NCT04247048

Brief Summary

The aim is to study the relationship between lipoprotein(a) \[Lp(a)\] and PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) in humans with a kinetic study of lipoproteins in patients with dramatic increase of Lp(a) and controls.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jul 2020

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 2, 2019

Completed
5 months until next milestone

First Posted

Study publicly available on registry

January 29, 2020

Completed
6 months until next milestone

Study Start

First participant enrolled

July 31, 2020

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 23, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 23, 2021

Completed
Last Updated

February 23, 2022

Status Verified

February 1, 2022

Enrollment Period

1.4 years

First QC Date

September 2, 2019

Last Update Submit

February 22, 2022

Conditions

Cholesterol; Metabolic DisorderLipoproteinemia

Outcome Measures

Primary Outcomes (1)

  • To study in humans by a study of the kinetics of apo (a), the relationships between the metabolism of Lp (a) and the plasma levels of PCSK9.

    1. Correlation between PCSK9 plasma levels and apo (a) production rate (fractional production rate (RPF) and absolute production rate (APR)) in patients with Lp (a)\> 80 mg / dl and control subjects with Lp (a) levels \<30mg / dl. 2. Correlation between PCSK9 plasma levels and apo (a) fractional clearance rate (FCR) in patients with Lp (a)\> 80 mg / dl and control subjects with Lp (a) levels \<30mg / dl.

    14 hours after leucine infusion

Secondary Outcomes (3)

  • To evaluate the impact of PCSK9 metabolism on metabolic parameters of Lp (a).

    14 hours after leucine infusion

  • To evaluate the impact of PCSK9 metabolism on metabolic parameters of Lp

    14 hours after leucine infusion

  • To measure the impact of PCSK9 metabolism on metabolic parameters of Lp

    14 hours after leucine infusion

Study Arms (2)

Control group

EXPERIMENTAL

Patients with no major LDL cholesterol abnormalities (patients eligible for LDL-apheresis, eg LDL-C\> 200 mg / dL for secondary prevention and 300 mg / LDL-C) dl in primary prevention)) and a level of Lp (a) \<50 mg / dl

Other: infusion of tracer [5,5,5-2H3] -L-leucine

High-dose group

EXPERIMENTAL

Patients with no major LDL-cholesterol abnormalities (LDL-apheresis eligible patients, eg LDL-C\> 200 mg / dL for secondary prevention and 300 mg / dl in primary prevention)) and a level of Lp (a)\> 80 mg / dl

Other: infusion of tracer [5,5,5-2H3] -L-leucine

Interventions

infusion of tracer [5,5,5-2H3] -L-leucineOTHER

A bolus of 6ml of \[5,5,5-2H3\] -L-leucine tracers will be performed followed by an infusion of 90 ml of \[5,5,5-2H3\] -L-leucine infused over 14 hours. This tracer participates in protein synthesis and especially in the synthesis of all apolipoproteins and PCSK9. Blood samples will be taken at T0, T2min, T5min, T10 minutes, T30 minutes and then every hour until 14 hours (a total of 240 ml of blood will be collected) to measure the stable tracer enrichment in the proteins of interest.

Control groupHigh-dose group

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • age: 18 to 75 years
  • For subjects in the "Control" group: Patients with no major LDL-cholesterol deficiency (patients eligible for LDL-apheresis, eg LDL-C\> 200 mg / dL for secondary prevention and 300 mg / dl in primary prevention)) and a level of Lp (a) \<50 mg / dl or
  • For subjects in the "high-dose" group: Patients with no major LDL-cholesterol abnormalities (LDL-apheresis eligible patients, eg LDL-C\> 200 mg / dL for secondary prevention and 300 mg / dl in primary prevention)) and a level of Lp (a)\> 80 mg / dl Whenever possible, groups will be balanced for age, sex, familial forms of hypercholesterolemia and their major groups of mutations.

You may not qualify if:

  • Patients treated with PCSK9 antibodies.
  • Patients with acute illness and considered incompatible by the investigator
  • Uncontrolled diabetes (HbA1c\> 8.5%)
  • Severe hepatic insufficiency
  • Creatinine clearance \<30 ml / min
  • Patients not covered by a social security scheme or beneficiary of such a scheme
  • Patients unable to understand and / or sign consent
  • Pregnant or lactating women
  • Minors
  • Majors under guardianship or trusteeship or safeguard of justice

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Nantes University Hospital

Nantes, 44093, France

Location

MeSH Terms

Conditions

Metabolic Diseases

Interventions

Leucine

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Branched-ChainAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, Essential

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
PARALLEL
Model Details: Kinetic study of lipoprotein metabolism with stable isotope tracers.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 2, 2019

First Posted

January 29, 2020

Study Start

July 31, 2020

Primary Completion

December 23, 2021

Study Completion

December 23, 2021

Last Updated

February 23, 2022

Record last verified: 2022-02

Locations

FR(1)