Phosphatidylethanol and Other Ethanol Consumption Markers

Overview

This study is intended to help the investigators understand how a biomarker found in the blood may be used to better identify the quantity and different patterns of alcohol use. The investigators hope that the results of this study will help identify the uses of alcohol-use markers in the blood in future alcohol prevention and treatment programs. It is hoped that the information learned from this study will benefit other people in the future. The study participants will come into the lab and will (1) consume alcohol in the lab designed to produce a peak blood alcohol concentration of 0.06% and have blood collected over 6 hours followed by abstinence for 10 days to give a small blood sample 4 times and (2) to give a small amount of blood 5 times within 28 days (naturalistic drinking) and provide answers about alcohol use.

Detailed description

The study goal is to account for individual differences in biological variables likely influencing Phosphatidylethanol (PEth) formation to determine the extent to which the investigators can improve their ability to characterize alcohol consumed previously. Investigators propose three experiments that combine: (a) controlled human laboratory studies in vivo, (b) clinical laboratory studies of important enzymatic and biological variables measured ex vivo, and (c) the creation and testing of regression models to predict drinking during a naturalistic observational study using PEth levels and key biological variables identified in the lab.

Aim 1 is an in vivo pharmacokinetic study that whereby participants will consume a dose of alcohol to achieve a target blood alcohol concentration of 0.06%. Blood samples will be collected repeatedly during a 6-hour period to characterize blood/breath alcohol concentrations and PEth syntheses. Then PEth elimination half-life will be characterized across a 10-day period while remaining alcohol abstinent outside the lab.

In Aim 2, alcohol-free blood collected from Aim 1 will be examined ex vivo to characterize key biological variables (e.g., enzyme activity, red blood cell count, precursor levels) involved in PEth synthesis and elimination. Regression formulas will evaluate these variables for their ability to explain the previously unexplained between-subject differences in the PEth levels formed after the same amount of alcohol is consumed.

Finally, in Aim 3, regression equations will be used to evaluate the value of using these biological/enzyme variables to improve (above and beyond that of PEth alone) the prediction of naturalistic drinking self-reported by participants over a 28-day period.

Interventions

• Other Alcohol (Ethanol)
  Alcohol will be administered to participants by research staff. In Phase 1, participants will consume alcohol designed to produce a targeted blood alcohol concentration (BAC) of 0.06% using the modified Widmark equation.

Primary outcome measures

• Phosphatidylethanol (PEth) concentrations on alcohol administration day in Males/Females [Time frame: Baseline to 360 minutes]
• Breath alcohol concentrations on alcohol administration day in Males/Females [Time frame: Baseline to 360 minutes]
• PEth Concentrations for half-life in Males/Females [Time frame: End of Day 0 to 10 days]
• PEth concentrations once weekly during 28 days naturalistic drinking in Males/Females [Time frame: Baseline to 28 days]
• Self-reported drinking during the 28 days naturalistic drinking in Males/Females [Time frame: Baseline to 28 days]
• PEth Concentrations during the 28 days naturalistic drinking in Males/Females [Time frame: Baseline to 28 days]
• Red blood cell count (RBC) in Males/Females [Time frame: One time (baseline)]]
• Phosphatidylcholine (PC) content in Males/Females [Time frame: One time (baseline)]
• Ex vivo PEth formation for PLD activity in blood from Males/Females [Time frame: Baseline to 90 minutes]

Eligibility criteria

Inclusion criteria

• are ≥ 21 years old;
• are height and weight proportionate (body mass index 18-30); and
• report drinking on > 1 days in the last month, with at least one day equal to at least achieving \~0.06% BAC.

Exclusion criteria

• have significant current or predicted alcohol withdrawal symptoms (CIWA-AR scores ≥ 10);
• are currently in alcohol treatment;
• have substance use disorder (except nicotine, and/or caffeine);
• have a medical condition that would contraindicate participation (a positive urine pregnancy test, self-reported scheduled surgery or liver disease);
• are currently breast feeding;
• have a presence of a DSM-5 psychiatric disorder with symptoms of psychosis and/or delirium; or
• are unable to comprehend the informed consent process or study instructions.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 2 centers

• University of North Texas — Denton
• University of Texas Health Science Center San Antonio — San Antonio

Identifiers

NCT: NCT06747364 · STUDY00000887 · R01AA022361

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