Cholesterol; Metabolic DisorderHuLaUPNCT04247048
Kinetic Study of Lp(a) and PCSK9 in Humans
A study testing infusion of tracer [5,5,5-2H3] -L-leucine in people with Cholesterol; Metabolic Disorder and Lipoproteinemia, run by Nantes University Hospital at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cholesterol; Metabolic Disorder, Lipoproteinemia
- What is being tested?
- infusion of tracer [5,5,5-2H3] -L-leucine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteFrance
- Study dates
- 31 Jul 2020to 23 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- Patients unable to understand and / or sign consent
- Pregnant or lactating women
- Minors
- Majors under guardianship or trusteeship or safeguard of justice
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Kinetic Study of Lipoprotein in Humans for a Better Understanding of Lipoprotein(a) Metabolism Under PCSK9 Variations (Hu-La-u-P Study)
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.
Read the detailed description
Elevated plasma levels of lipoprotein(a) [Lp(a)] are independently associated with an increased risk of cardiovascular diseases (CVD). Recently an unexpected and significant 15 to 30 % reduction of Lp(a) was reported with PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors. The relation between Lp(a) and PCSK9 are unclear and debated.
Kinetic studies of lipoprotein are an important tool to decipher the complexity of apolipoprotein metabolism in human. The comparison of apoprotein(a) and PCSK9 kinetic parameters of patients with extreme lipid disorder link to PCSK9 and apo(a) will allow to better understand the impact of PCSK9 on apo(a). From one previous in vitro study, the hypothesize is that PCSK9 increases the production rate and the assembly of Lp(a).
The objectives are to explore the relationship between the plasma concentration of PCSK9 and apo(a) production rate as well as the impact on the catabolic rate. Patients with extreme Lp(a) levels and healthy controls will be explored by performing a continuous infusion of deuterated leucine for 14 hours. LC/MS-MS will be used to analyze the samples and kinetic data of apo(a) and PCSK9 will be generated from a compartmental model. Tracer enrichment analysis could be complicated for proteins with low plasma concentrations as PCSK9. This issue will be solved with SPE and/or immune affinity concentration techniques. Non-parametrical test and multivariate analysis will be use to describe the relationship between these two variables.
This study will provide new knowledge on Lp(a) and PCSK9 metabolism and their interactions in humans.
- Conditions
- Cholesterol; Metabolic Disorder, Lipoproteinemia
- Being tested
- infusion of tracer [5,5,5-2H3] -L-leucine
- Medical subject headings
- Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: infusion of tracer [5,5,5-2H3] -L-leucine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
- 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.
- 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.
Measured: 14 hours after leucine infusion
Secondary outcomes (3)
To evaluate the impact of PCSK9 metabolism on metabolic parameters of Lp (a).
Correlation between the PCSK9 (fractional production rate (RPF) and absolute production rate (APR) synthesis rate and the rate of synthesis and degradation of apo (a) (fractional production rate (FPR) and absolute production rate ( APR)) and fractional clearance rate (FCR) in patients with Lp (a)> 80 mg / dl and control subjects with Lp (a) <30mg / dl.
Measured: 14 hours after leucine infusion
To evaluate the impact of PCSK9 metabolism on metabolic parameters of Lp
Correlation between PCSK9 (fractional clearance rate (FCR)) and the rate of synthesis and degradation of apo (fractional production rate (RPF) and absolute production rate (APR)) and (fractional clearance rate spleen (FCR)) in patients with Lp (a)> 80 mg / dl and control subjects with Lp (a) <30mg / dl.
Measured: 14 hours after leucine infusion
To measure the impact of PCSK9 metabolism on metabolic parameters of Lp
Correlation between the production and degradation rates of Lp (a), PCSK9 and apoB100 in patients with Lp (a)> 80 mg / dl and control subjects with Lp (a) ) <30 mg / dl.
Measured: 14 hours after leucine infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2020
- Study start31 Jul 2020
- Primary completion23 Dec 2021
- Study completion23 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cholesterol; Metabolic DisorderStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Kinetic study of lipoprotein metabolism with stable isotope tracers.
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Centre de Recherche en Nutrition Humaine Ouest (CRNH)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04247048
- Sponsor's protocol ID
- RC18_0281
- Acronym
- HuLaUP
- Status last verified
- Feb 2022
- First submitted
- 2 Sep 2019
- Last updated
- 23 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Kinetic Study of Lipoprotein in Humans for a Better Understanding of Lipoprotein(a) Metabolism Under PCSK9 Variations (Hu-La-u-P Study)
- ClinicalTrials.gov ID
- NCT04247048
- Acronym / sponsor ID
- HuLaUP / RC18_0281
- Conditions
- Cholesterol; Metabolic Disorder, Lipoproteinemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Collaborators
- Centre de Recherche en Nutrition Humaine Ouest (CRNH)
- Study start
- 31 Jul 2020 (actual)
- Primary completion
- 23 Dec 2021 (actual)
- Study completion
- 23 Dec 2021 (actual)
- First posted
- 29 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Elevated plasma levels of lipoprotein(a) [Lp(a)] are independently associated with an increased risk of cardiovascular diseases (CVD). Recently an unexpected and significant 15 to 30 % reduction of Lp(a) was reported with PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors. The relation between Lp(a) and PCSK9 are unclear and debated.
Kinetic studies of lipoprotein are an important tool to decipher the complexity of apolipoprotein metabolism in human. The comparison of apoprotein(a) and PCSK9 kinetic parameters of patients with extreme lipid disorder link to PCSK9 and apo(a) will allow to better understand the impact of PCSK9 on apo(a). From one previous in vitro study, the hypothesize is that PCSK9 increases the production rate and the assembly of Lp(a).
The objectives are to explore the relationship between the plasma concentration of PCSK9 and apo(a) production rate as well as the impact on the catabolic rate. Patients with extreme Lp(a) levels and healthy controls will be explored by performing a continuous infusion of deuterated leucine for 14 hours. LC/MS-MS will be used to analyze the samples and kinetic data of apo(a) and PCSK9 will be generated from a compartmental model. Tracer enrichment analysis could be complicated for proteins with low plasma concentrations as PCSK9. This issue will be solved with SPE and/or immune affinity concentration techniques. Non-parametrical test and multivariate analysis will be use to describe the relationship between these two variables.
This study will provide new knowledge on Lp(a) and PCSK9 metabolism and their interactions in humans.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Kinetic study of lipoprotein metabolism with stable isotope tracers.
| Arm | Type | Receives |
|---|---|---|
| Control group | Experimental | Other: infusion of tracer [5,5,5-2H3] -L-leucinePatients 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 |
| High-dose group | Experimental | Other: infusion of tracer [5,5,5-2H3] -L-leucinePatients 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| infusion of tracer [5,5,5-2H3] -L-leucineA 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. | Other | Control group, High-dose group |
Primary outcome
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.
Time frame: 14 hours after leucine infusion
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.
3 secondary outcomes
To evaluate the impact of PCSK9 metabolism on metabolic parameters of Lp (a).
Time frame: 14 hours after leucine infusion
To evaluate the impact of PCSK9 metabolism on metabolic parameters of Lp
Time frame: 14 hours after leucine infusion
To measure the impact of PCSK9 metabolism on metabolic parameters of Lp
Time frame: 14 hours after leucine infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing infusion of tracer [5,5,5-2H3] -L-leucine in people with Cholesterol; Metabolic Disorder and Lipoproteinemia, run by Nantes University Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 14 hours after leucine infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2022.