Effect of Ellagic Ácid on the Components of Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion

Study Overview
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Brief Summary
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Metabolic syndrome (MetS) is a group of important cardiovascular risk factors: abdominal obesity, dyslipidemia, hyperglycemia, and high blood pressure. Treatment requires lifestyle changes and pharmacological therapy with different medications for each component. Ellagic acid (EA) is a polyphenol that has shown health benefits in multiple experimental studies. Patients consume EA without prescription; considering there aren't studies that demonstrate its effectiveness on MetS, it is important to evaluate the possible effects of AE on this pathology. METHODOLOGY: Current study is a double-blind, placebo-controlled clinical trial. The aim of this study is to evaluate the effect of AE on the components of metabolic syndrome, insulin sensitivity, and insulin secretion.

Detailed Description
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INTRODUCTION: Ellagic acid (EA) is a polyphenol that has shown health benefits in multiple experimental studies; mainly as an antioxidant, but also in hepatic steatosis, endothelial damage, hypertension, diabetes mellitus, visceral fat accumulation, dyslipidemia, insulin resistance, atherosclerosis, etc. There aren't studies that demonstrate the effectiveness of EA on MetS; since patients consume it without any prescription, it is important to evaluate the effect of the administration of EA on the components of metabolic syndrome, insulin sensitivity, and insulin secretion. The current design is a randomized double-blind, placebo-controlled, clinical trial. METHODS: Male and female volunteers between 30 to 59 years of age, with a diagnosis of MetS according to the International Diabetes Federation criteria will be included, whether they accept participating and signing the informed consent. Patients with one or more of the following criteria will be excluded: History of liver, kidney, heart, or thyroid disease; diabetes mellitus or arterial hypertension, alcohol, drug abuse or tobacco use, systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, fasting blood glucose ≥126 mg / dL, triglycerides ≥500 mg/dL, LDL cholesterol >190 mg/dL; suspected or confirmed pregnancy, lactation, menopausal period <1 year, hormonal contraceptive or replacement therapy, pharmacological, dietary or herbal therapy in the last 3 months before trial, allergy to any of the interventions. Patients included, may be withdrawn from the study if they meet any of the following conditions: Withdrawal of the informed consent, severe adverse reaction, loss of follow-up, treatment adherence <80%; intolerance to EA or placebo. OBJECTIVES: The main objective is to evaluate the effect of EA or placebo on metabolic syndrome components, insulin sensitivity, and insulin secretion. HEADQUARTERS: The study will be carried out in the facilities of the Institute of Experimental and Clinical Therapeutics (INTEC), of the University Center of Health Sciences, at the University of Guadalajara. Guadalajara, Jalisco, Mexico.

Official Title
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Effect of Ellagic Acid Administration on the Components of Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Drug: Ellagic Acid / Pomegranate Extract
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metabolic Syndrome diagnosis based on IDF criteria Acceptance and signing of Informed Consent Exclusion Criteria: Prior diagnosis of kidney, liver, pancreas, heart or thyroid disease Diabetes mellitus or arterial hypertension Alcoholism, drug abuse or tobacco use Systolic blood pressure ≥140 mmHg Diastolic blood pressure ≥90 mmHg Fasting plasma glucose ≥126 mg/dL TG ≥500 mg/dL C-LDL > 190 mg/dL BMI: ≥35 kg/m2 Pregnancy (suspected or confirmed) or lactation Menopausal period <1 year Hormonal contraceptive or replacement therapy Known allergy to any of the interventions Imposibility to shallow capsules Pharmacological, dietary or herbal therapy in the last 3 months before trial Weight variability above ±2.0 kg throughout the last 3 months before intervention

