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NCT Number: NCT06584448

Drinking, Acetate, and Stress

The purpose of this study is to learn how drinking alcohol affects how people experience stress and how that is affected by the body's chemistry. Specifically, the investigators will be studying relationships of drinking and a stress hormone called cortisol. The investigators believe that results will lead us to find more effective ways to help people stop or reduce drinking when participants are drinking at harmful levels.

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Key information

Conditions

Alcohol Use Disorder Alcohol Drinking Alcohol Use Disorder, Moderate, in Sustained Remission Alcohol Use, Unspecified Alcohol-Related Disorders Alcoholic Intoxication Alcoholism Behavior Chemically-Induced Disorders Drinking Behavior Heavy Drinker Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Mental Disorders Neoplasms Neoplasms by Histologic Type Substance-Related Disorders

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

The Anlyan Center, 300 Cedar St., New Haven, Connecticut, United States

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About this study

Brain acetate consumption will be measured with a novel method called Deuterium Metabolic Imaging (DMI), in which sodium acetate that has been labeled with deuterium, a non-radioactive isotope of hydrogen, is administered intravenously over two hours, while Magnetic Resonance Spectroscopy (MRS) is used to map the appearance of the deuterium in glutamate and glutamine regionally through the brain. That combination of glutamate and glutamine, called Glx, serves as a tag to measure the brain's rate of acetate consumption. That is, the more deuterium appears in Glx, the more acetate that part of the brain consumes. In the same people, investigators will perform structural Magnetic Resonance Imaging (MRI) for co-registration with the MRI and assess regional brain volumes. Investigators will also obtain measures of drinking and stress, and will measure participants serum cortisol levels and rates of cortisol turnover. Each set of measures will be compared across groups, and the measurements of acetate uptake will be compared with all other measures for associations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Medically stable male or female, aged 18-55.
  • Able to read, write and complete a multitude of self-assessments in English
  • Meets DSM-5 criteria for current Alcohol Use Disorder (AUD)
  • Participants who have Alcohol Use Disorder and are actively drinking must be willing to receive (at no cost) inpatient treatment for AUD for a period of up to 30 days. Participants who have been treated for an Alcohol Use Disorder and are now sober three months or longer will NOT be required to go inpatient.

Exclusion criteria

  • Subjects with any significant current medical conditions (neurological, cardiovascular, endocrine, thyroid, renal, liver), seizures (for LTS subjects only- seizures directly related to alcohol detoxification are not an exclusion) , delirium or hallucinations, or other unstable medical conditions, including HIV.
  • Current DSM-5 substance use disorder (other than AUD or tobacco use disorder)
  • Any metallic objects implanted in their body which would make imaging unsafe (pacemaker, etc)
  • Claustrophobia, or other inability to participate in an MRI
  • A positive test result at intake appointment and subsequent appointments on urine drug screens conducted for illicit drugs. (Note: participants will not be paid for study visits if they test positive for an illicit drug and will be immediately excluded from study).
  • Women who are pregnant or nursing. Women who have an IUD that would make imaging unsafe.
  • Recent taking of medications that may influence study outcomes (e.g., disulfiram, naltrexone, acamprosate, anticonvulsants).
  • Subjects likely to exhibit clinically significant alcohol withdrawal during the study.

Treatment and study plan

Deuterium Metabolic Imaging with deuterated acetate tracer

Other

Deuterium Metabolic Imaging (DMI) is a method by which Magnetic Resonance Spectroscopy (MRS) is used to map the appearance of deuterium from a tracer source (e.g., deuterated acetate) in products of metabolism. In this case we will map the combination of glutamate and glutamine, called Glx, to serve as a tag to measure the brain's rate of acetate consumption. That is, the more deuterium appears in Glx, the more acetate that part of the brain consumes.

