Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®

Hypercholesterolemia, Familial Clinical Trial

Official title:

Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04313270
• Other study ID #: 2015/261
• Status: Recruiting
• Start date: December 1, 2017
• Est. completion date: December 1, 2025

Study information

• Verified date: March 2021
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Protein convertase subtilisin kexin type 9 (PCSK-9) inhibitors demonstrated efficacy in cholesterol reduction and in the prevention of cardiovascular events. The investigators will evaluate changes in lipid profile, oxidation markers and subclinical atherosclerosis in patients with familial hypercholesterolemia (FH) during 12 weeks of treatment with a PCSK-9 inhibitor, Evolocumab®.

Description:

Several studies emphasize the role of high levels of low-density lipoprotein cholesterol (LDL-C) as the main causative factor in atherosclerosis development. Among patients with hypercholesterolemia, those with very high levels of LDL-C exhibit increased prevalence of subclinical atherosclerosis and a higher atherosclerosis progression, thus leading to a significantly higher CV risk. Endothelial dysfunction is the earliest stage of the atherosclerotic process and even a trigger of CV events. Flow-mediated dilation (FMD) is widely accepted as an accurate and non-invasive method to assess vascular reactivity and, in turn, as a surrogate marker of subclinical atherosclerosis and an independent predictor of CV events. It's well known that hypercholesterolemia has been associated with decreased endothelial function and increased oxidative stress. Although statin treatment represented for years the gold standard as lipid lowering therapy, the target LDL-C is not always achieved, mainly among patients with very high levels of LDL-C. More recently, PCSK-9 inhibitors demonstrated efficacy in LDL-C reduction, in the prevention from CV events and in atherosclerotic burden regression. Some data showed an effect of PCSK-9 inhibitors on endothelial function, but no evidence is available on effect on LDL subfractions. Small dense LDL (sd-LDL) are considered an emerging risk factor for cardiovascular disease due to a greater atherogenic potential [ ] and are important markers for predicting CV risk.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• diagnosis of FH (clinical and/or genetic)
• eligibility of patients to start a treatment with PCSK-9 according to 2016 ESC guidelines.

Exclusion Criteria:

• age < 18 years
• inability to understand or sign the informed consent
• high level of transaminases ( >3x upper normal limit)
• hypertriglyceridemia ( >150 mg/dl)
• end-stage renal disease (filtration rate < 30 ml/min/mq)
• current malignant disease or a diagnosis of malignancy in the 2 years prior to the first visit
• previous exposure to PCSK-9 inhibitors
• presence of hypercholesterolemia secondary to other causes (hypothyroidism, hormone therapies, corticosteroids etc.)

Related Conditions & MeSH terms

• Atherosclerosis
• Hypercholesterolemia
• Hypercholesterolemia, Familial
• Hyperlipoproteinemia Type II

Intervention

Drug:
• Evolocumab
12 weeks of treatment with Evolocumab

Locations

Country	Name	City	State
Italy	Matteo Di Minno	Napoli

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subclinical atherosclerosis	evaluation of subclinical atherosclerosis in patients receiving Evolocumab	12 weeks