Clinical trial NCT01690676: Effect of an Apple Polyphenol Extract on Brachial Artery Flow-mediated Vasodilatory Function
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Borderline Hypertension
Keywords: FMD
epicatechin
apple polyphenol
borderline hypertension
Lead sponsor: Danisco
Sponsor class: INDUSTRY
Collaborators: name: University of Turku
name: 4Pharma Ltd.
First posted: 2012-09-24
Enrollment: 57
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: Effect of apple polyphenols on FMD.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Brachial flow-mediated dilation test (FMD)
timeFrame: 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 outcomes:
measure: Nitrate-mediated vasodilatation response (NMD)
timeFrame: At the first and last visits of both periods, approximately 10 minutes after FMD.
measure: Circulating biomarkers of vascular function
timeFrame: 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
measure: BP
timeFrame: 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.
measure: Plasma epicatechin concentration
timeFrame: 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
Other outcomes:
Locations:
city: Turku
country: Finland
facility: University of Turku
Study officials:
affiliation: Danisco
name: Kirsti Tiihonen, PhD
role: STUDY_DIRECTOR
affiliation: University of Turku, Turku, Finland, The Research Centre of Applied and Preventive Cardiovascular Medicine
name: Olli Raitakari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Turku, Turku, Finland, The Research Centre of Applied and Preventive Cardiovascular Medicine
name: Pia Salo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Research Services Turku
name: Anne Lithonius
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Research Services Turku
name: Mika Scheinin, MD, PhD
role: STUDY_CHAIR
affiliation: 4Pharma Ltd.
name: Jari Turunen, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Saarenhovi M, Salo P, Scheinin M, Lehto J, Lovro Z, Tiihonen K, Lehtinen MJ, Junnila J, Hasselwander O, Tarpila A, Raitakari OT. The effect of an apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers on brachial artery flow-mediated vasodilatory function in volunteers with elevated blood pressure. Nutr J. 2017 Oct 27;16(1):73. doi: 10.1186/s12937-017-0291-0.