Overview

This trial is active, not recruiting.

Conditions cardiac allograft vasculopathy, antibody mediated rejection
Treatments optical coherence tomography, acetylcholine, brachial artery flow mediated dilation
Phase phase 1
Sponsor University of Pittsburgh
Start date September 2012
End date September 2014
Trial size 12 participants
Trial identifier NCT01848301, American Heart Association, PRO12060201

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose diagnostic
Arm
(Experimental)
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.
optical coherence tomography OCT
OCT imaging of the LAD coronary artery
acetylcholine Miochol
Infusion in the coronary artery to study endothelial function
brachial artery flow mediated dilation
Assess peripheral brachial artery endothelial function

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

Inclusion Criteria: - Subjects who are 1 year post heart transplantation - Subjects will include both male and females - Be at least 18 years of age Exclusion Criteria: - Known coronary artery disease after transplantation - Evidence of strong or moderate antibodies already present at the time of the transplant - Severe renal dysfunction defined as creatinine clearance of <30 or on hemodialysis. - 3 or more episodes of acute cellular rejection - Females who are pregnant - Patients requiring endomyocardial biopsy at the time of catheterization - Patients unable to tolerate heparin or systemic anticoagulation - History of multi-organ transplant - Patients unable to give consent

Additional Information

Official title Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation
Principal investigator Catalin Toma, MD
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by University of Pittsburgh.