Pomegranate Consumption by Poly-medicated Metabolic Syndrome Patients

Study Overview
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Brief Summary
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The objective is to evaluate whether the medication in polymedicated metabolic syndrome patients could determine the effects of a pomegranate extract on i) metabolic markers, ii) inflammatory markers, and iii) the modulation of the gut microbiota.

Official Title
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Effect of a Pomegranate Extract on Metabolic and Inflammatory Markers, and the Gut Microbiota of Poly-medicated Metabolic Syndrome Patients

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Dietary Supplement: Pomegranate extract
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index >30 kg/m2 or waist circumference >94/80 cm (males/females) in European-Caucasians subjects, plus two of the following: Triglycerides >150 mg/dL or under treatment against hypertrigliceridemia. Fasting glucose ≥100 mg/dL Diagnosed type 2 diabetes mellitus HDL-cholesterol (mg/dl) <40/50 (males/females) or under treatment against low HDLc values. Systolic blood pressure >130 mmHg o diastolic blood pressure >85 mmHg, or under anti-hypertensive drug treatment. Exclusion Criteria: Age under 18 years Pregnancy or breastfeeding Antibiotic treatment within one month before inclusion in the trial Pomegranate allergy or intolerance (known or suspected) Chronic intestinal inflammatory diseases (ulcerative colitis, Crohn's disease, etc.) Malignancies Consumption of botanicals or dietary supplements within one month before the inclusion and during the trial. Consumption of ellagitannin-rich sources within one week before the inclusion and during the trial (pomegranate, walnuts, strawberries, raspberries, tea, blackberries and oak-aged wine).

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled and crossover trial.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pomegranate extract-1<br>Consumption of 2 daily capsules (900 mg pomegranate extract, PE) for 4 weeks | Dietary Supplement: Pomegranate extract<br>* Pomegranate extract consumption (900 mg/day) for 4 weeks<br>|
| Placebo Comparator: Placebo-1<br>Consumption of 2 daily capsules (900 mg microcrystalline cellulose, PLA) for 4 weeks | Other: Placebo<br>* Placebo (microcrystalline cellulose) consumption (900 mg/day) for 4 weeks<br>|
| Placebo Comparator: Placebo-2<br>Consumption of 2 daily capsules (900 mg microcrystalline cellulose, PLA) for 4 weeks. This arm is the previous PE-1 after crossover and one month of wash-out | Other: Placebo<br>* Placebo (microcrystalline cellulose) consumption (900 mg/day) for 4 weeks<br>|
| Experimental: Pomegranate extract-2<br>Consumption of 2 daily capsules (900 mg pomegranate extract, PE) for 4 weeks. This arm is the previous PLA-1 after crossover and one month of wash-out. | Dietary Supplement: Pomegranate extract<br>* Pomegranate extract consumption (900 mg/day) for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change (1 log units) of Bacteroidetes per gram of feces | Modulation of gut microbiota (decrease Firmicutes to Bacteroidetes ratio) | Change from baseline at 30 days vs placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change (10%) of circulating levels of lipopolysaccharide binding protein (LBP) | Evaluation of metabolic endotoxemia | Changes from baseline at 30 days vs placebo | 
| Change (10%) of ghrelin, TNF-α, GLP-1, IL-6, PYY, resistin, HGF, MCP-1, C-Peptide, and BDNF (pg/mL). | Determination of metabolic and inflammatory markers in serum samples. | Changes from baseline at 30 days vs placebo | 
| Change (10%) of PAI-1, adiponectin, RBP4, and leptin (ug/mL). | Determination of fibrinolytic, inflammatory and metabolic markers in serum samples | Changes from baseline at 30 days vs placebo | 
| Change (10%) of ICAM-1, VCAM-1, and P-selectin (ng/mL) | Measurement of cell adhesion molecules in serum samples | Changes from baseline at 30 days vs placebo | 
| Change (10%) of blood glucose, total cholesterol, LDLc and HDLc concentrations (mg/dL) | Measurement of serobiochemical variables (blood glucose and lipids levels) in serum samples | Changes from baseline at 30 days vs placebo | 
| Evaluation of genotype frequencies for 60 single nucleotide polymorphisms (SNPs) related to the incidence of obesity, metabolism, diabetes and cardiovascular diseases | SNP genotyping of patients (DNA extracted from whole blood) | Baseline values at inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metabolic syndrome, pomegranate, gut microbiota, polyphenol, polymedication, inflammation, obesity, diabetes, hypertension, hyperlipidemia, urolithins