Effect of Administration of Resveratrol on Glycemic Variability in Individuals With Type 2 Diabetes Mellitus

Effect of Administration of Resveratrol on Glycemic Variability in Individuals With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin

Type 2 diabetes mellitus [ T2DM ] has quickly become the epidemic of the XXI century and challenging global health . Estimates of the World Health Organization [ WHO ] indicate that globally , from 1995 to date has nearly tripled the number of people living with diabetes mellitus [DM ]. Resveratrol has been extensively studied as a regulator of glucose through its antioxidant effects and protecting pancreatic β cells by activation of sirtuin -1 [ SIRT1 ] dependent deacetylase nicotinamide adenine diphosphate [ NAD ]. Therefore, it is important to know the effect of resveratrol on the glycemic variability [GV ] in patients with T2DM who are not in control with metformin monotherapy based.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Resveratrol

Detailed Description

The objective is to evaluate the effect of administration of resveratrol on GV in individuals with T2DM inadequately controlled on metformin, for which we will conduct a double-blind trial, randomized, placebo control group, each group 11 male and female patients 30-60 years of age with T2DM inadequately controlled with metformin [2000 mg / day and glycosylated hemoglobin A1c (A1C) ≥% 7], with body mass index [BMI] form 25.0 to 34.9 kg / m2. Randomization will determine who will receive the intervention during the 8-week trial [resveratrol capsules, 500 mg 3 times daily with the first bite of each meal or approved placebo capsules], both groups also continue with metformin. The clinical findings and laboratory tests include a metabolic profile and biosafety, which will be made at baseline and at 8 weeks. Body weight, body fat, BMI and blood pressure will be determined during the initial and final visit, likewise, plasma glucose concentrations every hour recorded over 72 hours by continuous monitoring system outpatient glucose [MACG] via iPro ™ 2 [Medtronic MiniMed, Northridge] system, through which the mean amplitude of glucose excursions [MAGE] is calculated and AUC glucose, which will serve to assess the GV. Adverse events and adherence to treatment will be documented. Statistical analysis: Mann-Whitney U test, Wilcoxon and Fisher exact test. It is considered with significance at p <0.05.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI from 25.0-34.9 kg/m2
• Diagnosis of T2DM
• Fasting plasma glucose >130 and <250 mg/dl at the time of scrutiny
• A1C between 7 and 10%
• Metformin monotherapy
• Written informed consent

Exclusion Criteria:

• Women pregnant or breastfeeding
• Untreated thyroid disease and/or uncontrolled hypertension [≥150 systolic and diastolic ≥90]
• Consumption of oral agents or other medications or supplements, unlike metformin, with proven properties that modify the behavior of glucose
• Total cholesterol >400 mg/dL
• Triglycerides ≥400 mg/dL
• Liver enzymes [ALT and AST] more than twice the normal range
• Glomerular filtration rate <60 mL/min [Cockcroft-Gault]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resveratrol; Individuals with T2DM inadequately controlled with metformin 2000 mg/day and A1C ≥7%.	Drug: Resveratrol; Resveratrol capsules, 500 mg 3 times daily with the first bite of each meal; Other Names: Trans-resveratrol
Placebo Comparator: Placebo; Individuals with T2DM inadequately controlled with metformin 2000 mg/day and A1C ≥7%.	Drug: Placebo; Placebo capsules, 500 mg 3 times daily with the first bite of each meal; Other Names: Calcined Magnesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve	Before and after intervention with ambulatory continuous glucose monitoring during 72 h, oxidase glucose iPro ™ 2	56 days
Mean amplitude of glucose excursions (MAGE)	Before and after intervention with ambulatory continuous glucose monitoring during 72 h, oxidase glucose iPro ™ 2	56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting plasma glucose	Before and after intervention by spectrophotometry	56 days
Postprandial glucose	Before and after intervention with ambulatory continuous glucose monitoring during 72 h, oxidase glucose iPro ™ 2	56 days
A1C	Before and after intervention by high-performance liquid chromatography	56 days
Total cholesterol	Before and after intervention by spectrophotometry	56 days
Triglycerides	Before and after intervention by spectrophotometry	56 days
High-density lipoprotein cholesterol	Before and after intervention by spectrophotometry	56 days
Low-density lipoprotein cholesterol	Friedewald formula	56 days
Very-low density lipoprotein	Friedewald formula	56 days
Alanine aminotransferase	Before and after intervention by spectrophotometry	56 days
Aspartate aminotransferase	Before and after intervention by spectrophotometry	56 days
Creatinine	Before and after intervention by spectrophotometry	56 days
Blood pressure	Before and after intervention using a digital manometer	56 days
Body and visceral fat %	Before and after intervention using a impedance bascule, Tanita MR	56 days

Collaborators and Investigators

• Sponsor: University of Guadalajara
• Investigators: Principal Investigator: Esperanza Martínez-Abundis, PhD, Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): February 1, 2018

Study Registration Dates

• First Submitted: September 9, 2015
• First Submitted That Met QC Criteria: September 11, 2015
• First Posted (Estimate): September 15, 2015

Study Record Updates

• Last Update Posted (Actual): May 8, 2018
• Last Update Submitted That Met QC Criteria: May 2, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Resveratrol; MAGE; Glycemic Variability
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: ERVGDM2