Brief Summary
This is a multi-center, prospective, single cohort, observational study of pediatric heart transplant recipients designed to determine the impact of preformed versus de novo human leukocyte antigen (HLA) donor-specific antibodies (DSA), and antibodies to the self-antigens cardiac myosin and vimentin, on chronic allograft function. In addition, the investigators will explore mechanisms of action and predictors of DSA, rejection and altered pathophysiology.
Brief Title
Impact of Allo- and Autoantibodies on Chronic Cardiac Allograft Function
Detailed Description
Participants that were enrolled in the CTOTC-04 study (ClinicalTrials.gov Identifier NCT01005316) are invited to enroll in this CTOTC-09 study. Conversion from the CTOTC-04 to CTOTC-09 study will occur in such a manner as to avoid/minimize discontinuity of follow-up between the planned CTOTC-04 and CTOTC-09 study visits. In addition, subjects added to the United Network for Organ Sharing (UNOS) system-or Canadian equivalent agency-at a participating study site, who are less than 21 years of age and fulfill all study eligibility criteria, will be invited to enroll in CTOTC-09.
This study focuses on the importance of antibodies against the newly transplanted heart in pediatric heart transplant recipients. The investigators aim to determine if certain antibodies lead to problems with the heart transplant. Antibodies are small proteins in the blood that the body makes to fight off infections, for example with bacteria or viruses. Since a new heart is "foreign" to the recipient's body, their immune system might try to attack it with antibodies, as if it were an infection. For many years it was thought that only white blood cells attacked the new heart, causing rejection.
Now there is new information showing that antibodies may also cause rejection or long-term damage to the heart. At this time, very little is known about how antibodies might cause problems after heart transplantation in transplant recipients younger than 21 years at the time of transplant.
This study will collect a medical history and blood samples at specified times for research. The blood samples will be used to measure antibodies in the blood, and to perform special tests to see how these antibodies might damage the heart.
Participant follow-up is from the day of the heart transplant to year 5 post-transplant.
This study focuses on the importance of antibodies against the newly transplanted heart in pediatric heart transplant recipients. The investigators aim to determine if certain antibodies lead to problems with the heart transplant. Antibodies are small proteins in the blood that the body makes to fight off infections, for example with bacteria or viruses. Since a new heart is "foreign" to the recipient's body, their immune system might try to attack it with antibodies, as if it were an infection. For many years it was thought that only white blood cells attacked the new heart, causing rejection.
Now there is new information showing that antibodies may also cause rejection or long-term damage to the heart. At this time, very little is known about how antibodies might cause problems after heart transplantation in transplant recipients younger than 21 years at the time of transplant.
This study will collect a medical history and blood samples at specified times for research. The blood samples will be used to measure antibodies in the blood, and to perform special tests to see how these antibodies might damage the heart.
Participant follow-up is from the day of the heart transplant to year 5 post-transplant.
Completion Date
Completion Date Type
Actual
Conditions
Pediatric Heart Transplantation
Pediatric Heart Transplant Recipients
Eligibility Criteria
Inclusion Criteria:
* Subject and/or parent guardian able to understand and provide informed consent and where applicable assent
* Planned long-term follow-up at one of the study sites
AND either:
-Enrolled in the CTOTC-04 study and actively followed at one of the study sites
OR
-Listed at participating study sites, less than 21 years of age and not yet transplanted.
The inclusion criteria for enrollment of new study patients in the CTOTC-09 Protocol will be the same as the CTOTC-04 study (refer to ClinicalTrials.gov ID NCT01005316).
Exclusion Criteria:
* Parental withdrawal of consent from the CTOTC-04 study
* Past or current medical problems or findings from physical examination or laboratory testing that, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study
* Listed for simultaneous multiple organ transplant.
* Subject and/or parent guardian able to understand and provide informed consent and where applicable assent
* Planned long-term follow-up at one of the study sites
AND either:
-Enrolled in the CTOTC-04 study and actively followed at one of the study sites
OR
-Listed at participating study sites, less than 21 years of age and not yet transplanted.
The inclusion criteria for enrollment of new study patients in the CTOTC-09 Protocol will be the same as the CTOTC-04 study (refer to ClinicalTrials.gov ID NCT01005316).
Exclusion Criteria:
* Parental withdrawal of consent from the CTOTC-04 study
* Past or current medical problems or findings from physical examination or laboratory testing that, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study
* Listed for simultaneous multiple organ transplant.
Inclusion Criteria
Inclusion Criteria:
* Subject and/or parent guardian able to understand and provide informed consent and where applicable assent
* Planned long-term follow-up at one of the study sites
AND either:
-Enrolled in the CTOTC-04 study and actively followed at one of the study sites
OR
-Listed at participating study sites, less than 21 years of age and not yet transplanted.
The inclusion criteria for enrollment of new study patients in the CTOTC-09 Protocol will be the same as the CTOTC-04 study (refer to ClinicalTrials.gov ID NCT01005316).
* Subject and/or parent guardian able to understand and provide informed consent and where applicable assent
* Planned long-term follow-up at one of the study sites
AND either:
-Enrolled in the CTOTC-04 study and actively followed at one of the study sites
OR
-Listed at participating study sites, less than 21 years of age and not yet transplanted.
The inclusion criteria for enrollment of new study patients in the CTOTC-09 Protocol will be the same as the CTOTC-04 study (refer to ClinicalTrials.gov ID NCT01005316).
Gender
All
Gender Based
false
Keywords
alloantibodies
donor specific antibodies (DSA)-preformed, de novo
self-antigens
chronic allograft function
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
20 Years
NCT Id
NCT02752789
Org Class
Nih
Org Full Name
National Institute of Allergy and Infectious Diseases (NIAID)
Org Study Id
DAIT CTOTC-09
Overall Status
Completed
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
An Observational Cohort Study to Determine the Impact of Alloantibodies and Antibodies to Self Antigens on Chronic Graft Function up to 5 Years After Pediatric Heart Transplantation (CTOTC-09)
Primary Outcomes
Outcome Measure
Pulmonary capillary wedge pressure at heart catheterization
Outcome Time Frame
3 years post-transplantation
Secondary Outcomes
Outcome Description
Cardiac hemodynamic findings: right and left ventricular end diastolic pressures, right atrial pressure, pulmonary artery pressure and cardiac index
Outcome Time Frame
3 and 5 years post-transplantation
Outcome Measure
Other invasive cardiac hemodynamic findings at cardiac catheterization
Outcome Time Frame
3 years post-transplantation
Outcome Measure
Frequency of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin
Outcome Time Frame
3 years post-transplantation
Outcome Measure
Time course of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin.
Outcome Time Frame
From >1 year to 5 years post-transplantation
Outcome Measure
Frequency of first episode of late acute rejection
Outcome Description
Late acute rejection is defined as occurring \>1 year post-transplantation
Outcome Time Frame
From >1 year to 5 years post-transplantation
Outcome Measure
Time to first episode of late acute rejection
Outcome Time Frame
Up to 5 years post-transplantation
Outcome Measure
Frequency to recurrent (two or more) late acute rejections
Outcome Description
Recurrent defined as two or more late acute rejection episodes
Outcome Time Frame
Up to 5 years post-transplantation
Outcome Measure
Time to recurrent late acute rejections
Outcome Time Frame
Up to 5 years post-transplantation
Outcome Measure
Frequency to first episode of late acute rejection with hemodynamic compromise
Outcome Time Frame
Up to 5 years post-transplantation
Outcome Measure
Time to first episode of late acute rejection with hemodynamic compromise
Outcome Time Frame
One year and up to 5 years post-transplantation
Outcome Measure
Time to graft loss (death or retransplantation) conditional to surviving one year post-transplantation
Outcome Time Frame
3 and 5 years post-transplantation
Outcome Measure
N-terminal pro-brain Natriuretic Peptide (NT-proBNP)/Brain Natriuretic Peptide (BNP)
Outcome Description
Graft function as assessed by echocardiography
Outcome Time Frame
3 and 5 years
Outcome Measure
Systolic and diastolic graft function
Outcome Time Frame
3 and 5 years post-transplantation
Outcome Measure
Proportion of participants with angiographic evidence of coronary artery disease
Outcome Time Frame
Up to 5 years post-transplantation
Outcome Measure
Time to graft loss (death or retransplantation) after first late rejection
Outcome Time Frame
Up to 5 years post-transplantation
Outcome Measure
Medication Adherence Measure (MAM) after hospital discharge
Outcome Time Frame
Up to 5 years post-transplantation
Outcome Measure
Variability of maintenance tacrolimus levels
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Study Population
Participants that were enrolled in CTOTC-04 (ClinicalTrials.gov ID NCT01005316) who consent to long-term follow-up and new participants at the nine designated sites who are listed for isolated orthotopic heart transplantation
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
20
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Daphne Hsu
Investigator Email
dhsu@montefiore.org
Investigator Phone
718-741-2538