PLIN1 Variants in Precocious ACS (SCAPLIN)

Acute Coronary Syndrome Clinical Trial

Official title:

Involvement of Perilipin-1 Variants in Precocious Acute Coronary Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04904432
• Other study ID #: 2021-06
• Status: Recruiting
• Phase: N/A
• Start date: September 15, 2021
• Est. completion date: June 1, 2024

Study information

• Verified date: October 2022
• Source: Assistance Publique Hopitaux De Marseille
• Contact: Nathalie BONELLO-PALOT
• Phone: 04 91 38 77 87
• Email: nathalie.bonello[@]ap-hm.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to identify a genetic predisposition factor of precocious acute coronary syndrome occurrence (ACS). ACS is a major public health problem and the first cause of mortality in the world. It can be due to several risk factor such as heredity. the investigators make the hypothesis that occurrence of early ACS (defined as <50yo for men and <55yo for women) could be the initiatory event of a mild form of genetic lipodystrophy . Our previous study shown an occurrence risk of ACS about 8.3 in patients carrying a mutation in the PLIN1 gene versus patients without a mutation. The PLIN1 gene encode for perilipin 1 protein localized on the lipid droplet surface. This protein phosphorylation activates the triglycerides lipolysis. Our goals in this study are multiple: to validate the high frequency of mutations in this gene in patients with early ACS, to determine differences in triglycerides metabolism and also relapse rate between carrier and non-carrier patients of mutation in PLIN1. Our first aim will be to carry out the inclusion of 200 patients with precocious ACS. This will allow us to obtain around 15 patients carrying a mutation in the PLIN1 gene based on our previous study. the investigators will reprogramme patients' cells (carrying or not a PLIN1 mutation) in human Induce Pluripotent Stem cells (hIPSc). These hIPSc will be differentiated in cell types of interest as adipocytes or macrophages. the investigators will then study triglycerides metabolism (lipid droplet formation, localization and phosphorylation of perlipin 1) in these cells and atheroma plaque formation. Finally, the investigators will study clinical data such as relapse rate and searching for correlation with PLIN1 mutation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 55 Years

Eligibility

Inclusion Criteria:

• Age of the patient when ACS occurs (between 18 and 50yo for men, between 18 and 55yo for women)

• Written informed consent

Exclusion Criteria:

• Men <18yo or >50yo

• Women <18yo or >55yo

• ACS causes (toxic, coronary dissection)

• Congenital cardiac malformations

• Familial hypercholesterolaemia

• Pregnancy, breast-feeding women or vulnerable profile.

• Patient refusal to participate or previously included in a clinical research trial.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Syndrome

Intervention

Genetic:
• PLIN1 gene sequencing
One supplementary blood sample will be taken (compare to classical ACS treatment and follow up) to realize genetic analyse of PLIN1 gene, looking for mutations

Locations

Country	Name	City	State
France	Assistance Publique Hôpitaux de Marseille	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PLIN1 mutation	sequencing PLIN1 gene to look for mutation	1 month
Primary	Lipid droplets	Analyze size of lipid droplets in differentiated hIPS cells	3 years
Secondary	relapse rate	Ischaemic relapse rate during the year of classical following-up	1 year