search
Back to results

Resveratrol and First-degree Relatives of Type 2 Diabetic Patients

Primary Purpose

Pre-diabetes

Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
placebo
resveratrol
Sponsored by
Maastricht University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Pre-diabetes focused on measuring Resveratrol, Diabetes Mellitus, Diabetes Mellitus, Type 2, Insulin Resistance, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Hyperinsulinism, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Pharmacologic Actions, Anti-Inflammatory Agents, Therapeutic Uses, Antirheumatic Agents, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Antioxidants, Molecular Mechanisms of Pharmacological Action, Protective Agents, Enzyme Inhibitors, Platelet Aggregation Inhibitors, Hematologic Agents, Antimutagenic Agents, Anticarcinogenic Agents, Central Nervous System Agents, Brown Adipose Tissue

Eligibility Criteria

40 Years - 70 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Male sex
  • Age: 40-70 years
  • BMI 27-35 kg/m2
  • Has first-degree relative(s) diagnosed with type 2 diabetes
  • Sedentary
  • Not more than 2 hours of sports a week
  • No active job that requires strenuous physical activity
  • Stable dietary habits: no weight gain or loss > 5kg in the last three months
  • Insulin resistant: glucose clearance rate below < 350 ml/kg/min, as determined using OGIS120
  • Willingness to abstain from resveratrol-containing food products
  • Subjects will only be included when the dependent medical doctor of this study approves participation after evaluating data obtained during screening

Exclusion Criteria:

  • Use of anticoagulants
  • Uncontrolled hypertension
  • Haemoglobin <7.8 mmol/l
  • In case of an abnormal ECG in rest: this will be discussed with the responsible medical doctor
  • HBA1C > 6.5%
  • Diagnosed with type 2 diabetes
  • Medication use known to interfere with glucose homeostasis/metabolism
  • Current alcohol consumption > 20 grams/day
  • Subjects who don't want to be informed about unexpected medical findings during the screening /study, or do not wish that their physician is informed, cannot participate in the study.
  • Subjects who intend to donate blood during the intervention or subjects who have donated blood less than three months before the start of the intervention.
  • Participation in another biomedical study within 1 month before the first screening visit
  • Any condition, disease or abnormal laboratory test result that, in the opinion of the Investigator, would interfere with the study outcome, affect trial participation or put the subject at undue risk

  • Any contra-indication to MRI scanning. These contra-indications include patients with following devices:

    • Central nervous system aneurysm clip
    • Implanted neural stimulator
    • Implanted cardiac pacemaker of defibrillator
    • Cochlear implant
    • Insulin pump
    • Metal containing corpora aliena in the eye or brains

Sites / Locations

  • Maastricht University Medical Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

resveratrol

placebo

Arm Description

resveratrol will be given for 30 or 34 days (if included in brown adipose tissue measurement), twice daily. One pill, which contains 75 mg of resveratrol, will be provided with lunch, and the other pill of 75 mg will be provided with dinner. So in total 150 mg/day of resveratrol will be given.

A placebo will be given for 30 or 34 days (if included in brown adipose tissue measurement), twice daily. One pill will be provided with lunch and the other pill will be provided with dinner.

Outcomes

Primary Outcome Measures

insulin sensitivity: overall, muscle- and liver specific
Hyperinsulinemic euglycemic clamp combined with indirect calorimetry: Glucose infusion rate (GIR), rate of appearance and disappearance of glucose (Ra, Rd), endogenous glucose production (EGP), oxidative and non-oxidative glucose disposal, carbohydrate and lipid oxidation, energy expenditure.

