The goal of this study is to determine whether intravenous infusion of allopregnanolone (ALLO) attenuates stress-induced craving and stress-induced anxiety in a clinical laboratory setting. The secondary objective of this project is to characterize the behavioral effects of ALLO in heavy drinkers.
This is a double-blind, placebo-controlled study that will randomize heavy "at risk" drinkers to 2 groups: targeted dose of 100 nM of ALLO or placebo. Participants will receive a continuous infusion of ALLO (or placebo) for approximately 175 min. Sixty minutes after the start of the infusion, when ALLO levels are relatively stable, the stress induction paradigm will be introduced. Participants will be presented with a stress cue and a neutral cue in random order. Stress and neutral cues will consist of personalized 5-minute scripts created prior to testing. Measures of stress-induced craving and stress-induced anxiety will be presented before the cue (pre), immediately following the cue (post) and 10 minutes after (recovery). An alcohol infusion (40mg%) begins at approximately 120 minutes into ALLO Infusion. Once the alcohol infusion has reached the targeted dose of 40mg% the infusion is clamped for approximately 20 minutes. The study outcomes will include measures of stress-induced craving and stress-induced anxiety as well as measures of subjective mood effects, cognitive performance, and motor coordination.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
HEALTH_SERVICES_RESEARCH
Masking
QUADRUPLE
Enrollment
10
neurosteroid
placebo
VA Connecticut Healtcase System
West Haven, Connecticut, United States
Alcohol Urge Questionnaire (AUQ) Pre-script
The Alcohol Urge Questionnaire (AUQ) is an 8-question, self-administered measure of drinking urges. Questions are in the form of a 7-point scale with participants endorsing the extent to which they agree or disagree with statements relating to desire to drink (4 items), expectation of a desired outcome from drinking (2 items), and inability to avoid drinking if alcohol was available (2 items). Total scores range from 8 (strongly disagree) to 56 (strongly agree).
Time frame: Pre-Script 40 minutes before trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Pre-Script
The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 3. "I feel upset" (scored individually): the scoring for "I feel upset is: a = 1, b = 2, c = 3, and d = 4 (1 not at all upset to 4 very much upset)
Time frame: Pre-Script 40 minutes before trauma/neutral script is presented
Alcohol Urge Questionnaire (AUQ) Post-Script
The Alcohol Urge Questionnaire (AUQ) is an 8-question, self-administered measure of drinking urges. Questions are in the form of a 7-point scale with participants endorsing the extent to which they agree or disagree with statements relating to desire to drink (4 items), expectation of a desired outcome from drinking (2 items), and inability to avoid drinking if alcohol was available (2 items). Total scores range from 8 (strongly disagree) to 56 (strongly agree).
Time frame: Post-Script 5 minutes after trauma/neutral script is presented
Alcohol Urge Questionnaire (AUQ) Recovery
The Alcohol Urge Questionnaire (AUQ) is an 8-question, self-administered measure of drinking urges. Questions are in the form of a 7-point scale with participants endorsing the extent to which they agree or disagree with statements relating to desire to drink (4 items), expectation of a desired outcome from drinking (2 items), and inability to avoid drinking if alcohol was available (2 items). Total scores range from 8 (strongly disagree) to 56 (strongly agree).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Recovery 10 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Post-Script
The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 3. "I feel upset" (scored individually): the scoring for "I feel upset is: a = 1, b = 2, c = 3, and d = 4 (1 not at all upset to 4 very much upset)
Time frame: Post-Script 5 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Recovery
The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 3. "I feel upset" (scored individually): the scoring for "I feel upset is: a = 1, b = 2, c = 3, and d = 4 (1 not at all upset to 4 very much upset)
Time frame: Recovery 10 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Pre-Script
The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 5. "I feel content" (scored individually): the scoring for "I feel content is: a = 4, b = 3, c = 2, and d = 1 (4 not at all content to 1 very much content)
