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

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.

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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:

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