KF2023#1-Trial: Influence of Statin Intake on Cellular Readouts

Pharmacodynamics Clinical Trial

Official title:

KF2023#1-Trial: Influence of Statin Intake on Cellular Readouts

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06469450
• Other study ID #: KF2023#1
• Status: Recruiting
• Phase: Phase 1
• Start date: April 20, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2024
• Source: Helsinki University Central Hospital
• Contact: Mikko Niemi, MD, PhD
• Phone: +35894711
• Email: mikko.niemi[@]hus.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

1. a signed written informed consent

2. age 18-40 years

3. healthy, and

4. 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.

5. Fully vaccinated against COVID-19.

Exclusion Criteria:

1. significant disease

2. smoking

3. SLCO1B1 poor function genotype

4. oral contraception or other continuous medication

5. pregnancy, planning of pregnancy or breastfeeding

6. participating in a clinical trial less than 3 months ago

7. donating blood less than 3 months ago

8. marked obesity

9. anticipated difficulties in drawing blood samples

10. weight less than 45 kg

11. BMI less than 18.5 kg/m2 or

12. inadequate Finnish language skills

Related Conditions & MeSH terms

• Pharmacodynamics

Intervention

Drug:
• Atorvastatin
one 40 mg atorvastatin tablet once daily for 28 days

Locations

Country	Name	City	State
Finland	Department of Clinical Pharmacology	Helsinki

Sponsors (2)

Lead Sponsor	Collaborator
Mikko Niemi	University of Helsinki

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline and once a week for 5 weeks
Secondary	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.	Baseline and once a week for 5 weeks
Secondary	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.	Baseline and once a week for 5 weeks
Secondary	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.	Once a week during the 4 week atorvastatin treatment