Time frame: Pre-Script 40 minutes before trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Post-Script
The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 5. "I feel content" (scored individually): the scoring for "I feel content is: a = 4, b = 3, c = 2, and d = 1 (4 not at all content to 1 very much content)
Time frame: Post-Script 5 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Recovery
The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 5. "I feel content" (scored individually): the scoring for "I feel content is: a = 4, b = 3, c = 2, and d = 1 (4 not at all content to 1 very much content)
Time frame: Recovery10 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I am Worried - Pre-Script
The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 6. "I am worried" (scored individually): the scoring for "I feel content is: a = 1, b = 2, c = 3, and d = 4 (1 not at all worried to 4 very much worried)
Time frame: Pre-Script 40 minutes before trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I am Worried - Post-Script
The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 6. "I am worried" (scored individually): the scoring for "I feel content is: a = 1, b = 2, c = 3, and d = 4 (1 not at all worried to 4 very much worried)
Time frame: Post-Script 5 minutes after trauma/neutral script is presented
The State-Trait Anxiety Inventory (STAI-6) I am Worried - Recovery
The State Trait Anxiety Inventory (STAI-6) is a 6-item self-rated instrument used to assess anxiety state. The STAI-6 questions included: 1. "I feel calm"; 2. "I am tense"; 3. "I feel upset"; 4. "I am relaxed"; 5. "I feel content"; 6. "I am worried". Each of these questions were rated as: a) "not at all"; b) "somewhat"; c) "moderately"; d) "very much". For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. This outcome is for 6. "I am worried" (scored individually): the scoring for "I feel content is: a = 1, b = 2, c = 3, and d = 4 (1 not at all worried to 4 very much worried)
Time frame: Recovery 10 minutes after trauma/neutral script is presented
Biphasic Alcohol Effects Scale (BAES) Sedation Items - Pre-Script
Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol.
Time frame: Pre-Script 40 minutes before trauma/neutral script is presented
Biphasic Alcohol Effects Scale (BAES) Sedation Items
Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol. Data presented here is mean at 90 minutes.
Time frame: Pre-infusion (at 0 minutes), during infusion (approximately 20 minutes) and post-infusion (approximately 90 minutes)
Biphasic Alcohol Effects Scale (BAES) Sedation Items - Target Alcohol Dose (40mg%)
Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol.
Time frame: Target Alcohol dose (40mg%) 90 minutes after trauma/neutral script is presented
Biphasic Alcohol Effects Scale (BAES) Sedation Items - End of Test Day
Biphasic Alcohol Effects Scale (BAES) Sedation items - sum of subjective responses - 0(not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES sedation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater sedative effects of alcohol.
Time frame: End of test day 150 minutes after trauma/neutral script is presented
Biphasic Alcohol Effects Scale (BAES) Stimulation Items - Pre-Script
Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol.
Time frame: Pre-Script 40 minutes before trauma/neutral script is presented
Biphasic Alcohol Effects Scale (BAES) Stimulation Items
Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol. Data presented here is mean at 90 minutes.
Time frame: Pre-infusion (at 0 minutes), during infusion (approximately 20 minutes) and post-infusion (approximately 90 minutes)
Biphasic Alcohol Effects Scale (BAES) Stimulation Items - Target Alcohol Dose (40mg%)
Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol.
Time frame: Target Alcohol Dose (40mg%) 90 minutes after trauma/neutral script is presented
Biphasic Alcohol Effects Scale (BAES) Stimulation Items - End of Test Day
Biphasic Alcohol Effects Scale (BAES) Simulation items - sum of subjective responses - 0 (not at all) to 10 (extremely) for 7 sedation related questions regarding effects of alcohol. Total BAES stimulation subscale score: 0 (lower sedation) -70 (higher sedation) with higher numbers indicating greater stimulating effects of alcohol.
Time frame: End of Test Day 150 minutes after trauma/neutral script is presented