Relevance of the Ethanol Dose in the Generation of Endogenous Hydroxytyrosol

Study Overview
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Brief Summary
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Health benefits for humans derived from low dose intake of ethanol could partially be explained by its interaction with dopamine (DA) oxidative metabolism. Ethanol is expected to induce an increase in the formation of a DA minor metabolite: DOPET (hydroxytyrosol). Hydroxytyrosol is one of the most potent antioxidants present in Mediterranean Diet. The study is aimed at establishing the contribution of ethanol on hydroxytyrosol formation.

Official Title
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Hydroxytyrosol as an Endogenous and Natural Antioxidant: Modulation by Alcohol Intake. Substudy 1. Evaluating the Relevance of the Ethanol Dose in the Generation of Endogenous Hydroxytyrosol (DOPET).

Conditions
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Contribution of Ethanol on Hydroxytyrosol Formation

Intervention / Treatment
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* Dietary Supplement: Ethanol
* Other: Water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. The body mass index (BMI=weigh/height2) will range from 19 to 27 kg/m2, and the weight from 50 to 110 kg. Understanding and accepting the study procedures and signing the informed consent. Exclusion Criteria: Not meeting the inclusion criteria. History or clinical evidence of alcoholism, drug abuse, or regular use of psychoactive drugs. Having suffered any organic disease or major surgery in the three months prior to the study start. History of psychiatric disorders. Smokers of more than 20 cigarettes per day. Taking more than 30 g of alcohol a day Regular use of any drug in the month prior to the study sessions.The treatment with single or limited doses of symptomatic medicinal products in the week prior to the study sessions will not be a reason for exclusion if it is calculated that it has been cleared completely the day of the experimental session. Blood donation 8 weeks before or participation in other clinical trials with drugs in the previous 12 weeks. Subjects with intolerance or adverse reactions to ethanol History or clinical evidence of gastrointestinal, liver, renal or other disorders which may lead to suspecting a disorder in drug absorption, distribution, metabolism or excretion, or that suggest gastrointestinal irritation due to drugs. Subjects unable to understand the nature, consequences of the study and the procedures requested to be followed. Subjects with positive serology to Hepatitis B, C or HIV. To be eligible, the subjects must agree to follow a diet free from ethanol and olive oil in the 72 hours prior to the start of each session and until the end of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Water<br>Lemon-flavoured water (150 ml) | Other: Water<br> <br> |
| Active Comparator: Ethanol high dose<br>The high dose corresponds to 30 g of ethanol in pilot cohort 1, to 12 g of ethanol in pilot cohort 2 and to 42 g of ethanol in pilot cohort 3. For the definitive study the high dose corresponds to 30 g of ethanol. Ethanol was administered as a single dose of pure ethanol diluted in lemon-flavoured water (150 ml each beverage). | Dietary Supplement: Ethanol<br> <br> |
| Active Comparator: Ethanol low dose<br>The low dose corresponds to 18 g of ethanol in pilot cohort 1, to 6 g of ethanol in pilot cohort 2 and to 24 g of ethanol in pilot cohort 3. For the definitive study the low dose corresponds to 18 g of ethanol. Ethanol was administered as a single dose of pure ethanol diluted in lemon-flavoured water (150 ml each beverage). | Dietary Supplement: Ethanol<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hydroxytyrosol biological fluids concentrations | Hydroxytyrosol concentrations in plasma and urine | 0-24h after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective drunkenness | Ethanol subjective effects measured using a visual analog scale | 0-6h after administration | 
| Vital signs | Blood pressure, oral temperature and heart rate | 0-6h after administration | 
| Ethanol concentration | Ethanol blood concentrations | 0-6h after administration | 
| Ethanol metabolites concentrations | Ethanol metabolites recovery in urine | 0-24h after administration | 
| Dopamine metabolites concentrations | Dopamine metabolites recovery in urine | 0-24h after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antioxidants, Central Nervous System Agents