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, placebo-controlled clinical trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>16 patients to receive 1 homologated placebo capsule (calcined magnesia 500 mg) every 12 hours along 12 weeks | Drug: Placebo oral capsule<br>* Calcined magnesia in 500mg capsules. Homologated to the other intervention. Dosage twice a day orally every 12 hours during 12 weeks<br>* Other names: calcined magnesia;|
| Experimental: Ellagic acid<br>16 patients to receive 1 homologated intervention capsule (ellagic acid 500 mg) every 12 hours along 12 weeks | Drug: Ellagic Acid / Pomegranate Extract<br>* Polyphenol, ellagitannin, it is found in a wide variety of fruits and nuts; in this particular case, pomegranate extract with 90% ellagic acid, 500 mg capsules. Homologated to the other intervention. Dosage twice a day orally every 12 hours during 12 weeks<br>* Other names: benzoaric acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| waist circunference | Main criteria for metabolic syndrome diagnosis | baseline to week 12 (end of intervention) | 
| blood pressure | systolic blood pressure and diastolyc blood pressure by digital blood pressure monitor | baseline to week 12 (end of intervention) | 
| fasting plasma glucose | fasting plasma glucose by enzimatic-colorimetric automatized technique | baseline to week 12 (end of intervention) | 
| Fasting plasma triglycerides | fasting plasma triglycerides by enzimatic-colorimetric automatized technique | baseline to week 12 (end of intervention) | 
| Fasting plasma HDL-c concentration | fasting plasma high density lypoprotein-cholesterol by enzimatic-colorimetric automatized technique | baseline to week 12 (end of intervention) | 
| Insulin sensitivity | Estimated with Matsuda index. From an oral glucose tolerance test with glucose 75g intake, and each 30 minutes sampling to get insulin and glucose levels; minuted glucose and insulin results will be analized with Matsuda Index to get insulin sensitivity | baseline to week 12 (end of intervention) | 
| Insulin secretion | Stumvoll index will be used to calculate first-phase and area under curve (AUC) and ratio insulin AUC/glucose AUC for total insulin secretion | baseline to week 12 (end of intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| body weight | body weight measured by bioelectrical impedance scale | baseline to week 12 (end of intervention) | 
| body mass index | body mass index (BMI) calculated by Quetelet index | baseline to week 12 (end of intervention) | 
| body fat mass | body fat will be estimated by bioelectrical impedance analysis. Percentage. | baseline to week 12 (end of intervention) | 
| Fasting plasma uric acid | fasting plasma uric acid by enzimatic-colorimetric automatized technique | baseline to week 12 (end of intervention) | 
| Fasting plasma insulin | Fasting plasma insulin concentration by immunoassay | baseline / week 12 (end of intervention) | 
| 2 hours after oral-load glucose | plasma glucose 2 hours after a 75 g oral glucose load | baseline / week 12 (end of intervention) | 
| 2 hours after oral-load insulin | plasma insulin 2 hours after a 75 g oral glucose load | baseline / week 12 (end of intervention) | 
| total cholesterol | fasting plasma total cholesterol by enzimatic-colorimetric automatized technique | baseline to week 12 (end of intervention) | 
| Fasting plasma LDL-c concentration | fasting plasma low-density lipoprotein- cholesterol by enzimatic-colorimetric automatized technique | baseline to week 12 (end of intervention) | 
| Fasting plasma VLDL concentration | fasting plasma very low-density lipoprotein by enzimatic-colorimetric automatized technique | baseline to week 12 (end of intervention) | 
| Concentration of plasma AST | aminotransferases by enzimatic-colorimetric automatized technique | baseline / week 12 (end of intervention) | 
| Concentration of plasma ALT | aminotransferases by enzimatic-colorimetric automatized technique | baseline / week 12 (end of intervention) | 
| Concentration of plasma creatinine | creatinine by enzimatic-colorimetric automatized technique | baseline / week 12 (end of intervention) | 
| Incidence of Adverse events related to placebo or ellagic acid | Incidence of placebo or ellagic acid, emergent adverse events will be identified by clinical evaluation | baseline to week 12 (continuous surveillance) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ellagic acid, metabolic syndrome, insulin resistance, insulin secretion, insulin sensitivity