NCT03829046

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)

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 41 (actual)
• Sponsor: Robert Rosenson · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Atherosclerotic Vascular Disease
• Type2 Diabetes
• Microvascular Dysfunction

Interventions

Type	Name	Description
DRUG	Placebo	12 weeks of treatment
DRUG	Evolocumab	12 weeks of treatment

Timeline

• Start date: 2019-06-03
• Primary completion: 2021-11-15
• Completion: 2021-11-15
• First posted: 2019-02-04
• Last updated: 2023-03-08
• Results posted: 2023-03-08

Locations

2 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study