Dose-response Effect of Alcohol Ingestion on Steroid Profile

Study Overview
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Brief Summary
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The aim of the clinical trial is to study the intra-individual variation of steroid profile parameters after experimental administration of different doses of ethanol in Caucasian women.

Detailed Description
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The introduction of the so called 'endocrine module' of the athlete's biological passport needs to consider the numerous reports showing the effect of ethanol ingestion on the steroid profile. A steroid profile would only be useful for longitudinal monitoring and statistical evaluation if it has not been altered by any uncontrolled circumstance, very particularly alcohol consumption. There is an urgent need to study the perpetuation that alcohol ingestion causes to the individual steroid profile and if possible establish cut-off values for markers of ethanol ingestion granting that the steroid profile determined has not been affected by such ingestion. Subjects will be genotyped for genetic deletion polymorphism in the uridine diphosphoglucuronosyltransferase family 2 member B17 gene (UGT2B17) related to testosterone glucuronidation regulation. The objective of the clinical trial is to study the intra-individual variation of steroid profile parameters as a result of the ingestion of different doses of ethanol in Caucasian women (complementing previous studies performed in men).

Official Title
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Dose-response Effect of Alcohol Ingestion on Steroid Profile: Gender and Ethnic Aspects

Conditions
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Alcohol Consumption, Healthy

Intervention / Treatment
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* Dietary Supplement: 10 g ethanol
* Dietary Supplement: 20 g ethanol
* Dietary Supplement: Water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants will be healthy women aged 18 to 55 years. Women will enter in studies at the follicular phase of the menstrual cycle, in order to avoid the interference of estrogens. Female subjects (if not postmenopausal) possessing regular menstrual cycle between 26 and 32 days and willing to use effective methods of contraception through the study (sexual abstinence, vasectomized partner, sterilization, intrauterine device, double-barrier method). 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 18.5 to 29.9 kg/m2, and the weight from 50 to 100 kg. Understanding and accepting the study procedures and signing the informed consent. Agreeing to follow a diet free from ethanol in the 72 hours prior to the start of each session and until the end of the study. Subjects with social or recreational alcohol consumption, at least 3 standard drinks/week and subjects with experience in several drunkenness. 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. Women presenting amenorrhea or who suffer from moderate to intense premenstrual syndrome. Female subjects using hormonal contraceptive hormones. 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. Ingestion of vitamin supplements or antioxidants or nonsteroidal anti-inflammatory drugs in the two weeks preceding the study. 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. Subjects who have suffered a hospitalization caused by alcohol intoxication or who have received treatment for drunkenness 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. Subjects who follow a vegetarian diet.

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

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| Experimental: 10 g ethanol<br>31 mL of Vodka Absolut® diluted in 369 mL of lemon flavored-water (LFW) Fontvella®. A total volume of 400 mL of the drink will be administered, distributed in three 133 mL cool glasses. Administration of ethanol beverage will be controlled: participants will have 5 minutes to drink each glass. | Dietary Supplement: 10 g ethanol<br>* 31 mL of Vodka Absolut® diluted in 369 mL of lemon flavored-water (LFW) Fontvella®. A total volume of 400 mL of the drink will be administered, distributed in three 133 mL cool glasses. Administration of ethanol beverage will be controlled: participants will have 5 minutes to drink each glass.<br>* Other names: Vodka Absolut®;|
| Experimental: 20 g ethanol<br>63 mL of Vodka Absolut® diluted in 337 mL of lemon flavored-water (LFW) Fontvella®. A total volume of 400 mL of the drink will be administered, distributed in three 133 mL cool glasses. Administration of ethanol beverage will be controlled: participants will have 5 minutes to drink each glass. | Dietary Supplement: 20 g ethanol<br>* 63 mL of Vodka Absolut® diluted in 337 mL of lemon flavored-water (LFW) Fontvella®. A total volume of 400 mL of the drink will be administered, distributed in three 133 mL cool glasses. Administration of ethanol beverage will be controlled: participants will have 5 minutes to drink each glass.<br>* Other names: Vodka Absolut®;|
| Placebo Comparator: Water<br>400 mL of lemon flavored-water Fontvella®. A total volume of 400 mL of the drink will be administered, distributed in three 133 mL cool glasses. The administration will be controlled: participants will have 5 minutes to drink each glass. | Dietary Supplement: Water<br>* 400 mL of lemon flavored-water Fontvella®. A total volume of 400 mL of the drink will be administered, distributed in three 133 mL cool glasses. The administration will be controlled: participants will have 5 minutes to drink each glass.<br>* Other names: Lemon flavored-water Fontvella®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline steroid profile | 24 hours urine will be collected before each experimental session and also up to 24 hours after administration. | From one day before administration till 24 hours after administration | 
| Change from baseline Ethyl glucuronide concentrations | Ethyl glucuronide in urine will be measured by Liquid chromatography-mass spectrometry (LC-MS) using deuterated analogs as Internal Standards. | From baseline till 24 hours after administration | 
| Change from baseline Urine Ethyl sulfate concentrations | Ethyl sulfate in urine will be measured by Liquid chromatography-mass spectrometry (LC-MS) using deuterated analogs as Internal Standards. | From baseline till 24 hours after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline alcohol breath air concentrations | Alcohol concentration in breath air will be determined baseline (pre-administration) and up to 6 hours post-administration. | From baseline till 6 hours after administration | 
| Urine Creatinine concentrations | Creatinine will be determined in each urine sample | From one day before administration till 24 hours after administration | 
| Change from baseline subjective effects of ethanol | Participants will self-report their experience on a Visual Analogical Scale (VAS): before administration and till 6h post-administration | From baseline till 6 hours after administration | 
| Number of Participants with Serious and Non-Serious Adverse Events | Collection of adverse effects spontaneously by the participants and/or observed by the investigators. | Through study completion, an average of 1 year | 
| Change from baseline heart rate | Monitoring heart rate before administration and till 6h post-administration. | From baseline to 6 hours after administration | 
| Change from baseline oral temperature | Monitoring oral temperature before administration and till 6h post-administration. | From baseline to 6 hours after administration | 
| Change from baseline blood pressure | Monitoring blood pressure before administration and till 6h post-administration. | From baseline to 6 hours after administration | 
| Urine pH | pH will be determined in each urine sample | From one day before administration till 24 hours after administration | 
| Urine specific gravity | Specific gravity will be determined in each urine sample | From one day before administration till 24 hours after administration | 
| Uridine diphosphoglucuronosyltransferase family 2 member B17 (UGT2B17) deletion genotype | A blood sample for genotyping will be collected. The buffy coat will be stored a -20 degrees celsius (ºC). If deemed necessary for the interpretation of results, DNA will be extracted and evaluated following quantitative multiplex amplification polymerase chain reaction (PCR) for the evaluation of UGT2B17 deletion and copy number variation (CNVs) | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ethanol, Steroid profile, Pharmacokinetics