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Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation

This study has been terminated.
(loss of funding)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01848301
First Posted: May 7, 2013
Last Update Posted: September 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Catalin Toma, MD, University of Pittsburgh
May 2, 2013
May 7, 2013
September 6, 2017
September 2012
September 2014   (Final data collection date for primary outcome 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 ]
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: 2 years ]
Complete list of historical versions of study NCT01848301 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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: 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: 2 years ]
  • Gene expression of white blood cells by microRNA and how this relates to endothelial function and intimal thickness. [ Time Frame: 2 years ]
  • Plaque characterization in coronary artery by OCT [ Time Frame: 2 years ]
  • Natural progression of coronary allograft vasculopathy over first 2 years after transplantation [ Time Frame: 2 years ]
  • Comparison of endothelial function in the coronary artery with presence or absence of donor specific antibodies. [ Time Frame: 2 years ]
Not Provided
Not Provided
 
Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation
Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation

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.

Not Provided
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
  • Cardiac Allograft Vasculopathy
  • Antibody Mediated Rejection
  • Device: Optical Coherence Tomography
    OCT imaging of the LAD coronary artery
    Other Name: OCT
  • Drug: Acetylcholine
    Infusion in the coronary artery to study endothelial function
    Other Names:
    • Miochol
    • Miochol-e
  • Procedure: Brachial Artery Flow Mediated Dilation
    Assess peripheral brachial artery endothelial function
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.
Interventions:
  • Device: Optical Coherence Tomography
  • Drug: Acetylcholine
  • Procedure: Brachial Artery Flow Mediated Dilation
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
12
May 1, 2017
September 2014   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 80 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01848301
PRO12060201
American Heart Association ( Other Grant/Funding Number: 12CRP11550009 )
Yes
Not Provided
Not Provided
Catalin Toma, MD, University of Pittsburgh
Gladwin, Mark, MD
Not Provided
Principal Investigator: Catalin Toma, MD University of Pittsburgh
University of Pittsburgh
September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP