Effect of Polyphenol Extract on Cardiovascular Health Markers: a 4 Way Randomised Crossover Study (Activ Acute)

Endothelial dysfunction is an early predictor of cardiovascular events in at-risk patients. It is characterized by impaired endothelium-dependent dilation and is primarily caused by reduced nitric oxide bioavailability secondary to oxidative stress and inflammation. Finding dietary/dietary supplement-oriented approaches to improving endothelial function is of public health interest.

A randomized double-blind placebo controlled 4-way crossover study will be conducted to determine if acute consumption of a proprietary polyphenol extract (156 mg / 222 mg / 333 mg) will have a dose dependent response on endothelium-dependent flow-mediated dilation (ED-FMD) in fasting conditions, in comparison to a placebo (maltodextrin) in male smokers (20 - 45 years; n=20).FMD and blood pressure will be assessed at 0 & 2 hour timepoints following consumption of a single dose of polyphenol extract, accompanying blood samples will be collected to assess a range of endpoints including nitric oxide metabolites, angiotensin and polyphenols metabolites. Endothelium-independent vasodilation will also be measured 2 hours post consumption.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Blood Pressure; Endothelial Dysfunction
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Polyphenol extract

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christopher Gill; Phone Number: +442870123181; Email: c.gill@ulster.ac.uk

Study Locations

• United Kingdom
  • Co.Londonderry
    • Coleraine, Co.Londonderry, United Kingdom, BT52 1SA
      • Recruiting
      • Human Intervention Studies Unit, Ulster University
      • Contact: Ruth K Price; Phone Number: +442870123878; Email: rk.price@ulster.ac.uk
      • Contact: Julie J Sittlington; Phone Number: +442870124101; Email: jj.sittlington@ulster.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• At least two of the following risk markers; a BMI 25-30, waist circumference >94 cm, high normal blood pressure defined as either systolic 85-89 mmHg or diastolic 130-139 mmHg and have a normal ECG.

Exclusion Criteria:

• An individual who has tested positive (self reported) 2 weeks before the study period.
• A COVID-19 vaccinated individual who while receive the 1st or 2nd dose or booster 2 weeks before V0 or during the study period, due to the potential interaction of vaccine on markers assessed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polyphenol extract low dose; 156mg single dose	Dietary supplement: Polyphenol extract; Single dose
Experimental: Polyphenol extract medium dose; 222mg single dose	Dietary supplement: Polyphenol extract; Single dose
Experimental: Polyphenol extract high dose; 333mg single dose	Dietary supplement: Polyphenol extract; Single dose
Placebo Comparator: Placebo; Maltodextrin single dose	Dietary supplement: Placebo; Maltodextrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow Mediated Dilation	Acute change in endothelium-dependent flow-mediated dilation	Change over 2 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelium-independent vasodilation	Acute change in endothelium-independent vasodilation in response to Glyceryl trinitrate (GTN) drug	Change after 2 hours post dose
Systolic blood pressure	Measured by brachial cuff	Change over 2 hours post dose
Diastolic blood pressure	Measured by brachial cuff	Change over 2 hours post dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid profile	Measured in serum	Visit 1, 0 hour only
Glucose	Measured in plasma	Visit 1, 0 hour only
Tolerance and acceptability of extract	Safety parameter. Measured on a 3-point likert scale (a lower value being a better outcome: 1, totally acceptable - 3, not at all acceptable)	Immediately after each intervention
Height	Measured in metres	Visit 1, 0 hour only
Weight	Measured in kg	0 hour, at each time-point
Angiotensin-converting enzyme (ACE)	Exploratory outcome	Change over 2 hours
Circulating polyphenol metabolites	Exploratory outcome. Measured in plasma	Change over 2 hours
Endothelin1	Exploratory outcome. Measured in serum	Change over 2 hours

Collaborators and Investigators

• Sponsor: University of Ulster
• Collaborators: University of Parma; Activ'inside

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): December 1, 2021
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: November 26, 2021
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 11, 2022
• Last Update Submitted That Met QC Criteria: March 10, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Endothelial Function; Cardiovascular Disease; Polyphenols; Flow Mediated Dilation
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: REC/21/0029

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No