Clinical trial NCT01848301: Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation
Official title: Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cardiac Allograft Vasculopathy
Antibody Mediated Rejection
Keywords: Optical Coherence Tomography
OCT
Coronary Allograft Vasculopathy
Donor Specific Antibodies
Acetylcholine
Coronary endothelial function
Brachial Artery Flow Mediated Dilation
Heart transplantation
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2013-05-07
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.


Eligibility criteria: 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

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.
timeFrame: 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.
timeFrame: baseline (year 1 post transplant) and annually for 2 years
measure: Prospectively determine the association of HLA and non-HLA donor specific antibodies that activate complement with endothelial dysfunction and intimal thickening.
timeFrame: baseline (year 1 post transplant) and annually for 2 years
measure: Gene expression of white blood cells by microRNA and how this relates to endothelial function and intimal thickness.
timeFrame: baseline (year 1 post transplant) and annually for 2 years
measure: Plaque characterization in coronary artery by OCT
timeFrame: baseline (year 1 post transplant) and annually for 2 years
measure: Natural progression of coronary allograft vasculopathy over first 2 years after transplantation
timeFrame: baseline (year 1 post transplant) and annually for 2 years
measure: Comparison of endothelial function in the coronary artery with presence or absence of donor specific antibodies.
timeFrame: baseline (year 1 post transplant) and annually for 2 years
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Catalin Toma, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Khandhar SJ, Yamamoto H, Teuteberg JJ, Shullo MA, Bezerra HG, Costa MA, Selzer F, Lee JS, Marroquin OC, McNamara DM, Mulukutla SR, Toma C. Optical coherence tomography for characterization of cardiac allograft vasculopathy after heart transplantation (OCTCAV study). J Heart Lung Transplant. 2013 Jun;32(6):596-602. doi: 10.1016/j.healun.2013.02.005. Epub 2013 Mar 15.