Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation
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|ClinicalTrials.gov Identifier: NCT01848301|
Recruitment Status : Terminated (loss of funding)
First Posted : May 7, 2013
Last Update Posted : September 6, 2017
Coronary allograft vasculopathy (CAV) is the leading cause of late graft failure and second leading cause of late mortality after heart transplantation. CAV has been associated with a variety of traditional risk factors for atherosclerosis; however, immune mediated injury from development of de-novo donor-specific antibodies after transplantation also likely plays an important role. Similar to the progression of traditional atherosclerosis, it is likely that endothelial dysfunction is the precursor to the development of intimal thickening and CAV.
The investigators hypothesize that coronary allograft vasculopathy after heart transplantation as defined by progressive neointimal hyperplasia is preceded by endothelial dysfunction, which in turn is at least partly mediated by donor specific antibodies.
The investigators are proposing a prospective study in humans to test the above hypothesis and further mechanistically understand how CAV progresses. In this study the investigators will test for coronary endothelial function by infusing acetylcholine into the coronary artery and measure intimal hyperplasia by optical coherence tomography (OCT) and compare findings in patients with and without donor specific antibodies.
|Condition or disease||Intervention/treatment||Phase|
|Cardiac Allograft Vasculopathy Antibody Mediated Rejection||Device: Optical Coherence Tomography Drug: Acetylcholine Procedure: Brachial Artery Flow Mediated Dilation||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation|
|Study Start Date :||September 2012|
|Actual Primary Completion Date :||September 2014|
|Actual Study Completion Date :||May 1, 2017|
Experimental: Single arm
All subjects will undergo a Brachial Artery Flow Medicated Dilation prior to heart catheterization. After routine heart catheterization, images of their coronary artery will be recorded by Optical Coherence Tomography (OCT) during infusion of Acetylcholine.
Device: Optical Coherence Tomography
OCT imaging of the LAD coronary artery
Other Name: OCT
Infusion in the coronary artery to study endothelial function
Procedure: Brachial Artery Flow Mediated Dilation
Assess peripheral brachial artery endothelial function
- The primary endpoint will be a comparison of intimal thickness in the coronary artery by Optical Coherence Tomography with presence or absence of donor specific antibodies. [ Time Frame: baseline (year 1 post transplant) and annually for 2 years ]
- Assessment of epicardial coronary endothelial function by measuring change in vessel size in response to acetylcholine and how this compares to peripheral endothelial function. [ Time Frame: baseline (year 1 post transplant) and annually for 2 years ]
- Prospectively determine the association of HLA and non-HLA donor specific antibodies that activate complement with endothelial dysfunction and intimal thickening. [ Time Frame: baseline (year 1 post transplant) and annually for 2 years ]
- Gene expression of white blood cells by microRNA and how this relates to endothelial function and intimal thickness. [ Time Frame: baseline (year 1 post transplant) and annually for 2 years ]
- Plaque characterization in coronary artery by OCT [ Time Frame: baseline (year 1 post transplant) and annually for 2 years ]
- Natural progression of coronary allograft vasculopathy over first 2 years after transplantation [ Time Frame: baseline (year 1 post transplant) and annually for 2 years ]
- Comparison of endothelial function in the coronary artery with presence or absence of donor specific antibodies. [ Time Frame: baseline (year 1 post transplant) and annually for 2 years ]
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): NCT01848301
|United States, Pennsylvania|
|University of Pittsburgh Medical Center|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||Catalin Toma, MD||University of Pittsburgh|