Cardiovascular DiseaseDOPET3NCT02783989
Effects on Cardiovascular Risk Factors of the Endogenous Hydroxytyrosol Generation After the Combined Intake of Wine and Tyrosol in Humans
A study testing white wine and tyrosol in people with Cardiovascular Disease, run by Parc de Salut Mar at 1 site in Spain.
Trial summary
The present study will assess whether the beneficial effects of a market moderate-alcohol drinking in the form of white wine in humans could be derived from the endogenous formation of hydroxytyrosol (also known DOPET), a potent dietary anti-inflammatory and antioxidant molecule. Read more about this study
- Who is it for?
- Ages 50 to 80 years
- Conditions the study is for
- Cardiovascular Disease
- What is being tested?
- white wine and tyrosol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteSpain
- Study dates
- 20 Jan 2016to 25 Jun 2018
- 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 50 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Understanding and accepting the study procedures and signing the informed consent.
- Male and female volunteers aged 50 to 80 years.
- Participants with at least three major cardiovascular risk factors, including:
- current smoking (>1 cig/day during the last month)
- hypertension ≥140/90 mmHg or antihypertensive medication
- low-density lipoprotein (LDL)-cholesterol >130 mg/dl or lipid-lowering therapy
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- low high-density lipoprotein (HDL)-cholesterol ≤40 mg/dl in men or ≤50 mg/dl in women
- overweight/obesity (body mass index≥25 kg/m2)
- a family history of premature coronary heart disease (CHD).
- Clinical diagnosis of type 2 diabetes.
- Clinical history and physical examination demonstrating no organic or psychiatric disorders.
- The ECG and general blood and urine laboratory tests performed before the study should be within normal ranges. Minor or occasional changes from normal ranges are accepted if, in the investigator's opinion, considering the current state of the art, they are not clinically significant, are not life-threatening for the subjects and do not interfere with the product assessment. These changes and their non-relevance will be justified in writing specifically.
- Subjects socially drinking and who had ingested wine at least once.
- Acceptance of following a controlled diet with a moderate content of antioxidants along the study, in which time it will be not permitted the consumption of wine/champagne (except in the framework of treatment conditions in the clinical trial) or other alcoholic drinks (beer, spirits…), but it will be allowed a maximum of:
- Vegetables (including pulses): one serving (small dish)/day; (ii) Fruits (or juices): 2 pieces/day; (iii) Commercial olive oil: maximum 25 mL/day; (iv) Drinks containing xanthines (coffee, tea, cola, energy drinks…): maximum 3 cups/day; (v) Chocolate: maximum one piece (small, 15 gr)/day; (vi) Nuts: maximum 30 g (a small handful)/week; and (vii) Fish: maximum 3 times per week (150g/serving).
Who cannot join
- Not meeting the inclusion criteria.
- Participants with BMI >40kg/m2
- Participants who intake antioxidant supplements.
- Participants with multiple allergies or intestinal diseases.
- Participants who follow special diets (vegetarian and vegan diets included).
- Participants with any condition limiting their mobility, making study visits impossible or worsening the adherence to the treatments.
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- Participants with history of hypersensitivity or intolerance to ethanol.
- Ethanol users of >80 g/d (v) and illicit drug users.
- Illiteracy.
- Participants with an acute infection or inflammatory process in the last three months (may be included if the episode developed prior to 3 months).
- Participants with history of previous cardiovascular disease (coronary heart disease or stroke)
- Participants taking medication with sedative effects or interacting with ethanol.
- Participation in other clinical trials with drugs in the previous 12 weeks
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-center, Crossover, Randomized and Controlled Nutritional Intervention Clinical Trial. A Nutritional Intervention Study
The present study will assess whether the beneficial effects of a market moderate-alcohol drinking in the form of white wine in humans could be derived from the endogenous formation of hydroxytyrosol (also known DOPET), a potent dietary anti-inflammatory and antioxidant molecule.
