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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Overweight

Intervention / Treatment
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* Dietary Supplement: Pomegranate extract-first dose-Group A
* Dietary Supplement: Placebo-first dose-Group B
* Dietary Supplement: Pomegranate extract-first dose-Group B
* Dietary Supplement: Placebo-first dose-Group A
* Dietary Supplement: Pomegranate extract-second dose-Group A
* Dietary Supplement: Placebo-second dose-Group B
* Dietary Supplement: Pomegranate extract-second dose-Group B
* Dietary Supplement: Placebo-second dose-Group A


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pomegranate extract<br>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<br>* Group A will consume 1 daily capsule of pomegranate extract for 3 weeks<br>* Other names: Group A consumes pomegranate extract (first dose);Dietary Supplement: Pomegranate extract-first dose-Group B<br>* After 3 weeks of washout, group B will consume 1 daily capsule of pomegranate extract for 3 weeks.<br>* Other names: Group B consumes pomegranate extract (first dose);Dietary Supplement: Pomegranate extract-second dose-Group A<br>* After 3 weeks of washout, group A will consume 4 daily capsules of pomegranate extract for 3 weeks.<br>* Other names: Group A consumes pomegranate extract (second dose);Dietary Supplement: Pomegranate extract-second dose-Group B<br>* After 3 weeks of washout, group B will consume 4 daily capsules of pomegranate extract for 3 weeks.<br>* Other names: Group B consumes pomegranate extract (second dose);|
| Placebo Comparator: Placebo<br>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<br>* Group B will consume 1 daily capsules of placebo for 3 weeks.<br>* Other names: Group B consumes placebo (first dose);Dietary Supplement: Placebo-first dose-Group A<br>* After 3 weeks of washout, group A will consume 1 daily capsule of placebo for 3 weeks.<br>* Other names: Group A consumes placebo (first dose);Dietary Supplement: Placebo-second dose-Group B<br>* After 3 weeks of washout, group B will consume 4 daily capsules of placebo for 3 weeks.<br>* Other names: Group B consumes placebo (second dose);Dietary Supplement: Placebo-second dose-Group A<br>* After 3 weeks of washout, group A will consume 4 daily capsules of placebo for 3 weeks.<br>* Other names: Group A consumes placebo (second dose);|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pomegranate, Cardiovascular, Urolithins, Microbiota, Polyphenols, Nutraceutical, Dietary supplement