HypertensionNCT01691404
Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure (FLAVO)
A study testing Epicatechin and Quercetin in people with Hypertension and Endothelial Dysfunction, run by Wageningen University at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 30 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension, Endothelial Dysfunction
- What is being tested?
- Epicatechin and Quercetin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2012to Mar 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Hypertension, Endothelial Dysfunction
- Being tested
- Epicatechin, Quercetin, Placebo
- Keywords
- Flavonoids, Quercetin, Epicatechin, Vascular function, Blood pressure, Endothelial function
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpicatechinDietary supplement
Subjects will be asked to consume supplements containing 100mg of epicatechin daily
QuercetinDietary supplement
Subjects will be asked to consume 160mg of quercetin-3-glucoside daily
PlaceboDietary supplement
Subjects will be asked to consume capsules containing placebo (cellulose) daily
| Study group | Role | What they receive |
|---|---|---|
| Epicatechin | Active comparator | Subjects will be asked to consume supplements containing 100mg of epicatechin daily Receives: Dietary Supplement: Epicatechin |
| Quercetin | Active comparator | Subjects will be asked to consume supplements containing 160mg of quercetin-3-glucoside daily Receives: Dietary Supplement: Quercetin |
| Placebo | Placebo comparator | Subjects will be asked to consume capsules containing a placebo (cellulose) daily Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Endothelium-dependent flow-mediated dilation as a result of epicatechin and quercetin-3-glucoside supplementation
Change in arterial diameter as a result of 5 minute arterial occlusion (200mmHg). Arterial diameter will be measured by means of ultrasonography.
Measured: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
Secondary outcomes (8)
Change in blood pressure as a result of epicatechin and quercetin-3-glucoside supplementation
Office BP (Dinamap, 4 consecutive measurements with 2-min intervals)and 24-hour ABPM (Spacelab; 1x24h)
Measured: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
Change in pulse wave velocity as a result of epicatechin and quercetin supplementation
Measured using a SphygmoCor device at baseline and the end of each intervention
Measured: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
Change in vasomotion as a result of epicatechin and quercetin supplementation
Measured using a PeriFlux 5001 device at baseline and the end of each intervention.
Measured: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
Changes in biomarkers of endothelial function as a result of epicatechin and quercetin supplementation
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
Measured: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
Changes in peripheral blood mononuclear cell gene expression of markers of inflammation as a result of epicatechin and quercetin supplementation
PBMC gene expression of markers of inflammation
Measured: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
Change in cardiovascular parameters in plasma as a result of epicatechin and quercetin supplementation
Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin and glucose
Measured: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
Changes in pulse wave analysis as a result of epicatechin and quercetin supplementation
Measured using a SphygmoCor device at baseline and the end of each intervention
Measured: Baseline and every 4 weeks thereafter (weeks 4, 8, 12, 16 and 20)
Adverse events
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.
Measured: Baseline and every 2 weeks thereafter (weeks 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2012 (estimated)
- Study startSep 2012
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wageningen University
- Sponsor type
- University, hospital or other
- Collaborators
- Top Institute Food and Nutrition
- Responsible party
- Sponsor
- Investigators
- Peter Hollman, PhD, Principal investigator, Wageningen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01691404
- Sponsor's protocol ID
- NL4077208112
- Status last verified
- Nov 2012
- First submitted
- 12 Sep 2012
- Last updated
- 23 Apr 2013
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 30398646Dower 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.
PubMed 25972527Dower 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.
PubMed 25934864
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study on the Effects of Epicatechin and Quercetin Supplementation on Vascular Function and Blood Pressure in Untreated (Pre)Hypertensive Subjects
- ClinicalTrials.gov ID
- NCT01691404
- Acronym / sponsor ID
- NL4077208112
- Conditions
- Hypertension, Endothelial Dysfunction
- Keywords
- Flavonoids, Quercetin, Epicatechin, Vascular function, Blood pressure, Endothelial function
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Wageningen UniversityUniversity, hospital or other
- Collaborators
- Top Institute Food and Nutrition
- Study start
- Sep 2012
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 24 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Epicatechin | Active comparator | Dietary Supplement: EpicatechinSubjects will be asked to consume supplements containing 100mg of epicatechin daily |
| Quercetin | Active comparator | Dietary Supplement: QuercetinSubjects will be asked to consume supplements containing 160mg of quercetin-3-glucoside daily |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboSubjects will be asked to consume capsules containing a placebo (cellulose) daily |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EpicatechinSubjects will be asked to consume supplements containing 100mg of epicatechin daily | Dietary supplement | Epicatechin |
| QuercetinSubjects will be asked to consume 160mg of quercetin-3-glucoside daily | Dietary supplement | Quercetin |
| PlaceboSubjects will be asked to consume capsules containing placebo (cellulose) daily | Dietary supplement | Placebo |
Primary outcome
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)
Change in arterial diameter as a result of 5 minute arterial occlusion (200mmHg). Arterial diameter will be measured by means of ultrasonography.
8 secondary outcomes
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)
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)
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)
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)
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)
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)
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)
Adverse events
Time frame: Baseline and every 2 weeks thereafter (weeks 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2013.
- Derived from this study: PubMed 30398646Van 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.
- Derived from this study: PubMed 25972527Dower 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.
- Derived from this study: PubMed 25934864Dower 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.
- Website for the study (in dutch)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Hollman, PhD principal investigator
Wageningen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Epicatechin and Quercetin in people with Hypertension and Endothelial Dysfunction, run by Wageningen University at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01691404, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2013.