Clinical trial NCT06532890: Optimal Pediatric Heart Transplant Immunosuppression With MicroRNAs (OPTIMA)
Official title: Optimal Pediatric Heart Transplant Immunosuppression With MicroRNAs
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cardiac Failure
Graft Rejection
Lead sponsor: Inova Health Care Services
Sponsor class: OTHER
First posted: 2024-08-01
Enrollment: 150
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients ≤ 18 years of age from geographically and socioeconomically diverse regions of the U.S. who have undergone orthotopic heart transplant (OHT).

Patients will be screened for eligibility and enrolled \~1 month after pediatric heart transplantation.

Brief summary: 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.

Detailed 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 \~1 month 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:

1. specified time intervals after transplant and
2. when a clinical event of interest occurs, including rejection, infection, or major change in immunosuppression.

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 criteria: Inclusion Criteria:

* Age ≤ 18 years at enrollment
* Receipt of orthotopic heart transplant (OHT) within the prior 1 month ± 2 weeks
* 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
* Active infection requiring either a) hospitalization b) treatment with antimicrobial therapy or c) reduction in immunosuppression
* History of rejection prior to enrollment
* Inability to collect specified blood volume at enrollment +/- 1 week

Primary outcomes:
measure: Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Infection in Pediatric Heart Transplant Recipients
timeFrame: up to 2 years post-transplant
measure: Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Rejection in Pediatric Heart Transplant Recipients
timeFrame: up to 2 years post-transplant
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New York
country: United States
facility: Columbia University
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Falls Church
country: United States
facility: Inova Health System
state: Virginia
Study officials:
affiliation: Inova Schar Heart and Vascular
name: Palak Shah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inova L.J. Murphy Children's Hospital
name: Jason Goldberg, MD
role: STUDY_DIRECTOR
References:
citation: Shah P, Agbor-Enoh S, Bagchi P, deFilippi CR, Mercado A, Diao G, Morales DJ, Shah KB, Najjar SS, Feller E, Hsu S, Rodrigo ME, Lewsey SC, Jang MK, Marboe C, Berry GJ, Khush KK, Valantine HA; GRAfT Investigators. Circulating microRNAs in cellular and antibody-mediated heart transplant rejection. J Heart Lung Transplant. 2022 Oct;41(10):1401-1413. doi: 10.1016/j.healun.2022.06.019. Epub 2022 Jun 28.