Steroid Profile: Differentiating Testosterone Administration From (Simultaneous) Ethanol Consumption

NCT04166786 | Completed Phase 1

• 1 other identifier: IMIMFTCL/SPOL/1
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Testosterone is an anabolic steroid widely known to improve physical performance. Its consumption is banned by the World Anti-Doping Agency (WADA). The steroid profile is one of the components of the Athlete's Biological Passport (ABP), which consists of selected biological variables that indirectly reveal the effects of doping. Alcohol consumption has been proved to alter the steroid profile and this may lead to the use of ethanol as a masking agent for testosterone administration. Hypothesis: Ratios of different testosterone biomarkers vary after ethanol administration: \[6-hydroxy-androsterone-3-glucuronide (6OH-Andros3G) / epitestosterone-glucuronide (EG)\] and \[6-hydroxy-etiocholanolone-3-glucuronide (6OH-Etio3G) / EG\] decrease, while \[testosterone-glucuronide (TG) / EG\] increases. Primary objective: To evaluate if the combination of the markers TG, EG, 6OH-Andros3G and 6OH-Etio3G, as well as ethyl glucuronide (EtG) and ethyl sulfate (EtS), can be routinely used to differentiate between changes in the steroid profile due exclusively to the consumption of alcohol and those produced when alcohol is consumed during a testosterone administration. Secondary objectives:

1. 1.To explore the potential of the simultaneous determination of both phase I and phase II metabolites in alternative matrices (plasma from blood samples collected as for the haematological module of ABP, or saliva) in the screening of testosterone misuse.
2. 2.To look for the differences into a comprehensive steroid profile (determined in urine, plasma and saliva) between samples collected after testosterone administration and after the combination of testosterone and ethanol.

Conditions

Healthy Volunteers

Keywords

Testosterone; Ethanol; Anti-doping control; Athletic performance

Outcome Measures

Primary Outcomes (5)

• Change in steroid profile in urine

  Variation of the concentration of different endogenous steroids (testosterone, epitestosterone, androsterone, etiocholanolone, 3a,5a-androstanediol, 3a,5b-androstanediol, DHEAS, 5PTS, 5PDS, PTG, PDG) in urine before and after treatment administration.

  From baseline (pre-administration) to 48 hours after last administration (fractions: 0-2, 2-4, 4-6, 6-8, 8-24 hours each day, and 24-48 hours post-administration last day)

• Change in new steroid profile markers in plasma

  Variation of the concentration of new steroid profile markers (6OH-Andros3G, 6OH-Etio3G, testosterone free TG, Andros, Andros3G, Etio, Etio3G) in plasma before and after treatment administration.

  From baseline (pre-administration) to 8 hours post-administration (at 0, 2, 4, 6, 8 hours each day)

• Change in new steroid profile markers in saliva

  Variation of the concentration of new steroid profile markers (6OH-Andros3G, 6OH-Etio3G, testosterone free TG, Andros, Andros3G, Etio, Etio3G) in saliva before and after treatment administration.

  From baseline (pre-administration) to 8 hours post-administration (at 0, 2, 4, 6, 8 hours each day)

• Change in Ethyl glucuronide in urine

  Variation of the concentration of Ethyl glucuronide in urine before and after treatment administration.

  From baseline (pre-administration) to 48 hours post-administration (fractions: 0-2, 2-4, 4-6, 6-8, 8-24, 24-48 hours)

• Change in Ethyl sulfate in urine

  Variation of the concentration of Ethyl sulfate in urine before and after treatment administration.

  From baseline (pre-administration) to 48 hours post-administration (fractions: 0-2, 2-4, 4-6, 6-8, 8-24, 24-48 hours)

Study Arms (4)

Testosterone + Ethanol

EXPERIMENTAL

Subjects receive a 3-day treatment with testosterone in combination with ethanol consumption. Subjects have to collect urine in different fractions until 48h post-administration. Blood and saliva samples are also obtained.

Drug: Testosterone gel; Drug: Ethanol Solution

Testosterone placebo + Ethanol

OTHER

Subjects receive a 3-day treatment with testosterone placebo (vaseline) in combination with ethanol consumption. Subjects have to collect urine in different fractions until 48h post-administration. Blood and saliva samples are also obtained.

Drug: Ethanol Solution; Drug: Testosterone placebo (vaseline)

Testosterone + Ethanol placebo

OTHER

Subjects receive a 3-day treatment with testosterone in combination with ethanol placebo (lemon-flavoured water). Subjects have to collect urine in different fractions until 48h post-administration. Blood and saliva samples are also obtained.

Drug: Testosterone gel; Drug: Ethanol placebo (lemon-flavoured water)

Testosterone placebo + Ethanol placebo

PLACEBO COMPARATOR

Subjects receive a 3-day treatment with testosterone placebo (vaseline) in combination with ethanol placebo (lemon-flavoured water). Subjects have to collect urine in different fractions until 48h post-administration. Blood and saliva samples are also obtained.

Drug: Testosterone placebo (vaseline); Drug: Ethanol placebo (lemon-flavoured water)

Interventions

Testosterone gel DRUG

Subjects receive a daily transdermal dose of 100 mg of testosterone (2 sachets of 5 g of gel) during 3 days.

Also known as: Testogel 50 mg®

Testosterone + Ethanol; Testosterone + Ethanol placebo

Ethanol Solution DRUG

Subjects receive a daily administration of 30 g of ethanol (94 mL of Vodka Absolut® diluted in 300 mL of lemon-flavoured water Fontvella®) during 3 days.

Also known as: Vodka Absolut®

Testosterone + Ethanol; Testosterone placebo + Ethanol

Testosterone placebo (vaseline) DRUG

Subjects receive a daily transdermal dose of 5 g of pure vaseline ointment during 3 days.

Also known as: Vaselina Pura Pege®

Testosterone placebo + Ethanol; Testosterone placebo + Ethanol placebo

Ethanol placebo (lemon-flavoured water) DRUG

Subjects receive a daily administration of 394 mL of lemon-flavored-water Fontvella® during 3 days.

Also known as: Lemon flavored-water Fontvella®

Testosterone + Ethanol placebo; Testosterone placebo + Ethanol placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy Caucasian men aged 18 to 40 years.
• 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 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 Drink/week and subjects with experience in several drunkenness.
• Volunteers with normal steroidal profile for Caucasian population (0.7 ≤T / E ≤3)

You may not qualify if:

• Allergy, idiosyncrasy, hypersensitivity or adverse reactions to the active substance of Testogel gel®, which is synthesized from soy, or to any of the excipients or to vaseline ointment.
• Subjects with intolerance or adverse reactions to ethanol.
• History or clinical evidence of alcoholism, drug abuse, or regular use of psychoactive drugs.
• History or clinical evidence of cardiovascular, respiratory, renal, hepatic, endocrine, gastrointestinal, hematological, neurological, dermatological or other acute or chronic diseases that, in the opinion of the Principal Investigator or the collaborators designated by it, may pose a risk to the subjects or interfere with the objectives of the study. Especially history of epilepsy and migraine, edema, hypertension, diabetes mellitus, hypercalcemia or polyglobulia.
• History of psychiatric disorders.
• 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 with contraindications to treatment with the study drugs (according to the respective technical data sheets). Especially a history of breast cancer, liver cancer, suspicion or confirmation of prostate carcinoma Subjects and subjects who have suffered a hospitalization caused by alcohol intoxication or who have received treatment for drunkenness
• Having suffered any organic disease or major surgery in the three months prior to the study start.
• Symptoms compatible with a prostatic syndrome: increase in the number of urinations, difficulty to initiate urination, thinner and less potent urine stream, urination in several times, incomplete emptying of urine feeling.
• Prostate-specific antigen (PSA) values outside the normal range for the volunteer's age.
• Subjects with positive serology to Hepatitis B, C or HIV.
• Presence of bacterial, fungal or deep cuts in the area of skin chosen for cutaneous applications.
• Blood donation 8 weeks before or participation in other clinical trials with drugs in the previous 12 weeks.
• Smokers of more than 20 cigarettes per day.
• Taking more than 40 g of alcohol a day

Sponsors & Collaborators

• Parc de Salut Mar: lead

Study Sites (1)

IMIM (Hospital del Mar Medical Research Institute)

Barcelona, 08003, Spain

Location

MeSH Terms

Interventions

Petrolatum

Intervention Hierarchy (Ancestors)

Hydrocarbons; Organic Chemicals

Study Officials

• Ana M Aldea Perona, Dr

  IMIM (Hospital del Mar Medical Research Institute)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Placebo treatments are administered in the same posology as active treatments (testosterone and ethanol). Ethanol is diluted in placebo (lemon-flavoured water) to prevent differentiation.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects receive 4 different treatment conditions (testosterone+ethanol placebo, ethanol+testosterone placebo, testosterone+ethanol, and placebo testosterone+placebo ethanol), separated by a wash-out period of 15 days. The order of the treatment conditions is randomly assigned.

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 18, 2019
• Study Start: May 6, 2019
• Primary Completion: September 26, 2019
• Study Completion: September 26, 2019
• Last Updated: November 18, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)