Atrial FibrillationNCT03478410
Role of Exosomes Derived From Epicardial Fat in Atrial Fibrillation
A study testing Epicardial fat biopsy in people with Atrial Fibrillation, run by Sheba Medical Center at 1 site in Israel.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Epicardial fat biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteIsrael
- Study dates
- 21 Jan 2018to 21 Jan 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Undergoing an elective cardiac surgery
Who cannot join
- Undergoing a non-elective surgery
- Suffering from severe renal impairment prior to surgery (creatinine clearance <30 mL/min)
- Experienced hepatic dysfunction other than mild
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Sheba medical center
Ramat Gan, 52621
Diana Kogan, 972-52-8646402, Diana.Kogan@sheba.health.gov.il
Eilon ram, MD, 972-54-4929101, eilon.ram@sheba.health.gov.il
About this study
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.
Read the 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.
- Conditions
- Atrial Fibrillation
- Being tested
- Epicardial fat biopsy
- Keywords
- Epicardial fat
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epicardial fat biopsyProcedure or surgery
A 1 cm (~0.5 g) of epicardial pat biopsy from the area of the pulmonary artery
| Study group | Role | What they receive |
|---|---|---|
| Atrial fibrillation | Other | An epicardial fat biopsy will be taken from patients with chronic atrial fibrillation or paroxysmal atrial fibrillation who undergo any cardiac surgery Receives: Procedure: Epicardial fat biopsy |
| Control | Other | An epicardial fat biopsy will be taken from patients without any history of atrial fibrillation who undergo any cardiac surgery Receives: Procedure: Epicardial fat biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 9 days
Secondary outcomes (1)
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.
Measured: 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2018
- Study start21 Jan 2018
- Primary completion21 Jan 2022 (estimated)
- Study completion21 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Comparative study between patients with and without atrial fibrillation
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Dr. Eilon Ram, Sheba Medical Center
- Investigators
- Eilon Ram, MD, Principal investigator, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03478410
- Sponsor's protocol ID
- SHEBA-18-4516-ER-CTIL
- Status last verified
- Apr 2021
- First submitted
- 20 Mar 2018
- Last updated
- 8 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Results: The exosomes content in patients with and without atrial fibrillation
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Exosomes Derived From Epicardial Fat in Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT03478410
- Acronym / sponsor ID
- SHEBA-18-4516-ER-CTIL
- Conditions
- Atrial Fibrillation
- Keywords
- Epicardial fat
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 21 Jan 2018 (actual)
- Primary completion
- 21 Jan 2022 (estimated)
- Study completion
- 21 Jan 2022 (estimated)
- First posted
- 27 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Comparative study between patients with and without atrial fibrillation
| Arm | Type | Receives |
|---|---|---|
| Atrial fibrillation | Other | Procedure: Epicardial fat biopsyAn epicardial fat biopsy will be taken from patients with chronic atrial fibrillation or paroxysmal atrial fibrillation who undergo any cardiac surgery |
| Control | Other | Procedure: Epicardial fat biopsyAn epicardial fat biopsy will be taken from patients without any history of atrial fibrillation who undergo any cardiac surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age ≥ 18 years
- Undergoing an elective cardiac surgery
Key exclusion criteria (3 listed)
- Undergoing a non-elective surgery
- Suffering from severe renal impairment prior to surgery (creatinine clearance <30 mL/min)
- Experienced hepatic dysfunction other than mild
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Epicardial fat biopsyA 1 cm (~0.5 g) of epicardial pat biopsy from the area of the pulmonary artery | Procedure or surgery | Atrial fibrillation, Control |
Primary outcome
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.
1 secondary outcome
Inflammatory cytokines secretion from epicardial fat
Time frame: 9 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2021.
- Individual participant dataSharing planned: Undecided. Results: The exosomes content in patients with and without atrial fibrillation
Related trials for Atrial Fibrillation
Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eilon Ram, MD principal investigator
Sheba Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Epicardial fat biopsy in people with Atrial Fibrillation, run by Sheba Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eilon Ram, MD (972-54-4929101, eilon.ram@sheba.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Exosomes quantity excreted from the epicardial fat (nm) (time frame: 9 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2021.