Secondary Outcome Measures

muscle mitochondrial oxidative capacity (in vivo and ex vivo)
In vivo: Phosphocreatine levels will be measured by P-MRS (before, during, and after exercise) as a marker for in vivo mitochondrial function in the vastus lateralis muscle. Ex vivo mitochondrial function in skeletal muscle will be measured by oxygen consumption in muscle fibres (muscle biopsy) on lipid-derived and carbohydrate-derived substrates.
intramyocellular lipid content
Skeletal muscle lipid accumulation measured by immunohistochemistry in muscle biopsy from vastus lateralis muscle
intrahepatic lipid content
Intrahepatic lipid content measured with H-MRS
intracardiac lipid content
Intracardiac lipid content measured with H-MRS
heart function
Cardiac function: diastolic and systolic heart function will be measured with ultrasound
brown adipose tissue activity
subjects will be exposed to an individualized cooling protocol, after which an 18F-FDG PET/CT scan is made

Full Information

First Posted
April 24, 2014
Last Updated
August 7, 2017
Sponsor
Maastricht University Medical Center
Collaborators
DSM Nutritional Products, Inc., Diabetes Fonds
search

1. Study Identification

Unique Protocol Identification Number
NCT02129595
Brief Title
Resveratrol and First-degree Relatives of Type 2 Diabetic Patients
Official Title
Effects of Resveratrol on Insulin Sensitivity, Brown Adipose Tissue and Metabolic Profile in First-degree Relatives of Type 2 Diabetic Patients
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
April 2014 (undefined)
Primary Completion Date
April 2017 (Actual)
Study Completion Date
July 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maastricht University Medical Center
Collaborators
DSM Nutritional Products, Inc., Diabetes Fonds

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main objective of the study is to investigate if resveratrol supplementation can improve overall and muscle-specific insulin sensitivity in first-degree relatives of type 2 diabetic patients. As a secondary objective the investigators want to investigate whether the improved insulin sensitivity can be attributed to improved muscle mitochondrial oxidative capacity and a reduced intrahepatic and cardiac lipid content. Furthermore, in a subset of the participants the investigators want to investigate the effect of resveratrol on glucose uptake in brown adipose tissue.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pre-diabetes
Keywords
Resveratrol, Diabetes Mellitus, Diabetes Mellitus, Type 2, Insulin Resistance, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Hyperinsulinism, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Pharmacologic Actions, Anti-Inflammatory Agents, Therapeutic Uses, Antirheumatic Agents, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Antioxidants, Molecular Mechanisms of Pharmacological Action, Protective Agents, Enzyme Inhibitors, Platelet Aggregation Inhibitors, Hematologic Agents, Antimutagenic Agents, Anticarcinogenic Agents, Central Nervous System Agents, Brown Adipose Tissue

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
resveratrol
Arm Type
Active Comparator
Arm Description
resveratrol will be given for 30 or 34 days (if included in brown adipose tissue measurement), twice daily. One pill, which contains 75 mg of resveratrol, will be provided with lunch, and the other pill of 75 mg will be provided with dinner. So in total 150 mg/day of resveratrol will be given.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
A placebo will be given for 30 or 34 days (if included in brown adipose tissue measurement), twice daily. One pill will be provided with lunch and the other pill will be provided with dinner.
Intervention Type
Dietary Supplement
Intervention Name(s)
placebo
Intervention Description
A placebo will given for 30 days or 34 days (if included in brown adipose tissue measurement), twice daily. One pill will be provided with lunch, and the other pill will be provided with dinner.
Intervention Type
Dietary Supplement
Intervention Name(s)
resveratrol
Other Intervention Name(s)
resVida (99% pure trans-resveratrol)
Intervention Description
resveratrol will be given for 30 days or 34 days (if included in brown adipose tissue measurement), twice daily. One pill, which contains 75 mg of resveratrol, will be provided with lunch, and the other pill, also containing 75 mg will be given with dinner. So in total a dose of 150 mg/day will be given.
Primary Outcome Measure Information:
Title
insulin sensitivity: overall, muscle- and liver specific
Description
Hyperinsulinemic euglycemic clamp combined with indirect calorimetry: Glucose infusion rate (GIR), rate of appearance and disappearance of glucose (Ra, Rd), endogenous glucose production (EGP), oxidative and non-oxidative glucose disposal, carbohydrate and lipid oxidation, energy expenditure.
Time Frame
30 days after supplementation
Secondary Outcome Measure Information:
Title
muscle mitochondrial oxidative capacity (in vivo and ex vivo)
Description
In vivo: Phosphocreatine levels will be measured by P-MRS (before, during, and after exercise) as a marker for in vivo mitochondrial function in the vastus lateralis muscle. Ex vivo mitochondrial function in skeletal muscle will be measured by oxygen consumption in muscle fibres (muscle biopsy) on lipid-derived and carbohydrate-derived substrates.
Time Frame
30 days after supplementation
Title
intramyocellular lipid content
Description
Skeletal muscle lipid accumulation measured by immunohistochemistry in muscle biopsy from vastus lateralis muscle
Time Frame
30 days after supplementation
Title
intrahepatic lipid content
Description
Intrahepatic lipid content measured with H-MRS
Time Frame
30 days after supplementation
Title
intracardiac lipid content
Description
Intracardiac lipid content measured with H-MRS
Time Frame
30 days after supplementation
Title
heart function
Description
Cardiac function: diastolic and systolic heart function will be measured with ultrasound
Time Frame
30 days after supplementation
Title
brown adipose tissue activity
Description
subjects will be exposed to an individualized cooling protocol, after which an 18F-FDG PET/CT scan is made
Time Frame
34 days after supplementation
Other Pre-specified Outcome Measures:
Title
Maximal aerobic capacity (VO2max)
Time Frame
27 days after supplementation
Title
Blood pressure
Time Frame
30 days after supplementation

