Recruiting

Phase 1

Phase 2

GenisteinGenistein in trAnSthyretin recePtor Amyloid caRdiomyopathy

Sponsor:

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

Code:

NCT06634108

Conditions

Amyloid Cardiomyopathy

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Not accepted

Interventions

Genistein

Study Details

Brief 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.

Conditions

Amyloid Cardiomyopathy

Study ID

NCT06634108

Start date

Sep 27, 2024

Status verified date

Jun, 2025

Completion date

Dec 1, 2025

Anticipated

Primary completion date

Sep 1, 2025

Anticipated

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Genistein Treatment and Washout

The Investigators plan to recruit 40 heart failure participants, including 20 participants with heart failure with reduced ejection fraction (LVEF<40%) and 20 participants with transthyretin amyloid (ATTR) cardiomyopathy. After an initial telephone call to screen participants, the Investigators will invite qualified people for informed consent and a baseline fasting blood draw. Participants will receive escalating doses of genistein after their baseline fasting blood and stool sample collections. At baseline and again at 3 months, the Investigators will also perform transthoracic echocardiography and a 6-minute walk test.

Interventions

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.

Primary outcome measure

Inflammatory markers [ Time Frame: These parameters will be assessed at baseline (week 0) and with each dose escalation (week 4, week 8, and week 12) and after washout (week 18). ]
Cardiac markers [ Time Frame: These parameters will be assessed at baseline (week 0) and with each dose escalation (week 4, week 8, and week 12) and after washout (week 18). ]
Complete metabolic profile [ Time Frame: These parameters will be assessed at baseline (week 0) and with each dose escalation (week 4, week 8, and week 12) and after washout (week 18). ]

Central Contacts and Locations

Central contacts

Mark JK Chandy, MD PhD

5196612111 mark.chandy@lhsc.on.ca

Kerry-Ann Nakrieko, PhD

5196112111 knakrie@uwo.ca

Locations

London Regional Health Science Centre

Recruiting

London, Ontario, Canada, N6A 5A5

Contacts

Mark Chandy, MD PhD

5196612111 mark.chandy@lhsc.on.ca

More Information

Sponsor

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

Last update posted

Jun 15, 2025

Last verified

Jun, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's on 2025-06-15.