Drinking, Acetate, and Stress

August 10, 2026 updated by: Yale University

Role of Acetate in Heavy Drinking

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520
      • New Haven, Connecticut, United States, 06519
        • Recruiting
        • The Anlyan Center, 300 Cedar St.
        • Contact:
        • Principal Investigator:
          • Graeme Mason, Ph.D

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Light/Non Drinking (LD)
Participants will complete an initial telephone screen. Participants found to be potentially eligible will be scheduled for an in-person Intake Session (consisting of an interview, questionnaires, lab work, and a urine drug screen). Participants found to be eligible will be scheduled for an infusion study. Participants will undergo brain imaging with intravenous administration of deuterated sodium acetate. Deuterium is a naturally occurring, non-radioactive substance that allows us to measure rates of metabolism. Neurocognitive tests will be performed to assess the impact of alcohol drinking.
Other: Deuterium Metabolic Imaging with deuterated acetate tracer
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
Experimental: Heavy/Non-Dependent Risky Drinking (HD)
Participants will complete an initial telephone screen. Participants found to be potentially eligible will be scheduled for an in-person Intake Session (consisting of an interview, questionnaires, lab work, and a urine drug screen). Participants found to be eligible will be scheduled for an infusion study. Participants will undergo brain imaging with intravenous administration of deuterated sodium acetate. Deuterium is a naturally occurring, non-radioactive substance that allows us to measure rates of metabolism. Neurocognitive tests will be performed to assess the impact of alcohol drinking.
Other: Deuterium Metabolic Imaging with deuterated acetate tracer
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
Experimental: Treatment Seeking (TS)
Participants will complete an initial telephone screen. Participants to be potentially eligible will be scheduled for an in-person Intake Session (consisting of an interview, questionnaires, lab work, and a urine drug screen). If found to be eligible participants will be scheduled for an inpatient admission. Participants will take part in an inpatient, medically supervised detoxification. In early sobriety (normally within one week of the last drink) and after approximately one month, participants will undergo brain imaging with intravenous administration of deuterated sodium acetate. Deuterium is a naturally occurring, non-radioactive substance that allows us to measure rates of metabolism. Neurocognitive tests will be performed to assess the impact of alcohol drinking.
Other: Deuterium Metabolic Imaging with deuterated acetate tracer
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
Experimental: Long-Term Recovery (LTS)
Participants will complete an initial telephone screen. Participants found to be potentially eligible will be scheduled for an in-person Intake Session (consisting of an interview, questionnaires, lab work, and a urine drug screen). Participants found to be eligible will be scheduled for an infusion study. Participants will undergo brain imaging with intravenous administration of deuterated sodium acetate. Deuterium is a naturally occurring, non-radioactive substance that allows us to measure rates of metabolism. Neurocognitive tests will be performed to assess the impact of alcohol drinking.
Other: Deuterium Metabolic Imaging with deuterated acetate tracer
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline and for TS, once within approximately one week and again at approximately one month
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.
Baseline and for treatment seekers, once after 1 month sober.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline and for treatment seekers, once after 1 month sober.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline and for treatment seekers, once after 1 month sober.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Graeme Mason, Ph.D., Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 6, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 4, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2000035790
  • R01AA031401 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data to be shared for all groups are neurocognitive assessments at intake and, for the AUD group, at the one-month time, anatomic MRI, 1H MRS measures, and DMI brain maps of acetate oxidation, and blood cortisol concentrations and isotopic enrichments.

IPD Sharing Time Frame

The research community will have access to data at publication or at the end of the award, whichever comes first. OpenNeuro standard submission deadlines will be taken into consideration to comply with the timeline requirements. Studies will be uploaded to the OpenNeuro before publication to include their own digital object identifiers (DOI) to aid in findability. We will include that DOI in the relevant publications. OpenNeuro will make decisions about how long to preserve the data. This repository has not deleted any deposited data as far as we know.

IPD Sharing Access Criteria

After an optional 36-month embargo period, all datasets are published into the public domain. Prior to being made public, access to a dataset is controlled through strict authentication policies and an isolated storage backend to further guard against unintended access. Metadata describing each dataset snapshot is indexed for searching, and copies of ingested content are provided via persistent Digital Object Identifiers (DOIs) minted for each version of a dataset.

IPD Sharing Supporting Information Type

  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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