Endothelial Injury and Development of Coronary Intimal Thickening After Heart Transplantation

NCT ID: NCT01848301

Last Updated: 2017-09-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2017-05-01

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.

Conditions

Cardiac Allograft Vasculopathy; Antibody Mediated Rejection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Optical Coherence Tomography

Intervention Type: DEVICE

OCT imaging of the LAD coronary artery

Acetylcholine

Intervention Type: DRUG

Infusion in the coronary artery to study endothelial function

Brachial Artery Flow Mediated Dilation

Intervention Type: PROCEDURE

Assess peripheral brachial artery endothelial function

Interventions

Optical Coherence Tomography

OCT imaging of the LAD coronary artery

Intervention Type: DEVICE

Acetylcholine

Infusion in the coronary artery to study endothelial function

Intervention Type: DRUG

Brachial Artery Flow Mediated Dilation

Assess peripheral brachial artery endothelial function

Intervention Type: PROCEDURE

Other Intervention Names

OCT; Miochol; Miochol-e

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gladwin, Mark, MD

INDIV

Sponsor Role: lead

Responsible Party

Catalin Toma, MD

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Catalin Toma, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23499356 (View on PubMed)

Other Identifiers

American Heart Association

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

PRO12060201

Identifier Type: -

Identifier Source: org_study_id