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| Name | Class |
|---|---|
| Clinical Trials in Organ Transplantation in Children | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pediatric Heart Transplant Recipients | CTOTC-04 (ClinicalTrials.gov ID NCT01005316) participants who consent to long-term follow-up as part of this study as well as candidates less than 21 years of age who are listed for isolated orthotopic heart transplantation at one of the participating sites |
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| Measure | Description | Time Frame |
|---|---|---|
| Pulmonary capillary wedge pressure at heart catheterization | 3 years post-transplantation |
| Measure | Description | Time Frame |
|---|---|---|
| Other invasive cardiac hemodynamic findings at cardiac catheterization | Cardiac hemodynamic findings: right and left ventricular end diastolic pressures, right atrial pressure, pulmonary artery pressure and cardiac index | 3 and 5 years post-transplantation |
| Frequency of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory: Microvascular pathology | Microvascular pathology as defined by:
| Up to 5 years post-transplantation |
Inclusion Criteria:
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:
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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
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| Name | Affiliation | Role |
|---|---|---|
| Steven A. Webber, MBChB, MRCP | Monroe Carell Jr. Children's Hospital at Vanderbilt: Pediatric Transplantation | Study Chair |
| Steven A. Webber, MBChB, MRCP | Monroe Carell Jr. Children's Hospital at Vanderbilt: Pediatric Transplantation | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University School of Medicine | Atlanta | Georgia | 30060 | United States | ||
| Children's Hospital Boston |
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| Label | URL |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | View source |
| Division of Allergy, Immunology, and Transplantation (DAIT) | View source |
| Clinical Trials in Organ Transplantation in Children (CTOT-C) |
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Whole blood, plasma, PBMC and tissue
| 3 years post-transplantation |
| Time course of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin. | 3 years post-transplantation |
| Frequency of first episode of late acute rejection | From >1 year to 5 years post-transplantation |
| Time to first episode of late acute rejection | Late acute rejection is defined as occurring >1 year post-transplantation | From >1 year to 5 years post-transplantation |
| Frequency to recurrent (two or more) late acute rejections | Up to 5 years post-transplantation |
| Time to recurrent late acute rejections | Recurrent defined as two or more late acute rejection episodes | Up to 5 years post-transplantation |
| Frequency to first episode of late acute rejection with hemodynamic compromise | Up to 5 years post-transplantation |
| Time to first episode of late acute rejection with hemodynamic compromise | Up to 5 years post-transplantation |
| Time to graft loss (death or retransplantation) conditional to surviving one year post-transplantation | One year and up to 5 years post-transplantation |
| N-terminal pro-brain Natriuretic Peptide (NT-proBNP)/Brain Natriuretic Peptide (BNP) | 3 and 5 years post-transplantation |
| Systolic and diastolic graft function | Graft function as assessed by echocardiography | 3 and 5 years |
| Proportion of participants with angiographic evidence of coronary artery disease | 3 and 5 years post-transplantation |
| Time to graft loss (death or retransplantation) after first late rejection | Up to 5 years post-transplantation |
| Medication Adherence Measure (MAM) after hospital discharge | Up to 5 years post-transplantation |
| Variability of maintenance tacrolimus levels | Up to 5 years post-transplantation |
| Exploratory: Expression of cytoprotective genes Bcl2 and HO-1, ICAM, VCAM and selectins, Complement inhibitory proteins CD55, CD59, CR1, CR2 and CR3. |
Endothelial Cell (EC) Culture Model is used to study factors that will predict and contribute to the protection of the graft following transplantation across sub-threshold concentrations of DSA. Exploratory: Expression of cytoprotective genes Bcl2 and HO-1, Intercellular adhesion molecules (ICAM), Vascular Cell Adhesion Molecule (VCAM) and selectins, Complement inhibitory proteins (cluster of differentiation antigen 55 (CD55), cluster of differentiation antigen 59 (CD59), Complement Receptor 1 (CR1), (CR2) and (CR3). |
| After exposure to alloantibody (or control) (At Year 1) |
| Exploratory: Cellular immune responses to allo-antigens and self-antigens (vimentin and myosin) | Cellular immune responses to allo-antigens and self-antigens (vimentin and myosin) will be measured by:
| 24 hours prior transplantation, Months 3 and 6 post transplantation |
| Exploratory: Role of Interleukin-33 (IL-33) and its Receptor (ST2) in cardioprotection against effects of DSA | Role of IL-33 and its Receptor (ST2) in cardioprotection against effects of DSA will be measured by:
| Month 5 post transplantation |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| St. Louis Children's Hospital | St Louis | Missouri | 63110 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| Children's Hospital at Montefiore | New York | New York | 10467 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15224 | United States |
| Monroe Carell Jr. Children's Hospital | Nashville | Tennessee | 37232 | United States |
| Hospital for Sick Children | Toronto | M5G 1X8 | Canada |
| View source |