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Impact of LDL-cholesterol Lowering on Platelet Activation

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ClinicalTrials.gov Identifier: NCT03331666
Recruitment Status : Not yet recruiting
First Posted : November 6, 2017
Last Update Posted : January 17, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Nan Wang, Columbia University

Brief Summary:

The primary goal is to assess the impact of Evolocumab therapy on platelet function of familial hypercholesterolemia (FH) patients in a randomized, double blind study. Evolocumab is a humanized monoclonal antibody that targets circulating PCSK9, increases hepatic LDL receptor, decreases plasma LDL cholesterol and reduces risk of cardiovascular events. Evolocumab (brand name Rapatha) has been approved by FDA along with diet and maximally tolerated statin therapy in adults with FH or atherosclerotic heart or blood vessel problems, who need additional lowering of LDL cholesterol.

The secondary goal is to determine if platelet activation or the response to Evolocumab therapy is modified by rs3184504 polymorphism. The investigators believe that these investigations will complement ongoing studies to demonstrate that Evolocumab reduces athero-thrombotic risk and aid the decision-making as to whether Evolocumab can reduce the atherothrombotic risk in ACS patients.


Condition or disease Intervention/treatment Phase
Familial Hypercholesterolemia Drug: Evolocumab Phase 4

Detailed Description:
Hyperlipidemia as exemplified by familial hypercholesterolemia is associated with increased platelet activation and an underlying pro-coagulant state. Hyperlipidemia primes platelets and increases platelet activation in response to various agonists. Plasma cholesterol levels appear to have a critical role in modulating platelet activity as hypercholesterolemia increases platelet activation more potently than hypertriglyceridemia. Increased platelet reactivity may contribute to the increased risk of atherothrombosis associated with hypercholesterolemia. Plasma levels of platelet activation markers such as thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), soluble CD40L (sCD40L) or P-selectin exposure at surface of platelets are increased in hypercholesterolemic patients. Increased levels of the platelet activation markers are associated with increased platelet membrane cholesterol content in hypercholesterolemia.Statins may show antithrombotic properties.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Impact of LDL-cholesterol Lowering on Platelet Activation
Estimated Study Start Date : January 2018
Estimated Primary Completion Date : February 1, 2020
Estimated Study Completion Date : June 1, 2020


Arm Intervention/treatment
Active Comparator: Evolocumab
Subjects will start with placebo and will receive Evolocumab 140 mg every 14 days starting Day 14 until Day 88.
Drug: Evolocumab
140 mg every 14 days A monoclonal antibody designed for the treatment of hyperlipidemia
Other Name: REPATHA
Placebo Comparator: Placebo
Subjects will start with placebo and will receive Evolocumab 140 mg every 14 days starting Day 28 until Day 88.
Drug: Evolocumab
140 mg every 14 days A monoclonal antibody designed for the treatment of hyperlipidemia
Other Name: REPATHA



Primary Outcome Measures :
  1. Change in P2Y12 Reaction Units [ Time Frame: Day 7, Day 14, Day 21, Day 28, Day 88 ]
    ADP-stimulated platelet aggregation as assessed by the commercially-available VerifyNow P2Y12 assay (Accriva Diagnostics) will be performed. Unit: PRU.


Secondary Outcome Measures :
  1. Change in platelet P-selectin level [ Time Frame: Day 7, Day 14, Day 21, Day 28, Day 88 ]
    Platelet activation measured by flow cytometry or commercially-available enzyme-linked immunoassays (ELISAs). Reported as % positive cells (out of 50,000 cells counted) showed a mean reduction ± standard deviation (SD)



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who have a clinical diagnosis of familial hypercholesterolemia (FH)
  • Subjects who are referred to Dr. Ginsberg's Lipid Practice for treatment with PCSK9 inhibitor
  • Subjects with LDL cholesterol levels >100 mg/dl on baseline treatment with statins and/or ezitimibe

Exclusion Criteria:

  • Children under 18 years of age

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03331666


Contacts
Contact: Nan Wang, PhD 212-342-1761 nw30@cumc.columbia.edu
Contact: Lilian Oling, MA 212-305-9851 lao2106@cumc.columbia.edu

Locations
United States, New York
Columbia University Medical Center Not yet recruiting
New York, New York, United States, 10032
Contact: Nan Wang, PhD    212-342-1761    nw30@cumc.columbia.edu   
Contact: Wei Wang, PhD    212-305-6596    ww2351@cumc.columbia.edu   
Principal Investigator: Nan Wang, PhD         
Sponsors and Collaborators
Columbia University
Amgen
Investigators
Study Director: Henry Ginsberg, MD Columbia University
Principal Investigator: Nan Wang, PhD Columbia University

Publications:

Responsible Party: Nan Wang, Associate Professor of Medical Sciences (in Medicine) at the Columbia University Medical Center, Columbia University
ClinicalTrials.gov Identifier: NCT03331666     History of Changes
Other Study ID Numbers: AAAR1041
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Nan Wang, Columbia University:
Hyperlipidemia, Hypercholesterolemia, atherothrombosis

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs