Back to resultsCocoa and Metabolic Health in Prediabetes
Primary Purpose
Prediabetes
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Cocoa
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Prediabetes focused on measuring Cacao, Polyphenols, Prediabetic State, Blood Glucose, Glucose Intolerance, Diabetes Mellitus, Type 2, Obesity, Muscle, Skeletal, Endotoxins, Gut Permeability, Incretins, Metabolic Flexibility
Eligibility Criteria
Inclusion Criteria:
- Body Mass Index (BMI) greater than or equal to 25 and less than 40.
- Have at least one of the following: 1) impaired fasting glucose (IFG) after an overnight fast with plasma glucose concentration between 100-125 mg/dl, 2) impaired glucose tolerance (IGT) as identified by the standard Oral Glucose Tolerance Test (OGTT) with 2 hour plasma glucose concentration between 140-200 mg/dl following 75 g glucose OGTT, 3) HbA1c levels between 5.7-6.4% or 4) considered at risk to developing type 2 diabetes by the American Diabetes Association risk assessment. If subjects are above the prediabetic range for any of these tests (indicating they may be type 2 diabetic), they will be excluded and referred to their physician.
- Weight stable (+/-2 kg) for the last 6 months.
- Sedentary to recreationally active (less than 2 d/wk, 20 min/d).
- Have a blood pressure that is less than 160/100 mmHg, total cholesterol that is less than 300 mg/dl and a triglyceride concentration of less than 450 mg/dl.
Exclusion Criteria:
- Past or current history of coronary heart disease, stroke or major cardiovascular disease events, respiratory diseases, endocrine or metabolic diseases (including type 1 and type 2 diabetes), inflammatory bowel disease, cancer, or neurological or hematological disorders that would compromise the study or the health of the subject.
- Past or current history of gastrointestinal disorders (including lactose intolerance, ulcers, cancer (stomach, intestinal, colon, pancreatic, liver, etc) NASH, NAFLD, cirrhosis, IBD/IBS, celiac disease, etc).
- Current use of any medication including but not limited to cholesterol lowering medication (including fibric acid derivatives and niacin), antibiotics, immunosuppressive drugs, azole antifungals, non-steroidal anti-inflammatory drugs (NSAIDs), hormone replacement therapy or antioxidants/supplements.
- Use of antibiotics, prebiotics, or probiotics within the prior 3 months.
- Smoking or other tobacco use
- Habitual consumption of alcohol more than 2 servings/d for males and 1 serving/d for females.
- Strict vegetarians or vegans, or strong aversions to major food groups that may be part of the controlled diet.
- Recent surgery
- History of alcohol or drug abuse.
- Pregnant or plan to become pregnant
- Allergic to either lidocaine or bupivacaine
Sites / Locations
- Human Integrative Physiology Laboratory
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Cocoa
Placebo
Arm Description
3 servings of polyphenol-rich cocoa beverage consumed per day.
3 servings of non-cocoa beverage consumed per day.
Outcomes
Primary Outcome Measures
Change in insulin sensitivity
Insulin sensitivity will be determined using Bergman's minimal model (MINMOD Millennium software) via a frequently sampled intravenous glucose tolerance test (IVGTT). Fasting baseline blood samples will be taken prior to the dextrose injection (0.3 g/kg; 50% solution) at minute 0. Venous samples will be collected at minutes 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, and 18. Insulin (0.025 U/kg) will be injected at minute 20. Venous sampling will continue at minutes 22, 23, 24, 25, 27, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180. Glucose concentration will be immediately analyzed an automated glucose oxidase analyzer. Insulin will be later measured from serum using the Immulite 1000 immunoassay analyzer.
Secondary Outcome Measures
Change in blood glucose response to a mixed meal
The test meal will be 2-8 oz. servings of a meal replacement beverage providing a mixed macronutrient profile, supplemented with either a cocoa beverage dry mix (10 g cocoa) or a calorie-matched placebo beverage mix (0 g cocoa). Blood samples will be taken at baseline and subsequently 1, 2, 3, and 4 hours after the first sip of the test beverage. Plasma glucose concentrations will be analyzed immediately using a glucose auto-analyzer (Yellow Springs Instruments).
Change in hormone secretion response to a mixed meal
Serum insulin, GLP-1, GIP, and C-peptide concentrations will be determined using commercially available enzyme-linked immunosorbent assay (ELISA) kits from the blood samples drawn at baseline, 1, 2, 3, and 4 hours during the mixed meal challenge.
