OPtimal Adult Heart Transplant Immunosuppression With MicroRNA Levels

NCT06939751 | Recruiting

• 2 other identifiers: INOVA-2024-3721R01HL173248-01A1
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Cardiac Failure; Graft Rejection

Outcome Measures

Primary Outcomes (2)

• 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

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Inova Health Care Services: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (7)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 37232, United States

RECRUITING

Baylor University Medical Center

Dallas, Texas, 75246, United States

RECRUITING

Inova Health System

Falls Church, Virginia, 22042, United States

NOT YET RECRUITING

Related Publications (2)

• 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.

  PMID: 28940102 BACKGROUND

• 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.

  PMID: 35872109 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma and RNA

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Palak Shah, MD

  Inova Schar Heart and Vascular

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Palak Shah, MD

CONTACT

(703) 776-8000; palak.shah@inova.org

Stephanie Wolak, MPH

CONTACT

571-472-8558; stephanie.wolak@inova.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: April 23, 2025
• Study Start: October 28, 2025
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2032
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)