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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Polyphenols of pomegranate fruit peel extract (PoPex); Drug: Placebo

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] -

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Republic Of Srpska
    • Banja Luka, Republic Of Srpska, Bosnia and Herzegovina, 78000
      • Public Health Institution Dom zdravlja Banja Luka

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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:

1. TG ≥ 1,7 mmol/l, or present therapy for dyslipidemia
2. HDL <1,03 mmol/l men, <1,29 mmol/l women
3. Arterial blood pressure ≥130/85 mmHg
4. 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

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: 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.

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

Collaborators and Investigators

• Sponsor: University of Banja Luka
• Investigators: Study Chair: Ranko Škrbić, Professor, University of Banja Luka

Publications and helpful links

General Publications

• Grabez M, Skrbic R, Stojiljkovic MP, Vucic V, Rudic Grujic V, Jakovljevic V, Djuric DM, Surucic R, Savikin K, Bigovic D, Vasiljevic N. A prospective, randomized, double-blind, placebo-controlled trial of polyphenols on the outcomes of inflammatory factors and oxidative stress in patients with type 2 diabetes mellitus. Rev Cardiovasc Med. 2022 Feb 11;23(2):57. doi: 10.31083/j.rcm2302057.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): December 20, 2023
• Study Completion (Estimated): August 20, 2024

Study Registration Dates

• First Submitted: June 13, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Oxidative stress; Obesity; Metabolic syndrome; Inflamation; Polyphenols of Pomegranate Fruit Peel Extract
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome
• Other Study ID Numbers: PoPexMetSy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No