Protocol Number: 02-CC-0266

Title:

Acute Cardiac Allograft Cellular Rejection and Cardiac Allograft Vasculopathy: Identification of Diagnostic Biomarkers and Target Pathways for Preventive Therapy

Number:

02-CC-0266

Summary:

This study will investigate the causes of acute and chronic rejection of transplanted hearts. To find better ways to detect, treat and possibly prevent heart transplant rejection, more information about the cause is needed. Acute and chronic heart transplant rejection may be caused by certain substances the body produces in response to the new heart. This study will try to find a blood or urine test that detects genes and proteins that can serve as markers of rejection. Such a test may lead to earlier detection and improved treatment.

Patients 18 years and above who are on a wait list for heart transplant at a UNOS-approved heart transplant center, whose institutional review board has approved this protocol, may be eligible for this study. Healthy volunteers will also be included in the study to establish a database of normal values for comparison with patients undergoing heart transplant. In addition, patients who have had a heart transplant within the past 1 to 5 years will be enrolled in a pilot study. Normal volunteers will be screened for participation with an electrocardiogram (EKG) and echocardiogram, non-invasive tests to evaluate heart function.

Participants will undergo the following procedures:

- Review of medical records - Patients who have had a heart transplant and those on a wait list to receive a heart will have their medical records reviewed to collect information on their condition.

- Blood samples - 60 cc (about 3 tablespoons) of blood will be collected from all participants by needle stick in a vein. The sample will be analyzed for genes and proteins that might predict heart rejection. In addition, many genes in blood cells and cells lining blood vessels that are unrelated to heart transplant rejection and whose functions or significance are unknown will also be examined for ideas for future research. Patients enrolled while on a wait list will, after transplantation, have an additional 44 cc (about 2 tablespoons) of blood collected at each heart biopsy and rejection episode during the first year of transplant, and 60 cc collected with each yearly biopsy for the next 9 years.

- Urine samples - Between 100 and 300 cc (3 to 10 ounces) of urine may be collected from all participants to confirm blood test results

Sponsoring Institute:

National Institutes of Health Clinical Center (CC)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA - for Transplant Patients:

Adult heart transplant center generally accepts patients within the physiologic age range of 12 to 65 years old, however, for our study heart transplant patients must be 18 years of age or above.

Indication for cardiac transplantation as outlined by the 24th Bethesda Conference on Cardiac Transplantation. These are as follows:

-Peak VO(2) less than 10 ml/kg per minute or less than 50% of maximal predicted VO(2) with achievement of anaerobic metabolism.

-Severe cardiac ischemia consistently limiting routine activity not amenable to surgical or percutaneous revascularization.

-Recurrent symptomatic ventricular arrhythmias refractory to all accepted therapeutic modalities.

EXCLUSION CRITERIA - for Transplant Patients:

Adult heart transplant centers exclude infants, toddlers, and children with a physiologic age less than 12, and adults with advanced physiologic age (less than 65), however, for our study we will exclude heart transplant patients less than 18 years of age.

The final decision to exclude a candidate from cardiac transplantation will be made by the hospital's heart transplant committee. The committee uses, as a guideline, the criteria outlined in the 24th Bethesda conference.

INCLUSION CRITERIA - for Control Subjects:

Any healthy normal man or women who is the appropriate age and gender for matching to a transplant patient.

EXCLUSION CRITERIA - For Control Subjects:

EKG with evidence of clinically relevant heart disease.

Echocardiogram with evidence of clinically relevant heart disease.

Any disease process that is not well controlled by medications.

Total tobacco use for greater than one month over the last 10 years.

Symptoms of coronary or cardiac insufficiency.

More than one major risk factor for coronary artery disease excluding gender or age.

Confirmed intrauterine pregnancy in women.

Special Instructions:

Currently Not Provided

Keywords:

Genes

Heart

Lymphocytes

Proteomics

Transplant

Recruitment Keyword(s):

Heart Transplant

Healthy Volunteer

HV

Normal Control

Condition(s):

Heart Transplantation

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

Warren G. Magnuson Clinical Center

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Kirklin JK, Naftel DC, McGiffin DC, McVay RF, Blackstone EH, Karp RB Analysis of morbid events and risk factors for death after cardiactransplantation J Am Coll Cardiol 1988 May;11(5):917-24 PMID: 3281995

Adv Cardiol 1988;36:278-92 Risk factors for death and related events after cardiac transplantationKirklin JK, Naftel DC, Kirklin JW, Blackstone EH Department of Surgery, University of Alabama, Birmingham School of Medicine PMID: 307110

Transplant Proc 1981 Mar;13(1 Pt 1):207-11 Complications in long-term survivors of cardiac transplantation Bieber CP, Hunt SA, Schwinn DA, Jamieson SA, Reitz BA, Oyer PE, Shumway NE, Stinson EB PMID: 7022823

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

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