Read the detailed description
Epidemiological studies support that light to moderate alcohol drinking (10-20g per day), may reduce the risk of cardiovascular disease (CVD), stroke, dementia, depression, and all-cause mortality. In addition, moderate red wine consumption has recently shown to be inversely associated with a decline in global cognitive function and the domains of memory and flexibility. The claimed beneficial effects of the Mediterranean diet include prevention of several age-related dysfunctions including cardiovascular and neurodegenerative diseases. These effects have been related to the protection against cognitive decline associated with aging and disease by a number of polyphenols found in red wine and virgin olive oil. Neurodegenerative diseases, as all chronic degenerative diseases, are linked to inflammation and its inter-twined phenomena: the oxidation and the oxidative damage. The interrelationship among chronic degenerative diseases is also evidenced by the fact that vascular (cardiovascular) risk factors are associated to cognitive decline, and these vascular factors are currently the only known modifiable risk factors for Alzheimer disease.
There is evidence suggesting that DOPET, also known as hydroxytyrosol (HOTYR), has a role in the cardioprotective and neuroprotective properties of wine. It is a phenolic compound present in virgin olive oil and wine, and it is a potent dietary anti-inflammatory and antioxidant molecule. Biological effects of HOTYR may explain in part some of the beneficial effects for human health that have been credited to moderate ethanol intake (in form of wine).
The present project is not intended to provide support for the clinical use of moderate- dose alcohol as a treatment modality for CVD risk patients. Nevertheless, it will investigate a novel mechanism of action that may explain in part beneficial health effects associated to moderate alcohol consumption. This novel mechanism of action is mediated by compounds that at mid/long-term run are susceptible of a pharmaceutical and/or nutraceutical food development.
- Conditions
- Cardiovascular Disease
- Being tested
- white wine, tyrosol
- Keywords
- Endothelial function, Inflammation, Genes related to vascular risk
- Medical subject headings
- Cardiovascular Diseases, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
white wineOther
A dietary beverage: a market white wine, 13º alcohol
tyrosolDietary supplement
tyrosol in capsules
| Study group | Role | What they receive |
|---|---|---|
| White wine | Active comparator | Two glasses of a market white wine (2x135 mL, 13º), each (135 mL) equivalent to 14 g of ethanol (in case of women only one glass, 135 mL), being the daily dose of 28 g (14 g in women). It is estimated that wine will contain about 8-9 mg/l of tyrosol. Therefore the dose of tyrosol ingested in two glasses would be 2-2.5 mg (1-1.25 mg in women). Receives: Other: white wine |
| White wine plus tyrosol capsules | Experimental | Two glasses of white wine (2x135 mL, 13º), each (135 mL) equivalent to 14 g of ethanol (in case of women only one glass, 135 mL), being the daily dose of 28 g (14g in women), in combination with capsules of 25 mg of TYR (each one to be ingested with a glass of wine), two capsules along the day for men (at lunch and at dinner) and one for woman (at lunch). Receives: Other: white wine; Dietary Supplement: tyrosol |
| Water | No intervention | Drinking water along with meals |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolic: changes in hydroxytyrosol generation
Hydroxytyrosol generation from tyrosol ingestion in urine (24 hours urine collection)
Measured: change from baseline at 4 weeks
Vascular effects: changes in endothelial function
It will be measured in the morning by monitoring endothelium-mediated changes in the digital pulse waveform, known as the Peripheral Arterial Tone (PAT) signal.
Measured: change from baseline at 4 weeks
Metabolic effects (n=12)
Additionally, 12 participants will be asked to collect a 24-hour urine specimen at two intervals (0-8 h and 8-24 h) the first day of each intervention, following the treatment ingestion (n=12).
Measured: up to 24 hours
Secondary outcomes (10)
changes in glucose profile
Glucose will be determined by enzymatic methods (PENTRA 400).
Measured: change from baseline at 4 weeks
changes in lipid profile
total-cholesterol will be determined by enzymatic methods (PENTRA 400).
Measured: change from baseline at 4 weeks
changes in lipid profile
HDL-cholesterol will be determined by enzymatic methods (PENTRA 400).
Measured: change from baseline at 4 weeks
changes in lipid profile
Triglycerides will be determined by enzymatic methods (PENTRA 400).
Measured: change from baseline at 4 weeks
changes in lipid profile
LDL-cholesterol concentrations will be calculated with the Friedewald equation.
Measured: change from baseline at 4 weeks
changes in oxidation profile
plasma oxidized LDL in urine will be measured by ELISA methods.
Measured: change from baseline at 4 weeks
changes in inflammation enzymes
High sensitivity C-reactive protein (CRP) (immunoturbidimetry) in plasma by high sensitivity enzyme-immunoassays (ELISAs)
Measured: change from baseline at 4 weeks
change in endothelial function
Nitric oxide (NO) plasma concentrations will be measured through nitrates/nitrites ratio by colorimetry and those of Endothelin-1 by ELISA (both techniques from Cayman Chem. Co., Ann Arbor, USA).
Measured: change from baseline endothelial function at 4 weeks
Alcohol biomarker
Ethyl glucuronide in urine by Thermo Scientific Ethyl Glucuronide Enzyme Immunoassay.
Measured: change from baseline at 4 weeks
Gene expression
Microfluidic cards (TaqMan® Gene Expression Array Microfluidic Card, 32.1 format, Applied Biosystems), 30 genes related with endothelial function and inflammation of a sub-sample of 30 subjects (15 by gender) will be determined in peripheral blood mononucleated cell (PBMC).
Measured: change from baseline at 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2016 (estimated)
- Study start20 Jan 2016
- Primary completion25 Jun 2018
- Study completion25 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseaseStudies 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
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Parc de Salut Mar
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rafael de la Torre, Parc de Salut Mar
- Investigators
- Rafael De la Torre Fornell, Pharm, PhD, Principal investigator, IMIM-Hospital del Mar Medical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02783989
- Sponsor's protocol ID
- IMIMFTCLFT/DOPET/3
- Acronym
- DOPET3
- Status last verified
- May 2019
- First submitted
- 11 May 2016
- Last updated
- 7 May 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Crossover, Randomized and Controlled Nutritional Intervention Clinical Trial. A Nutritional Intervention Study
- ClinicalTrials.gov ID
- NCT02783989
- Acronym / sponsor ID
- DOPET3 / IMIMFTCLFT/DOPET/3
- Conditions
- Cardiovascular Disease
- Keywords
- Endothelial function, Inflammation, Genes related to vascular risk
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Parc de Salut MarUniversity, hospital or other
- Study start
- 20 Jan 2016 (actual)
- Primary completion
- 25 Jun 2018 (actual)
- Study completion
- 25 Jun 2018 (actual)
- First posted
- 26 May 2016 (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.
The present study will assess whether the beneficial effects of a market moderate-alcohol drinking in the form of white wine in humans could be derived from the endogenous formation of hydroxytyrosol (also known DOPET), a potent dietary anti-inflammatory and antioxidant molecule.
Detailed description
Epidemiological studies support that light to moderate alcohol drinking (10-20g per day), may reduce the risk of cardiovascular disease (CVD), stroke, dementia, depression, and all-cause mortality. In addition, moderate red wine consumption has recently shown to be inversely associated with a decline in global cognitive function and the domains of memory and flexibility. The claimed beneficial effects of the Mediterranean diet include prevention of several age-related dysfunctions including cardiovascular and neurodegenerative diseases. These effects have been related to the protection against cognitive decline associated with aging and disease by a number of polyphenols found in red wine and virgin olive oil. Neurodegenerative diseases, as all chronic degenerative diseases, are linked to inflammation and its inter-twined phenomena: the oxidation and the oxidative damage. The interrelationship among chronic degenerative diseases is also evidenced by the fact that vascular (cardiovascular) risk factors are associated to cognitive decline, and these vascular factors are currently the only known modifiable risk factors for Alzheimer disease.
There is evidence suggesting that DOPET, also known as hydroxytyrosol (HOTYR), has a role in the cardioprotective and neuroprotective properties of wine. It is a phenolic compound present in virgin olive oil and wine, and it is a potent dietary anti-inflammatory and antioxidant molecule. Biological effects of HOTYR may explain in part some of the beneficial effects for human health that have been credited to moderate ethanol intake (in form of wine).
