Effect of an Apple Polyphenol Extract on Brachial Artery Flow-mediated Vasodilatory Function

Study Overview
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Brief Summary
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Effect of apple polyphenols on FMD.

Detailed Description
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The aim of this single centre, repeated-dose, double-blind, placebo-controlled, crossover study is to test the hypothesis that an orally ingested apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers improves brachial artery endothelium-dependent vasodilation function (FMD) in volunteer subjects with borderline hypertension. FMD and endothelium-independent nitrate-mediated vasodilatation (NMD) of the left brachial artery will be investigated with ultrasonography at the start and end of both treatment periods. Biomarkers of vascular function and epicatechin (and metabolite) concentrations will be determined from blood samples taken at the start and end of both treatment periods. Diet diary data will be collected for the evaluation of the possible effects of diet on the study results. Adverse events data will be collected throughout the study. Safety laboratory determinations will be performed at the last visit of both treatment periods.

Official Title
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The Effect of an Apple Polyphenol Extract Rich in Epicatechin and Flavan-3-ol Oligomers (Evesse™ EPC) on Brachial Artery Flow-mediated Vasodilatory Function (FMD)in Volunteer Subjects

Conditions
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Borderline Hypertension

Intervention / Treatment
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* Dietary Supplement: Epicatechin
* Dietary Supplement: Microcrystalline cellulose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Borderline hypertension Otherwise healthy Aged 40-65 years (inclusive) Not consuming high amounts (over 20 mg daily) of flavonoids Exclusion Criteria: BMI >32 kg/m2 Total serum cholesterol ≥ 8 mmol/l Any abnormal safety laboratory parameter or abnormal finding in ECG evaluated to be clinically significant Coronary artery disease Pregnancy or lactating Alcohol abuse as evaluated by medical history Regular smoking/using nicotine products Diabetes mellitus Apple allergy Use of lipid lowering medications Regular use of any medication that is known or believed to affect endothelial function or blood vessel constriction Any other condition or medication that in the opinion of the investigator would interfere with the evaluation of the study results or constitute a health risk for the subject High consumption of vitamin products, herbal remedies or products containing flavonoids

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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Epicatechin<br>The subjects will receive the study product and corresponding placebo once a day for 4 weeks in randomised order. There will be a four to five-weeks wash-out between the treatment periods. | Dietary Supplement: Epicatechin<br> <br> |
| Placebo Comparator: Microcrystalline cellulose<br>The subjects will receive the study product and corresponding placebo once a day for 4 weeks in randomised order. There will be a four to five-weeks wash-out between the treatment periods. | Dietary Supplement: Microcrystalline cellulose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial flow-mediated dilation test (FMD) | ultrasonography, FMDmax% | At first visits of both periods baseline FMD will be recorded followed by FMD recording 1.5 hours after first dose. After 4 weeks intervention, at last visits of both periods FMD will be recorded, last dose will be taken and FMD recorded 1.5 hours after. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nitrate-mediated vasodilatation response (NMD) | ultrasonography, NMDmax% | At the first and last visits of both periods, approximately 10 minutes after FMD. | 
| Circulating biomarkers of vascular function | depends on the biomarker | Once at the first visit of both periods and once at the last visit of both periods. Blood sampling prior to the morning dose and appr. 2 h thereafter | 
| BP |  | Once at the first visit of both periods and once at the last visit of both periods. Blood pressure will be recorded twice prior to the morning dose. | 
| Plasma epicatechin concentration | HPLC | At the first visit of both periods and at the last visit of both periods. Blood sampling prior to the morning dose and appr. 2 h thereafter | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FMD, epicatechin, apple polyphenol, borderline hypertension