Computer-Assisted Self-Administration of Ethanol
|First Received Date ICMJE||July 10, 2008|
|Last Updated Date||July 3, 2013|
|Start Date ICMJE||July 2008|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||1) BrAC Exposure (peak, average, AUC). 2) changes in subjective perceptions, heart-rate, skin blood flow.|
|Original Primary Outcome Measures ICMJE
||BrAC Exposure (peak, average, AUC). 2) changes in subjective perceptions, heart-rate, skin blood flow.|
|Change History||Complete list of historical versions of study NCT00713492 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Effect of sex and drinking history on self-administration.|
|Original Secondary Outcome Measures ICMJE
||Effect of sex and drinking history on self-administration|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Computer-Assisted Self-Administration of Ethanol|
|Official Title ICMJE||Computer-Assisted Self-Administration of Ethanol (CASE) in Humans|
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.
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.
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 healthy non-dependent participants. 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.
Study population: Participants will be 21-45 year-old male and female social drinkers and binge drinkers in good health, as determined by medical history, physical exam, ECG and lab tests. Participants with Axis-I psychiatric illness including alcohol or substance dependence 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., 100 mg%).
Following screening, participants will undergo IV ethanol self-administration sessions. Participants will be enrolled in four 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 and skin blood flow 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.
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 and skin blood flow 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.
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.
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Alcoholic Intoxication|
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||250|
|Estimated Completion Date||June 2014|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||21 Years to 45 Years|
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00713492|
|Other Study ID Numbers ICMJE||080178, 08-AA-0178|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute on Alcohol Abuse and Alcoholism (NIAAA)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||January 2013|
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