Change in skeletal muscle metabolic flexibility
Subjects will consume a high fat meal containing 820 kcal; 52 g total carbohydrates, 24 g protein, and 58 g fat. During the high fat challenge session, two skeletal muscle biopsies will be conducted on alternate legs; one before the high fat meal and one 4 hours later. Biopsies of the vastus lateralis will be performed using a 5 mm modified Bergström needle. Collected tissue will be washed in 0.9% sterile saline to remove blood and tissue. Samples will be weighed and added to buffer and placed on ice for immediate analysis of substrate flexibility. For substrate flexibility, pyruvate oxidation will be used to assess the activity of pyruvate dehydrogenase. Calculated metabolic flexibility is expressed as a ratio of pyruvate oxidation to pyruvate oxidation + free fatty acids.
Change in blood endotoxin levels
During the high fat challenge (see Outcome 4), blood samples will be collected at baseline and 1, 2, 3, and 4 h after the first bite of the meal. Serum endotoxin will be measured in duplicate using Limulus Amebocyte Lysate Pyrogent ® 5000 assay kits.
Change in gut permeability
The four-sugar [40 g sucrose, 1 g mannitol, 1 g sucralose and 5 g lactulose] probe test will be used to assess total gut permeability. After an overnight fast and urine evacuation, participants will be asked to consume the sugar-probe beverage within 5 minutes. They will be given two breakfast sandwiches to consume immediately. Participants will be instructed to collect all of their urine in a provided container from the time the beverage was consumed (0 h) until 5 h. A second urine collection container will be filled between 6-24 h. Twenty-four hours later, the volume of urine in each container will be measured and aliquots collected for later analysis. Gastroduodenal permeability is defined as sucrose/mannitol ratio (0-5 h). Small intestinal permeability is defined as the calculated lactulose/mannitol ratio for 0-5 samples. Colonic permeability is defined as both the 6-24 h lactulose/mannitol ratio and 6-24 h sucralose/mannitol ratio.
Full Information
NCT ID
NCT02203240
First Posted
July 26, 2014
Last Updated
September 18, 2023
Sponsor
Virginia Polytechnic Institute and State University
Collaborators
The Hershey Company
1. Study Identification
Unique Protocol Identification Number
NCT02203240
Brief Title
Cocoa and Metabolic Health in Prediabetes
Official Title
Dietary Cocoa for Inhibition of Metabolic Endotoxemia and Glucose Intolerance
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
May 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Virginia Polytechnic Institute and State University
Collaborators
The Hershey Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the impact of consuming cocoa on blood glucose levels, glucose metabolism, and other markers of pre-diabetes in overweight and/or obese individuals. Our hypothesis is that consumption of cocoa improves insulin sensitivity and glucose metabolism in subjects at risk for developing type-2 diabetes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prediabetes
Keywords
Cacao, Polyphenols, Prediabetic State, Blood Glucose, Glucose Intolerance, Diabetes Mellitus, Type 2, Obesity, Muscle, Skeletal, Endotoxins, Gut Permeability, Incretins, Metabolic Flexibility
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cocoa
Arm Type
Experimental
Arm Description
3 servings of polyphenol-rich cocoa beverage consumed per day.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
3 servings of non-cocoa beverage consumed per day.
Intervention Type
Other
Intervention Name(s)
Cocoa
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change in insulin sensitivity
Description
Insulin sensitivity will be determined using Bergman's minimal model (MINMOD Millennium software) via a frequently sampled intravenous glucose tolerance test (IVGTT). Fasting baseline blood samples will be taken prior to the dextrose injection (0.3 g/kg; 50% solution) at minute 0. Venous samples will be collected at minutes 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, and 18. Insulin (0.025 U/kg) will be injected at minute 20. Venous sampling will continue at minutes 22, 23, 24, 25, 27, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180. Glucose concentration will be immediately analyzed an automated glucose oxidase analyzer. Insulin will be later measured from serum using the Immulite 1000 immunoassay analyzer.
Time Frame
Baseline and 4 weeks
Secondary Outcome Measure Information:
Title
Change in blood glucose response to a mixed meal
Description
The test meal will be 2-8 oz. servings of a meal replacement beverage providing a mixed macronutrient profile, supplemented with either a cocoa beverage dry mix (10 g cocoa) or a calorie-matched placebo beverage mix (0 g cocoa). Blood samples will be taken at baseline and subsequently 1, 2, 3, and 4 hours after the first sip of the test beverage. Plasma glucose concentrations will be analyzed immediately using a glucose auto-analyzer (Yellow Springs Instruments).
Time Frame
Baseline and 1 week
Title
Change in hormone secretion response to a mixed meal
Description
Serum insulin, GLP-1, GIP, and C-peptide concentrations will be determined using commercially available enzyme-linked immunosorbent assay (ELISA) kits from the blood samples drawn at baseline, 1, 2, 3, and 4 hours during the mixed meal challenge.
