Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01848301
First received: May 2, 2013
Last updated: May 7, 2013
Last verified: May 2013
  Purpose

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Plaque characterization in coronary artery by OCT [ Time Frame: baseline (year 1 post transplant) and annually for 2 years ] [ Designated as safety issue: No ]
  • Natural progression of coronary allograft vasculopathy over first 2 years after transplantation [ Time Frame: baseline (year 1 post transplant) and annually for 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: September 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01848301

Contacts
Contact: Sameer J Khandhar, MD 4126470211 khandharsj@upmc.edu
Contact: Mary Catherine Coast 4126476992 coastmc@upmc.edu

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Sameer J Khandhar, MD University of Pittsburgh
  More Information

Publications:
Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01848301     History of Changes
Other Study ID Numbers: PRO12060201, American Heart Association
Study First Received: May 2, 2013
Last Updated: May 7, 2013
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Vascular Diseases
Wounds and Injuries
Cardiovascular Diseases
Acetylcholine
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014