KF2023#1-Trial: Influence of Statin Intake on Cellular Readouts
ConditionPharmacodynamics
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-40
SponsorMikko Niemi
About this trial
A majority of high-risk patients does not achieve their cholesterol target levels and most of these patients do not receive more effective combination therapy, which goes beyond statin monotherapy. Large interindividual differences in treatment outcomes have been observed for patients receiving statins. Statins block cholesterol synthesis and increase cellular low-density lipoprotein (LDL) uptake. Importantly, LDL uptake is highly divergent in individuals.The aim of this trial is to investigate how atorvastatin influences leukocyte readouts of LDL uptake and lipid storage in humans. The trial is a single-arm, open-label, interventional trial. A total of 15 healthy volunteers will receive 40 mg atorvastatin once a day for 4 weeks. The participants will provide blood samples before starting the atorvastatin intervention, each week when taking atorvastatin, and one week after the end of the intervention for the measurement of leukocyte readouts of LDL uptake and lipid storage.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
a signed written informed consent
age 18-40 years
healthy, and
Accepted results from laboratory tests (blood haemoglobin, basic blood count and blood platelets, alanine aminotransferase, alkaline phosphatase, glutamyl transferase, creatinine, plasma potassium and sodium). Negative pregnancy test result (serum human chorionic gonadotropin) for women.
Disqualifiers
significant disease
smoking
SLCO1B1 poor function genotype
oral contraception or other continuous medication
Trial design
Design model
Single group
Treatments tested in this trial
Atorvastatin
Drugone 40 mg atorvastatin tablet once daily for 28 days
Treatment groups
15 Participants
are divided into 1 treatment groupGroup A: AtorvastatinExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Lipid trafficking score LT-Mo
The primary outcome measurement is the "lipid trafficking score LT-Mo" is a combination of LDL uptake and lipid droplet quantifications in monocytes. The participants provide blood samples before starting the atorvastatin intervention, each week when taking atorvastatin (4 times in total), and one week after the end of the intervention.
Time frame
Baseline and once a week for 5 weeksSecondary outcomes
1
Leukocyte LDL uptake
Systematic quantification of leukocyte uptake of low-density lipoprotein (LDL). Leukocytes are exposed to fluorescently labelled LDL particles and internalized LDL particles are quantified with microscopy and automated image analysis. The specific readouts are overall fluorescent LDL intensity and the number of endosomal organelles filled with fluorescent LDL particles for monocyte and lymphocyte subpopulations.
Time frame
Baseline and once a week for 5 weeks2
Leukocyte lipid storage
A systematic semi-automated approach is used to quantify cellular lipid droplets, dedicated storage organelles for lipids. Individual lipid droplets, their size and area are quantified in each cell and either used as individual readouts or combined with LDL uptake readouts to derive lipid trafficking scores.
Time frame
Baseline and once a week for 5 weeks3
Atorvastatin plasma concentration
The plasma concentrations of atorvastatin and its metabolites will be quantified with liquid chromatography tandem mass spectrometry (LC-MS/MS) from plasma samples.
Time frame
Once a week during the 4 week atorvastatin treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Mikko Niemi
Lead sponsor
Helsinki University Central Hospital
Sponsor institution
University of Helsinki
Collaborator
Source ClinicalTrials.gov