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The Effects of Evolocumab in Patients With Diabetes and Atherosclerotic Vascular Disease | Clinical Trials | Clareo Health

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The Effects of Evolocumab in Patients With Diabetes and Atherosclerotic Vascular Disease

The Effects of Evolocumab on Endothelial and Inflammatory Biocellular Markers in Patients With Diabetes and Atherosclerotic Vascular Disease (METCHNIKOFF)

NCT03829046•Robert Rosenson

View on ClinicalTrials.gov

Summary

Experimental models have linked lipid lowering therapies with systemic inflammation; however, relatively little is known about this network in clinical populations and specifically how it changes with PCSK9 inhibition. The eligible subjects will have 6 visits in 13 to 16 weeks and will have Repatha/placebo 140mg subcutaneous every 4 weeks for 3 times since randomization visit, blood tests will be done in each visit to evaluate the effects of evolocumab upon biocellular markers potentially altered by PCSK9 inhibition in a population of type 2 diabetes patients with microvascular dysfunction. Primary Aims: Determine the ACUTE and SHORT-TERM effects of PCSK9 inhibition with evolocumab on biocellular markers of inflammation, immune mediated thrombosis and rheology. The data from this trial will be used to support a clinical trial to assess the role of PCSK9 inhibition in type 2 diabetes patients with cardiac microvascular dysfunction. Secondary Aims: 1. To define the association between PCSK 9 concentrations and immune-related phenotype. 2. To define the association between Lp(a) concentrations, oxidized phospholipids (OxPL), ApoB, biocellular markers of inflammation, tissue factor and immunothrombosis.

Detailed Description

Multi-center, double-blind, randomized, placebo-controlled, parallel group Phase IV study with two treatment arms: evolocumab SC 420 mg/dL QM or matching placebo. The population will include 40 participants with documented Atherosclerotic Vascular Disease (CAD, Stroke, PAD) and type 2 diabetes who receive treatment with maximal tolerated statin therapy and stable doses of anti-hyperglycemic therapy. Subjects will be followed for 12 weeks during the treatment phase, maintaining the double-blind throughout. Assessments of ACUTE and SHORT-TERM effects of PCSK9 inhibition with evolocumab on biocellular markers of endothelial function will be measured at baseline, Week 2, and Week 12. Safety assessments will be undertaken at each study visit.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Subjects ≥18 years of age signing of informed consent;
•A history of clinical ASCVD, which is defined as: acute coronary syndrome, or a history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral arterial disease presumed to be of atherosclerotic origin;
•Clinical diagnosis of type 2 diabetes according to ADA/ CDA guidelines;
•Subject on stable dose of maximally-tolerated statin therapy for ≥4 weeks prior to screening and LDL-c ≥70mg/dL. For subjects whose maximally tolerated dose of statin is no type or dose (i.e. determined to be statin intolerant by primary investigator), background lipid-lowering therapy is not required;
•Fasting triglycerides ≤400mg/dL (4.52mmol/L) by central laboratory at screening;
•Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures;
•Abnormal urinary Albumin Creatinine Ratio (ACR) as defined by an ACR ≥2;
•Subject tolerates screening placebo injection.

Exclusion Criteria

•Personal or family history of hereditary muscular disorders;
•NYHA III or IV heart failure, or last know left ventricular ejection fraction (LVEF) \<30%;
•Uncontrolled serious cardiac arrhythmia defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications, in the past 6 weeks prior to randomization;
•Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery graft (CABG) or stroke within 3 months prior to randomization;
•Planned cardiac surgery or revascularization;
•Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) \<30mL/min/1.73m2 at screening;
•Type 1 diabetes, poorly controlled type 2 diabetes (HbA1c \>10%), newly diagnosed type 2 diabetes (within 6 months of randomization), or laboratory evidence of diabetes during screening (fasting serum glucose ≥126mg/dL \[7.0mmol/L\] or HbA1c ≥6.5% without prior diagnosis of diabetes;
•Uncontrolled hypertension, defined as sitting systolic blood pressure (SBP) \>160mmHg or diastolic BP (DBP) \>100mmHg;
•Subject who has taken a cholesterol easter transfer protein (CETP) inhibitor in the last 12 months prior to LDL-c screening, such as: anacetrapib, dalcetrapib or evacetrapib;
•Treatment in the last 3 months prior to LDL-c screening with any of the following drugs: systemic cyclosporine, systemic steroids (e.g. IV, intramuscular \[IM\], or PO) (Note: hormone replacement therapy is permitted), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (e.g. Accutane); (Note: vitamin A in a multivitamin preparation is permitted). Topical retinol prescription and non-prescription derivatives or creams are permitted;
+17 more criteria

Locations (2)

Icahn School of Medicine at Mount Sinai

New York, New York, United States

St. Michael's - University of Toronto

Toronto, Ontario, Canada

Key Dates

Start Date

June 3, 2019

Primary Completion Date

November 15, 2021

Completion Date

November 15, 2021

Last Updated

March 8, 2023

Enrollment

ACTUAL participants

Conditions

Atherosclerotic Vascular DiseaseType2 DiabetesMicrovascular Dysfunction

Interventions

Placebo

DRUG

Evolocumab

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 8, 2023Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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The Effects of Evolocumab in Patients With Diabetes and Atherosclerotic Vascular Disease

Inclusion Criteria

Exclusion Criteria

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