RecruitingPhase 1Phase 2NCT06634108

Genistein in trAnSthyretin recePtor Amyloid caRdiomyopathy

Cardiovascular Genistein Therapy for Heart Failure Inflammation

Sponsor

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Enrollment

20 participants

Start Date

Sep 27, 2024

Study Type

INTERVENTIONAL

Conditions

Amyloid Cardiomyopathy

Summary

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.

Eligibility

Min Age: 40 YearsMax Age: 80 Years

Plain Language Summary

Simplified for easier understanding

This study, called GASPAR, is testing whether genistein — a natural compound found in soy — can improve heart function in people with heart failure or a condition called ATTR cardiomyopathy (a type of heart disease where a protein called transthyretin builds up in the heart muscle). The study uses a special cardiac ultrasound with a contrast agent to track heart function over time. **You may be eligible if...** - You are between 40 and 80 years old - You have heart failure with reduced pumping function (ejection fraction under 40%) OR have ATTR cardiomyopathy - Your heart medications have been stable for at least 3 months - You have elevated heart stress markers in your blood (NT-proBNP above certain levels) **You may NOT be eligible if...** - You had a heart procedure or intervention in the past 3 months - You are pregnant - You have endometriosis or uterine fibroids - You have cancer, a family history of cancer, or a gene mutation (BRCA1/BRCA2) raising cancer risk - You are on a vegan diet, or take soy/isoflavone/resveratrol supplements - You drink heavily (more than the limits specified in the study) - You have significant liver or kidney disease, uncontrolled diabetes, or blood clotting disorders - You are on hormone replacement therapy or thyroid supplements - You have been recently hospitalized for reasons other than heart failure Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGGenistein

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.