Effect of a Grape Seed Extract (GSE) on Insulin Resistance

Study Overview
=================
Brief Summary
-----------------
In people with the metabolic syndrome, the investigators hypothesize that administration of a single 300 mg dose of a grape seed extract (GSE) will reduce insulin resistance (how well cells in the body can take up and use glucose), oxidative stress, and the amount of oxidized LDL in the blood during a 24 hour period. These measurements will be assessed at hourly intervals during the 24 hour study day protocol. Additionally, the investigators hypothesize that daily administration of 300 mg of GSE for 30 days will decrease baseline insulin resistance, oxidative stress, and the level of oxidized LDL in the blood.

Detailed Description
-----------------
In people with the metabolic syndrome, the investigators hypothesize that administration of a single 300 mg dose of a grape seed extract (GSE) will reduce insulin resistance (how well cells in the body can take up and use glucose), oxidative stress, and the amount of oxidized LDL in the blood during a 24 hour period. Each of these can be elevated after eating high fat meals, which are commonly found in the average Western diet. To better assess the impact of these high fat eating patterns, three standardized high fat meals will be served during the study day: breakfast, lunch, and dinner. Measurements in the blood will be assessed at hourly intervals during the 24 hour study day protocol. Additionally, the investigators hypothesize that daily administration of 300 mg of GSE for 30 days will decrease baseline insulin resistance, oxidative stress, and the level of oxidized LDL in the blood when this 24 hour study day protocol is repeated and breakfast, lunch, and dinner are again served. Insulin resistance will be measured using a comparison of insulin and glucose levels in the blood. Oxidative stress, a measure of inflammation, will be measured by cytokines levels in the blood. The level of oxidized LDL will be measured in the blood. The investigators also plan to undertake a subsidiary pharmacokinetic study on the various polymers which are known to be present in grape seed extracts to determine their bio-availability and their relationship to the biological effects observed.

Official Title
-----------------
Effect of a Grape Seed Extract (GSE) on Insulin Resistance

Conditions
-----------------
Metabolic Syndrome

Intervention / Treatment
-----------------
* Dietary Supplement: Grape Seed Extract
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Metabolic Syndrome, based on subject meeting at least 3 of the following criteria: Abdominal obesity with waist circumference > 40 inches in men or > 35 inches in women, Pre-hypertension with blood pressure > 135/85, Fasting blood glucose levels above 110 mg/dl, Plasma triglyceride levels in excess of 150 mg/dl, HDL levels below 40 mg/dl in men or 50 mg/dl in women. Exclusion Criteria: Any known systemic disease, Diabetes, Alcohol consumption > 1-2 drinks/week, Taking any medications or supplements that will affect metabolism, their ability to exercise or oxidative status, Smokers, Female subjects having abnormal menstrual cycles, taking oral contraceptives, pregnant or lactating.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 70 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Grape Seed Extract<br>This is a 30 day arm. At the baseline study visit, subjects will consume one 300 mg capsule of MegaNatural Gold followed by 3 high fat meals: breakfast, lunch, and dinner. Blood will be drawn at specified intervals throughout the day. Flow mediated dialysis will be performed before breakfast and again 1.5 hours later, after capsule consumption and breakfast. A minimum 14 day washout period will be between arms if this is the first arm in the randomized cross-over. | Dietary Supplement: Grape Seed Extract<br>* 300 mg capsule of Grape Seed Extract; 1 capsule will be consumed for an acute post-prandial study day and 1 capsule will be consumed daily for 30 days.<br>* Other names: MegaNatural Gold;|
| Placebo Comparator: Placebo<br>This is a 30 day arm. At the baseline study visit, subjects will consume one placebo (maltodextrin) capsule followed by 3 high fat meals: breakfast, lunch, and dinner. Blood will be drawn at specified intervals throughout the day. Flow mediated dialysis will be performed before breakfast and again 1.5 hours later, after capsule consumption and breakfast. A minimum 14 day washout period will be between arms if this is the first arm in the randomized cross-over. | Dietary Supplement: Placebo<br>* 300 mg capsule of maltodextrin; 1 capsule will be consumed for an acute post-prandial study day and 1 capsule will be consumed daily for 30 days.<br>* Other names: Maltodextrin;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in insulin resistance | Insulin resistance will be assessed by comparing the baseline fasting insulin concentration to the fasting insulin concentration after intervention period of 30 days; the Homeostatic Model Assessment (HOMA) value will be utilized for comparisons. | Baseline and 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in oxidized LDL (oxLDL) concentrations | Changes in oxLDL concentrations will be assessed by ELISA methodology. Changes in the 24 hour post-prandial response will be assessed at one hour intervals during the post-prandial study days, after capsule consumption and eating 3 high fat meals. | Baseline and 24 hour post-prandial response | 
| Changes in oxidative stress | Changes in the 24 hour post-prandial oxidative stress response will be assessed at one hour intervals during the post-prandial study days, after capsule consumption and eating 3 high fat meals. Changes in oxidative stress will be assessed by measuring cytokine production using ELISA methodology. | Baseline and 24 hour post-prandial response | 
| Changes in vascular stress | Changes in oxidative stress will be assessed by flow mediated dialysis (FMD). Changes will be assessed at baseline and one hour after capsule consumption and eating a high fat breakfast meal. | Baseline and 1 hour post-prandial | 
| Changes in insulin response | Changes in the 24 hour post-prandial insulin response will be assessed at one hour intervals during the post-prandial study days, after capsule consumption and eating 3 high fat meals. | Baseline and 24 hour post-prandial response | 
| Changes in oxidized LDL (oxLDL) concentrations | Changes in oxLDL concentrations will be assessed by ELISA methodology. Changes in the 24 hour post-prandial response will be assessed at one hour intervals during the post-prandial study days, after capsule consumption and eating 3 high fat meals. The response from the baseline visit will be compared to the response obtained during the day 30 visit. | Baseline and 30 days | 
| Changes in insulin response | Changes in the 24 hour post-prandial insulin response will be assessed at one hour intervals during the post-prandial study days, after capsule consumption and eating 3 high fat meals. The response from the baseline visit will be compared to the response obtained during the day 30 visit. | Baseline and 30 days | 
| Changes in oxidative stress | Changes in the 24 hour post-prandial oxidative stress response will be assessed at one hour intervals during the post-prandial study days, after capsule consumption and eating 3 high fat meals. Changes in oxidative stress will be assessed by measuring cytokine production using ELISA methodology. The response from the baseline visit will be compared to the response obtained during the 30 day visit. | Baseline and 30 days | 
| Changes in vascular stress | Changes in oxidative stress will be assessed by flow mediated dialysis (FMD). Changes will be assessed at baseline and one hour after capsule consumption and eating a high fat breakfast meal. Results obtained during the first post-prandial study visit will be compared to those obtained 30 days later. | Baseline and 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Insulin resistance, Central adiposity, Elevated blood pressure, Vascular reactivity, Elevated triglycerides, Low high-density lipoprotein (HDL)