Coronary Artery Disease
Conditions
Keywords
arteries, blood flow, coronary artery disease, diet
Brief summary
The aim of this study is to investigate the effect of genistein administration on coronary arteries in humans. We will measure the size of a coronary artery and the speed and amount of blood flow in response after subjects have ingested Supro® drinks (a soy protein drink containing genistein).
Interventions
DRUGGenistein
Drink taken once daily
DRUGPlacebo
Drink taken once daily
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Aged 30-75 years * Patients requiring diagnostic coronary angiography * Presence of coronary artery disease on angiogram but with at least one non-obstructed (lesions \<70% narrowed compared with the adjacent normal part of the vessel) atheromatous vessel (confirmed at diagnostic cardiac catheterisation) * Female patients must be postmenopausal (FSH\>40 IU/L) * Willing to give informed, written consent
Exclusion criteria
* Age \<30 or \>75 years * Allergy to radiographic contrast media * Sino-atrial disease or significant bradycardia * Concomitant medication with persantin (dipyridamole) or theophyllines * Asthma * Hypertension * Left ventricular hypertrophy or dysfunction (clinical/ECG/echo/CXR) * Female patients with FSH\<40 IU/L (postmenopausal) * Female patients currently taking hormone therapy, or who have taken hormone therapy in previous 6 months * Unwilling to give written informed consent * Participation in another study within previous 60 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coronary Artery Diameter | Day 3-4 after Supro/placebo started. | Coronary angiograms were acquired digitally using a real-time digital image acquisition system (Siemens AG, Berlin and Munich, Germany) and analysed off-line using quantitative coronary angiography (MEDIS, Leiden, The Netherlands). Basal luminal diameter of the entire coronary artery (mean luminal diameter) was measured for all subjects. Mean luminal diameter and luminal diameter approximately 4 mm distal to the tip of the Doppler wire were measured. The latter measurements were used to quantify volume flow as described previously. Data below are mean coronary artery diameter response following infusion of acetylcholine (ACh 10-5 M). |
| Coronary Blood Flow | Day 3-4 after Supro/placebo started. | Measurement of diameter 4mm distal to the Doppler wire tip (measured using quantitative coronary angiography) and blood flow velocity, measured using intracoronary Doppler), were made at baseline and at peak velocity change. A quantitative estimate of coronary blood flow was calculated from the Doppler flow velocity and quantitative angiographic data using the following equation: Q = 3.14(D2/4)(APV/2)(0.6) where Q is flow (ml/min), D is vessel diameter (mm) and APV is average peak velocity (cm/s). Data below are measurements taken at peak blood flow response following an infusion of acetylcholine (10-5M). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Genistein Concentrations | Day 3 after Supro/placebo started. | Measured from serum using liquid-chromatographic tandem mass spectrometric bioanalytical assays (HFL Ltd, Fordham, Cambridgeshire, UK). |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Genistein Supro drink once daily for 3 days
Genistein: Drink taken once daily | 13 |
| Placebo Drink identical to Supro but containing no genistein, once daily for 3 days
Placebo: Drink taken once daily | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 20 | 26 |
Baseline characteristics
| Characteristic | Placebo | Total | Genistein |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 22 Participants | 13 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United Kingdom | 12 participants | 25 participants | 13 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Male | 9 Participants | 22 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 0 / 13 | 0 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 |
Outcome results
Primary
Coronary Artery Diameter
Coronary angiograms were acquired digitally using a real-time digital image acquisition system (Siemens AG, Berlin and Munich, Germany) and analysed off-line using quantitative coronary angiography (MEDIS, Leiden, The Netherlands). Basal luminal diameter of the entire coronary artery (mean luminal diameter) was measured for all subjects. Mean luminal diameter and luminal diameter approximately 4 mm distal to the tip of the Doppler wire were measured. The latter measurements were used to quantify volume flow as described previously. Data below are mean coronary artery diameter response following infusion of acetylcholine (ACh 10-5 M).
Time frame: Day 3-4 after Supro/placebo started.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genistein | Coronary Artery Diameter | 3.1 mm | Standard Deviation 0.4 |
| Placebo | Coronary Artery Diameter | 2.7 mm | Standard Deviation 0.4 |
Primary
Coronary Blood Flow
Measurement of diameter 4mm distal to the Doppler wire tip (measured using quantitative coronary angiography) and blood flow velocity, measured using intracoronary Doppler), were made at baseline and at peak velocity change. A quantitative estimate of coronary blood flow was calculated from the Doppler flow velocity and quantitative angiographic data using the following equation: Q = 3.14(D2/4)(APV/2)(0.6) where Q is flow (ml/min), D is vessel diameter (mm) and APV is average peak velocity (cm/s). Data below are measurements taken at peak blood flow response following an infusion of acetylcholine (10-5M).
Time frame: Day 3-4 after Supro/placebo started.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Genistein | Coronary Blood Flow | 77 ml/min | Standard Deviation 34 |
| Placebo | Coronary Blood Flow | 68 ml/min | Standard Deviation 32 |
Secondary
Serum Genistein Concentrations
Measured from serum using liquid-chromatographic tandem mass spectrometric bioanalytical assays (HFL Ltd, Fordham, Cambridgeshire, UK).
Time frame: Day 3 after Supro/placebo started.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Genistein | Serum Genistein Concentrations | 340 ng/ml |
| Placebo | Serum Genistein Concentrations | 3.9 ng/ml |