Clinical trial NCT02783989: Effects on Cardiovascular Risk Factors of the Endogenous Hydroxytyrosol Generation After the Combined Intake of Wine and Tyrosol in Humans
Official title: A Single-center, Crossover, Randomized and Controlled Nutritional Intervention Clinical Trial. A Nutritional Intervention Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease
Keywords: Endothelial function
Inflammation
Genes related to vascular risk
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
First posted: 2016-05-26
Enrollment: 33
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Understanding and accepting the study procedures and signing the informed consent.
2. Male and female volunteers aged 50 to 80 years.
3. 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
   * 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).
4. Clinical diagnosis of type 2 diabetes.
5. Clinical history and physical examination demonstrating no organic or psychiatric disorders.
6. 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.
7. Subjects socially drinking and who had ingested wine at least once.
8. 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:

   (i) 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).

Exclusion Criteria:

1. Not meeting the inclusion criteria.
2. Participants with BMI \>40kg/m2
3. Participants who intake antioxidant supplements.
4. Participants with multiple allergies or intestinal diseases.
5. Participants who follow special diets (vegetarian and vegan diets included).
6. Participants with any condition limiting their mobility, making study visits impossible or worsening the adherence to the treatments.
7. Participants with history of hypersensitivity or intolerance to ethanol.
8. Ethanol users of \>80 g/d (v) and illicit drug users.
9. Illiteracy.
10. Participants with an acute infection or inflammatory process in the last three months (may be included if the episode developed prior to 3 months).
11. Participants with history of previous cardiovascular disease (coronary heart disease or stroke)
12. Participants taking medication with sedative effects or interacting with ethanol.
13. Participation in other clinical trials with drugs in the previous 12 weeks

Primary outcomes:
measure: Metabolic: changes in hydroxytyrosol generation
timeFrame: change from baseline at 4 weeks
measure: Vascular effects: changes in endothelial function
timeFrame: change from baseline at 4 weeks
measure: Metabolic effects (n=12)
timeFrame: up to 24 hours
Secondary outcomes:
measure: changes in glucose profile
timeFrame: change from baseline at 4 weeks
measure: changes in lipid profile
timeFrame: change from baseline at 4 weeks
measure: changes in lipid profile
timeFrame: change from baseline at 4 weeks
measure: changes in lipid profile
timeFrame: change from baseline at 4 weeks
measure: changes in lipid profile
timeFrame: change from baseline at 4 weeks
measure: changes in oxidation profile
timeFrame: change from baseline at 4 weeks
measure: changes in inflammation enzymes
timeFrame: change from baseline at 4 weeks
measure: change in endothelial function
timeFrame: change from baseline endothelial function at 4 weeks
measure: Alcohol biomarker
timeFrame: change from baseline at 4 weeks
measure: Gene expression
timeFrame: change from baseline at 4 weeks
Other outcomes:
measure: Liver function test
timeFrame: through study completion, an average of 6 months
Locations:
city: Barcelona
country: Spain
facility: IMIM (Hospital del Mar Medical Research Institute)
Study officials:
affiliation: IMIM-Hospital del Mar Medical Research Institute
name: Rafael De la Torre Fornell, Pharm, PhD
role: PRINCIPAL_INVESTIGATOR
References: