Neuroendocrine Response to Oral Alcohol Administration

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 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, heart rate variability, alcohol craving, and alcohol stimulant and sedative effects. This knowledge could be significant in developing new therapies for the treatment of alcoholism.

Study Overview

• Status: Completed
• Conditions: Alcohol Abuse
• Intervention / Treatment: Drug: Ethanol; Other: Alcoholic Beverage; Other: Non-Alcoholic Beverage

Detailed Description

This study was a single-blind, mixed Between Subjects and repeated measures across Alcohol and Placebo conditions in separate sessions in a 2 scan neuroimaging experiment. The two groups of participants were Moderate Social Drinkers and Binge/Heavy Social Drinkers, categorized on the basis of NIAA criteria for moderate non-binge and binge/heavy drinking. Subjects were randomly assigned to receive alcoholic or non-alcoholic beer in scanning condition 1 or condition 2. Before each scan, they were exposed to 3 12 Oz. alcoholic beer or 3 12 Oz. non-alcoholic beer via an Alcohol Taste Test (ATT) during which they were asked to taste the beers to determine if they were same or different. The order of the two conditions was counterbalanced and randomized across participants. Cerebral blood flow (CBF) was then measured using Arterial Spin Labeling. In addition to measuring the different effects of alcoholic beer vs. non-alcoholic beer on CBF, the investigators also measured subjective alcohol effects, alcohol craving, breath alcohol levels, cortisol, and ACTH. Statistical tests were performed to determine if these dependent measures were due to Group, Condition, or a Group x Condition interaction. Finally, the relationship between these variables and the amount of beer consumed at the second post-scan ATT was examined. The post-scan ATT only presented with the choice to drink non-alcoholic beer in order to more clearly predict behavioral motivation for alcohol from PreATT alcohol response in cortisol, CBF and subjective ratings. Data was obtained by research staff, nurse, and MRI technician who were blind to condition as were the subjects but PI and project director were not blind.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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; and provide negative urine toxicology screens during initial appointments and at admission for IV/fMRI sessions.
• Body Mass Index between 20-28.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alcoholic Beverage; Participants will complete an MRI and oral alcohol session.	Drug: Ethanol; Other: Alcoholic Beverage; In addition to the oral delivery, an IV line will be placed for the purpose of drawing blood during the MRI session.
Placebo Comparator: Non-Alcoholic Beverage; Participants will complete an MRI and oral non-alcoholic session.	Drug: Ethanol; Other: Non-Alcoholic Beverage; In addition to the oral delivery, an IV line will be placed for the purpose of drawing blood during the MRI session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 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 consumption of alcohol or alcohol 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.	End of Procedure (45 minutes)
Change in Amount of drink consumed (alcohol or placebo)	Amount of drink consumed (alcohol or placebo) during the Alcohol Taste Test (ATT)	Pre-scan ATT and immediately Post scan ATT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Alcohol Effects (BAES)	Alcohol effects will be measured using the Biphasic Alcohol Effects Scale (BAES). The BAES is a 12 item questionnaire with a 12-120 range. The higher the total value (up to 120), the greater the measured effects of alcohol. The change in alcohol effects 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.	Post follow up to Procedure (125 minutes)
Changes in Alcohol Effects (DEQ)	Alcohol effects will be measured using the Drug Effects Questionnaire (DEQ). The DEQ consists of 5 questions with 5-25 total point distribution. The greater the total points, the greater the measured effect of alcohol. The change in alcohol effects 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.	Post follow up to Procedure (125 minutes)
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.	Post follow up to Procedure (125 minutes)
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.	Post follow up to Procedure (125 minutes)

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Sara Blaine, PhD, Addictions, Division of Yale Stress Center; Principal Investigator: Rajita Sinha, PhD, Professor of Psychiatry, Yale Center for Clinical Investigation

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2016
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: May 19, 2017
• First Submitted That Met QC Criteria: May 22, 2017
• First Posted (Actual): May 24, 2017

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: 1502015387; 1R21AA025277-01 (U.S. NIH Grant/Contract); 1K99AA025401-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes