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Endothelin-1 and Cardiac Allograft Vasculopathy (CAV)

Sponsor
University of California, Los Angeles (Other)
Overall Status
Recruiting
CT.gov ID
NCT05373108
Collaborator
American Heart Association (Other), Janssen, LP (Industry)
30
Enrollment
1
Location
1
Arm
7.4
Anticipated Duration (Months)
4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Many patients with end-stage heart failure, a condition in which the heart fails to pump enough blood to support the body's other organs, are fortunate enough to receive a heart transplant. However, despite taking medicines aimed at blunting the immune system's response to the donor heart, some of them will develop transplant-related disease in the coronary arteries supplying their hearts. Fifty years after the first human-to-human heart transplant, this disorder-cardiac allograft vasculopathy (CAV)-remains a leading cause of long-term death and has been coined the 'Achilles' Heel' of heart transplantation. Indeed, a better understanding of how CAV occurs and improved therapies to prevent and/or slow its development are desperately needed to meaningfully impact patient outcomes.

Endothelin-1 (ET-1) is a key molecular regulator of arterial health, and our prior data suggests that it is associated with accelerated CAV. In this particular study of recent heart transplant recipients, we are asking: Does ET-1 contribute to the coronary artery's capacity to dilate/constrict? To answer this question, during the cardiac catheterization at 1 year post-transplant (standard of care), we will measure blood levels of ET-1 and perform an invasive evaluation of coronary vasomotor function inn a consecutive subset of patients who will have received a 1-week course of the oral endothelin receptor antagonist (macitentan) prior this catheterization, which will allow us to test how much ET-1 contributes to coronary responsiveness.

The findings from this study may provide the necessary foundation to study whether endothelin receptor antagonists are able to effectively reduce the rate of accelerated CAV.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Impact of Endothelin-1 on the Development of Cardiac Allograft Vasculopathy in Heart Transplant Recipients: Endothelin Receptor Antagonism and Vasomotor Function
Anticipated Study Start Date :
May 19, 2022
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Intervention Arm

A consecutive subset of eligible patients based on inclusion/exclusion criteria will receive a 1-week course of Macitentan (10 mg po daily) prior to their routine 1-year coronary angiogram (7th and final dose of Macitentan will occur on the day of the angiogram).

Drug: Macitentan
Macitentan is a nonselective ERA that is approved for use in PAH; the use of Macitentan in post-heart transplant patients is considered investigational.
Other Names:
  • Opsumit

    		•

    Outcome Measures

    Primary Outcome Measures

    1. ET-1 Bioactivity [Measured during catheterization at 1-year post-transplant]

      ET-1 bioactivity as measured by contribution to vasomotor tone via the Macitentan:Nitroglycerin luminal volume dilation ratio on IVUS

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Within 4 months post-transplant

    2. ≥18 years old

    3. Have a serum creatinine < 2.0 mg/dL (to minimize risk of contrast-induced nephropathy)

    4. Able to provide informed written consent.

    Exclusion Criteria:

    1. Multi-organ transplant

    2. Transplant-related complications and comorbidities that preclude the ability to safely perform an invasive coronary evaluation in the cardiac catheterization laboratory

    3. Pregnant women due to possible fetal harm; all women of childbearing potential must have a negative pregnancy test within 1 week of starting Macitentan, and 30 days after completing the one-week course of Macitentan.

    4. Patients who are taking potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) as these drugs can expose one to higher levels of macitentan

    5. Cirrhosis or baseline liver function tests (AST/ALT) > 3x the upper limit of normal

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ronald Regan UCLA Medical Center Los Angeles California United States 90095

    Sponsors and Collaborators

    • University of California, Los Angeles
    • American Heart Association
    • Janssen, LP

    Investigators

    • Principal Investigator: Rushi Parikh, MD, Assistant Clinical Professor; University of California, Los Angeles

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Rushi V. Parikh, Assistant Clinical Professor, Co-Assistant Director Interventional Cardiology Research, University of California, Los Angeles
    ClinicalTrials.gov Identifier:
    NCT05373108
    Other Study ID Numbers:
    • 18-001544
    First Posted:
    May 13, 2022
    Last Update Posted:
    May 13, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Rushi V. Parikh, Assistant Clinical Professor, Co-Assistant Director Interventional Cardiology Research, University of California, Los Angeles
    Heart Transplantation
    Endothelin-1
    Cardiac Allograft Vasculopathy
    Additional relevant MeSH terms:
    Vascular Diseases
    Macitentan

    Study Results

    No Results Posted as of May 13, 2022