Role of Exosomes Derived From Epicardial Fat in Atrial Fibrillation

Atrial Fibrillation Clinical Trial

Official title:

Role of Exosomes Derived From Epicardial Fat in Atrial Fibrillation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03478410
• Other study ID #: SHEBA-18-4516-ER-CTIL
• Status: Recruiting
• Phase: N/A
• Start date: January 21, 2018
• Est. completion date: January 21, 2022

Study information

• Verified date: April 2021
• Source: Sheba Medical Center
• Contact: Eilon Ram, MD
• Phone: 972-54-4929101
• Email: eilon.ram[@]sheba.health.gov.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Exosome plays an important role in the pathophysiology of the cardiovascular system. Since the field of cardiovascular exosome is still in its infancy, there are no available data regarding to its role in cardiac arrhythmias. The current study investigates the role of epicardial fat derived exosomes in patients who suffer from atrial fibrillation.

Description:

Myocardial cells communication is mediated via direct cell to cell contact, cell to matrix interaction, long-range signals, electrical signals, and via extracellular chemical molecules (such as proteins, nucleotides, lipids and short peptides). Cell to cell communication can be achieved through direct contact (i.e. Gap junction, cell surface protein/protein interaction) or via secreted signaling molecules (i.e. hormones, neurotransmitters, cytokines). In the last few decades, a third intercellular communication mechanism has gained intense attention

• extracellular vesicles that include: (1) apoptotic vesicles (1000-4000 nm), (2) microvesicles (100 nm - 1000 nm), and the smallest extracellular vesicles (3) exosomes (40-100 nm).

The exosomes are produced through the endosomal pathway and are able to carry cargo and transfer them to recipient cells, thus contributing to cell-to-cell communication. The exosomes cargo includes protein content, rRNA, tRNA, short DNA sequences, messenger RNA (mRNA) and microRNA (miRNA). The last two can change the gene expression within the target cells and by that affect myocardial cells.

Nowadays, it is known that in the cardiovascular system, exosome plays important roles in the pathophysiology of myocardial infarction (MI) and as an indicator for the damage and repair mechanisms post-acute MI (i.e. miR-126), in myocardial remodeling, and cardiac regeneration.

Since the field of cardiovascular exosome is still in its infancy, there are no available data regarding to its role in cardiac arrhythmias. Therefore, there is place to investigate the role of exosomes in patients who suffer from atrial fibrillation.

Some of the important issues to explore are: (1) Do the epicardial fat in patients with atrial fibrillation release quantitatively and qualitatively different exosomes than in patients without atrial fibrillation? (2) Can epicardial fat exosomes be a clinical biomarker for arrhythmias? (3) Can these exosomes be a target for the treatment and prevention of arrhythmias?

The current study will include patients who undergo any cardiac surgery and will give informed consent. An epicardial fat biopsy will be taken and cultured in a medium that contain M-199 medium, dexamethasone, gentamicin, and insulin for 9 days. The exosomes will be collected from the medium and analyzed.

The participants will be divided into two groups: (1) participants with atrial fibrillation, (2) participants who did not develop ever atrial fibrillation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: January 21, 2022
• Est. primary completion date: January 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Undergoing an elective cardiac surgery

Exclusion Criteria:

• Undergoing a non-elective surgery

• Suffering from severe renal impairment prior to surgery (creatinine clearance <30 mL/min)

• Experienced hepatic dysfunction other than mild

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Procedure:
• Epicardial fat biopsy
A 1 cm (~0.5 g) of epicardial pat biopsy from the area of the pulmonary artery

Locations

Country	Name	City	State
Israel	Sheba medical center	Ramat Gan

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exosomes quantity excreted from the epicardial fat (nm)	The differences in the quantity of exosomes derived epicardial fat in patients with and without atrial fibrillation.; The exosome isolation will be done by using ultra centrifuge for cells and cells debris removal.; Then the exosomes will examined by the Malvern NanoSight device both for particle size and concentration measurement.	9 days
Secondary	Inflammatory cytokines secretion from epicardial fat	The differences in the Inflammatory cytokines secreted from epicardial fat in patients with and without atrial fibrillation.; The investigators will detect the levels of cytokines and acute phase proteins such as IL1, IL2, IL6, IL8, IL10, IL12, CRP, VEGF, TNF-a, and TGF by Human Cytokine Array Kit.	9 days