Overview
This study aims to discover circulating microRNAs (associated with drug doses and levels) that can be used to characterize the overall immune state in pediatric heart transplant patients and predict patients that will go on to develop infection and rejection. MicroRNAs (miRs) are small, non-coding RNA molecules that regulate gene expression and serve as molecular biomarkers found in the circulation.
Description
The study objectives will be accomplished in a prospective, multicenter observational, longitudinal cohort study that includes 100-150 Pediatric Heart Transplant (PHT) patients from the United States. Patients will be screened for eligibility and enrolled 10-50 days after PHT. Study participation will last 24 months.
All patients will follow the center's standard of care surveillance schedule after transplant. Blood samples will be collected for miR evaluation at:
- specified time intervals after transplant and
- when a clinical event of interest occurs, including treated rejection, or infection.
Research samples will be collected and used to evaluate microRNA expression as well as other biomarkers related to heart transplantation and immunosuppression medications. Additional data collection will include demographics, medical history, medications, human leukocyte (HLA)/donor specific antibody (DSA) evaluations, endomyocardial biopsy (EMB), echocardiography, donor-derived cell-free DNA (dd-cfDNA), and other post-transplant events and testing.
This work will form the basis for a non-invasive, genomic blood test that can be used to monitor patients after heart transplant to mitigate complications of over-immunosuppression, such as infection, without increasing the risks of under-immunosuppression, such as rejection.
Eligibility
Inclusion Criteria:
- Age ≤ 18 years at time of transplant listing
- Subject is within 10-50 days post-orthotopic heart transplant at time of enrollment.
- Planned follow-up at the transplant center for a minimum of one-year.
- Caregiver able and willing to comply with the study visit schedule, study procedures, and study requirements.
Exclusion Criteria:
- Recipient of a multi-organ transplant
- History of prior solid organ transplant before the index heart transplant
- Ongoing mechanical circulatory support or hemodynamic instability after transplant
- Active infection requiring either a) hospitalization or b) treatment with antimicrobial drugs (does not include prophylaxis for infection or suppressive antibiotics given after transplant)
- History of treated rejection prior to study enrollment
- Inability to collect specified blood volume after enrollment and prior to 50 days post-transplant