Pediatric Heart Transplantation Clinical Trial
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)
Verified date | November 2019 |
Source | National Institute of Allergy and Infectious Diseases (NIAID) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
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.
Status | Completed |
Enrollment | 407 |
Est. completion date | November 1, 2019 |
Est. primary completion date | November 1, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 20 Years |
Eligibility |
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. |
Country | Name | City | State |
---|---|---|---|
Canada | Hospital for Sick Children | Toronto | |
United States | Emory University School of Medicine | Atlanta | Georgia |
United States | Children's Hospital Boston | Boston | Massachusetts |
United States | Monroe Carell Jr. Children's Hospital | Nashville | Tennessee |
United States | Children's Hospital at Montefiore | New York | New York |
United States | Columbia University Medical Center | New York | New York |
United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
United States | Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania |
United States | St. Louis Children's Hospital | Saint Louis | Missouri |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) | Clinical Trials in Organ Transplantation in Children |
United States, Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Exploratory: Microvascular pathology | Microvascular pathology as defined by: cytoprotective intracellular signaling (bcl2, Heme Oxygenase-1(HO-1)) interstitial capillary network endothelial cell progenitor influx and premature senescence obliterative microvasculopathy (arteriolopathy) |
Up to 5 years post-transplantation | |
Other | 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) | |
Other | 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: ELISPOT for Interleukin 17 (IL17) and Interleukin 10 (IL10) producing T cells Plasma cytokines by Luminex (IL-6, IL-1beta, IL-17, Cxcl12, IL-10 and Transforming Growth Factor-beta (TGF-beta) |
24 hours prior transplantation, Months 3 and 6 post transplantation | |
Other | 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: IL33 and ST2 expression in graft biopsies Soluble ST2 in serum |
Month 5 post transplantation | |
Primary | Pulmonary capillary wedge pressure at heart catheterization | 3 years post-transplantation | ||
Secondary | 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 | |
Secondary | Frequency of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin | 3 years post-transplantation | ||
Secondary | Time course of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin. | 3 years post-transplantation | ||
Secondary | Frequency of first episode of late acute rejection | From >1 year to 5 years post-transplantation | ||
Secondary | 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 | |
Secondary | Frequency to recurrent (two or more) late acute rejections | Up to 5 years post-transplantation | ||
Secondary | Time to recurrent late acute rejections | Recurrent defined as two or more late acute rejection episodes | Up to 5 years post-transplantation | |
Secondary | Frequency to first episode of late acute rejection with hemodynamic compromise | Up to 5 years post-transplantation | ||
Secondary | Time to first episode of late acute rejection with hemodynamic compromise | Up to 5 years post-transplantation | ||
Secondary | Time to graft loss (death or retransplantation) conditional to surviving one year post-transplantation | One year and up to 5 years post-transplantation | ||
Secondary | N-terminal pro-brain Natriuretic Peptide (NT-proBNP)/Brain Natriuretic Peptide (BNP) | 3 and 5 years post-transplantation | ||
Secondary | Systolic and diastolic graft function | Graft function as assessed by echocardiography | 3 and 5 years | |
Secondary | Proportion of participants with angiographic evidence of coronary artery disease | 3 and 5 years post-transplantation | ||
Secondary | Time to graft loss (death or retransplantation) after first late rejection | Up to 5 years post-transplantation | ||
Secondary | Medication Adherence Measure (MAM) after hospital discharge | Up to 5 years post-transplantation | ||
Secondary | Variability of maintenance tacrolimus levels | Up to 5 years post-transplantation |
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