Multimodal Neuroimaging of Alcohol Cues, Cortisol Response, and Compulsive Motivation

Alcohol Use Disorder Clinical Trial

Official title:

Multimodal Neuroimaging of Alcohol Cues, Cortisol Response, and Compulsive Motivation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04412824
• Other study ID #: 19-263 MR 1907
• Secondary ID: R00AA025401
• Status: Completed
• Phase: Early Phase 1
• Start date: May 22, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: March 2022
• Source: Auburn University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study proposes to examine both the peripheral and central nervous system responses when light social drinkers and binge/heavy social drinkers are exposed to visual ethanol cues, followed by oral ethanol. The findings will provide a greater understanding of the brain mechanisms (cerebral blood flow and functional connectivity) underlying the association between stress, cortisol release, alcohol craving, and alcohol stimulant and sedative effects. This knowledge could be significant in developing new therapies for the treatment of alcoholism.

Description:

Results from the 2014 National Survey on Drug Use and Health show that 26% of adults in the US engaged in binge drinking in the past month (SAMHSA 2014). Why some people "mature out" of this behavior while others persist may be due to one's physiological response to binge drinking. No previous study has assessed whether disrupted cortisol and neural network responses to alcohol cues may drive the compulsive alcohol consumption seen in binge drinking individuals who do not yet have an AUD.

The investigator will recruit beer drinking, non-smoking men and women ages 21-45 (N=80, equal gender) who are either moderate drinkers or binge/heavy drinkers for two neuroimaging and neuroendocrine assessments to determine if their "real world" drinking behavior, in a prospective one month follow up, can be predicted based upon the cortisol and neural network responses to alcohol cues (with a placebo control, counter-balanced and randomized). Finally, the influence of genetic variation in the FK506-binding protein 5 (FKBP5) gene, which regulates cortisol activity, on the cortisol and neural network responses to alcohol cues will be explored.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 45 Years

Eligibility

Inclusion Criteria:

• Binge/Heavy Social Drinkers (HSD): has never met DSM-IV criteria for alcohol or substance dependence; regular alcohol use over the past year of at least 10 drinks per week, including at lease one occasion per week consuming >4 drinks (males) or >3 drinks (females).

• Able to read and write English.

• Light Social Drinkers (LSD): has never met DSM-IV criteria for alcohol or substance dependence; regular alcohol use over the past year of 1-3 drinks per occasion, 1-3 times weekly, with no more than one occasion per month of drinking >4 drinks (male) or >3 drinks (females) (King et al., 2002).

• Do not meet criteria for any Axis I DSM-IV psychiatric diagnoses except for individuals with a past diagnosis of Post-Traumatic Stress Disorder, Major Depressive Disorder, or Obsessive Compulsive Disorder

• Provide negative urine toxicology screens during initial appointments and at admission for IV/fMRI sessions.

• Body Mass Index between 20-35.

• No current or former nicotine dependence.

Exclusion Criteria:

• Meet current criteria for dependence on any psychoactive substance, excluding caffeine.

• Current or past history of alcohol dependence or abuse.

• Any current use of opiates or past history of opiate abuse/dependence.

• Current use of any psychoactive drugs, including anxiolytics, antidepressants, naltrexone or antabuse.

• Any psychotic disorder or current psychiatric symptoms requiring specific attention, including need for psychiatric medications for current major depression and anxiety disorders.

• Any significant current medical condition such as neurological, cardiovascular, endocrine, renal, liver, thyroid pathology; subjects on medications for any medical condition will be excluded.

• Peri and post-menopausal women, and those with hysterectomies.

• Pregnant and lactating women will be excluded.

Related Conditions & MeSH terms

• Alcohol Use Disorder
• Alcoholism

Intervention

Drug:
• Intravenous blood draw
In addition to the oral delivery, an IV line will be placed for the purpose of drawing blood during the MRI session

Locations

Country	Name	City	State
United States	Auburn University MRI Center	Auburn	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
Auburn University	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Neural Blood Flow	Blood flow is measured in ml/100 grams/minute. The interpretation is that blood flow to that area indicates that region of the brain is responding to the visual alcohol or non-alcoholic beverage cues. Change in blood flow will be calculated as the change (and slope) of measurements taken at 10, 20, 30 and 45 minutes during the procedure.	During the Procedure: measurements taken at 10, 20, 30 and 45 minutes during the procedure.
Primary	Change in Cortisol	The units for cortisol are micrograms/deciliter and the interpretation is that amount has been released into the blood stream from the HPA axis in response to alcohol or alcohol cues. Change in Cortisol will be calculated by taking the change (and slopes) of measurements at 45, 30 and 5 minutes prior to procedure and comparing it to measurements taken at 65, 95, 110, 125 minutes following the procedure.	Before Procedure to 125 minutes after the procedure.
Primary	Drinking Behavior in daily experience outside of laboratory	A smartphone app will be used to collect 4 surveys a day for 30 days after completion of both arms. Multilevel modeling will be used to analyze patterns of drinking over time.	Day after Procedure to 30 days after procedure.
Primary	Amount of Alcohol Consumed	After exposure to alcoholic beverage and non-alcoholic beverage visual cues, quantity of alcohol consumed in a free choice test will be measured in milliliters.	Immediately after the procedure.
Secondary	Changes in Alcohol Urges (AUQ)	The urge to consume alcohol will be measured using the Alcohol Urge Questionnaire (AUQ). The AUQ consists of 8 questions 8-56 total point distribution. The greater the total points, the greater the measured urge to consume alcohol. The change in alcohol urge will be assessed with the taking the change (and slopes) of measurements at 45, 30 and 5 minutes prior to procedure and comparing it to measurements taken at 65, 95, 110, 125 minutes following the procedure.	Before Procedure to 125 minutes after the procedure.
Secondary	Stress levels in daily experience outside of laboratory	A smartphone app will be used to collect 4 surveys a day for 30 days after completion of both arms. Multilevel modeling will be used to analyze subjective experience of stress over time.	Post follow-up procedure (30 days)
Secondary	Genetic Risk Factors (Single Nucleotide Polymorphisms; SNPs) Association with Cerebral Blood Flow, Craving, and Real world drinking and stress	One sample of whole blood will be obtained and analyzed for genomic associations with other outcome measures.	Post follow up procedure (within 2 years after procedure)