Effect of a Pomegranate Extract on Cardiovascular Risk Markers in Overweight Healthy Subjects (POMEcardio)

Effect of an Ellagitannin Rich Pomegranate Extract on Cardiovascular Risk Markers in Overweight Healthy Subjects. A Double-blind, Cross-over, Dose-response, Randomized, Placebo-controlled Trial (The POMEcardio Study)

The investigators objective is to carry out a placebo-controlled, dose-response, randomized clinical trial to assess the effects of polyphenols or derived metabolites on cardiovascular disease risk in overweight adult subjects upon the consumption of pomegranate extract.

The investigators hypothesis is that chronic consumption of a ellagitannin-rich source such as pomegranate extract could decrease serum oxidized-LDL as well as other inflammatory markers. The correlation between the effect exerted and the subjects' microbiota (capacity to produce the ellagitannin-derived metabolites urolithins) will indicate a possible role of urolithins on the effects.

Study Overview

• Status: Completed
• Conditions: Overweight
• Intervention / Treatment: Dietary supplement: Pomegranate extract-first dose-Group A; Dietary supplement: Pomegranate extract-first dose-Group B; Dietary supplement: Pomegranate extract-second dose-Group A; Dietary supplement: Pomegranate extract-second dose-Group B; Dietary supplement: Placebo-first dose-Group B; Dietary supplement: Placebo-first dose-Group A; Dietary supplement: Placebo-second dose-Group B; Dietary supplement: Placebo-second dose-Group A

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Murcia, Spain, 30107
    • UCAM (San Antonio Catholic University from Murcia)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 40-65 years
• Body mass index (BMI) >27 kg/m2
• Healthy status (no illness in the previous 3-months).

Exclusion Criteria:

