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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Resveratrol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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]

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Resveratrol, Glycemic Variability, MAGE