Relevance of the Ethanol Dose in the Generation of Endogenous Hydroxytyrosol

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).

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.

Study Overview

• Status: Completed
• Conditions: Contribution of Ethanol on Hydroxytyrosol Formation
• Intervention / Treatment: Other: Water; Dietary supplement: Ethanol

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Parc de Salut Mar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Water; Lemon-flavoured water (150 ml)	Other: Water
Active Comparator: Ethanol high dose; 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
Active Comparator: Ethanol low dose; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Parc de Salut Mar
• Collaborators: Fundacion IMIM
• Investigators: Principal Investigator: Magí Farré, MD, PhD, Parc de Salut Mar

Publications and helpful links

General Publications

• Perez-Mana C, Farre M, Pujadas M, Mustata C, Menoyo E, Pastor A, Langohr K, de la Torre R. Ethanol induces hydroxytyrosol formation in humans. Pharmacol Res. 2015 May-Jun;95-96:27-33. doi: 10.1016/j.phrs.2015.02.008. Epub 2015 Mar 20.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: February 5, 2013
• First Submitted That Met QC Criteria: February 7, 2013
• First Posted (Estimate): February 11, 2013

Study Record Updates

• Last Update Posted (Estimate): February 11, 2013
• Last Update Submitted That Met QC Criteria: February 7, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Antioxidants, Central Nervous System Agents
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: Hidroxitirosol/FIS/1