OPtimal Adult Heart Transplant Immunosuppression With MicroRNA Levels (OPTIMAL)

This study aims to develop and refine a microRNA (miR) biomarker panel that can be used to phenotype net immune state after heart transplantation using circulating miRs (associated with drug doses and levels). These miRs will be used to characterize the overall immune state in adult 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.

Study Overview

• Status: Recruiting
• Conditions: Graft Rejection; Cardiac Failure

Detailed Description

The study objectives will be accomplished in a prospective, multicenter observational, longitudinal cohort study that includes ~250 Heart Transplant patients from the United States. Patients will be screened for eligibility and enrolled ~1 month (± 2 weeks) after transplant. Study participation will last 36 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 treated rejection, or infection.

Research samples will be collected and used to evaluate miR 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.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Palak Shah, MD; Phone Number: (703) 776-8000; Email: palak.shah@inova.org
• Study Contact Backup: Name: Stephanie Wolak, MPH; Phone Number: 571-472-8558; Email: stephanie.wolak@inova.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Principal Investigator: Jon Kobashigawa, MD
      • Contact: Lucilla Garcia; Email: lucilla.garcia@csmns.org
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University
      • Principal Investigator: Kiran Khush, MD
      • Contact: James Pak; Email: jamespak@stanford.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Recruiting
      • Tufts Medical Center
      • Contact: Abena Adwetewa-Badu; Phone Number: 617-636-9458; Email: Abena.Adwetewa-Badu@tuftsmedicine.org
      • Principal Investigator: Jeong Hwan Kim, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Melissa Amitrano; Email: amitrano@musc.edu
      • Principal Investigator: Ryan Tedford, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University
      • Contact: Lisa Slinger; Email: Lisa.slinger@vumc.org
      • Principal Investigator: Kelly Schlendorf, MD
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Baylor University Medical Center
      • Principal Investigator: Shelley Hall, MD
      • Contact: Jasha Harvey; Email: jasha.harvey@BSWHealth.org
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Not yet recruiting
      • Inova Health System
      • Contact: Michaela Ramandanes, MPH; Phone Number: 703-446-6466; Email: michaela.ramandanes@inova.org
      • Contact: Jacqueline Fikry, MSHS; Phone Number: (703) 776-3966; Email: Jacqueline.fikry@inova.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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 within ~ 1 month after heart transplant

Description

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.
• Patient 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 (e.g., inotrope or vasopressor therapy)
• Ongoing need for renal replacement therapy and/or dialysis
• Active infection requiring either a) hospitalization b) treatment with antimicrobial therapy or c) reduction in immunosuppression
• Active rejection being treated with intravenous medications or plasmapheresis

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Infection in Pediatric Heart Transplant Recipients	A time-to-event analysis will be performed to identify specific circulating microRNAs (miRs) that predict the risk of infection in heart transplant recipients. Infections are defined as any bacterial, viral, fungal, or opportunistic infection leading to: 1) hospitalization, 2) prescription of antimicrobial therapy, or 3) reduction in immunosuppression	up to 3 years post - transplant
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Rejection in Pediatric Heart Transplant Recipients	A time-to-event analysis will be performed to identify specific circulating microRNAs (miRs) that predict the risk of rejection in heart transplant recipients. Rejection is defined as treated rejection based on 1) endomyocardial biopsy (EMB) pathology, 2) unexplained graft dysfunction, or 3) molecular testing; leading to treatment with pulse dose steroids, monoclonal antibodies, plasmapheresis, and/or intravenous immunoglobulin (IVIg). EMB Pathology: Acute Cellular Rejection (ACR) Grade ≥ 2R and/or Antibody-mediated Rejection (AMR) Grade ≥ pAMR1, per International Society for Heart and Lung Transplantation (ISHLT) grading systems. Graft Dysfunction: Left Ventricular Ejection Fraction (LVEF) decline ≥ 10% from baseline and < 50% absolute LVEF by echocardiography. Molecular Testing: Presence of 2 of the following 3 criteria-presence of HLA-DSA, elevated donor-derived cell-free DNA (dd-cfDNA), or gene expression results from blood or EMB testing.	up to 3 years post - transplant

Collaborators and Investigators

• Sponsor: Inova Health Care Services
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Palak Shah, MD, Inova Schar Heart and Vascular

Publications and helpful links

General Publications

• 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.
• Shah P, Bristow MR, Port JD. MicroRNAs in Heart Failure, Cardiac Transplantation, and Myocardial Recovery: Biomarkers with Therapeutic Potential. Curr Heart Fail Rep. 2017 Dec;14(6):454-464. doi: 10.1007/s11897-017-0362-8.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2025
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2032

Study Registration Dates

• First Submitted: April 15, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 23, 2025

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: INOVA-2024-372; 1R01HL173248-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No