Isoflavones and the Coronary Circulation in Men and Women With Coronary Artery Disease

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT00287690
• Collaborator: (none)
• Enrollment: 71
• Location: 1
• Arms: 2
• Duration (Months): 46.6
• Patients Per Site Per Month: 1.5

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Genistein; Drug: Placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effect of Genistein (Supro®) on Coronary Artery Diameter and Blood Flow in Men and Women With Coronary Heart Disease
• Study Start Date: Oct 1, 1999
• Actual Primary Completion Date: Aug 18, 2003
• Actual Study Completion Date: Aug 18, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Genistein Supro drink once daily for 3 days	Drug: Genistein; Drink taken once daily; Other Names: Supro
Placebo Comparator: Placebo Drink identical to Supro but containing no genistein, once daily for 3 days	Drug: Placebo; Drink taken once daily

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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 Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Brompton & Harefield NHS Trust	London		United Kingdom	SW3 6NP

Sponsors and Collaborators

• Imperial College London

Investigators

• Principal Investigator: Peter Collins, MD, FRCP, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT00287690
• Other Study ID Numbers: 98-170
• First Posted: Feb 7, 2006
• Last Update Posted: Aug 5, 2019
• Last Verified: Feb 1, 2006

• Keywords provided by Imperial College London: arteries; blood flow; coronary artery disease; diet
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Genistein

Study Results

Participant Flow

Arm/Group Title	Genistein	Placebo
Arm/Group Description	Supro drink once daily for 3 days prior to coronary angiography Genistein: Drink taken once daily	Drink identical to Supro but containing no genistein, once daily for 3 days prior to coronary angiography. Placebo: Drink taken once daily
Period Title: Overall Study
STARTED	33	38
COMPLETED	13	12
NOT COMPLETED	20	26

Baseline Characteristics

Arm/Group Title	Genistein	Placebo	Total
Arm/Group Description	Supro drink once daily for 3 days Genistein: Drink taken once daily	Drink identical to Supro but containing no genistein, once daily for 3 days Placebo: Drink taken once daily	Total of all reporting groups
Overall Participants	13	12	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 100%	9 75%	22 88%
>=65 years	0 0%	3 25%	3 12%
Sex: Female, Male (Count of Participants)
Female	0 0%	3 25%	3 12%
Male	13 100%	9 75%	22 88%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	13 100%	12 100%	25 100%

Outcome Measures

1. Primary Outcome

Title	Coronary Artery Diameter
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Genistein	Placebo
Arm/Group Description	Supro drink once daily for 3 days prior to coronary angiography Genistein: Drink taken once daily	Drink identical to Supro but containing no genistein, once daily for 3 days prior to coronary angiography. Placebo: Drink taken once daily
Measure Participants	13	12
Mean (Standard Deviation) [mm]	3.1 (0.4)	2.7 (0.4)

2. Primary Outcome

Title	Coronary Blood Flow
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Genistein	Placebo
Arm/Group Description	Supro drink once daily for 3 days prior to coronary angiography Genistein: Drink taken once daily	Drink identical to Supro but containing no genistein, once daily for 3 days prior to coronary angiography. Placebo: Drink taken once daily
Measure Participants	13	12
Mean (Standard Deviation) [ml/min]	77 (34)	68 (32)

3. Secondary Outcome

Title	Serum Genistein Concentrations
Description	Measured from serum using liquid-chromatographic tandem mass spectrometric bioanalytical assays (HFL Ltd, Fordham, Cambridgeshire, UK).
Time Frame	Day 3 after Supro/placebo started.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Genistein	Placebo
Arm/Group Description	Supro drink once daily for 3 days prior to coronary angiography Genistein: Drink taken once daily	Drink identical to Supro but containing no genistein, once daily for 3 days prior to coronary angiography. Placebo: Drink taken once daily
Measure Participants	13	12
Median (95% Confidence Interval) [ng/ml]	340	3.9

Adverse Events

Time Frame	From enrollment to study end, approximately 1 week.
Arm/Group Title	Genistein		Placebo
Arm/Group Description	Supro drink once daily for 3 days prior to coronary angiography Genistein: Drink taken once daily		Drink identical to Supro but containing no genistein, once daily for 3 days prior to coronary angiography. Placebo: Drink taken once daily
All Cause Mortality
	Genistein		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Serious Adverse Events
	Genistein		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Genistein		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.