Pomegranate Consumption by Poly-medicated Metabolic Syndrome Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Pomegranate extract; Other: Placebo

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

Contacts and Locations

Study Locations

• Spain
  • Murcia, Spain, 30100
    • Spanish National Research Council (CSIC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pomegranate extract-1; Consumption of 2 daily capsules (900 mg pomegranate extract, PE) for 4 weeks	Dietary supplement: Pomegranate extract; Pomegranate extract consumption (900 mg/day) for 4 weeks
PLACEBO_COMPARATOR: Placebo-1; Consumption of 2 daily capsules (900 mg microcrystalline cellulose, PLA) for 4 weeks	Other: Placebo; Placebo (microcrystalline cellulose) consumption (900 mg/day) for 4 weeks
PLACEBO_COMPARATOR: Placebo-2; 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; Placebo (microcrystalline cellulose) consumption (900 mg/day) for 4 weeks
EXPERIMENTAL: Pomegranate extract-2; 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; Pomegranate extract consumption (900 mg/day) for 4 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Research Council, Spain
• Collaborators: Hospital General Universitario Reina Sofía de Murcia
• Investigators: Principal Investigator: Juan C Espín, PhD, Spanish National Research Council (CSIC)

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 10, 2018
• Primary Completion (ACTUAL): July 21, 2019
• Study Completion (ACTUAL): December 31, 2019

Study Registration Dates

• First Submitted: August 22, 2019
• First Submitted That Met QC Criteria: August 28, 2019
• First Posted (ACTUAL): August 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 10, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: diabetes; obesity; hypertension; inflammation; gut microbiota; metabolic syndrome; hyperlipidemia; polyphenol; pomegranate; polymedication; urolithins
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome
• Other Study ID Numbers: AGL2015-64124-R(2)

Drug and device information, study documents

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