• Smoking.
• Pregnancy/lactation.
• Severe medical illness/chronic disease/ or gastrointestinal pathology (ulcers, irritable bowel syndrome, ulcerative colitis, Crohn disease etc.).
• Previous gastrointestinal surgery
• Recent use of antibiotics (within 1-month prior to the study)
• Suspected hypersensitivity to pomegranate or any of its components
• Consumption of nutraceuticals, botanical extracts or other vitamin supplements or taking medication.
• Regular consumption of ellagitannin-containing foodstuffs (walnuts, pomegranate, strawberries, raspberries, oak-aged red wine) (after filling a food-frequency questionnaire).
• Intake of ellagitannins-containing foodstuffs the week before the pharmacokinetic intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pomegranate extract; Crossover and dose-response: Both groups A and B will consume pomegranate extract and placebo. Both groups will also consume two doses of pomegranate extract and placebo. Group A will consume 1 daily capsule of pomegranate extract and group B will consume 1 daily capsule of placebo for 3 weeks. After a wash-out period of 3 weeks, group A will consume 1 daily capsule of placebo and group B will consume 1 daily capsule of pomegranate extract for 3 weeks. After a washout period of 3 weeks, group A will consume 4 daily capsules of pomegranate extract for 3 weeks and group B will consume 4 daily capsules of placebo for 3 weeks. After a washout period of 3 weeks, group A will consume 4 daily capsules of placebo for 3 weeks and group B will consume 4 daily capsules of pomegranate for 3 weeks.	Dietary supplement: Pomegranate extract-first dose-Group A; Group A will consume 1 daily capsule of pomegranate extract for 3 weeks; Other Names: Group A consumes pomegranate extract (first dose); Dietary supplement: Pomegranate extract-first dose-Group B; After 3 weeks of washout, group B will consume 1 daily capsule of pomegranate extract for 3 weeks.; Other Names: Group B consumes pomegranate extract (first dose); Dietary supplement: Pomegranate extract-second dose-Group A; After 3 weeks of washout, group A will consume 4 daily capsules of pomegranate extract for 3 weeks.; Other Names: Group A consumes pomegranate extract (second dose); Dietary supplement: Pomegranate extract-second dose-Group B; After 3 weeks of washout, group B will consume 4 daily capsules of pomegranate extract for 3 weeks.; Other Names: Group B consumes pomegranate extract (second dose)
Placebo Comparator: Placebo; Crossover and dose-response: Both groups A and B will consume pomegranate extract and placebo. Both groups will also consume two doses of pomegranate extract and placebo. Group A will consume 1 daily capsule of pomegranate extract and group B will consume 1 daily capsule of placebo for 3 weeks. After a wash-out period of 3 weeks, group A will consume 1 daily capsule of placebo and group B will consume 1 daily capsule of pomegranate extract for 3 weeks. After a washout period of 3 weeks, group A will consume 4 daily capsules of pomegranate extract for 3 weeks and group B will consume 4 daily capsules of placebo for 3 weeks. After a washout period of 3 weeks, group A will consume 4 daily capsules of placebo for 3 weeks and group B will consume 4 daily capsules of pomegranate for 3 weeks.	Dietary supplement: Placebo-first dose-Group B; Group B will consume 1 daily capsules of placebo for 3 weeks.; Other Names: Group B consumes placebo (first dose); Dietary supplement: Placebo-first dose-Group A; After 3 weeks of washout, group A will consume 1 daily capsule of placebo for 3 weeks.; Other Names: Group A consumes placebo (first dose); Dietary supplement: Placebo-second dose-Group B; After 3 weeks of washout, group B will consume 4 daily capsules of placebo for 3 weeks.; Other Names: Group B consumes placebo (second dose); Dietary supplement: Placebo-second dose-Group A; After 3 weeks of washout, group A will consume 4 daily capsules of placebo for 3 weeks.; Other Names: Group A consumes placebo (second dose)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum oxidized LDL-cholesterol concentration	Effect on circulating levels of oxidized particles of LDL-cholesterol	Change from baseline at 3, 6, 9, 12, 15, 18, 21 and 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum lipids and lipoproteins levels	Effects on serum total cholesterol, LDL-cholesterol, HDL-cholesterol and apolipoproteins A1 (ApoA1), B (ApoB) and E (ApoE).	Change from baseline at 3, 6, 9, 12, 15, 18, 21 and 24 weeks
Change in serum sICAM, sVCAM and hsCRP	Effect on soluble intercellular adhesion molecule (sICAM), soluble vascular adhesion molecule (sVCAM) and high-sensitivity C-reactive protein (hsCRP)	Change from baseline at 3, 6, 9, 12, 15, 18, 21 and 24 weeks
Change in fecal microbiota	Prebiotic effect: Change in short fatty acids, bifidobacteria, lactobacilli and other selected species in feces	Change from baseline at 3, 6, 9, 12, 15, 18, 21 and 24 weeks
Number of volunteers with adverse events as a measure of safety and tolerability	Change in markers involved in hepatic and renal functions: GGT, AST, ALP, ALT, CPK, urate, creatinin, albumin, bilirubin, LDH.; Change in hematological variables: leucocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin, hematocrit, mean corpuscular volume, mean platelet volume, platelets, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration.; Intolerance, dyspepsia, allergic reactions, constipation, diarrhea, abdominal pain, nausea.	Change from baseline at 3, 6, 9, 12, 15, 18, 21 and 24 weeks
Change in phenolics and derived metabolites in plasma, feces and urine.	Dose-response effect of pomegranate intake on phenolics and gut-microbiota derived metabolites in plasma, feces and urine.	Change from baseline at 3, 6, 9, 12, 15, 18, 21 and 24 weeks

Collaborators and Investigators

• Sponsor: National Research Council, Spain
• Collaborators: Universidad Católica San Antonio de Murcia; The Scientific and Technological Research Council of Turkey
• Investigators: Principal Investigator: Dr. Juan Carlos Espín, PhD, National Research Council (CEBAS-CSIC, Murcia, Spain)

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: February 7, 2014
• First Submitted That Met QC Criteria: February 11, 2014
• First Posted (Estimate): February 12, 2014

Study Record Updates

• Last Update Posted (Estimate): April 14, 2015
• Last Update Submitted That Met QC Criteria: April 13, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Dietary supplement; Microbiota; Cardiovascular; Pomegranate; Urolithins; Nutraceutical; Polyphenols
• Additional Relevant MeSH Terms: Body Weight; Overweight
• Other Study ID Numbers: CEBAS-CSIC-4