Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation

Cardiac Allograft Vasculopathy Clinical Trial

Official title:

Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01848301
• Other study ID #: PRO12060201
• Secondary ID: American Heart A
• Status: Terminated
• Phase: Phase 1
• First received: May 2, 2013
• Last updated: September 1, 2017
• Start date: September 2012
• Est. completion date: May 1, 2017

Study information

• Verified date: September 2017
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: May 1, 2017
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Antibody Mediated Rejection
• Cardiac Allograft Vasculopathy
• Vascular Diseases

Intervention

Device:
• Optical Coherence Tomography
OCT imaging of the LAD coronary artery

Drug:
• Acetylcholine
Infusion in the coronary artery to study endothelial function

Procedure:
• Brachial Artery Flow Mediated Dilation
Assess peripheral brachial artery endothelial function

Locations

Country	Name	City	State
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Gladwin, Mark, MD

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		baseline (year 1 post transplant) and annually for 2 years
Secondary	Assessment of epicardial coronary endothelial function by measuring change in vessel size in response to acetylcholine and how this compares to peripheral endothelial function.		baseline (year 1 post transplant) and annually for 2 years
Secondary	Prospectively determine the association of HLA and non-HLA donor specific antibodies that activate complement with endothelial dysfunction and intimal thickening.		baseline (year 1 post transplant) and annually for 2 years
Secondary	Gene expression of white blood cells by microRNA and how this relates to endothelial function and intimal thickness.		baseline (year 1 post transplant) and annually for 2 years
Secondary	Plaque characterization in coronary artery by OCT		baseline (year 1 post transplant) and annually for 2 years
Secondary	Natural progression of coronary allograft vasculopathy over first 2 years after transplantation		baseline (year 1 post transplant) and annually for 2 years
Secondary	Comparison of endothelial function in the coronary artery with presence or absence of donor specific antibodies.		baseline (year 1 post transplant) and annually for 2 years