Drinking, Acetate, and Stress
Role of Acetate in Heavy Drinking
2 other identifiers
interventional
50
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Nov 2024
Longer than P75 for not_applicable
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 30, 2024
CompletedFirst Posted
Study publicly available on registry
September 4, 2024
CompletedStudy Start
First participant enrolled
November 6, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2030
July 28, 2025
July 1, 2025
4.2 years
August 30, 2024
July 25, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Rate of Conversion of Acetate to Glutamate + Glutamine (Glx) in the Brain
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
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 Outcomes (1)
Rate of Cortisol Turnover
Baseline and for treatment seekers, once after 1 month sober.
Other Outcomes (1)
Change in Alcohol and Stress Measures
Baseline and for treatment seekers, once after 1 month sober.
Study Arms (4)
Light/Non Drinking (LD)
EXPERIMENTALParticipants 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.
Heavy/Non-Dependent Risky Drinking (HD)
EXPERIMENTALParticipants 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.
Treatment Seeking (TS)
EXPERIMENTALParticipants 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.
Long-Term Recovery (LTS)
EXPERIMENTALParticipants 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
The Anlyan Center, 300 Cedar St.
New Haven, Connecticut, 06519, United States
Yale University
New Haven, Connecticut, 06520, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Graeme Mason, Ph.D.
Yale University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 30, 2024
First Posted
September 4, 2024
Study Start
November 6, 2024
Primary Completion (Estimated)
January 1, 2029
Study Completion (Estimated)
January 1, 2030
Last Updated
July 28, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- CSR
- 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.
- 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.
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.