Ignite Creation Date:
2024-05-05 @ 11:26 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00042614
Status:
COMPLETED
Last Update Posted:
2024-06-10
First Post:
2002-08-01
Brief Title:
Study of Heart Transplant Rejection
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Acute Cardiac Allograft Cellular Rejection and Cardiac Allograft Vasculopathy Identification of Diagnostic Biomarkers and Target Pathways for Preventive Therapy
Status:
COMPLETED
Status Verified Date:
2024-02-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
Detailed Description:
Cardiac transplantation has been successful in improving survival in end stage heart failure But graft rejection has limited survival after transplantation In the first year acute cellular rejection and infection remain the most common causes of morbidity and mortality Afterwards cardiac allograft vasculopathy CAV as a result of chronic vascular rejection is the major cause of morbidity and mortality Within the first year post-transplantation almost two-thirds of recipients will experience at least one rejection episode At five years post-transplantation nearly 50 of survivors will have CAV Clinically the symptoms of acute rejection are relatively nonspecific fatigue dyspnea fever Most CAV patients remain asymptomatic until they develop serious problems such as myocardial infarction heart failure ventricular dysrhythmias or sudden cardiac death Presently the gold standard for diagnosing acute cardiac allograft rejection is right ventricular endomyocardial biopsy This is an invasive method of diagnosis subject to morbidity and random sampling and interpretation error Likewise the gold standard for diagnosing CAV is cardiac catheterization with intravascular ultrasound an invasive procedure also subject to morbidity Noninvasive methods such as electrocardiography echocardiography and nuclear studies all have been studied but have been unsuccessful thus far for either condition Peripheral blood evaluations of cytokines and cytoimmunologic markers have also been unsuccessful in either condition This clinical trial studies the feasibility of using functional genomics and proteomics to identify genes and proteins respectively that can serve as reliable biomarkers of acute cardiac cellular rejection and CAV We plan to recruit subjects who are on the transplant waiting list We will analyze the blood of these patients pre-transplant and serially post-transplant over one year and then regularly on a yearly basis By correlating putative biomarkers with clinical histological and imaging based evidence of allograft disease we hope to build a database comprised of functional genomics cytokine cytoimmunologic and proteomics data relevant to the immunologic relationship between the donor organ and recipient With this database we hope to obtain a minimal subset of differentially expressed genes cytokines cytoimmunologic and protein change profiles that is most predictive of both acute allograft rejection and CAV This will eventually serve as the basis for a diagnostic blood test Thus with the application of functional genomics cytokine and cytoimmunologic analysis and proteomics we hope to derive a noninvasive method to detect both acute cellular cardiac allograft rejection and CAV thereby minimizing the need for invasive methods of diagnosis Further better understanding the genetic programs triggered and protein changes induced during rejection may lead to the identification of target pathways for developing new therapeutic approaches aimed at prevention
Recently several published reports have established that detection of donor DNA in recipient s blood can serve as a diagnostic tool of graft injury The level of donor DNA measured as percentage of circulating cell-free donor DNA ccfdDNA accurately diagnoses acute rejection with a high sensitivity and specificity at times several months before the diagnosis by examining endomyocardial biopsies The ability of cell free DNA to diagnose graft injury early opens a new window to re-examine markers of rejection These markers are traditionally evaluated using biopsy results often positive late during rejection ccfdDNA offers an opportunity to better characterize our analyses
Recently several published reports have established that detection of donor DNA in recipient s blood can serve as a diagnostic tool of graft injury The level of donor DNA measured as percentage of circulating cell-free donor DNA ccfdDNA accurately diagnoses acute rejection with a high sensitivity and specificity at times several months before the diagnosis by examining endomyocardial biopsies The ability of cell free DNA to diagnose graft injury early opens a new window to re-examine markers of rejection These markers are traditionally evaluated using biopsy results often positive late during rejection ccfdDNA offers an opportunity to better characterize our analyses
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-CC-0266 | None | None | None |