Clinical trial NCT02311686: Non-oxidative Metabolite Profiles After Increasing Doses of Ethanol
Official title: Identifying the Profile of the Main Non-oxidative Biomarkers of Alcohol (Ethyl Glucuronide, Ethyl Sulphate, Fatty Acid Ethyl Esters) After the Experimental Exposure to Increasing Doses of Alcohol in Adults.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alcohol Consumption
Healthy
Keywords: Ethanol
Fatty acid ethyl esters
Ethyl glucoronide
Ethyl sulphate
Pharmacokinetics
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
First posted: 2014-12-08
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of the study is to study the profile of ethanol and non-oxidative biomarkers (ethyl glucuronide, ethyl sulphate and fatty acid ethyl esters) after experimental administration of increasing doses of alcohol in adult subjects.

Detailed description: The abuse of alcohol causes serious health and social problems. Alcohol consumption can be monitored by detecting biomarkers. In current practice indirect biomarkers (mean corpuscular volume, transaminases, gammaglutamyl or carbohydrate-deficient transferrin) are used, although direct biomarkers of alcohol, including alcohol itself and metabolites also exist.

Biomarkers of alcohol consumption are used as tools to prevent health and social problems related with alcohol, allowing the identification of subjects at risk of abuse, dependence or withdrawal and to assess the efficacy of treatments for alcohol dependence.

Non-oxidative metabolites (ethyl glucuronide, ethyl sulphate and fatty acid ethyl esters) have longer biological half-life than ethanol and accumulate in tissues after consumption.

The objective of the study is to study the profile of ethanol and non-oxidative biomarkers (ethyl glucuronide, ethyl sulphate and fatty acid ethyl esters) after experimental administration of increasing doses of alcohol in adult subjects.

Subjects will be genotyped for genetic polymorphisms of proteins related to ethanol metabolism and effects (as alcohol dehydrogenase and aldehyde dehydrogenase), and the genotypes will be used to evaluate their influence in the results.

Eligibility criteria: Inclusion Criteria:

* Understand and accept the study's procedures and sign an informed consent form
* No evidence of somatic or psychiatric disorders as per past medical history and physical examination
* EKG, blood and urine tests taken before entry into the study within the normal range. Minor and transient abnormalities may be acceptable if, according to the Principal Investigator's criterion and the state of the art, they are felt to have no clinical relevance, entail no danger to the participant, and don't interfere with the product's assessment. These abnormalities and their non-relevance must be specifically justified in writing)
* Body mass index (BMI=weight/heigth2) between 19 and 29 kg/m2, weight between 50 and 100 kg (for the 60 and 80 g doses, subjects will be required to weigh a minimum of 67 kg)
* For premenopausal females, a regular menstrual cycle of 26-32 days duration.
* Social or recreational alcohol consumption of at least 1 unit per day (or its equivalent \[7 units\] over the whole week) and having experienced drunkenness several times

Exclusion Criteria:

* Evidence of a preexisting condition (including gastrointestinal, liver, or kidney disorders) that may alter the absorption, distribution, metabolism or excretion of the drug or symptoms suggestive of drug-induced gastrointestinal irritation
* Previous psychiatric disorders, alcoholism, abuse of prescription drugs or illegal substances or regular consumption of psychoactive drugs
* Having donated blood or having participated in this same study in the preceding 8 weeks, or having participated in any clinical trial with drugs in the preceding 12 weeks
* Having had any somatic disease or having undergone major surgery in the 3 months prior to inclusion in the trial
* Individuals intolerant or having experienced a severe adverse reaction to alcohol
* Having regularly taken medication in the month before the trial, except for vitamins, herb-based remedies, dietary supplements that if, according to the Principal Investigator or his appointed collaborators' opinion, they pose no threat to the subjects and they won't interfere with the study's objectives. Single doses of symptomatic drugs taken during the week before the experimental session will not constitute an exclusion criterion if it can be assumed that it has been completely eliminated on the day of the experimental session
* Smokers of \>10 cigarettes/day
* Consumption of \>20 g/day of alcohol (females) or of \>40 g/day (males)
* Daily consumption of more than 5 coffees, teas, cola drinks or other stimulant or xanthine-containing beverages in the 3 months prior to inclusion in the study
* Hepatitis B, hepatitis C or human immunodeficiency virus-positive individuals
* Pregnant or lactating women, or those using hormonal or unreliable contraceptive methods during the study period. Complete abstinence, intrauterine devices, double barrier methods or a vasectomized sexual partner will be considered acceptable
* Women with amenorrhea or suffering severe premenstrual syndrome
* Individuals of Asian ascent

Primary outcomes:
measure: Area Under the Concentration-Time Curve (AUC 0-24h)
timeFrame: From baseline to 24 hours after administration
Secondary outcomes:
measure: Area Under the Concentration-Time Curve (AUC 0-24h)
timeFrame: From baseline to 24 hours after administration
measure: Cumulative amount of drug excreted into urine up to collection time of last measurable concentration
timeFrame: From baseline to 72 hours after administration
measure: Elimination half-life
timeFrame: From baseline to 24 hours after administration
measure: Fatty acid ethyl esters and ethyl glucoronide hair concentrations
timeFrame: Baseline, 1 and 2 months after administration
measure: Change in subjective effects of ethanol
timeFrame: From baseline to 10 hours after administration
measure: Number of Participants with Serious and Non-Serious Adverse Events
timeFrame: From baseline to 24 hours after administration
measure: Change in Addiction Research Center Inventory (ARCI)
timeFrame: From baseline to 10 h after administration
measure: Change in Evaluation of Subjective Effects of Substances with Abuse Potential (VESSPA)
timeFrame: From baseline to 10 h after administration
measure: Ethanol dose identification questionaire
timeFrame: 10 h after administration
measure: Urinary drug concentrations
timeFrame: From 1 week to 2 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Parc de Salut Mar (IMIM)
Study officials:
affiliation: Parc de Salut Mar
name: Francina Fonseca, MD, PhD
role: STUDY_DIRECTOR
affiliation: Parc de Salut Mar
name: Clara Pérez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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