Drinking, Acetate, and Stress

Yale University

Status

Enrolling

Conditions

Heavy Drinker

Alcohol Use Disorder, Moderate, in Sustained Remission

Alcohol Use, Unspecified

Alcohol Use Disorder

Treatments

Other: Deuterium Metabolic Imaging with deuterated acetate tracer

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT06584448

R01AA031401 (U.S. NIH Grant/Contract)

2000035790

Details and patient eligibility

About

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.

Full 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.

Enrollment

50 estimated patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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.

Trial design

Primary purpose

Basic Science

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

50 participants in 4 patient groups

Light/Non Drinking (LD)

Experimental group

Description:

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.

Treatment:

Other: Deuterium Metabolic Imaging with deuterated acetate tracer

Heavy/Non-Dependent Risky Drinking (HD)

Experimental group

Description:

Treatment:

Other: Deuterium Metabolic Imaging with deuterated acetate tracer

Treatment Seeking (TS)

Experimental group

Description:

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.

Treatment:

Other: Deuterium Metabolic Imaging with deuterated acetate tracer

Long-Term Recovery (LTS)

Experimental group

Description:

Treatment:

Other: Deuterium Metabolic Imaging with deuterated acetate tracer