- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01691404
Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure (FLAVO)
Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure in Untreated (Pre)Hypertensive Subjects
Flavonoid-rich foods such as tea and cocoa have been identified as having a blood pressure-lowering effect. Part of this effect is thought to be due to the flavonoid content of these foods although it is currently unknown which flavonoids play a role. Epicatechin is one the major flavonoids in cocoa while quercetin is largely found in tea.
During this study the investigators plan to investigate the effects of pure epicatechin and quercetin supplementation on vascular function and blood pressure in untreated (prehypertensive) subjects by way of a three-armed double-blind crossover intervention. Participants will sequentially consume supplements containing quercetin, epicatechin or placebo for a period of 4 weeks. Before and after this 4 week period, measurements of vascular function and blood pressure will be taken.
The investigators hypothesize that the supplementation of epicatechin and quercetin will improve vascular function and blood pressure.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
By means of a three-armed double-blind crossover intervention, the effects of pure flavonoid supplementation will be investigated. The products under investigation will be epicatechin and quercetin-3-glucoside. Subjects will be asked to consume either 160mg of quercetin-3-glucoside, 100mg of epicatechin or a placebo capsule for a period of 4 weeks. Measurements of vascular function and blood pressure will be taken before and after each 4-week intervention period. A 4-week washout period will be planned between each intervention.
Measurements of vascular function will include flow-mediated dilation, pulse wave analysis, pulse wave velocity and vasomotion as well as biomarkers of inflammation and vascular function.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Wageningen, Netherlands, 6703 HD
- Wageningen University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Systolic Blood Pressure between 125 and 160 mmHg
- Age between 30 and 80 years
- BMI > 20 and ≤ 40
- No reported current or previous metabolic diseases
- No history of cardiovascular diseases
- No history of renal, liver or thyroid diseases
- No history of gastrointestinal diseases
- No diabetes mellitus
- Fasting laboratory parameters within normal range: complete blood count (RBC, WBC, PLT, HB, HT), renal function (serum creatinine, urea), liver function (ALAT, ASAT, ɣ-GT), and serum glucose.
Exclusion Criteria:
- Body mass index > 40 and ≤20
- Secondary hypertension
- Weight loss or weight gain of 5 kg or more during the last 2 months
- Usage of non-steroidal anti-inflammatory drugs (acetylsalicylic acid, ibuprofen, naproxen) and not able or willing to stop taking them from at least 4 weeks prior to the study
- Usage of cholesterol-lowering medication
- Daily usage of corticosteroids
- Medical treatment that may affect blood pressure and not able (or willing) to stop
- Taking nutritional supplements and unwilling to discontinue
- Lactating, pregnant or intention to become pregnant during study
- Reported dietary habits, medically prescribed diet, slimming diet
- Reported average alcohol consumption > 2 glasses/d (men) or >1 glass/d (women)
- Problems with consuming the supplements or following the study guidelines
- Unwilling to undergo home or office blood pressure measurements
- Recent blood donation i.e. 1 month (male subjects) or 2 months (female subjects) prior to the study and planned donation during the study period
- Reported intense sporting activities > 10 h/w
- Not agreeing to be informed about unexpected and medically relevant personal test-results, or not agreeing that their general practitioner will be informed about these results
- Participation in another biomedical trial less than 2 months before the start of the study or at the same time
- No signed informed consent form
- Clinical disorders that could interfere with the intervention
- Unable to comply with the study procedure (e.g. holidays, urine collection, blood sampling)
- Smokers
- Difficulty imaging brachial artery by ultrasonography
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Epicatechin
Subjects will be asked to consume supplements containing 100mg of epicatechin daily
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Subjects will be asked to consume supplements containing 100mg of epicatechin daily
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Active Comparator: Quercetin
Subjects will be asked to consume supplements containing 160mg of quercetin-3-glucoside daily
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Subjects will be asked to consume 160mg of quercetin-3-glucoside daily
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Placebo Comparator: Placebo
Subjects will be asked to consume capsules containing a placebo (cellulose) daily
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Subjects will be asked to consume capsules containing placebo (cellulose) daily
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Endothelium-dependent flow-mediated dilation as a result of epicatechin and quercetin-3-glucoside supplementation
Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Change in arterial diameter as a result of 5 minute arterial occlusion (200mmHg).
Arterial diameter will be measured by means of ultrasonography.
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Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in blood pressure as a result of epicatechin and quercetin-3-glucoside supplementation
Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Office BP (Dinamap, 4 consecutive measurements with 2-min intervals)and 24-hour ABPM (Spacelab; 1x24h)
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Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Change in pulse wave velocity as a result of epicatechin and quercetin supplementation
Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Measured using a SphygmoCor device at baseline and the end of each intervention
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Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Change in vasomotion as a result of epicatechin and quercetin supplementation
Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Measured using a PeriFlux 5001 device at baseline and the end of each intervention.
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Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Changes in biomarkers of endothelial function as a result of epicatechin and quercetin supplementation
Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Plasma analysis of endothelin-1, ADMA, MCP-1, sVCAM-1, sICAM-1, sE-selectin, sTM, CRP, SAA, IL-6, IL-8, TNF-α, vWF, nitric oxide
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Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Changes in peripheral blood mononuclear cell gene expression of markers of inflammation as a result of epicatechin and quercetin supplementation
Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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PBMC gene expression of markers of inflammation
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Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Change in cardiovascular parameters in plasma as a result of epicatechin and quercetin supplementation
Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin and glucose
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Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Changes in pulse wave analysis as a result of epicatechin and quercetin supplementation
Time Frame: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Measured using a SphygmoCor device at baseline and the end of each intervention
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Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
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Adverse events
Time Frame: Baseline and every 2 weeks thereafter (weeks 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20)
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During the study subjects will be asked to maintain a diary in which they can report any adverse events they may have a result of the supplements.
Diaries will be checked every 2 weeks.
Study subjects will also be asked to contact the research team if they experience repeated adverse events.
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Baseline and every 2 weeks thereafter (weeks 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20)
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Peter Hollman, PhD, Wageningen University
Publications and helpful links
General Publications
- Van den Eynde MDG, Geleijnse JM, Scheijen JLJM, Hanssen NMJ, Dower JI, Afman LA, Stehouwer CDA, Hollman PCH, Schalkwijk CG. Quercetin, but Not Epicatechin, Decreases Plasma Concentrations of Methylglyoxal in Adults in a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial with Pure Flavonoids. J Nutr. 2018 Dec 1;148(12):1911-1916. doi: 10.1093/jn/nxy236.
- Dower JI, Geleijnse JM, Gijsbers L, Schalkwijk C, Kromhout D, Hollman PC. Supplementation of the Pure Flavonoids Epicatechin and Quercetin Affects Some Biomarkers of Endothelial Dysfunction and Inflammation in (Pre)Hypertensive Adults: A Randomized Double-Blind, Placebo-Controlled, Crossover Trial. J Nutr. 2015 Jul;145(7):1459-63. doi: 10.3945/jn.115.211888. Epub 2015 May 13.
- Dower JI, Geleijnse JM, Gijsbers L, Zock PL, Kromhout D, Hollman PC. Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial. Am J Clin Nutr. 2015 May;101(5):914-21. doi: 10.3945/ajcn.114.098590. Epub 2015 Feb 25.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NL4077208112
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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