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male sex Age: 40-70 years BMI 27-35 kg/m2 Has first-degree relative(s) diagnosed with type 2 diabetes Sedentary Not more than 2 hours of sports a week No active job that requires strenuous physical activity Stable dietary habits: no weight gain or loss > 5kg in the last three months Insulin resistant: glucose clearance rate below < 350 ml/kg/min, as determined using OGIS120 Willingness to abstain from resveratrol-containing food products Subjects will only be included when the dependent medical doctor of this study approves participation after evaluating data obtained during screening Exclusion Criteria: Use of anticoagulants Uncontrolled hypertension Haemoglobin <7.8 mmol/l In case of an abnormal ECG in rest: this will be discussed with the responsible medical doctor HBA1C > 6.5% Diagnosed with type 2 diabetes Medication use known to interfere with glucose homeostasis/metabolism Current alcohol consumption > 20 grams/day Subjects who don't want to be informed about unexpected medical findings during the screening /study, or do not wish that their physician is informed, cannot participate in the study. Subjects who intend to donate blood during the intervention or subjects who have donated blood less than three months before the start of the intervention. Participation in another biomedical study within 1 month before the first screening visit Any condition, disease or abnormal laboratory test result that, in the opinion of the Investigator, would interfere with the study outcome, affect trial participation or put the subject at undue risk Any contra-indication to MRI scanning. These contra-indications include patients with following devices: Central nervous system aneurysm clip Implanted neural stimulator Implanted cardiac pacemaker of defibrillator Cochlear implant Insulin pump Metal containing corpora aliena in the eye or brains
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Schrauwen, PhD
Organizational Affiliation
Maastricht University Medical Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maastricht University Medical Centre
City
Maastricht
State/Province
Limburg
ZIP/Postal Code
6200 MD
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
29706321
Citation
de Ligt M, Bruls YMH, Hansen J, Habets MF, Havekes B, Nascimento EBM, Moonen-Kornips E, Schaart G, Schrauwen-Hinderling VB, van Marken Lichtenbelt W, Schrauwen P. Resveratrol improves ex vivo mitochondrial function but does not affect insulin sensitivity or brown adipose tissue in first degree relatives of patients with type 2 diabetes. Mol Metab. 2018 Jun;12:39-47. doi: 10.1016/j.molmet.2018.04.004. Epub 2018 Apr 18.
Results Reference
derived

Learn more about this trial

Resveratrol and First-degree Relatives of Type 2 Diabetic Patients

We'll reach out to this number within 24 hrs