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

• ClinicalTrials.gov Identifier: NCT01889368
• Recruitment Status: Completed
• First Posted: June 28, 2013
• Last Update Posted: June 27, 2017
• Sponsor: University of California, Davis
• Collaborator: Illinois Institute of Technology
• Information provided by (Responsible Party): University of California, Davis

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Metabolic Syndrome	Dietary Supplement: Grape Seed Extract; Dietary Supplement: Placebo	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Effect of a Grape Seed Extract (GSE) on Insulin Resistance
• Actual Study Start Date: November 2012
• Actual Primary Completion Date: March 2015
• Actual Study Completion Date: March 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Grape Seed Extract; 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; 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.; Other Name: MegaNatural Gold
Placebo Comparator: Placebo; 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; 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.; Other Name: Maltodextrin

Outcome Measures

Primary Outcome Measures :

1. Changes in insulin resistance [ Time Frame: Baseline and 30 days ]
   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.

Secondary Outcome Measures :

1. Changes in oxidized LDL (oxLDL) concentrations [ Time Frame: Baseline and 24 hour post-prandial response ]
   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.
2. Changes in oxidative stress [ Time Frame: Baseline and 24 hour post-prandial response ]
   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.
3. Changes in vascular stress [ Time Frame: Baseline and 1 hour post-prandial ]
   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.
4. Changes in insulin response [ Time Frame: Baseline and 24 hour post-prandial 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.
5. Changes in oxidized LDL (oxLDL) concentrations [ Time Frame: Baseline and 30 days ]
   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.
6. Changes in insulin response [ Time Frame: Baseline and 30 days ]
   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.
7. Changes in oxidative stress [ Time Frame: Baseline and 30 days ]
   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.
8. Changes in vascular stress [ Time Frame: Baseline and 30 days ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

VA Hospital, Mather

Mather, California, United States, 95655

Sponsors and Collaborators

University of California, Davis

Illinois Institute of Technology

Investigators

• Principal Investigator: Chulani T Kappagoda, MD, PhD; University of California, Davis

More Information

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT01889368
• Other Study ID Numbers: 329493; 329493-4 ( Other Identifier: UC Davis )
• First Posted: June 28, 2013
• Last Update Posted: June 27, 2017
• Last Verified: June 2017

Keywords provided by University of California, Davis:

Insulin resistance; Central adiposity; Elevated blood pressure; Vascular reactivity; Elevated triglycerides; Low high-density lipoprotein (HDL)

Additional relevant MeSH terms:

Metabolic Syndrome; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Grape Seed Extract; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs