Effect of Polyphenol Extract on Cardiovascular Health Markers: a 4 Way Randomised Crossover Study

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
Effect of Polyphenol Extract on Cardiovascular Health Markers: a 4 Way Randomised Crossover Study

Conditions
-----------------
Cardiovascular Diseases, Endothelial Dysfunction, Blood Pressure

Intervention / Treatment
-----------------
* Dietary Supplement: Polyphenol extract
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blind placebo controlled dose-response crossover study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polyphenol extract low dose<br>156mg single dose | Dietary Supplement: Polyphenol extract<br>* Single dose<br>|
| Experimental: Polyphenol extract medium dose<br>222mg single dose | Dietary Supplement: Polyphenol extract<br>* Single dose<br>|
| Experimental: Polyphenol extract high dose<br>333mg single dose | Dietary Supplement: Polyphenol extract<br>* Single dose<br>|
| Placebo Comparator: Placebo<br>Maltodextrin single dose | Dietary Supplement: Placebo<br>* Maltodextrin<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Flow Mediated Dilation, Polyphenols, Cardiovascular Disease, Endothelial Function