Relationships Between Plasma PCSK9 Levels, LDL-cholesterol Concentrations and Lipoprotein (a) Levels in Familial Hypercholesterolemia

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02225340

Enrollment

348

Registered

2014-08-26

Start date

2014-01-31

Completion date

2014-04-30

Last updated

2014-08-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Familial Hypercholesterolemia

Brief summary

Familial hypercholesterolemia (FH) is an autosomal codominant single gene disorder caused by mutations in the LDL receptor gene (LDLR) that disrupt the normal clearance of LDL particles from the plasma. Heterozygous patients (HeFH) present a two- to three-fold raise in plasma LDL-cholesterol (LDL-C) concentrations and coronary artery disease occurs earlier among HeFH carrying negative-receptor (NR) mutations as compared with HeFH subjects carrying defective-receptor (DR) variants. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL-C levels by binding to LDLR and by enhancing its intracellular degradation. The objective of this study is to examine to what extent variations in LDL-C and Lipoprotein (Lp) (a) concentrations are related to PCSK9 levels in a large French-Canadian cohort of HeFH subjects. The primary hypothesis is that that PCSK9 levels have a significant impact on LDL-C concentration variability and are associated with Lp(a) levels.

Interventions

None listed

Study design

Observational model

CASE_CONTROL

Time perspective

CROSS_SECTIONAL

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

Subjects with familial hypercholesterolemia: * Aged between 18-65 years * Carrier of a mutation in the LDL receptor gene Controls: * Aged between 18-60 years * HDL-cholesterol \> 1.1 mmol/L * Triglycerides \< 1.7 mmol/L * Fasting blood glucose \<6.1 mmol/L * Normal blood pressure (\<130/85)

Exclusion criteria

* Subjects with a previous history of cardiovascular disease * Subjects with Type 2 diabetes * Were pregnant or nursing; * Subjects with a history of cancer * Subjects with acute liver disease, hepatic dysfunction, or persistent elevations of serum transaminases * Subjects with a secondary hyperlipidemia due to any cause * History of alcohol or drug abuse within the past 2 years * hormonal treatment * Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study

Design outcomes

Primary

Measure	Time frame
Impact of PCSK9 on LDL-C concentrations	Week 1

Secondary

Measure	Time frame
Impact of PCSK9 on Lp(a) concentrations	Week 1

Countries

Canada

Outcome results