Time Frame
Baseline and 1 week
Title
Change in skeletal muscle metabolic flexibility
Description
Subjects will consume a high fat meal containing 820 kcal; 52 g total carbohydrates, 24 g protein, and 58 g fat. During the high fat challenge session, two skeletal muscle biopsies will be conducted on alternate legs; one before the high fat meal and one 4 hours later. Biopsies of the vastus lateralis will be performed using a 5 mm modified Bergström needle. Collected tissue will be washed in 0.9% sterile saline to remove blood and tissue. Samples will be weighed and added to buffer and placed on ice for immediate analysis of substrate flexibility. For substrate flexibility, pyruvate oxidation will be used to assess the activity of pyruvate dehydrogenase. Calculated metabolic flexibility is expressed as a ratio of pyruvate oxidation to pyruvate oxidation + free fatty acids.
Time Frame
Baseline and 4 weeks
Title
Change in blood endotoxin levels
Description
During the high fat challenge (see Outcome 4), blood samples will be collected at baseline and 1, 2, 3, and 4 h after the first bite of the meal. Serum endotoxin will be measured in duplicate using Limulus Amebocyte Lysate Pyrogent ® 5000 assay kits.
Time Frame
Baseline and 4 weeks
Title
Change in gut permeability
Description
The four-sugar [40 g sucrose, 1 g mannitol, 1 g sucralose and 5 g lactulose] probe test will be used to assess total gut permeability. After an overnight fast and urine evacuation, participants will be asked to consume the sugar-probe beverage within 5 minutes. They will be given two breakfast sandwiches to consume immediately. Participants will be instructed to collect all of their urine in a provided container from the time the beverage was consumed (0 h) until 5 h. A second urine collection container will be filled between 6-24 h. Twenty-four hours later, the volume of urine in each container will be measured and aliquots collected for later analysis. Gastroduodenal permeability is defined as sucrose/mannitol ratio (0-5 h). Small intestinal permeability is defined as the calculated lactulose/mannitol ratio for 0-5 samples. Colonic permeability is defined as both the 6-24 h lactulose/mannitol ratio and 6-24 h sucralose/mannitol ratio.
Time Frame
Baseline and 4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Body Mass Index (BMI) greater than or equal to 25 and less than 40.
Have at least one of the following: 1) impaired fasting glucose (IFG) after an overnight fast with plasma glucose concentration between 100-125 mg/dl, 2) impaired glucose tolerance (IGT) as identified by the standard Oral Glucose Tolerance Test (OGTT) with 2 hour plasma glucose concentration between 140-200 mg/dl following 75 g glucose OGTT, 3) HbA1c levels between 5.7-6.4% or 4) considered at risk to developing type 2 diabetes by the American Diabetes Association risk assessment. If subjects are above the prediabetic range for any of these tests (indicating they may be type 2 diabetic), they will be excluded and referred to their physician.
Weight stable (+/-2 kg) for the last 6 months.
Sedentary to recreationally active (less than 2 d/wk, 20 min/d).
Have a blood pressure that is less than 160/100 mmHg, total cholesterol that is less than 300 mg/dl and a triglyceride concentration of less than 450 mg/dl.
Exclusion Criteria:
Past or current history of coronary heart disease, stroke or major cardiovascular disease events, respiratory diseases, endocrine or metabolic diseases (including type 1 and type 2 diabetes), inflammatory bowel disease, cancer, or neurological or hematological disorders that would compromise the study or the health of the subject.
Past or current history of gastrointestinal disorders (including lactose intolerance, ulcers, cancer (stomach, intestinal, colon, pancreatic, liver, etc) NASH, NAFLD, cirrhosis, IBD/IBS, celiac disease, etc).
Current use of any medication including but not limited to cholesterol lowering medication (including fibric acid derivatives and niacin), antibiotics, immunosuppressive drugs, azole antifungals, non-steroidal anti-inflammatory drugs (NSAIDs), hormone replacement therapy or antioxidants/supplements.
Use of antibiotics, prebiotics, or probiotics within the prior 3 months.
Smoking or other tobacco use
Habitual consumption of alcohol more than 2 servings/d for males and 1 serving/d for females.
Strict vegetarians or vegans, or strong aversions to major food groups that may be part of the controlled diet.
Recent surgery
History of alcohol or drug abuse.
Pregnant or plan to become pregnant
Allergic to either lidocaine or bupivacaine
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew P Neilson, PhD
Organizational Affiliation
Virginia Polytechnic Institute and State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Human Integrative Physiology Laboratory
City
Blacksburg
State/Province
Virginia
ZIP/Postal Code
24061
Country
United States
12. IPD Sharing Statement
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Cocoa and Metabolic Health in Prediabetes
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