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Generation of Biological Samples Positive to Hydrochlorothiazide for Anti-doping Control

Phase 1
Completed
Conditions
Healthy Volunteers
Interventions
Registration Number
NCT04197622
Lead Sponsor
Parc de Salut Mar
Brief Summary

Background:

Hydrochlorothiazide is a diuretic that inhibits the reabsorption of sodium and chloride in the renal tubules, thus increasing the excretion of water.

The use of hydrochlorothiazide in athletes is prohibited by the World Anti-Doping Agency. Its fraudulent administration can lead to significant acute weight losses (body water reduction) and can mask the use of other doping substances, since it increases the urine volume and alters its pH (false negatives).

The main degradation product of hydrochlorothiazide is 4-amino-6-chloro-1,3-benzenedisulfonamide (ACB). ACB is detectable in urine for a longer time and in a greater concentration than hydrochlorothiazide. This suggests that ACB may be an important marker for the detection of hydrochlorothiazide doping.

Hypothesis:

The oral administration of 12,5 mg of hydrochlorothiazide in healthy subjects allows generating detectable concentrations of the drug in urine. Positive urine samples will enable to identify analytical strategies for doping control.

Objectives:

Primary objective: To measure the concentrations of hydrochlorothiazide in urine for anti-doping control samples.

Secondary objectives: To identify hydrochlorothiazide metabolites in urine. To explore the time window in which the drug or its metabolites can be detected in urine after administration. To assess safety and tolerability of the drug used.

Methods:

Phase I, open, non-randomized clinical trial, with a treatment condition (hydrochlorothiazide) administered in a single oral dose to 3 subjects.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
3
Inclusion Criteria
  • Male volunteers aged between 18 and 45 years.
  • Able to understand and accept the trial procedures and able to sign an informed consent.
  • History and physical examination that demonstrate not presenting organic or psychiatric disorders.
  • ECG, blood and urine tests performed at screening should be within normal limits. Minor or punctual variations of these limits of normality are admitted if, in the opinion of the Principal Investigator, they have no clinical significance, do not pose a risk to the subject and do not interfere with the evaluation of the product in study. These variations and their non-relevance will be justified in writing specifically.
  • Body mass index (weight/size^2) between 19 and 26 kg/m2, and weight between 50 and 90 kg. Subjects with BMI >26 kg/m2 may be included at the discretion of the Principal Investigator.
Exclusion Criteria
  • Failure to meet the inclusion criteria.
  • History of allergy, idiosyncrasy, hypersensitivity or adverse reactions to the active substance or any of the excipients. History of serious adverse reactions to other medications.
  • Subjects with contraindications to treatment with the study drug (according to Summary of Product Characteristics).
  • Background or clinical evidence of psychiatric disorders, alcoholism, regular consumption of psychoactive drugs, drug abuse or addiction to other substances (except for nicotine). Smokers of more than 5 cigarettes/day will be excluded.
  • Having participated in another clinical trial with medication in the three months prior to the start of the study.
  • Having donated blood during the month prior to the start of the study.
  • Having suffered an organic disease or major surgery in the three months prior to the start of the study.
  • Background 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 him, may pose a risk to the subjects, may interfere with the objectives of the study or may alter the pharmacokinetics of the drug.
  • Have taken medication regularly in the month prior to the study sessions, with the exception of vitamins, herbal remedies or dietary supplements that, in the opinion of the Principal Investigator or the collaborators designated by him, do not pose a risk to the subjects and do not interfere with the objectives of the study. Treatment with single doses of symptomatic medication in the week prior to the study sessions will not be exclusive if it is assumed that medication has been completely eliminated on the day of the experimental session.
  • Consumption of more than 15 g of alcohol per day.
  • Consumers of more than 3 coffees, teas, cola drinks and/or other stimulant drinks (xanthines) per day in the month prior to the start of the study.
  • Being unable to understand the nature of the trial and the procedures requested to follow.
  • Positive serology for hepatitis B, C or HIV.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
HydrochlorothiazideHydrochlorothiazideSubjects receive a single-dose treatment.Urine samples will be collected after administration (6 fractions: 0-4, 4-8, 8-12, 12-24, 24-36, 36-48 hours post-administration).
Primary Outcome Measures
NameTimeMethod
Urine concentration of hydrochlorothiazide36-48 hours post-administration

Concentration of hydrochlorothiazide in fraction-6 urine samples

Secondary Outcome Measures
NameTimeMethod
Urine concentration of hydrochlorothiazide metabolites36-48 hours post-administration

Concentration of hydrochlorothiazide metabolites (ACB and others) in fraction-6 urine samples

Trial Locations

Locations (1)

IMIM (Hospital del Mar Medical Research Institute)

🇪🇸

Barcelona, Spain

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