Cardiovascular Disease Protection Tissue

Myocardial Ischemia Clinical Trial

Official title:

Effects of ACE2/Ang-(1-7) on Cardiac Progenitor Cells From Heart Failure Patients and Explant Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02348515
• Other study ID #: IRB201300122-N
• Secondary ID: R01HL056921
• Status: Completed
• Start date: June 2013
• Est. completion date: September 28, 2018

Study information

• Verified date: November 2018
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Recent evidence of a potential role for cardiac progenitor cells (CPCs) in cardiac repair and the discovery of a vasoprotective axis of the renin-angiotensin system (RAS) offer such breakthroughs. Investigators have observed that an imbalance in the vasoprotective axis {angiotensin converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor} and the vasodeleterious axis [angiotensin converting enzyme (ACE)/angiotensin II (AngII)/AngII type 1 receptor (AT1R)] of the RAS within the CPCs affects their functionality and regenerative potential. Investigators believe that restoring the balance between these two axes of the RAS is essential to improve CPC function and enhance their reparative capabilities. These observations have led to the hypothesis that genetic modification of CPCs by overexpression of ACE2/Ang-(1-7) will enhance their reparative function and improve their potential to attenuate myocardial ischemia-induced cardiac damage.

Description:

As a participant undergoes a clinically indicated heart transplant, or a left ventricular assist device (LVAD) implantation, or a right heart biopsy, or atrial fibrillation surgery, or right atria cannulation, the following tissue samples will be collected:

In the subjects undergoing orthotopic heart transplant (n=20), failed myocardial tissue samples will be collected from the diseased heart.

For subjects undergoing left ventricular assist device implantation (n=60), small samples will be collected from the apex core (that would be routinely discarded at the time of the implantation procedure).

For heart transplant subjects undergoing clinically indicated right heart biopsy (n=20), the collection of multiple samples including, excess myocardial biopsy samples that will not be utilized by pathology.

For subjects undergoing any heart surgery (n=80), the collection of left atrial appendages that are routinely removed to prevent thrombosis during atrial fibrillation surgery and a piece of the right atria will be cut in order to implant the cannula.

In addition, a collection of 20ml (about one tablespoon) of blood will be taken from all subjects to analyze progenitor/inflammatory cells and inflammation cytokines and pertinent medical history.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: September 28, 2018
• Est. primary completion date: September 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• heart transplant surgery

• left ventricular assist device implantation

• heart surgery required for atrial fibrillation and right atria cannulation

Exclusion Criteria:

• We are collecting discarded tissues following surgery. There is no exclusion criteria for this study.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Ischemia
• Myocardial Ischemia

Intervention

Procedure:
• Heart failure or coronary disease
Small samples collected from the apex core in the heart. In addition, blood samples will be taken.
• Heart transplant patients
Heart samples collected including, excess myocardial biopsy samples. In addition, blood samples will be taken.
• Orthotopic Heart Transplant Patients
Myocardial tissue samples collected from the diseased heart. In addition, blood samples will be taken.
• Heart Surgery Patients
Heart samples will be collected from the left atrial appendages. In addition, blood samples will be taken.
• Blood Draw
All subjects will have 20 ml of blood drawn for further analysis.

Locations

Country	Name	City	State
United States	Yanfei Qi	Gainesville	Florida

Sponsors (3)

Lead Sponsor	Collaborator
University of Florida	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Imbalance of vasoprotective and vasodeleterious axes of the renin angiotensin system (RAS) is associated with dysfunction of CPC isolated from diseased tissue	CPCs will be isolated from the collected heart tissue. Function assay such as proliferation, migration, reactive oxygen species (ROS) level will be analyzed. Renin-angiotensin system (RAS) genes and inflammatory cytokines will be quantifies using polymerase chain reaction (PCR) and protein assay to investigate if the cell dysfunction is associated with the imbalance of vasoprotective and vasodeleterious axes of the RAS.	two years
Secondary	Screening for biomarkers related to clinic outcome in the blood	Progenitor/inflammatory cells, inflammatory cytokines, and growth factors will be measured to determine if they are associated with heart diseases.	two years