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

Sponsor

University of Banja Luka (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05915117

Collaborator

(none)

Enrollment

Location

Arms

16.7

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metabolic Syndrome	Dietary Supplement: Polyphenols of pomegranate fruit peel extract (PoPex) Drug: Placebo	N/A

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.

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).
Proinflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high sensitive CRP (hsCRP), leptin, resistin ,vaspin, chemerin, lipokalin-2 and katepsin .
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.

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Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Dec 20, 2023

Anticipated Study Completion Date :

Aug 20, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Polyphenols of pomegranate fruit peel extract (PoPex) 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) 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. Other Names: Granat
Placebo Comparator: Placebo All subjects will treated only with PoPex placebo capsules/orally over 8 weeks	Drug: Placebo Placebo in form of capsule will be orally administered in subjects with metabolic syndrome and obesity over 8 weeks.

Arm

Intervention/Treatment

Experimental: Polyphenols of pomegranate fruit peel extract (PoPex)

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)

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.

Other Names:

Granat

Placebo Comparator: Placebo

All subjects will treated only with PoPex placebo capsules/orally over 8 weeks

Drug: Placebo

Placebo in form of capsule will be orally administered in subjects with metabolic syndrome and obesity over 8 weeks.

Outcome Measures

Primary Outcome Measures

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). [From Baseline and after 8 weeks]
ELISA assey
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 [From Baseline and after 8 weeks]
ELISA assey
Change in antiinflammatori parametars:interleukin -5 (IL-5) ,interleukin-10(IL-10), interleukin-12 (IL-12) ,adiponectin and omentin [From Baseline and after 8 weeks]
ELISA assey

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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