Clinical trial NCT06584448: Drinking, Acetate, and Stress
Official title: Role of Acetate in Heavy Drinking
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alcohol Use Disorder
Alcohol Use, Unspecified
Heavy Drinker
Alcohol Use Disorder, Moderate, in Sustained Remission
Keywords: Brain
Stress
Imaging
Detoxification
Recovery
Sobriety
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2024-09-04
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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, 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.

Primary outcomes:
measure: Rate of Conversion of Acetate to Glutamate + Glutamine (Glx) in the Brain
timeFrame: Baseline and for TS, once within approximately one week and again at approximately one month
measure: Concentration of [2H]Glx in the brain during administration of [2H]acetate
timeFrame: Baseline and for treatment seekers, once after 1 month sober.
Secondary outcomes:
measure: Rate of Cortisol Turnover
timeFrame: Baseline and for treatment seekers, once after 1 month sober.
Other outcomes:
measure: Change in Alcohol and Stress Measures
timeFrame: Baseline and for treatment seekers, once after 1 month sober.
Locations:
city: New Haven
country: United States
facility: The Anlyan Center, 300 Cedar St.
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: Graeme Mason, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: