Cardiovascular DiseaseDTRTNCT02109575
Quantitative Detection of Circulating Donor-Specific DNA in Organ Transplant Recipients (DTRT-Multi-Center Study)
An observational study of Cardiovascular Disease and Acute Rejection of Cardiac Transplant, run by Medical College of Wisconsin at 8 sites in United States.
Trial summary
The primary goal of this Multicenter Study is to develop and to evaluate a method for measuring donor-specific cell free DNA in blood samples from transplant recipients as markers of rejection. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Cardiovascular Disease, Acute Rejection of Cardiac Transplant, Cardiac Transplant Rejection
- What is being tested?
- Blood Draw of up to 10 ml
- How many people
- 540 participants
- Where
- 8 sitesUnited States
- Study dates
- 1 Mar 2014to 30 Mar 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Study population will include people of any age who have undergone heart transplant or who are "listed" to undergo heart transplant.
Who may be able to join
- Any patient who is "listed" to undergo or has in the past undergone heart transplantation.
Who cannot join
- Any patient who is not currently listed to undergo heart transplantation or has not previously received a heart transplant;
- Any patient who is not anticipated to be available for follow-up of at least 1 year;
- Any patient who is unable or unwilling to provide documented informed consent for self or through a legally authorized representative.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Emory University
Atlanta, Georgia, 30322
Ann & Robert H. Lurie Children's Hospital Chicago
Chicago, Illinois, 60611
Duke University
Durham, North Carolina, 27711
Arkansas Children's Hosoptial Research Institute
Little Rock, Arkansas, 72202
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Froedtert Hospital
Milwaukee, Wisconsin, 53226
Vanderbilt University
Nashville, Tennessee, 37212
Columbia University
New York, New York, 10032
About this study
The primary goal of this Multicenter Study is to develop and to evaluate a method for measuring donor-specific cell free DNA in blood samples from transplant recipients as markers of rejection. Blood samples obtained periodically from heart transplant recipients are assessed for cell free DNA relative to clinical data in order to determine whether changes in the level of cell free DNA indicate rejection.
This research study proposes testing a blood sample obtained from the heart transplant recipient. The research seeks to establish whether this blood test will show when the patient is beginning to or already rejecting the transplanted heart.
Read more
BACKGROUND Identifying if a transplant patient is beginning to or already rejecting the heart is necessary, so that appropriate treatment can be started to halt the rejection. Heart catheterization with biopsy is the usual method used for assessing whether a patient may be rejecting the heart. There are also a number of other methods that transplant physicians will use to look for signs of rejection including other blood tests, echocardiograms, obtaining pressure readings during heart catheterization, and micro-array testing of blood obtained during biopsy. These technologies are limited in ability to consistently and accurately identify the presence of rejection.
The usual method of checking for rejection involves obtaining a sample of the heart tissue (heart biopsy); biopsy can only be accomplished through heart catheterization which is an invasive procedure that has risks associated with disturbing the heart such as puncturing the heart or causing the heart rate to change or damaging tissue in the heart. Overtime, repeating this invasive procedure can diminish the ease of the procedure because the veins can become scarred and more difficult to access. For these reasons, researchers believe that it would be good to have a blood test that gives information about the possibility of rejection so that it may not be necessary to do as many heart biopsies. Also, a blood test may be able to provide information about the heart or about rejection that is currently not available at all.
Read the detailed description
Early detection of rejection is a major focus of organ transplant care. The use of aggressive immunosuppressive therapy has been shown to alter the prognosis of heart transplant patients who have acute rejection1. There are many modalities utilized in the routine surveillance of heart transplant patients, each with limitations. Screening transthoracic echocardiography focusing on indices of systolic and diastolic dysfunction, along with regional wall abnormalities, has been shown to have poor sensitivity and does not effectively discriminate between patients with and without rejection. Newer echocardiographic parameters including myocardial performance or diastolic velocity indices may be a better means of detecting subtle changes in cardiac function in the setting of heart transplant, but these tools are most helpful after the insult caused by rejection has already occurred. Hemodynamic changes measured during heart catheterization have also been evaluated as a means of detecting rejection. Rosenthal et al found that although there were statistically significant differences between patients with higher or lower grades of rejection scores, heart catheterization did not permit effective discrimination of patients with moderate to severe rejection. Heart biomarkers, including c-reactive protein, brain natriuretic peptides, and troponin, have been studied as non-invasive measures of determining heart dysfunction or rejection. These surrogates are weakly associated with different rejection grades on biopsy and have a poor predictive capacity for biopsy-detected rejection3. Recently, microarray technology has been used to screen for genes expressed in heart allograft rejection using peripheral leukocytes from blood samples obtained at the time of endomyocardial biopsy. This technique was shown to have a high negative predictive value for the diagnosis of acute cellular rejection but it is unable to detect low grades of rejection4. Overall, these technologies are limited in the ability to consistently and accurately predict the presence of rejection and have low positive predictive values when compared to biopsy.
The current gold standard in detection of rejection is the use of endomyocardial biopsy. Attaining these samples is invasive and long term repeated central venous access can be difficult. Risk of endomyocardial biopsy includes perforation leading to cardiac tamponade, arrhythmias including atrial fibrillation, pneumothorax, hemothorax, and valvular regurgitation secondary to rupture of chordae or damage to valve leaflets themselves. There is variability in pathological interpretation of histologic grades, especially at higher grades of rejection due to the difficulty in interpretation of nodular infiltrates. The 2005 revised ISHLT grading system has simplified the grading system of cellular rejection and now includes assessment of antibody mediated rejection. This may improve the utility of endomyocardial biopsy, but much controversy still exists on the method of grading rejection and its clinical implications. Thus, the development of a noninvasive, relatively inexpensive method that accurately predicts the presence of rejection is critical.
- Conditions
- Cardiovascular Disease, Acute Rejection of Cardiac Transplant, Cardiac Transplant Rejection, Heart Transplant Failure and Rejection
- Being tested
- Blood Draw of up to 10 ml
- Keywords
- Acute Rejection, Cardiac Biomarkers, Cardiac Catheterization, Cardiomyopathy, Cell-Free DNA, Congenital Heart Defect, Congenital Heart Disease, Coronary Angiogram, Donor Specific DNA, Donor Specific Cell-Free DNA, Endomyocardial Biopsy, Heart Failure, Heart Transplant Failure, Heart Transplant, Heart Transplant Rejection
- Medical subject headings
- Cardiovascular Diseases, Rejection, Psychology, Cardiomyopathies, Heart Defects, Congenital, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood Draw of up to 10 mlDiagnostic test
In a laboratory setting, the blood will be spun for plasma and buffy coat, DNA will be extracted for processing using the diagnostic test. The results of the test are not provided back to the clinical setting.
| Study group | Role | What they receive |
|---|---|---|
| Heart Transplant Recipients | Up to 10 cc of blood will be drawn from heart transplant recipients at various time points prior to and after transplant. Blood draw is the only research activity that study participants will undergo. In addition to blood draw, data will be collected from clinical records representing the participant's transplant course such as the medical record, imaging, and biopsy slides with pathology reports. Receives: Diagnostic Test: Blood Draw of up to 10 ml |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assay and laboratory protocol development and optimization.
To develop and optimize an assay and protocol to detect donor-specific cell free DNA from recipient plasma.
Measured: Year 1-5
Secondary outcomes (1)
Biomarker Development
To determine the threshold of elevation of circulating donor specific cell free DNA (cfDNA)
Measured: Year 1-3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2014 (estimated)
- Study start1 Mar 2014
- Primary completion30 Mar 2020
- Study completion30 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 540 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Columbia University, Duke University, Arkansas Children's Hospital Research Institute, Emory University, Children's Healthcare of Atlanta, Vanderbilt University, TAI Diagnostics, Inc., Ann & Robert H Lurie Children's Hospital of Chicago, Children's Hospital and Health System Foundation, Wisconsin, University of California, Los Angeles, Children's Hospital Medical Center, Cincinnati, Phoenix Children's Hospital, The Cleveland Clinic
- Responsible party
- Principal investigator, Michael Mitchell, Medical College of Wisconsin
- Investigators
- Michael Mitchell, MD, Principal investigator, Medical College of WisconsinAoy Tomita-Mitchell, PhD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02109575
- Sponsor's protocol ID
- CHW 10/83
- Other IDs
- R01HL119747
- Acronym
- DTRT
- Status last verified
- Mar 2021
- First submitted
- 10 Feb 2014
- Last updated
- 26 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantitative Detection of Circulating Donor-Specific DNA in Organ Transplant Recipients (DTRT-Multi-Center Study)
- ClinicalTrials.gov ID
- NCT02109575
- Acronym / sponsor ID
- DTRT / CHW 10/83
- Conditions
- Cardiovascular Disease, Acute Rejection of Cardiac Transplant, Cardiac Transplant Rejection, Heart Transplant Failure and Rejection
- Keywords
- Acute Rejection, Cardiac Biomarkers, Cardiac Catheterization, Cardiomyopathy, Cell-Free DNA, Congenital Heart Defect, Congenital Heart Disease, Coronary Angiogram
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 540 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Columbia University, Duke University, Arkansas Children's Hospital Research Institute, Emory University, Children's Healthcare of Atlanta, Vanderbilt University, TAI Diagnostics, Inc., Ann & Robert H Lurie Children's Hospital of Chicago, Children's Hospital and Health System Foundation, Wisconsin, University of California, Los Angeles, Children's Hospital Medical Center, Cincinnati, Phoenix Children's Hospital, The Cleveland Clinic
- Study start
- 1 Mar 2014 (actual)
- Primary completion
- 30 Mar 2020 (actual)
- Study completion
- 30 Mar 2020 (actual)
- First posted
- 10 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary goal of this Multicenter Study is to develop and to evaluate a method for measuring donor-specific cell free DNA in blood samples from transplant recipients as markers of rejection. Blood samples obtained periodically from heart transplant recipients are assessed for cell free DNA relative to clinical data in order to determine whether changes in the level of cell free DNA indicate rejection.
This research study proposes testing a blood sample obtained from the heart transplant recipient. The research seeks to establish whether this blood test will show when the patient is beginning to or already rejecting the transplanted heart.
BACKGROUND Identifying if a transplant patient is beginning to or already rejecting the heart is necessary, so that appropriate treatment can be started to halt the rejection. Heart catheterization with biopsy is the usual method used for assessing whether a patient may be rejecting the heart. There are also a number of other methods that transplant physicians will use to look for signs of rejection including other blood tests, echocardiograms, obtaining pressure readings during heart catheterization, and micro-array testing of blood obtained during biopsy. These technologies are limited in ability to consistently and accurately identify the presence of rejection.
The usual method of checking for rejection involves obtaining a sample of the heart tissue (heart biopsy); biopsy can only be accomplished through heart catheterization which is an invasive procedure that has risks associated with disturbing the heart such as puncturing the heart or causing the heart rate to change or damaging tissue in the heart. Overtime, repeating this invasive procedure can diminish the ease of the procedure because the veins can become scarred and more difficult to access. For these reasons, researchers believe that it would be good to have a blood test that gives information about the possibility of rejection so that it may not be necessary to do as many heart biopsies. Also, a blood test may be able to provide information about the heart or about rejection that is currently not available at all.
Detailed description
Early detection of rejection is a major focus of organ transplant care. The use of aggressive immunosuppressive therapy has been shown to alter the prognosis of heart transplant patients who have acute rejection1. There are many modalities utilized in the routine surveillance of heart transplant patients, each with limitations. Screening transthoracic echocardiography focusing on indices of systolic and diastolic dysfunction, along with regional wall abnormalities, has been shown to have poor sensitivity and does not effectively discriminate between patients with and without rejection. Newer echocardiographic parameters including myocardial performance or diastolic velocity indices may be a better means of detecting subtle changes in cardiac function in the setting of heart transplant, but these tools are most helpful after the insult caused by rejection has already occurred. Hemodynamic changes measured during heart catheterization have also been evaluated as a means of detecting rejection. Rosenthal et al found that although there were statistically significant differences between patients with higher or lower grades of rejection scores, heart catheterization did not permit effective discrimination of patients with moderate to severe rejection. Heart biomarkers, including c-reactive protein, brain natriuretic peptides, and troponin, have been studied as non-invasive measures of determining heart dysfunction or rejection. These surrogates are weakly associated with different rejection grades on biopsy and have a poor predictive capacity for biopsy-detected rejection3. Recently, microarray technology has been used to screen for genes expressed in heart allograft rejection using peripheral leukocytes from blood samples obtained at the time of endomyocardial biopsy. This technique was shown to have a high negative predictive value for the diagnosis of acute cellular rejection but it is unable to detect low grades of rejection4. Overall, these technologies are limited in the ability to consistently and accurately predict the presence of rejection and have low positive predictive values when compared to biopsy.
The current gold standard in detection of rejection is the use of endomyocardial biopsy. Attaining these samples is invasive and long term repeated central venous access can be difficult. Risk of endomyocardial biopsy includes perforation leading to cardiac tamponade, arrhythmias including atrial fibrillation, pneumothorax, hemothorax, and valvular regurgitation secondary to rupture of chordae or damage to valve leaflets themselves. There is variability in pathological interpretation of histologic grades, especially at higher grades of rejection due to the difficulty in interpretation of nodular infiltrates. The 2005 revised ISHLT grading system has simplified the grading system of cellular rejection and now includes assessment of antibody mediated rejection. This may improve the utility of endomyocardial biopsy, but much controversy still exists on the method of grading rejection and its clinical implications. Thus, the development of a noninvasive, relatively inexpensive method that accurately predicts the presence of rejection is critical.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Heart Transplant Recipients | – | Diagnostic Test: Blood Draw of up to 10 mlUp to 10 cc of blood will be drawn from heart transplant recipients at various time points prior to and after transplant. Blood draw is the only research activity that study participants will undergo. In addition to blood draw, data will be collected from clinical records representing the participant's transplant course such as the medical record, imaging, and biopsy slides with pathology reports. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Study population will include people of any age who have undergone heart transplant or who are "listed" to undergo heart transplant.
Key inclusion criteria (1 listed)
- Any patient who is "listed" to undergo or has in the past undergone heart transplantation.
Key exclusion criteria (3 listed)
- Any patient who is not currently listed to undergo heart transplantation or has not previously received a heart transplant;
- Any patient who is not anticipated to be available for follow-up of at least 1 year;
- Any patient who is unable or unwilling to provide documented informed consent for self or through a legally authorized representative.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood Draw of up to 10 mlIn a laboratory setting, the blood will be spun for plasma and buffy coat, DNA will be extracted for processing using the diagnostic test. The results of the test are not provided back to the clinical setting. | Diagnostic test | Heart Transplant Recipients |
Primary outcome
Assay and laboratory protocol development and optimization.
Time frame: Year 1-5
To develop and optimize an assay and protocol to detect donor-specific cell free DNA from recipient plasma.
1 secondary outcome
Biomarker Development
Time frame: Year 1-3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Mitchell, MD principal investigator
Medical College of Wisconsin
Aoy Tomita-Mitchell, PhD principal investigator
Medical College of Wisconsin
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Disease and Acute Rejection of Cardiac Transplant, run by Medical College of Wisconsin at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assay and laboratory protocol development and optimization. (time frame: Year 1-5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2021.