Skip to main content
OpenTrials
Recruiting

NCT Number: NCT06501768

Cardiovascular Genistein Therapy for Heart Failure Inflammation

This Phase 1b/2a open-label study is designed to assess the safety and efficacy of genistein in patients with heart failure (HF). The investigation will focus on its impact on inflammatory and cardiometabolic biomarkers, as well as its effects on cardiac function and exercise capacity.

Blood samples will be collected at baseline, following each administration of genistein, and after a six-week placebo washout period. These samples will be subjected to comprehensive analyses to evaluate inflammatory cytokines and novel molecular markers. Routine tests, including Complete Blood Count (CBC), Basic Metabolic Panel (Chem 7), Liver Function Tests (LFT), Hemoglobin A1c (HbA1c), N-terminal pro b-type natriuretic peptide (NT-proBNP), C-Reactive Protein (CRP), and troponin T will be performed. Advanced assessments will include RNA sequencing (RNA-seq) on peripheral blood mononuclear cells (PBMCs) and the isolation of plasma exosomes to identify inflammatory biomarkers. In addition, a subset of the blood samples will be used to generate induced pluripotent stem cells (iPSCs) to further explore the treatment's impact on heart failure-related inflammatory markers.

Echocardiography, in accordance with the European Society of Cardiology (ESC) and the American Heart Association (AHA) guidelines, will be utilized to evaluate cardiac structure and function with a specific focus on the left and right ventricular functions and valvular integrity. Exercise capacity will be gauged through a standardized six-minute walk test. Levels of NT-proBNP will be measured as an indicator of cardiac stress and function.

Participants will be followed up for 18 weeks post-enrolment, with the primary endpoint being the change in inflammatory markers from baseline to the three-month mark. Secondary endpoints will include changes in cardiac function and exercise capacity over the same period. The trial aims to enrol 40 participants, following ethical committee approval and the acquisition of written informed consent. Each patient will receive genistein at a dosing regimen starting with 250 mg twice daily (BID) for 4 weeks, escalating to 500 mg BID for the subsequent 4 weeks, and 750 mg BID for another 4 weeks, culminating in a 6-week follow-up period.

The insights garnered from this study are expected to be pivotal in guiding future larger-scale studies and to elucidate the therapeutic potential of genistein in the management of heart failure.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Heart Failure Cardiovascular Diseases Heart Diseases

Age range

40 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Presence of heart failure of ischemic or nonischemic etiology with LVEF <40%.
  • ATTR cardiomyopathy with any LVEF.
  • Stable optimally tolerated dosages of HF therapies for 3 months with no change in medical management regimen for at least 1 month.
  • NT-proBNP >350 pg/mL.

Exclusion criteria

  • Coronary intervention in the past 3 months.
  • Pregnancy
  • Cancer
  • Patients on a vegan diet
  • Patients taking supplements such as isoflavonoid or resveratrol.
  • Ethanol abuse (men: >4 drinks on any day or more than 14 drinks by week; women: >3 drinks on any day or more than 7 drinks per week)
  • Liver dysfunction (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3X ULN or total bilirubin greater than 1.5 times ULN)
  • Renal dysfunction (eGFR less than 25 mL/min/1.73 m2)
  • Uncontrolled diabetes (HgbA1c >10%)
  • Coagulopathies
  • Cytopenia (leukocytopenia or hemoglobin < 9 mg/dl or platelets <100x103/mm3)
  • Any patients who had been hospitalized in the past 3 months for reasons other than heart failure.
  • NYHA Functional Class I or Functional Class IV symptoms.
  • Acute bacterial or viral infectious disease, or acute exacerbation of a chronic infectious disease
  • Known hypersensitivity to soy.

Treatment and study plan

Genistein

Drug

Escalation genistein dosing, followed by wash-out period

Primary outcomes

  1. HF inflammatory and cardiometabolic markers

    Time frame: 18 weeks

    To comprehensively assess the safety profile and determine the impact of Genistein on key inflammatory and cardiometabolic biomarkers in patients with HF, the following markers will be assessed using specific measurement tools:

    Inflammatory Markers:

    • Interleukin-6 (IL-6): Measured using ELISA.
    • Interleukin-8 (IL-8): Measured using ELISA.
    • Tumor Necrosis Factor-alpha (TNF-α): Measured using ELISA.
    • Interferon-gamma (IFN-γ): Measured using ELISA.

    Cardiometabolic Markers:

    • B-type Natriuretic Peptide (BNP): Measured using immunoassay.
    • C-reactive Protein (CRP): Measured using immunoassay.
    • Hemoglobin A1C (HgA1C): Measured using standard laboratory methods.
    • Complete Blood Count (CBC): Measured using automated hematology analyzer.
    • Comprehensive Metabolic Panel (Chem 7): Measured using standard laboratory methods.
    • Liver Function Tests (LFT): Measured using standard laboratory methods.

Secondary outcomes

  1. Exercise capacity and cardiac performance

    Time frame: 18 weeks

    Exercise capacity will be evaluated by 6-minute walk test, which will be performed by a blinded observer according to the standard protocol.

    Cardiac performance will be evaluated by echocardiography. The scans will assess left ventricle end-systolic- and end-diastolic volumes (LVESV and LVEDV), myocardial mass, assessment of LV systolic and diastolic function, left ventricular ejection fraction (LVEF), radial and longitudinal global- and segmental strain by two-dimensional speckle-tracking echocardiography (2D-STE), LV diastolic function will be assessed by E lateral and medial velocity, E/e', LA volume, and TR velocity). A comprehensive assessment of RV size, RV systolic and diastolic function, RV systolic pressures, RV 2D speckle tracking derived longitudinal strain analysis of the RV free wall averaged over three segments of the RV free wall (2D-STE), assessment of the valvular function and tissue Doppler parameters (e', s') will be performed.

Other outcomes

  1. Blood biomarkers

    Time frame: 18 weeks

    We will aim to examine alterations in blood biomarkers through unbiased proteomics using the SEER or OLink platform post-Genistein treatment and benchmark against baseline. The specific biomarkers and measurement tools are as follows:

    Proteomics Analysis:

    • Platform: OLink or RayBiotech proteomic profiling array.
    • Biomarkers: A comprehensive panel of proteins related to inflammation, oxidative stress, and cardiovascular health will be assessed.
    • Examples of Biomarkers:
    • Cytokines: IL-6, IL-8, TNF-α, IFN-γ.
    • Acute Phase Proteins: CRP, Serum Amyloid A.
    • Growth Factors: VEGF, EGF.
    • Metabolic Proteins: Adiponectin, Leptin.

    Units of Measure:

    • The biomarkers will be measured in their respective units, typically in picograms per milliliter (pg/mL) or nanograms per milliliter (ng/mL).

Study contacts

Contact information is provided by the study sponsor or research team.

Bojan Vrtovec, MD, PhD

CONTACT

[email protected]

+3861 522 1157

Sabina Frljak, MD, PhD

CONTACT

[email protected]

+3861 522 8537

Sponsors and collaborators

Lead sponsor

University Medical Centre Ljubljana

Other

Collaborators

  • Greenstone Biosciences

Registry information

Official study title

A Pilot Clinical Trial of Cardiovascular Genistein Therapy for Heart Failure Inflammation

Acronym: CARDIOGEN

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Jul 15, 2024
Registry last updated
Jul 15, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.