Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation
Information source: University of Pittsburgh
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cardiac Allograft Vasculopathy; Antibody Mediated Rejection
Intervention: Optical Coherence Tomography (Device); Acetylcholine (Drug); Brachial Artery Flow Mediated Dilation (Procedure)
Phase: Phase 1
Status: Recruiting
Sponsored by: University of Pittsburgh Official(s) and/or principal investigator(s): Sameer J Khandhar, MD, Principal Investigator, Affiliation: University of Pittsburgh
Overall contact: Sameer J Khandhar, MD, Phone: 4126470211, Email: khandharsj@upmc.edu
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.
Clinical Details
Official title: Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation
Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Primary outcome: 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.
Secondary outcome: Assessment of epicardial coronary endothelial function by measuring change in vessel size in response to acetylcholine and how this compares to peripheral endothelial function.Prospectively determine the association of HLA and non-HLA donor specific antibodies that activate complement with endothelial dysfunction and intimal thickening. Gene expression of white blood cells by microRNA and how this relates to endothelial function and intimal thickness. Plaque characterization in coronary artery by OCT Natural progression of coronary allograft vasculopathy over first 2 years after transplantation Comparison of endothelial function in the coronary artery with presence or absence of donor specific antibodies.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
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
Locations and Contacts
Sameer J Khandhar, MD, Phone: 4126470211, Email: khandharsj@upmc.edu
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, United States; Recruiting
Additional Information
Related publications: 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.
Starting date: September 2012
Last updated: May 7, 2013
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