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Role of Exosomes Derived From Epicardial Fat in Atrial Fibrillation

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ClinicalTrials.gov Identifier: NCT03478410
Recruitment Status : Recruiting
First Posted : March 27, 2018
Last Update Posted : April 8, 2021
Sponsor:
Information provided by (Responsible Party):
Dr. Eilon Ram, Sheba Medical Center

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Atrial Fibrillation Procedure: Epicardial fat biopsy Not Applicable

Detailed 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Comparative study between patients with and without atrial fibrillation
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Role of Exosomes Derived From Epicardial Fat in Atrial Fibrillation
Actual Study Start Date : January 21, 2018
Estimated Primary Completion Date : January 21, 2022
Estimated Study Completion Date : January 21, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Atrial fibrillation
An epicardial fat biopsy will be taken from patients with chronic atrial fibrillation or paroxysmal atrial fibrillation who undergo any cardiac surgery
 Procedure: Epicardial fat biopsy
A 1 cm (~0.5 g) of epicardial pat biopsy from the area of the pulmonary artery
Control
An epicardial fat biopsy will be taken from patients without any history of atrial fibrillation who undergo any cardiac surgery
 Procedure: Epicardial fat biopsy
A 1 cm (~0.5 g) of epicardial pat biopsy from the area of the pulmonary artery


Outcome Measures
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Primary Outcome Measures :
  1. Exosomes quantity excreted from the epicardial fat (nm) [ Time Frame: 9 days ]

    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.



Secondary Outcome Measures :
  1. Inflammatory cytokines secretion from epicardial fat [ Time Frame: 9 days ]

    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.



Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03478410


Contacts
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Contact: Eilon Ram, MD 972-54-4929101 eilon.ram@sheba.health.gov.il
Contact: Dina Kogan 972-52-8646402 Diana.Kogan@sheba.health.gov.il

Locations
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Israel
Sheba medical center Recruiting
Ramat Gan, Israel, 52621
Contact: Diana Kogan    972-52-8646402    Diana.Kogan@sheba.health.gov.il   
Contact: Eilon ram, MD    972-54-4929101    eilon.ram@sheba.health.gov.il   
Sponsors and Collaborators
Sheba Medical Center
Investigators
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Principal Investigator: Eilon Ram, MD Sheba Medical Center
More Information
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Responsible Party: Dr. Eilon Ram, Resident in cardiac surgery, Principal Investigator, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT03478410    
Other Study ID Numbers: SHEBA-18-4516-ER-CTIL
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: April 8, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Results: The exosomes content in patients with and without atrial fibrillation

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr. Eilon Ram, Sheba Medical Center:
Epicardial fat
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes