GSE: The Effect of Grape Seed Extract on Blood Pressure in People With Pre-Hypertension

• Sponsor: Clinical Nutrition Research Center, Illinois Institute of Technology (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00979732
• Collaborator: Polyphenolics, Inc. (Industry)
• Enrollment: 33
• Location: 1
• Arms: 2
• Actual Duration (Months): 59
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

In this research study, the investigators are interested in learning how extracts from grape seeds can help those individuals with high blood pressure. The investigators also hope to learn how grape seed extract effects your blood and cell functions.

The grape seed extract the investigators will use in the study will be provided either in a beverage or a capsule form and is currently available on the market. This study is also using a placebo; therefore the treatment subjects receive may or may not contain the grape seed extract.

The purpose of this study is to determine if the grape seed extract (GSE) will lower blood pressure in people with slightly high blood pressure (Pre-Hypertension).

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Dietary Supplement: grape seed extract; Dietary Supplement: grape seed extract placebo	N/A

Detailed Description

Elevated blood pressure, or hypertension, is a major risk factor for heart disease and stroke. Systolic and diastolic blood pressures meeting criteria for "pre-hypertension" double the absolute risk of stroke and ischemic heart disease over an extended age range from the 4th to the 8th decade of life. Lifestyle, particularly the diet, is critical in the prevention and management of hypertension. Polyphenolic compounds from various plant foods can promote blood pressure regulation and vascular health through protection of the endothelium from oxidant and or inflammatory stress and or stimulation of smooth muscle relaxation.

We will use a purified grape seed extract (GSE) in the proposed trial. This extract has been granted Generally Recognized as Safe (GRAS) status by Food and drug administration (GRAS Notice # GRN 000125, dated 08/18/2003, FDA, USA). Furthermore, GSE for use in the present trial has been used in previous human clinical trails and shown potent vasodilator properties in vitro and blood pressure lowering in metabolic syndrome patients. The proposed trial aims to verify the blood pressure lowering effect of GSE in an 'at risk' population for hypertension and to explore the extent to which other pathways of chronic disease may be modulated by GSE consumption.

Given this, the objectives of this study are as follows:

1. The primary objective of the proposed study is to demonstrate the effectiveness of GSE to lower blood pressure in pre-hypertensive individuals.

2. Secondary objectives will investigate the role of GSE to improve inflammatory- and oxidative stress- status, as well as its effect on endothelium function.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-blind, Placebo-controlled Trial to Investigate the Effect of Grape Seed Extract Delivered in a Beverage on Blood Pressure in Individuals With Pre-hypertension.
• Actual Study Start Date: Nov 15, 2009
• Actual Primary Completion Date: Oct 15, 2014
• Actual Study Completion Date: Oct 15, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: GSE beverage active grape seed extract beverage 150 mg/BID	Dietary Supplement: grape seed extract; grape seed extract 150 mg twice a day (BID) in beverage or capsule form
Placebo Comparator: GSE beverage placebo grape seed extract placebo beverage 150 mg/BID	Dietary Supplement: grape seed extract placebo; grape seed extract 150 mg twice a day (BID) in beverage or capsule form

Outcome Measures

Primary Outcome Measures

1. Systolic Blood Pressure [6 weeks]

   BP was monitored using ambulatory BP monitors (Ambulo2400; Tiba Medical, Inc.) that were programmed to take BP measurements automatically at 1-h intervals for a period of 24 h. BP measurements were scheduled at week 0 and 6 of the intervention (for efficacy assessment). Day-time BP and night-time BP were divided based on the subject's sleeping hours and hours awake.

Secondary Outcome Measures

1. Plasma Insulin Level Over 6 Weeks [6 weeks]

   After 10-12 h of overnight fasting, fasting blood samples were collected at week 0 (baseline) and week 3 and 6 of the intervention. plasma insulin were evaluated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• male and female

• pre-hypertensive

• systolic blood pressure (mmHg) 120 - 139 or

• diastolic blood pressure (mmHg) 80 -89

• no clinical evidence of cardiovascular, respiratory, renal, gastrointestinal or hepatic disease

Exclusion Criteria:

• pregnant and or lactating

• taking over the counter antioxidant supplements

• taking prescription medications that may interfere with study procedures or endpoints

• unusual dietary habits

• actively trying to lose or gain weight

• addicted to drugs and/or alcohol

• medically documented psychiatric or neurological disturbances

• smoker (past smoker may be allowed if cessation is > 2 years)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Nutrition Research Center	Chicago	Illinois	United States	60616

Sponsors and Collaborators

• Clinical Nutrition Research Center, Illinois Institute of Technology
• Polyphenolics, Inc.

Investigators

• Principal Investigator: Britt Burton-Freeman, PhD, Clinical Nutrition Research Center, Illinois Institute of Technology
• Principal Investigator: Indika Edirisinghe, PhD, Clinical Nutrition Research Center, Illinois Institute of Technology

Study Documents (Full-Text)

None provided.

More Information

Publications

• Brahmesh S, Edirisinghe I, Randolph J, Steinberg F and Kappagoda T. Effect of a polyphenoics extracts of grape seeds (GSE) on blood pressure in patients with metabolic syndrome (MetS). FASEBJ. 2006;20:A305.
• Edirisinghe I, Burton-Freeman B, Tissa Kappagoda C. Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract. Clin Sci (Lond). 2008 Feb;114(4):331-7.
• Sivaprakasapillai B, Edirisinghe I, Randolph J, Steinberg F, Kappagoda T. Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome. Metabolism. 2009 Dec;58(12):1743-6. doi: 10.1016/j.metabol.2009.05.030. Epub 2009 Jul 15.

• Responsible Party: Clinical Nutrition Research Center, Illinois Institute of Technology
• ClinicalTrials.gov Identifier: NCT00979732
• Other Study ID Numbers: GSE 2009-050
• First Posted: Sep 18, 2009
• Last Update Posted: Feb 11, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Clinical Nutrition Research Center, Illinois Institute of Technology: high blood pressure; dietary supplements; nutrition
• Additional relevant MeSH terms: Hypertension; Prehypertension; Grape Seed Extract

Study Results

Participant Flow

Recruitment Details	The study was performed at the Clinical Nutrition Research Center at the Illinois Institute of Technology (Chicago, IL, USA) from 2010 to 2014.
Pre-assignment Detail	Eligible subjects started with a 2-week run-in period drinking the Placebo beverage twice per day. After the 2-week run-in period, subjects were randomised to one of the two groups (Placebo or GSE beverage), equally allocated to each treatment (1:1 randomisation ratio).

Arm/Group Title	GSE Beverage Active	GSE Beverage Placebo
Arm/Group Description	grape seed extract beverage 150 mg/BID grape seed extract: grape seed extract 150 mg twice a day (BID) in beverage or capsule form	grape seed extract placebo beverage 150 mg/BID grape seed extract placebo: grape seed extract 150 mg twice a day (BID) in beverage or capsule form
Period Title: Overall Study
STARTED	15	18
COMPLETED	12	17
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	GSE Beverage Active	GSE Beverage Placebo	Total
Arm/Group Description	grape seed extract beverage 150 mg/BID grape seed extract: grape seed extract 150 mg twice a day (BID) in beverage or capsule form	grape seed extract placebo beverage 150 mg/BID grape seed extract placebo: grape seed extract 150 mg twice a day (BID) in beverage or capsule form	Total of all reporting groups
Overall Participants	12	17	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44 (10)	42 (10)	43 (10)
Sex: Female, Male (Count of Participants)
Female	6 50%	8 47.1%	14 48.3%
Male	6 50%	9 52.9%	15 51.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 8.3%	2 11.8%	3 10.3%
Not Hispanic or Latino	11 91.7%	15 88.2%	26 89.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 8.3%	2 11.8%	3 10.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 58.3%	7 41.2%	14 48.3%
White	4 33.3%	6 35.3%	10 34.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 11.8%	2 6.9%
Region of Enrollment (participants) [Number]
United States	12 100%	17 100%	29 100%

Outcome Measures

1. Primary Outcome

Title	Systolic Blood Pressure
Description	BP was monitored using ambulatory BP monitors (Ambulo2400; Tiba Medical, Inc.) that were programmed to take BP measurements automatically at 1-h intervals for a period of 24 h. BP measurements were scheduled at week 0 and 6 of the intervention (for efficacy assessment). Day-time BP and night-time BP were divided based on the subject's sleeping hours and hours awake.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

All completers

Arm/Group Title	GSE Beverage Active	GSE Beverage Placebo
Arm/Group Description	grape seed extract beverage 150 mg/BID grape seed extract: grape seed extract 150 mg twice a day (BID) in beverage or capsule form	grape seed extract placebo beverage 150 mg/BID grape seed extract placebo: grape seed extract 150 mg twice a day (BID) in beverage or capsule form
Measure Participants	12	17
Mean (Standard Error) [mmHg]	118 (2.3)	127 (1.9)

2. Secondary Outcome

Title	Plasma Insulin Level Over 6 Weeks
Description	After 10-12 h of overnight fasting, fasting blood samples were collected at week 0 (baseline) and week 3 and 6 of the intervention. plasma insulin were evaluated.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

All completer

Arm/Group Title	GSE Beverage Active	GSE Beverage Placebo
Arm/Group Description	grape seed extract beverage 150 mg/BID grape seed extract: grape seed extract 150 mg twice a day (BID) in beverage or capsule form	grape seed extract placebo beverage 150 mg/BID grape seed extract placebo: grape seed extract 150 mg twice a day (BID) in beverage or capsule form
Measure Participants	12	17
Mean (Standard Error) [µIU/mL]	17.8 (1.5)	20.9 (1.2)

Adverse Events

Time Frame	3 months
Arm/Group Title	GSE Beverage Active		GSE Beverage Placebo
Arm/Group Description	grape seed extract beverage 150 mg/BID grape seed extract: grape seed extract 150 mg twice a day (BID) in beverage or capsule form		grape seed extract placebo beverage 150 mg/BID grape seed extract placebo: grape seed extract 150 mg twice a day (BID) in beverage or capsule form
All Cause Mortality
	GSE Beverage Active		GSE Beverage Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/17 (0%)
Serious Adverse Events
	GSE Beverage Active		GSE Beverage Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	GSE Beverage Active		GSE Beverage Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/17 (0%)

Limitations/Caveats

The study was not sufficiently powered to detect significant differences on the secondary end points. We observed large inter-individual variability in plasma phenolic concentrations, requiring a greater sample size.

More Information

Certain Agreements

Principal Investigators are NOT 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.