Computer-Assisted Self-Administration of Ethanol
Condition: Alcoholic Intoxication
MeSH terms: Alcoholic Intoxication
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will test the reliability of a procedure for self-administering ethanol (alcohol)
      intravenously (through a vein), using a computer-assisted method. People ordinarily
      self-administer alcohol through drinking alcoholic beverages, but blood alcohol levels
      resulting from drinking vary greatly among individuals. For research on alcohol dependence
      and treatment, a tool for achieving precise blood levels is needed. In addition to testing
      this method of alcohol administration, the study will examine self-administration behavior
      and resulting breath alcohol concentration, the effects of alcohol on the participants, and
      differences between men and women in alcohol self-administration.

      Healthy normal volunteers between 21 and 45 years of age may be eligible for this study.
      Participants are assigned to one of two study groups. Group 1 undergoes three 7-hour study
      sessions and group 2 participates in two sessions, each of which includes the following
      procedures:

        -  Breathalyzer and urine tests for alcohol and illicit drug use.

        -  Urine pregnancy test for women.

        -  Light lunch.

        -  Questionnaire about health and recent drinking.

      Alcohol infusion: Subjects are seated in a comfortable chair and instructed on how to use a
      computer to give themselves a short infusion of alcohol through a catheter (plastic tube)
      that has been inserted into a vein in their the arm. Sensors are placed on their chest to
      monitor heart beat and their neck to record skin blood flow. At the start of the session,
      subjects complete questionnaires about any drug effects and urges to drink they may be
      feeling. They are trained on how to use the computer to administer alcohol and are then
      allowed to self-administer alcohol through the catheter any time they like, as long as their
      peak breath alcohol level does not exceed 0.1 g% (a level that would result from ingestion of
      4 to 6 drinks in most people). If that point is reached, the computer automatically
      inactivates self-administration until the level is lowered again. Breathalyzer readings are
      taken every 15 to 30 minutes. Subjects may read, watch television or videos or listen to
      music during the sessions.

      Recovery: At the end of the 2.5 hours of self-administration, the catheter is removed and
      subjects can eat, read, watch television and relax in the clinic until their breath alcohol
      level falls below 0.02 g%, usually after 2.5 to 3 hours, when they can go home by taxi or
      with a pre-arranged designated driver.
    

Detailed description: 
      Objective: The goal of this project is to characterize the computer-assisted
      self-administration of ethanol (CASE) paradigm by assessing intravenous (IV) alcohol
      self-administration behavior and the resulting breath alcohol concentration (BrAC) exposure
      and pharmacologic responses in humans. The study will also evaluate the test-retest
      reliability of alcohol self-administration and examine the influence of sex and recent
      drinking history, as well as the effect of acute stress cues on alcohol self-administration.
      Additionally, this study will test whether a novel experimental paradigm can be used to
      evaluate impaired control in

      heavy drinkers.

      Study population: Participants will be 21-60 year-old male and female social drinkers, binge
      drinkers and heavy drinkers in good health, as determined by medical history, physical exam,
      ECG and lab tests. Participants with Axis-I psychiatric illness (other than alcohol use
      disorder for Group 6) will be excluded.

      Design: The CASE system utilizes a model-based algorithm based on previously published
      methods to achieve and maintain pre-determined BrACs using IV alcohol infusions. The CASE
      system provides flexibility to participants in choosing when to push a button to receive
      alcohol, as well as flexibility to investigators in controlling the subsequent BrAC exposure.
      The CASE system allows the investigator to specify and assure the same BrAC increment across
      all participants, and is set up to prevent the BrAC from exceeding any pre-set upper limit
      (e.g., 120 mg%).

      Following screening, participants will undergo IV ethanol self-administration sessions.
      Participants will be enrolled in six groups: Group 1 will consist of the first 10
      participants who will participate in 3 self-administration sessions (a training session
      followed by 2 test sessions) to assess the test-retest reliability of alcohol
      self-administration behavior. Group 2 will consist of 50 participants, who will each
      participate in 2 self-administration sessions (a training session followed by a test
      session). During each session, participants will first undergo a directed priming period,
      lasting 25 min, where they will be prompted to push a button to receive small standardized
      alcohol infusions. This will be followed by an ad-lib period, lasting up to 2 hrs, where they
      will have free access to standardized IV alcohol infusions. During the session, BrAC will be
      measured, heart-rate will be continuously recorded, and subjective perceptions of alcohol
      effects and urges will be assessed. Group 3 will consist of 15 participants, who will undergo
      two identical progressive work self-administration sessions for evaluation of test-retest
      reliability. During each progressive ratio (PR) schedule session, participants will be
      required to push the button progressively higher number of times for each subsequent alcohol
      infusion over a 2.5 hr period. Group 4 will consist of 100 participants, who will each
      participate in 2 sessions: one ad lib self-administration session and one PR schedule
      self-administration session. Group 5 will consist of 40 participants, who will undergo a
      baseline self-administration session followed by an interview session for construction of
      guided imagery scripts. Following this, participants will undergo three alcohol
      self-administration sessions, following exposure to personalized stress-, alcohol- or
      neutral-condition associated scripts, presented in randomized order on separate days. Group
      6a will consist of a maximum of 15 participants who will undergo a baseline
      self-administration session followed by an experimental session in which they will be given
      the opportunity to resist receiving self-infusions of alcohol in return for monetary
      reinforcers. Group 6b will consist of 37 participants who will complete a baseline
      self-administration session followed by two experimental sessions, with and without a priming
      dose of alcohol, and two follow up visits. Group 6 participants will also be given an
      ecological momentary assessment (EMA) device and will complete random assessments of
      real-world measures of impaired control and alcohol consumption per day for the duration of
      the study.

      Outcome measures: The primary endpoint is the BrAC exposure (highest BrAC, average BrAC,
      area-under-the-BrAC-time-curve) achieved during the self-administration session.
      Additionally, changes in subjective perceptions of alcohol effects, as well as changes in
      heart rate will be evaluated. The influence of sex and recent drinking history as well as
      genetic polymorphisms on the self-administration of alcohol will also be examined.
      Furthermore, individual-specific cellular responses to alcohol exposure will be examined
      using induced pluripotent stem cells (iPSCs) from participants selected based on genotypic
      and phenotypic variation in self-administration measures. Outcome measures for group 5 will
      include stress and alcohol cue-induced craving and self-administration. Human laboratory
      outcome

      measures for Group 6 will include time to lapse during the delay phase, number of infusions,

      peak BrAC, and average BrAC during the ad-libitum phase. EMA outcomes will include

      total alcohol consumption, number of impaired control episodes, and severity of impaired

      control episodes. The CASE paradigm can be a valuable tool for evaluating determinants that
      may underlie self-administration behavior in humans. The effect of pharmacological agents on
      alcohol self-administration can be evaluated as a marker of the clinical effectiveness of
      these agents in the treatment of alcohol-dependence.
    

Intervention name(s): Alcohol
Intervention type(s): Drug
Intervention description(s): human laboratory alcohol consumption.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Alcohol; SELF-ADMINISTRATION; Intoxication