Other names: DMI

Primary outcomes

  1. Rate of Conversion of Acetate to Glutamate + Glutamine (Glx) in the Brain

    Time frame: Baseline and for TS, once within approximately one week and again at approximately one month

    DMI data will be acquired during infusions of 2H-labeled Ac, using a 4-Tesla magnet. Deuterium flow from [2,2,2-2H3]Ac to glutamate (Glu) and glutamine (Gln). Ac forms AcetylCoA at a rate CMRAc and is oxidized by astroglia (VtcaA), labeling the small glial Glu pool (5-10% of the total Glu110).Astroglial Glu is converted to Gln and sent to neurons (Vcycle), where it is converted to labeled Glu. It mixes with the large neuronal Glu pool, fed also by unlabeled carbon mostly from glucose via neuronal oxidation (VtcaN), and the diluted Glu is released and taken up by glia for reconversion to Gln. With 2H, the sum of Glu and Gln is detected as [2H]Glx. The faster the rate of acetate consumption, the faster the appearance of [2H]Glx.

  2. Concentration of [2H]Glx in the brain during administration of [2H]acetate

    Time frame: Baseline and for treatment seekers, once after 1 month sober.

    DMI data will be acquired during infusions of 2H-labeled Ac, using a 4-Tesla magnet. Deuterium flow from [2,2,2-2H3]Ac to glutamate (Glu) and glutamine (Gln). Ac forms AcetylCoA at a rate CMRAc and is oxidized by astroglia (VtcaA), labeling the small glial Glu pool (5-10% of the total Glu110).Astroglial Glu is converted to Gln and sent to neurons (Vcycle), where it is converted to labeled Glu. It mixes with the large neuronal Glu pool, fed also by unlabeled carbon mostly from glucose via neuronal oxidation (VtcaN), and the diluted Glu is released and taken up by glia for reconversion to Gln. With 2H, the sum of Glu and Gln is detected as [2H]Glx. The faster the rate of acetate consumption, the faster the appearance of [2H]Glx.

Secondary outcomes

  1. Rate of Cortisol Turnover

    Time frame: Baseline and for treatment seekers, once after 1 month sober.

    Plasma cortisol concentrations and enrichments will be measured in the Chemical Metabolism Core directed by Dr. Kibbey. Crashed plasma samples will be applied to a Phenomenex Kinetex F5 Core-shell LC column (100 x 2.1 mm, 2.6 µm), with 0.3 mL/min linear gradients from 100% aqueous phase (95% water, 5% acetonitrile and 0.1% formic acid) to 100% organic phase (95% acetonitrile, 5% water and 0.1% formic acid) in 20 min. Cortisol ions are measured in both positive and negative MS modes the Sciex TripleTOF 6600 using an information-dependent analysis (IDA) workflow consisting of a TOF MS scan (200 msec) and a high-resolution IDA experiment (70 msec each) monitoring 10 candidate ions per cycle. The ion source conditions are as follows; Ion spray voltage = 5000 V for positive mode and -4500V for negative mode, ion source gas 1 (GS1) = 50, ion source gas 2 (GS2) = 50, curtain gas (CUR) = 30, temperature (TEM) = 400 oC.

Other outcomes

  1. Change in Alcohol and Stress Measures

    Time frame: Baseline and for treatment seekers, once after 1 month sober.

    Measurements of stress and alcohol behaviors, based on questionnaires. Comparison of CMRac with baseline cortisol levels and measures of drinking and craving.Baseline cortisol levels will be compared among groups using a one-way ANOVA followed by post-hoc pairwise tests. Among AD subjects, differences between cortisol levels at 1 week, 1 month, and 3 months will be evaluated with linear mixed models using session (1 week vs. 1 month vs. 3 months). Correlation analysis will be used to examine associations between cortisol levels and levels of CMRac in HPA axis regions, drinking (e.g., # of drinks and drinking days in past 30 days, lifetime consumption), and craving. We will also consider multiple regression models to examine the independent and joint effects of group, cortisol levels, drinking, and craving in predicting CMRac.

Study contacts

Contact information is provided by the study sponsor or research team.

Graeme Mason, Ph.D.

CONTACT

[email protected]

203-737-1478

Luz Catarineau

CONTACT

[email protected]

475-375-6141

Sponsors and collaborators

Lead sponsor

Yale University

Other

Collaborators

  • National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Registry information

Official study title

Role of Acetate in Heavy Drinking

Important dates

Study start
2024
Primary completion
2029
Study completion
2030
First posted
Sep 4, 2024
Registry last updated
Jun 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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