HIV, hepatitis, and active cancer, active infection, or any other medical condition or concomitant medications as determined by the investigator that may affect study results. * Pregnant

Treatments and study arms

PCSK9 Antibody, PCSK9 Enzyme

Drug

In-vitro demonstration of the direct effect if the PCSK9 enzyme on platelets. The study will use commercially available recombinant PCSK9 enzyme to promote platelet activity and the PCSK9 antibody to inhibit activity. In each patient, platelet function testing will occur in the absence of PCSK9 enzyme, after the addition of PCSK9 enzyme, and after the addition of both PCSK9 enzyme and antibody reagent to the blood sample prior to testing.

Primary outcomes

Difference in ADP-induced platelet aggregation (%) with and without PCSK9 enzymeThroughout study completion, an average of about 1 year

Difference in ADP-induced platelet aggregation (%) with and without addition of PCSK9 enzyme in blood collected from healthy volunteers and subjects with cardiovascular risk factors.

Difference in collagen related peptide -induced platelet aggregation (%) with and without PCSK9 enzymeThroughout study completion, an average of about 1 year

Difference in collagen related peptide-induced platelet aggregation (%) with and without PCSK9 enzyme in blood collected from healthy volunteers and subjects with cardiovascular risk factors.

Study locations

0 locations were listed when this page was built. The first 40 are shown.

No public site location was included in this record. Check the original registry for updates.