Effects of Polyphenols of Pomegranate Fruit Peel Extract on Inflammation and Oxidative Stress in Metabolic Syndrome

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the effects of polyphenols of pomegranate fruit peel extract compared to placebo on oxidative stress and inflammation in overweight and obese subjects with metabolic syndrome.

Detailed Description
-----------------
This is a Phase 3, randomized, double-blind, placebo-controlled evaluation of the efficacy of polyphenols of pomegranate fruit peel extract on oxidative stress and inflammation in overweight and obese subjects with metabolic syndrome. Study site: a single study center (Primary Health Care Institution in Banja Luka, as recruiter center) as recruitment center including Center for Biomedical Research, Faculty of Medicine University of Banja Luka, as local laboratory and coordinator. Sample size: 60 subjects, randomized in a 1:1 allocation ratio. Primary objectives are to investigate an effect of polyphenols pomegranate fruit peel extract on: Anthropometric parameters such as body mass index, and arterial blood pressure, glycemia, lipoprotein profile, homeostatic model assessment for insulin resistance (HOMAIR), homocysteine, vitamin B complex: folic acid, vitamin B6, vitamin B9 and vitamin B12. 2. To investigate the effects polyphenols from pomegranate fruit peel extract has on impact on lipid peroxidation index, nitric oxide metabolites, hydrogen peroxide (H2O2), superoxide anion radical (O2-), and glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD). 3. Proinflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high sensitive CRP (hsCRP), leptin, resistin ,vaspin, chemerin, lipokalin-2 and katepsin . 4. Anti-infammatory markers IL-5, IL-10, IL-12 ,adiponectin and omentin. Treatments arms: Polyphenols of pomegranate fruit peel extract (PoPeEx) (500 mg/day) Placebo Treatment duration : 8 weeks Assessment - clinical and laboratory sampling: Informed consent and Screening - 7 days prior to randomization Study visits (V): V1 - Randomization and Enrollment (Baseline) V2 - 4 weeks after Baseline V3 - 8 weeks after Baseline. No interim analysis is planned. The analysis will be performed at the end of the study after data review and freezing of the database according to the intent to treat principle. - Page 2 of 6 [DRAFT] -

Official Title
-----------------
Randomized, Double-blind, Placebo-controlled Study of Efficacy Polyphenols of Pomegranate Fruit Peel Extract on Inflammatory Parameters and Oxidative Stress in Overweight and Obese Subjects With Metabolic Syndrome

Conditions
-----------------
Metabolic Syndrome

Intervention / Treatment
-----------------
* Dietary Supplement: Polyphenols of pomegranate fruit peel extract (PoPex)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Informed consent signed Adults of 20 to 60 years BMI ≥ 25.00 kg/m2 Met criteria for metabolic syndrome such as visceral obesity( for men ≥ 94 cm and ≥ 80 cm for women) and at least two risk factors: TG ≥ 1,7 mmol/l, or present therapy for dyslipidemia HDL <1,03 mmol/l men, <1,29 mmol/l women Arterial blood pressure ≥130/85 mmHg Glycemia ≥ 5.6 mmol/l and < 6.9 mmol/l Exclusion Criteria: Subjects with malignant and other acute and chronic infectious and non-infectious disease requiring active pharmacotherapy. Subjects with with insulin dependent diabetes mellitus or subjects with insulin independent diabetes mellitus taking oral hypoglycemic therapy Subjects with uncontrolled chronic cardiovascular, endocrine, autoimmune, psychiatric, and autoimmune diseases or other condition based on the investigator judgement. Non adherent subject Systematic use of corticosteroids Pregnant or lactating women Chronic use of supplements (omega 3 unsaturated acids, silymarin, mineral-vitamin supplements) Participation in any other interventional study

Ages Eligible for Study
-----------------
Minimum Age: 20 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: Polyphenols of pomegranate fruit peel extract (PoPex)<br>All subjects will treated only with PoPex in total daily dosis of 500 mg/orally over 8 weeks. | Dietary Supplement: Polyphenols of pomegranate fruit peel extract (PoPex)<br>* PoPex in form of capsule will be orally administered in total daily dose of 500/mg in subjects with metabolic syndrome and obesity over 8 weeks.<br>* Other names: Granat;|
| Placebo Comparator: Placebo<br>All subjects will treated only with PoPex placebo capsules/orally over 8 weeks | Drug: Placebo<br>* Placebo in form of capsule will be orally administered in subjects with metabolic syndrome and obesity over 8 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in oxidative stress biomarkers levels: lipid peroxidation index, nitric oxide metabolites, hydrogen peroxide (H2O2), superoxide anion radical (O2-), and glutation (GSH), catalasis(CAT) and superoxid dismutasis(SOD). | ELISA assey | From Baseline and after 8 weeks | 
| Change in proinflammatori parametars:interleukin-6 (IL-6), tumor necrosis factor-α (TNF- α), high sensitive CRP (hsCRP), leptin, resistin ,vaspin, chemerin ,lipokalin -2 and katepsin | ELISA assey | From Baseline and after 8 weeks | 
| Change in antiinflammatori parametars:interleukin -5 (IL-5) ,interleukin-10(IL-10), interleukin-12 (IL-12) ,adiponectin and omentin | ELISA assey | From Baseline and after 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in inflammation marker level : high sensitivity CRP Turbid mertic test | Turbid metric test | From Baseline and after 8 weeks | 
| Change in total choleterol (TC), low -density lipoprotein ( LDL), high-density lipoprotein (HDL) and trglicerides Turbid mertic test | Clinical biochemistry (colorimetric) test and results will be expressed in mmol/l | From Baseline,after 4 and 8 weeks | 
| Change in serum levels homocystein | Detection by fluoroscence polarization immunoassay | From Baseline,after 4 and 8 weeks | 
| Change in serum levels of vitamin B6-piridoxin ,vitamin B9-folic acid ,vitamin B12-cianocobalamin | Microparticle enzyme immunoassey | From Baseline, after 4 and 8 weeks | 
| Change in serum levels of glycemia, insulinemia | glycemia-hexokinase method,insulinemia-ultrasensitivity test,immunoenzyme test:sandwich | From Baseline,after 4 and after 8 weeks | 
| Change in serum levels of liver function tests | IFCC,reference method with pyridoxyl phosphate | From Baseline,after 4 and after 8 weeks | 
| Change in body weight | weight ( kg) | From Baseline and after 8 weeks | 
| Change in systolic and diastolic blood presure | mm/HG | From Baseline and after 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metabolic syndrome, Inflamation, Oxidative stress, Obesity, Polyphenols of Pomegranate Fruit Peel Extract