Cardiovascular Genistein Therapy for Heart Failure Inflammation

NCT ID: NCT06501768

Last Updated: 2024-07-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-01
• Study Completion Date: 2026-09-01

Brief Summary

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.

Conditions

Heart Failure

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Genistein Therapy

Participants will consume 250 mg of genistein BID (500 mg total) by mouth for the first 4 weeks before blood samples are collected. And then, patients will take 500 mg of genistein BID (1000 mg total) for the next 4 weeks before blood are collected. Afterward, patients will take 750 mg of genistein BID (1500 mg total) for 4 weeks before blood samples are collected. Afterward, patients will be off Genistein for 6 weeks before returning for blood sample collection. The Genistein capsules are manufactured and obtained from MCS Formulas. The genistein is certified to be 98% pure genistein by HPLC and is good laboratory practice (GLP) certified. At baseline, and again before Genistein discontinuation (at 12 weeks), we will also perform transthoracic echocardiography and a 6-minute walk test.

Group Type: EXPERIMENTAL

Genistein

Intervention Type: DRUG

Escalation genistein dosing, followed by wash-out period

Interventions

Genistein

Escalation genistein dosing, followed by wash-out period

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Greenstone Biosciences

UNKNOWN

Sponsor Role: collaborator

University Medical Centre Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UMC Ljubljana

Ljubljana, , Slovenia

Site Status: RECRUITING

Countries

Slovenia

Central Contacts

Bojan Vrtovec, MD, PhD

Role: CONTACT

bojan.vrtovec@kclj.si

+3861 522 1157

Sabina Frljak, MD, PhD

Role: CONTACT

sabina.frljak@kclj.si

+3861 522 8537

Facility Contacts

Bojan Vrtovec, MD, PhD

Role: primary

bojan.vrtovec@kclj.si

+3861 522 1157

Sabina Frljak, MD, PhD

Role: backup

sabina.frljak@kclj.si

+3861 522 8537

Other Identifiers

CARDIOGEN

Identifier Type: -

Identifier Source: org_study_id