Clinical trial NCT06501768: Cardiovascular Genistein Therapy for Heart Failure Inflammation
Official title: A Pilot Clinical Trial of Cardiovascular Genistein Therapy for Heart Failure Inflammation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Heart Failure
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: Greenstone Biosciences
First posted: 2024-07-15
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: HF inflammatory and cardiometabolic markers
timeFrame: 18 weeks
Secondary outcomes:
measure: Exercise capacity and cardiac performance
timeFrame: 18 weeks
Other outcomes:
measure: Blood biomarkers
timeFrame: 18 weeks
Locations:
city: Ljubljana
country: Slovenia
facility: UMC Ljubljana
Study officials:
References: