Non-oxidative Metabolite Profiles After Increasing Doses of Ethanol

Healthy Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02311686
• Other study ID #: Biomarcadores/PNSD/1
• Status: Completed
• Phase: Phase 1
• First received: December 3, 2014
• Last updated: May 13, 2016
• Start date: December 2014
• Est. completion date: May 2016

Study information

• Verified date: May 2016
• Source: Parc de Salut Mar
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Alcohol Consumption
• Alcohol Drinking
• Healthy

Intervention

Dietary Supplement:
• 10 g ethanol
Alcohol single oral dose
• 20 g ethanol
Alcohol single oral dose
• 40 g ethanol
Alcohol single oral dose
• 60 g ethanol
Alcohol single oral dose
• 80 g ethanol
Alcohol single oral dose

Locations

Country	Name	City	State
Spain	Parc de Salut Mar (IMIM)	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Parc de Salut Mar

Country where clinical trial is conducted

Spain, 

References & Publications (30)

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Böttcher M, Beck O, Helander A. Evaluation of a new immunoassay for urinary ethyl glucuronide testing. Alcohol Alcohol. 2008 Jan-Feb;43(1):46-8. Epub 2007 Oct 17. — View Citation

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Morfin JP, Kulig C, Everson G, Beresford T. Controlling for serum albumin level improves the correlation between serum fatty acid ethyl esters and blood ethanol level. Alcohol Clin Exp Res. 2007 Feb;31(2):265-8. — View Citation

Morini L, Marchei E, Vagnarelli F, Garcia Algar O, Groppi A, Mastrobattista L, Pichini S. Ethyl glucuronide and ethyl sulfate in meconium and hair-potential biomarkers of intrauterine exposure to ethanol. Forensic Sci Int. 2010 Mar 20;196(1-3):74-7. doi: 10.1016/j.forsciint.2009.12.035. Epub 2010 Jan 8. — View Citation

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Sarkola T, Iles MR, Kohlenberg-Mueller K, Eriksson CJ. Ethanol, acetaldehyde, acetate, and lactate levels after alcohol intake in white men and women: effect of 4-methylpyrazole. Alcohol Clin Exp Res. 2002 Feb;26(2):239-45. — View Citation

Schröder H, de la Torre R, Estruch R, Corella D, Martínez-González MA, Salas-Salvadó J, Ros E, Arós F, Flores G, Civit E, Farré M, Fiol M, Vila J, Fernandez-Crehuet J, Ruiz-Gutiérrez V, Lapetra J, Sáez G, Covas MI; PREDIMED Study Investigators. Alcohol consumption is associated with high concentrations of urinary hydroxytyrosol. Am J Clin Nutr. 2009 Nov;90(5):1329-35. doi: 10.3945/ajcn.2009.27718. Epub 2009 Sep 16. — View Citation

Soderberg BL, Sicinska ET, Blodget E, Cluette-Brown JE, Suter PM, Schuppisser T, Vetter W, Laposata M. Preanalytical variables affecting the quantification of fatty acid ethyl esters in plasma and serum samples. Clin Chem. 1999 Dec;45(12):2183-90. — View Citation

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Wurst FM, Wiesbeck GA, Metzger JW, Weinmann W. On sensitivity, specificity, and the influence of various parameters on ethyl glucuronide levels in urine--results from the WHO/ISBRA study. Alcohol Clin Exp Res. 2004 Aug;28(8):1220-8. — View Citation

* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration-Time Curve (AUC 0-24h)	Calculation of the AUC for plasma fatty acid ethyl esters (palmitic, stearic, linoleic and oleic acid ethyl esters) concentrations. Blood samples will be obtained baseline and at 0,25, 0,50, 0,75,1, 1,25, 1,50, 1,75, 2, 2,5, 3, 3,5, 4, 5, 6, 8, 10, 24h. Additional samples will be collect at 72 h and 1 week, 1 and 2 months after administration. At 3 months a sample will be obtained in selected participants.	From baseline to 24 hours after administration	No
Secondary	Area Under the Concentration-Time Curve (AUC 0-24h)	Calculation of the AUC for plasma and saliva concentrations of ethanol and its non-oxidative metabolites ethyl sulphate and ethyl glucoronide. Blood samples will be obtained baseline and at 0,25, 0,50, 0,75,1, 1,25, 1,50, 1,75, 2, 2,5, 3, 3,5, 4, 5, 6, 8, 10, 24. Additional samples will be collected at 72 h and 1 week, 1 month and 2 months after administration. At 3 months a sample in selected participants. Saliva samples at baseline and 0,5, 1, 2, 3, 4, 6, 10 and 24 h after administration	From baseline to 24 hours after administration	No
Secondary	Cumulative amount of drug excreted into urine up to collection time of last measurable concentration	Urine will be collected in the following intervals 0-6h, 6-12h, 12-24h, 24-48h, 48-72h and the total amount of ethanol and its non-oxidative metabolites ethyl sulphate and ethyl glucoronide will be calculated.	From baseline to 72 hours after administration	No
Secondary	Elimination half-life	Calculation of elimination half-life from ethanol and its non-oxidative metabolites (fatty acid ethyl esters, ethyl sulphate and ethyl glucoronide) concentrations in plasma	From baseline to 24 hours after administration	No
Secondary	Fatty acid ethyl esters and ethyl glucoronide hair concentrations	Concentrations of fatty acid ethyl esters and ethyl glucoronide in hair at baseline, one and two month after administration. An additional sample at 3 months in selected participants.	Baseline, 1 and 2 months after administration	No
Secondary	Change in subjective effects of ethanol	Participants will self-report their experience on a visual analogue scale of drunkenness and Biphasic alcohol effects scale (BAES) at baseline and 0.5,0.75,1,1.5,2,4,6,8,10 after administration.	From baseline to 10 hours after administration	No
Secondary	Number of Participants with Serious and Non-Serious Adverse Events	Collection of adverse effects spontaneously reported by the participants and/or observed by the investigators	From baseline to 24 hours after administration	Yes
Secondary	Change in Addiction Research Center Inventory (ARCI)	ARCI will be administered baseline and 10 h after administration (subjects should answer at 10 h remembering their experience at the moment of maximum effects)	From baseline to 10 h after administration	No
Secondary	Change in Evaluation of Subjective Effects of Substances with Abuse Potential (VESSPA)	VESSPA will be administered baseline and 10 h after administration (subjects should answer at 10 h remembering their experience at the moment of maximum effects)	From baseline to 10 h after administration	No
Secondary	Ethanol dose identification questionaire	Participants should guess the dose they have ingested during the experimental session among 5 options (10, 20, 40, 60 and 80 g of ethanol)	10 h after administration	No
Secondary	Urinary drug concentrations	Urinary concentrations of ethanol and its non-oxidative metabolites ethyl sulphate and ethyl glucoronide will measured at 1 week, 1 and 2 months after administration (3 months in selected subjects)	From 1 week to 2 months	No