Grape Polyphenols and Second-meal Effect

Study Overview
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Brief Summary
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The aim of this is study is to evaluate the effects of a single intake of grapes (a polyphenol-rich food) in postprandial metabolism in subjects with obesity, including a first intake (high-fat breakfast) after overnight fasting a second one (medium-fat lunch). Studies on the effects of polyphenols on postprandial (glucidic and lipidic) metabolism have commonly been performed in animal models and have used grape extracts, ignoring the whole pool of polyphenols present in grapes (extractable and non-extractable polyphenols). Besides, the contribution of polyphenols to the so-called second-meal effect has not been explored. It should be highlighted that this study aims to explore the potential beneficial role of fresh grapes, consumed as fruit; in order to ensure the stability of the product, they will be provided as freeze-dried milled material, but the amount received by the subjects could be incorporated into a common diet, being equivalent to 300 g of fresh grapes.

Detailed Description
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Twenty-five subjects with obesity will be were recruited. Detailed inclusion and exclusion criteria are provided below. The subjects will receive, after overnight fasting, either a monodose of freeze-dried grapes (equivalent to 300 g of fresh grapes) or isocaloric placebo solved in water, together with a high-fat breakfast. Blood samples will be collected before the intake, up to 5 h after breakfast, then a medium-fat lunch will be provided and blood samples will be collected for three additional hours. Both interventions will be separated by two weeks. The following determinations will be performed in blood samples collected at different periods: glucose, insulin, triglycerides, uric acid, viscosity, antioxidant capacity. Additionally, a satiety test will be provided. It is expected that grape supplementation, as compared with an isocaloric placebo, causes significant modifications in all the parameters indicated. Nevertheless, the primary outcome of this study is the area under the curve for glucose after the second meal (300-420 min from basal time).

Official Title
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Potential Modulatory Effect of Whole Grape on Second-meal Tolerance in Obese Subjects: Role of Polyphenols

Conditions
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Obesity

Intervention / Treatment
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* Other: Freeze-dried grape (GRAP)/Placebo (PLA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obesity (BMI = 30-40 kg/m2). Exclusion Criteria: Subjects with a pharmaceutical treatment set to modify blood pressure, lipid profile or glucose. Subjects with diagnoses of type 2 diabetes, cardiovascular diseases or thyroid diseases. Values above the following ones: glucose, > 115 mg/dL; triglycerides, > 350 mg/dL; total cholesterol, > 280 mg/dL; systolic blood pressure, > 150 mmHg; diastolic blood pressure, > 100 mmHg Previous bariatric surgery. Volunteers participating in other studies (currently or during last year) or weight loss plans. Pregnant or breastfeeding women. Adherence to vegetarian diets or usual consumption of dietary supplements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: GRAP: dried and milled grape pomaces. PLA: control period. All the subjects will pass the two periods: one half will receive the acute PLA supplementation followed by the acute GRAP supplementation, and the other half will do it inversely. The assignment to each order will be done randomly. Both period will be separated by a two weeks washing period.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>All subjects will receive a high-fat breakfast and a medium-fat lunch twice. They will consume together with the breakfast the placebo (PLA) the first time and grape (GRAP) the second time. | Other: Freeze-dried grape (GRAP)/Placebo (PLA)<br>* The subjects will receive, after overnight fasting, either a monodose of freeze-dried grapes (equivalent to 300 g of fresh grapes) or isocaloric placebo solved in water, together with a high-fat breakfast. Blood samples will be collected before the intake, up to 5 h after breakfast, then a medium-fat lunch will be provided and blood samples will be collected for three additional hours. A total of 10 samples will be collected: 0-30-60-120-180-240-300-330-360-420 min. Both interventions will be separated by two weeks. Subjects will be instructed not to modify their dietary habits during the development of the study, but during the 72 h before each visit they will have to restrict the intake of polyphenol-rich foods (a detailed list will be provided).<br>|
| Experimental: 2<br>All subjects will receive a high-fat breakfast and a medium-fat lunch twice. They will consume together with the breakfast grape (GRAP) the first time and the placebo (PLA) the second time. | Other: Freeze-dried grape (GRAP)/Placebo (PLA)<br>* The subjects will receive, after overnight fasting, either a monodose of freeze-dried grapes (equivalent to 300 g of fresh grapes) or isocaloric placebo solved in water, together with a high-fat breakfast. Blood samples will be collected before the intake, up to 5 h after breakfast, then a medium-fat lunch will be provided and blood samples will be collected for three additional hours. A total of 10 samples will be collected: 0-30-60-120-180-240-300-330-360-420 min. Both interventions will be separated by two weeks. Subjects will be instructed not to modify their dietary habits during the development of the study, but during the 72 h before each visit they will have to restrict the intake of polyphenol-rich foods (a detailed list will be provided).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial glucose (300-420 min) | Changes of postprandial blood glucose as result of supplementation with grapes, measured area under the curve for the period 300-420 min | Up to two months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polyphenols, Obesity, Grape, Postprandial, Insulin resistance, Second meal effect