Effect of Allopregnanolone on Stress-induced Craving
- Registration Number
- NCT04015869
- Lead Sponsor
- Yale University
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 10
- Non-treatment seeking individuals with current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) alcohol use disorder (AUD)
- No current substance use disorder (except tobacco, alcohol, and marijuana)
- No current medical problems and normal electrocardiogram (ECG)
- For women, not pregnant as determined by pregnancy screening, not breast feeding.
- Current major psychiatric illnesses including mood, psychotic, or anxiety disorders
- History of major medical illnesses; including liver diseases, heart disease, chronic pain or other medical conditions that the physician investigator deems contraindicated for the subject to be in the study
- Liver function tests (ALT or AST) greater than 3 times normal
- weight >120kg
- renal impairment
- patients on the following medications: a) medications for alcoholism (e.g. naltrexone, disulfiram, topiramate, acamprosate); b) psychotropic medications that promote sedation (please note patients on psychotropic medications for current psychiatric conditions will also be excluded); and c) patients currently taking antibiotics or antifungals
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description allopregnanolone Allopregnanolone Allopregnanolone infusion dose of 100nM over 175 min placebo Placebos Placebo infusion
- Primary Outcome Measures
Name Time Method Alcohol Urge Questionnaire (AUQ) Pre-script Pre-Script 40 minutes before trauma/neutral script is presented 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).
Alcohol Urge Questionnaire (AUQ) Recovery Recovery 10 minutes after trauma/neutral script is presented 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).
The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Pre-Script Pre-Script 40 minutes before trauma/neutral script is presented 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)Alcohol Urge Questionnaire (AUQ) Post-Script Post-Script 5 minutes after trauma/neutral script is presented 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).
The State-Trait Anxiety Inventory (STAI-6) I am Worried - Post-Script Post-Script 5 minutes after trauma/neutral script is presented 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)The State-Trait Anxiety Inventory (STAI-6) I am Worried - Recovery Recovery 10 minutes after trauma/neutral script is presented 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)The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Post-Script Post-Script 5 minutes after trauma/neutral script is presented 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)The State-Trait Anxiety Inventory (STAI-6) I Feel Upset - Recovery Recovery 10 minutes after trauma/neutral script is presented 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)The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Pre-Script Pre-Script 40 minutes before trauma/neutral script is presented 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)The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Post-Script Post-Script 5 minutes after trauma/neutral script is presented 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)The State-Trait Anxiety Inventory (STAI-6) I Feel Content - Recovery Recovery10 minutes after trauma/neutral script is presented 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)The State-Trait Anxiety Inventory (STAI-6) I am Worried - Pre-Script Pre-Script 40 minutes before trauma/neutral script is presented 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)
- Secondary Outcome Measures
Name Time Method Biphasic Alcohol Effects Scale (BAES) Sedation Items - Pre-Script Pre-Script 40 minutes before trauma/neutral script is presented 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.
Biphasic Alcohol Effects Scale (BAES) Sedation Items Pre-infusion (at 0 minutes), during infusion (approximately 20 minutes) and post-infusion (approximately 90 minutes) 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.
Biphasic Alcohol Effects Scale (BAES) Sedation Items - Target Alcohol Dose (40mg%) Target Alcohol dose (40mg%) 90 minutes after trauma/neutral script is presented 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.
Biphasic Alcohol Effects Scale (BAES) Sedation Items - End of Test Day End of test day 150 minutes after trauma/neutral script is presented 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.
Biphasic Alcohol Effects Scale (BAES) Stimulation Items - Pre-Script Pre-Script 40 minutes before trauma/neutral script is presented 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.
Biphasic Alcohol Effects Scale (BAES) Stimulation Items Pre-infusion (at 0 minutes), during infusion (approximately 20 minutes) and post-infusion (approximately 90 minutes) 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.
Biphasic Alcohol Effects Scale (BAES) Stimulation Items - Target Alcohol Dose (40mg%) Target Alcohol Dose (40mg%) 90 minutes after trauma/neutral script is presented 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.
Biphasic Alcohol Effects Scale (BAES) Stimulation Items - End of Test Day End of Test Day 150 minutes after trauma/neutral script is presented 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.
Trial Locations
- Locations (1)
VA Connecticut Healtcase System
🇺🇸West Haven, Connecticut, United States
VA Connecticut Healtcase System🇺🇸West Haven, Connecticut, United States