The present project is not intended to provide support for the clinical use of moderate- dose alcohol as a treatment modality for CVD risk patients. Nevertheless, it will investigate a novel mechanism of action that may explain in part beneficial health effects associated to moderate alcohol consumption. This novel mechanism of action is mediated by compounds that at mid/long-term run are susceptible of a pharmaceutical and/or nutraceutical food development.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| White wine | Active comparator | Other: white wineTwo glasses of a market white wine (2x135 mL, 13º), each (135 mL) equivalent to 14 g of ethanol (in case of women only one glass, 135 mL), being the daily dose of 28 g (14 g in women). It is estimated that wine will contain about 8-9 mg/l of tyrosol. Therefore the dose of tyrosol ingested in two glasses would be 2-2.5 mg (1-1.25 mg in women). |
| White wine plus tyrosol capsules | Experimental | Other: white wine, Dietary Supplement: tyrosolTwo glasses of white wine (2x135 mL, 13º), each (135 mL) equivalent to 14 g of ethanol (in case of women only one glass, 135 mL), being the daily dose of 28 g (14g in women), in combination with capsules of 25 mg of TYR (each one to be ingested with a glass of wine), two capsules along the day for men (at lunch and at dinner) and one for woman (at lunch). |
| Water | No intervention | –Drinking water along with meals |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Understanding and accepting the study procedures and signing the informed consent.
- Male and female volunteers aged 50 to 80 years.
- Participants with at least three major cardiovascular risk factors, including:
- Clinical diagnosis of type 2 diabetes.
- Clinical history and physical examination demonstrating no organic or psychiatric disorders.
Key exclusion criteria (13 listed)
- Not meeting the inclusion criteria.
- Participants with BMI >40kg/m2
- Participants who intake antioxidant supplements.
- Participants with multiple allergies or intestinal diseases.
- Participants who follow special diets (vegetarian and vegan diets included).
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 |
|---|---|---|
| white wineA dietary beverage: a market white wine, 13º alcohol | Other | White wine, White wine plus tyrosol capsules |
| tyrosoltyrosol in capsules | Dietary supplement | White wine plus tyrosol capsules |
Primary outcome
Metabolic: changes in hydroxytyrosol generation
Time frame: change from baseline at 4 weeks
Hydroxytyrosol generation from tyrosol ingestion in urine (24 hours urine collection)
Vascular effects: changes in endothelial function
Time frame: change from baseline at 4 weeks
It will be measured in the morning by monitoring endothelium-mediated changes in the digital pulse waveform, known as the Peripheral Arterial Tone (PAT) signal.
Metabolic effects (n=12)
Time frame: up to 24 hours
Additionally, 12 participants will be asked to collect a 24-hour urine specimen at two intervals (0-8 h and 8-24 h) the first day of each intervention, following the treatment ingestion (n=12).
10 secondary outcomes
changes in glucose profile
Time frame: change from baseline at 4 weeks
changes in lipid profile
Time frame: change from baseline at 4 weeks
changes in lipid profile
Time frame: change from baseline at 4 weeks
changes in lipid profile
Time frame: change from baseline at 4 weeks
changes in lipid profile
Time frame: change from baseline at 4 weeks
changes in oxidation profile
Time frame: change from baseline at 4 weeks
changes in inflammation enzymes
Time frame: change from baseline at 4 weeks
change in endothelial function
Time frame: change from baseline endothelial function at 4 weeks
Alcohol biomarker
Time frame: change from baseline at 4 weeks
Gene expression
Time frame: change from baseline at 4 weeks
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 7 May 2019.
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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.
Rafael De la Torre Fornell, Pharm, PhD principal investigator
IMIM-Hospital del Mar Medical Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing white wine and tyrosol in people with Cardiovascular Disease, run by Parc de Salut Mar at 1 site in Spain.
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 15 inclusion and 13 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 7 May 2019. 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 Spain. 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. 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?
Metabolic: changes in hydroxytyrosol generation (time frame: change from baseline at 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 May 2019.