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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Genistein in trAnSthyretin recePtor Amyloid caRdiomyopathy

Cardiovascular Genistein Therapy for Heart Failure Inflammation

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

This Phase 1b/2a study aims to investigate the safety and efficacy of genistein in patients with Transthyretin (TTR) Amyloidosis. The focus is on its impact on inflammatory and cardiometabolic biomarkers, along with the effects on cardiac function and exercise capacity. Blood samples will be collected at baseline, following each dose of genistein, and after a six-week placebo washout period. These samples will undergo extensive analyses, including profiling for inflammatory cytokines and novel molecular markers, and routine tests like CBC, Chem 7, LFT, HbA1c, NT-proBNP, CRP, troponin T, and serum TTR. RNA-seq analyses on peripheral blood mononuclear cells (PBMCs) and isolation of plasma exosomes for inflammatory biomarkers are also part of the protocol. Following ESC/AHA guidelines, echocardiography will assess cardiac structure and function, focusing on the left and right ventricles and valvular function. Additionally, exercise capacity will be evaluated through a standardized 6-minute walk test, and NT-proBNP levels will be measured as a cardiac stress biomarker. The trial will include an 18-week follow-up period post-enrolment, with the primary endpoint being the change in inflammatory markers from baseline to three months. Secondary endpoints are cardiac function and exercise capacity changes over the same timeframe. This study aims to provide significant insights into genistein's therapeutic potential for TTR Amyloidosis and its broader implications in managing heart failure. Following ethical committee approval and written informed consent, the Investigators aim is to enroll 40 participants. This is an open-label study. Each patient will receive genistein by mouth: 250 mg twice a day for 4 weeks (500 mg total/day), 500 mg twice a day for 4 weeks (1000 mg total/day), and 750 mg twice a day (1500 mg total/day) for an additional 4 weeks. This will be followed by a 6-week washout period to conclude the study. An 18-month study is anticipated based on the average enrollment rates. Results from this study are expected to offer critical insights for future larger studies.

Who May Be Eligible (Plain English)

Who May Qualify: - Age: 40-80 years - Heart failure with Reduced Ejection Fraction - ischemic or nonischemic etiology - LVEF \<40% by echocardiography, MUGA, or MRI - ATTR cardiomyopathy - any LVEF by echocardiography, MUGA, or MRI - Stable optimally tolerated dosages of HF therapies for 3 months with no change in medical management regimen for at least 1 month - NT-proBNP - for participants \< 75 years old with NT-proBNP \> 125 pg/mL - for participants \> 75 years old with NT-proBNP \> 450 pg/mL Who Should NOT Join This Trial: - Coronary intervention in the past 3 months - Pregnancy - Endometriosis - Uterine fibroids - Cancer: - including breast cancer - predisposition to cancer such as abnormal mammogram - family history - BRCA1 or BRCA2 positive - Patients on a vegan diet - Patients taking supplements such as isoflavonoid, genistein, or resveratrol - Ethanol abuse - Men: \>4 drinks on any day or more than 14 drinks per week - Women: \>3 drinks on any day or more than 7 drinks per week - Liver dysfunction: - aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3X ULN - total bilirubin greater than 1.5 times ULN - hormone replacement therapy (HRT) - thyroid supplement - Renal dysfunction (eGFR less than 25 mL/min/1.73 m2) - Uncontrolled diabetes (HgbA1c \>10%) - Coagulopathies - Cytopenia: - leukocytopenia - hemoglobin \< 9 mg/dl - 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 - allergy to genistein or inulin - allergy to perflutren dye used in contrast echocardiography Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * Age: 40-80 years * Heart failure with Reduced Ejection Fraction * ischemic or nonischemic etiology * LVEF \<40% by echocardiography, MUGA, or MRI * ATTR cardiomyopathy * any LVEF by echocardiography, MUGA, or MRI * Stable optimally tolerated dosages of HF therapies for 3 months with no change in medical management regimen for at least 1 month * NT-proBNP * for participants \< 75 years old with NT-proBNP \> 125 pg/mL * for participants \> 75 years old with NT-proBNP \> 450 pg/mL Exclusion Criteria: * Coronary intervention in the past 3 months * Pregnancy * Endometriosis * Uterine fibroids * Cancer: * including breast cancer * predisposition to cancer such as abnormal mammogram * family history * BRCA1 or BRCA2 positive * Patients on a vegan diet * Patients taking supplements such as isoflavonoid, genistein, or resveratrol * Ethanol abuse * Men: \>4 drinks on any day or more than 14 drinks per week * Women: \>3 drinks on any day or more than 7 drinks per week * Liver dysfunction: * aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3X ULN * total bilirubin greater than 1.5 times ULN * hormone replacement therapy (HRT) * thyroid supplement * Renal dysfunction (eGFR less than 25 mL/min/1.73 m2) * Uncontrolled diabetes (HgbA1c \>10%) * Coagulopathies * Cytopenia: * leukocytopenia * hemoglobin \< 9 mg/dl * 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 * allergy to genistein or inulin * allergy to perflutren dye used in contrast echocardiography

Treatments Being Tested

DRUG

Genistein

The genistein capsules are manufactured and obtained from MCS Formulas, and each capsule contains 250 mg genistein and 50 mg inulin. The genistein is certified to be 98% pure genistein by HPLC and is certified by Good Laboratory Practice (GLP). They will consume 250 mg of genistein BID (500 mg total) by mouth for the first 4 weeks before blood and stool samples are collected. Then, participants will take 500 mg of genistein BID (1000 mg total) for the next 4 weeks before collecting fasting blood and stool samples. Afterward, participants will take 750 mg of genistein BID (1500 mg total) for 4 weeks before collecting fasting blood and stool samples. Afterward, participants will have a washout for 6 weeks before returning for fasting blood and stool sample collection.

Locations (1)

London Regional Health Science Centre
London, Ontario, Canada