Impact of Consuming Plant Sterols on Endothelial Function and Blood Pressure

Study Overview
=================
Brief Summary
-----------------
The purpose of the research is to assess the impact of co-consuming plant sterols-enriched food product as part of a healthy eating pattern diet on endothelial function (brachial artery FMD, vasodilation-related and vasoconstriction-related biomarkers) and blood pressure management (24-hour ambulatory and classic blood pressure) in Singapore individuals with MetS.

Detailed Description
-----------------
This is a 13-wk double-blinded, randomized, crossover study design. Following a 1-wk pre-intervention baseline period, subjects will be randomly assigned to follow a healthy eating pattern diet either contain 2.0 g free plant sterols equivalent of their palmityl esters (Plant Sterol Diet) or do not contain plant sterols (Control Diet) for 4 weeks. After a 4-week dietary 'washout' period, they will consume the alternative diet for 4 weeks. The random assignment will be done with SAS 9.4 software. Body size measurement, dietary assessment, brachial artery FMD and blood pressure measurements, and fasting-state blood collection will be conducted at week 1, 5, 9, and 13, which correspond to before and during the last 1 week of the two 4-week intervention periods. During study week 1 and weeks 6-9, all subjects will consume their habitual, unrestricted self-chosen diets. During study weeks 2-5 and 10-13, all subject will follow a healthy eating pattern diet, referred to as the My Healthy Plate designed by HPB. Each subject's energy requirement will be estimated using sex-specific equations and Recommended Dietary Allowances for healthy Singaporean. One-on-one dietary counselling and written instructions for each subject will be provided by a research dietitian and trained research staff to achieve a healthy eating pattern diet. Compliance with the plant sterols consumption will be promoted by frequent online and in-person contact.

Official Title
-----------------
Impact of Co-consuming a Plant Sterols-enriched Food Product With a Healthy Eating Pattern Diet on Endothelial Function and Blood Pressure Management in Individuals With Metabolic Syndrome

Conditions
-----------------
Cardiovascular Diseases, Endothelial Dysfunction, Metabolic Syndrome, Diet Modification

Intervention / Treatment
-----------------
* Dietary Supplement: plant sterols
* Other: healthy diet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ability to give an informed consent; Age>35 years old; Meet any 3 of the 5 following NCEP-ATP III MetS criteria (waist circumference > 90 cm (male), > 80 cm (female); fasting glucose concentration ≥ 100 mg/dL or on medication; triglyceride ≥ 150 mg/dL or on medication; high density lipoprotein cholesterol (HDL) < 40 mg/dL (male), < 50 mg/dL (female); systolic or diastolic blood pressure > 130/80 mmHg or on medication); Weight change < 3kg in the past 3 months; No exercising vigorously over the past 3 months; No allergy to plant sterols; no acute illness; not smoking; No drinking more than 2 alcoholic drinks per day; No pregnant, lactating, or planning pregnancy in the next 6 months. Exclusion Criteria: Unable to give an informed consent; Age<35 years old; Meet less than 3 of following NCEP-ATP III MetS criteria (waist circumference > 90 cm (male), > 80 cm (female); fasting glucose concentration ≥ 100 mg/dL or on medication; triglyceride ≥ 150 mg/dL or on medication; high density lipoprotein cholesterol (HDL) < 40 mg/dL (male), < 50 mg/dL (female); systolic or diastolic blood pressure > 130/80 mmHg or on medication); Weight change > 3kg in the past 3 months; Exercise vigorously over the past 3 months; Allergy to plant sterols; no acute illness; not smoking; Drinking more than 2 alcoholic drinks per day; Pregnant, lactate, or plan pregnancy in the next 6 months.

Ages Eligible for Study
-----------------
Minimum Age: 35 Years

Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plant sterol with a healthy diet<br>Each subject will be provided one-to-one dietary counselling by a research dietitian and an instruction sheet to achieve the healthy eating pattern diet. Subjects will also be provided with specific instructions to consume plant sterols-enriched food (contains 2 g plant sterols). | Dietary Supplement: plant sterols<br>* Consumption a healthy eating pattern diet with a plant sterols-enriched food product<br>Other: healthy diet<br>* Compliance with a healthy diet in accordance to the recommendation by the Singapore Health Promotion Board.<br>|
| Active Comparator: Healthy diet<br>Each subject will be provided one-to-one dietary counselling by a research dietitian and an instruction sheet to achieve the healthy eating pattern diet. | Other: healthy diet<br>* Compliance with a healthy diet in accordance to the recommendation by the Singapore Health Promotion Board.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in brachial artery flow-mediated dilation (FMD) | Brachial artery FMD will be measured by high-frequency and ultrasonographic imaging. | Every 4 weeks (Week 1, week 5, week 9, week 13) | 
| Change in vasodilation and vasoconstriction related biomarkers | Vasodilation and vasoconstriction related biomarkers contains nitric oxide, endothelial nitric oxide synthase, and endothelin-1. They will be measured using the commercially available ELISA assay kits. | Every 4 weeks (Week 1, week 5, week 9, week 13) | 
| Change in blood pressure | Classical and 24-hour ambulatory blood pressure: Systolic and diastolic blood pressure and 5-day of 24-hour ambulatory blood pressure will be measured. | Every 4 weeks (Week 1, week 5, week 9, week 13) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood lipid-lipoproteins | Assessing the blood lipid-lipoproteins profile includes the measurements of plasma total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations. | Every 4 weeks (Week 1, week 5, week 9, week 13) | 
| Change in skin carotenoid status | Measured using resonance Raman spectroscopy. | Every 4 weeks (Week 1, week 5, week 9, week 13) | 
| Height | Height (cm) | Pre-intervention only | 
| Change in weight | Weight (kg) | Every 4 weeks (Week 1, week 5, week 9, week 13) | 
| Change in waist circumference | Waist circumference (cm) | Every 4 weeks (Week 1, week 5, week 9, week 13) | 
| Change in diet | Dietary assessment, 3-day food record | Every 4 weeks (Week 1, week 5, week 9, week 13) | 
| Change in sleep quality (Pittsburgh sleep quality index questionnaire (PSQI)) | Recall based questionnaire assessing sleep habits for the past one month only which includes sleeping timing habits and quality of sleep (Very good, Fairly good, Fairly bad and very bad) | Every 4 weeks (Week 1, week 5, week 9, week 13) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Endothelial function, Blood pressure, healthy diet