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Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation

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ClinicalTrials.gov Identifier: NCT01848301
Recruitment Status : Terminated (loss of funding)
First Posted : May 7, 2013
Last Update Posted : September 6, 2017
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Cardiac Allograft Vasculopathy Antibody Mediated Rejection Device: Optical Coherence Tomography Drug: Acetylcholine Procedure: Brachial Artery Flow Mediated Dilation Phase 1

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation
Study Start Date : September 2012
Primary Completion Date : September 2014
Study Completion Date : May 1, 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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.
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

Outcome Measures

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. Plaque characterization in coronary artery by OCT [ Time Frame: baseline (year 1 post transplant) and annually for 2 years ]
  5. Natural progression of coronary allograft vasculopathy over first 2 years after transplantation [ Time Frame: baseline (year 1 post transplant) and annually for 2 years ]
  6. 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

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01848301

United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Gladwin, Mark, MD
Principal Investigator: Catalin Toma, MD University of Pittsburgh
More Information

Responsible Party: Catalin Toma, MD, Assistant Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01848301     History of Changes
Other Study ID Numbers: PRO12060201
American Heart Association ( Other Grant/Funding Number: 12CRP11550009 )
First Posted: May 7, 2013    Key Record Dates
Last Update Posted: September 6, 2017
Last Verified: September 2017

Keywords provided by Catalin Toma, MD, University of Pittsburgh:
Optical Coherence Tomography
Coronary Allograft Vasculopathy
Donor Specific Antibodies
Coronary endothelial function
Brachial Artery Flow Mediated Dilation
Heart transplantation

Additional relevant MeSH terms:
Vascular Diseases
Cardiovascular Diseases
Vasodilator Agents
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs