This is a double-blind, randomized, placebo-controlled, crossover design trial that will test the effect of pitolisant on alcohol self-administration and craving following a priming dose of alcohol. The specific objective of this proposal is to determine whether pitolisant has effects on alcohol consumption and craving
The present proposal is intended to answer the call for accelerating drug development by exploring the potential of a novel anticonvulsant, Pitolisant as a candidate medication for the treatment of AUD. Pitolisant is an H-3 receptor inverse agonist that is FDA-approved for treating narcolepsy which has been found to have effects of on alcohol craving and consumption in preclinical studies. The aims of this study are to test the effects of Pitolisant on alcohol self-administration and craving among a sample of non-treatment seeking heavy drinkers. The effects of 5-days of pitolisant (8.9mg) or placebo will be evaluated in a human laboratory using an alcohol self-administration methodology. In this within-subjects crossover design, heavy drinkers (N=28) will be randomized to the order of exposure (Pitolisant or placebo) prior to completing two alcohol self-administration trials. Subjects will receive a priming drink of alcohol and will have access to 8 alcoholic drinks over a 2-hour period. The investigators anticipate that subjects will consume less alcohol during an alcohol self-administration trial when receiving Pitolisant compared to when they are receiving placebo. Significant Pitolisant-induced reductions in the quantity of alcohol self-administered will be considered to be an indication that this drug may have value as an AUD medication. This study may provide a rationale for phase II clinical studies testing Pitolisant with a treatment-seeking AUD population.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
9
8.9mg Pitolisant for 5 days
Inert ingredients
Boston University Psychiatry Research Center, Clinical Studies Unit
Boston, Massachusetts, United States
Alcohol Consumption in Alcohol Self-Administration Trials
Alcohol consumption will be measured by using a graduated cylinder to determine the amount of alcohol given to the subject that was not consumed. This outcome will be measured as standard drink units (SDU). A standard drink contains approximately 0.6 fluid ounces of pure alcohol. Lower SDUs are favorable.
Time frame: 2.6 hours
Alcohol Consumption (BAC): Observation Period, Minute 10
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable
Time frame: 1 minute
Alcohol Consumption (BAC): Observation Period, Minute 20
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Time frame: 1 minute
Alcohol Consumption (BAC): Observation Period, Minute 30
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Time frame: 1 minute
Alcohol Consumption (BAC): Observation Period, Minute 40
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Time frame: 1 minute
Alcohol Consumption (BAC): Self-administration Block 1, Minute 30
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Time frame: 1 minute
Alcohol Consumption (BAC): Self-administration Block 1, Minute 60
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Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Time frame: 1 minute
Alcohol Consumption (BAC): Self-administration Block 2, Minute 30
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Time frame: 1 minute
Alcohol Consumption (BAC): Self-administration Block 2, Minute 60
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Time frame: 1 minute
Alcohol Craving During 12-day Drug Exposure
The Visual Analog Scale (VAS) will be used to assess alcohol craving during the medication exposure period. The VAS is a 10 cm straight line with one end meaning no alcohol craving and the other end meaning intense alcohol craving. Higher VAS scores are associated with more cravings. Lower VAS scores are favorable.
Time frame: 12 days
Alcohol Consumption During the 12-day Drug Exposure
Alcohol consumption during the 12 days of drug exposure will be measured using the timeline followback method. Lower (Standard Drink Units) SDUs are favorable.
Time frame: 12 days
Alcohol-induced Stimulation: Observation Period, Minute 10
Whether pitolisant increases the stimulant effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher BAES scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on stimulation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Stimulation: Observation Period, Minute 20
Whether pitolisant increases the stimulant effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on stimulation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Stimulation: Observation Period, Minute 30
Whether pitolisant increases the stimulant effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on stimulation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Stimulation: Observation Period, Minute 40
Whether pitolisant increases the stimulant effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on stimulation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Stimulation: Self-Administration Block 1, Minute 30
Whether pitolisant increases the stimulant effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on stimulation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Stimulation: Self-Administration Block 1, Minute 60
Whether pitolisant increases the stimulant effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on stimulation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Stimulation: Self-Administration Block 2, Minute 30
Whether pitolisant increases the stimulant effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on stimulation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Stimulation: Self-Administration Block 2, Minute 60
Whether pitolisant increases the stimulant effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on stimulation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Sedation: Observation Period, Minute 10
Whether pitolisant increases the sedative effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on sedation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Sedation: Observation Period, Minute 20
Whether pitolisant increases the sedative effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on sedation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Sedation: Observation Period, Minute 30
Whether pitolisant increases the sedative effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on sedation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Sedation: Observation Period, Minute 40
Whether pitolisant increases the sedative effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on sedation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Sedation: Self-Administration Block 1, Minute 30
Whether pitolisant increases the sedative effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on sedation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Sedation: Self-administration Block 1, Minute 60
Whether pitolisant increases the sedative effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on sedation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Sedation: Self-administration Block 2, Minute 30
Whether pitolisant increases the sedative effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on sedation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol-induced Sedation: Self-administration Block 2, Minute 60
Whether pitolisant increases the sedative effects of a priming drink of alcohol will be assessed using the Biphasic Alcohol Effects Scale (BAES). It is a self-report, unipolar adjective rating scale that is designed to measure both stimulant and sedative effects of alcohol. It consists of fourteen items, that comprise two subscales (stimulant and sedative). Items are rated on a eleven-point scale from 0 (not at all) to 10 (extremely). The stimulant subscale can range from 0 to 70 and the sedative scale can rage from 0 to 50. Higher scores are associated with more stimulant and sedative effects, respectively. This section focuses solely on sedation. Lower BAES scores are favorable.
Time frame: 1 minute
Alcohol Urge: Self-administration Block 1, Minute 30
The Alcohol Urge questionnaire (AUQ) is an 8 item measure of self-reported urges to drink in human laboratory studies that assesses the participant's urge for an alcoholic drink at the time the questionnaire is completed, Questions are in the form of a 7-point Likert scale (from strongly disagree to strongly agree) and participants select the extent to which they disagree or agree with the 8 statements relating to desire to drink, expectation of a desired outcome from drinking, and inability to avoid drinking if alcohol was available. The minimum AUQ score is 8 and the maximum score is 56. Lower AUQ scores are associated with less urge for an alcoholic drink, and therefore more favorable.
Time frame: 1 minute
Alcohol Urge: Self-administration Block 1, Minute 60
The Alcohol Urge questionnaire (AUQ) is an 8 item measure of self-reported urges to drink in human laboratory studies that assesses the participant's urge for an alcoholic drink at the time the questionnaire is completed, Questions are in the form of a 7-point Likert scale (from strongly disagree to strongly agree) and participants select the extent to which they disagree or agree with the 8 statements relating to desire to drink, expectation of a desired outcome from drinking, and inability to avoid drinking if alcohol was available. The minimum AUQ score is 8 and the maximum score is 56. Lower AUQ scores are associated with less urge for an alcoholic drink, and therefore more favorable.
Time frame: 1 minute
Alcohol Urge: Self-administration Block 2, Minute 30
The Alcohol Urge questionnaire (AUQ) is an 8 item measure of self-reported urges to drink in human laboratory studies that assesses the participant's urge for an alcoholic drink at the time the questionnaire is completed, Questions are in the form of a 7-point Likert scale (from strongly disagree to strongly agree) and participants select the extent to which they disagree or agree with the 8 statements relating to desire to drink, expectation of a desired outcome from drinking, and inability to avoid drinking if alcohol was available. The minimum AUQ score is 8 and the maximum score is 56. Lower AUQ scores are associated with less urge for an alcoholic drink, and therefore more favorable.
Time frame: 1 minute
Alcohol Urge: Self-administration Block 2, Minute 60
The Alcohol Urge questionnaire (AUQ) is an 8 item measure of self-reported urges to drink in human laboratory studies that assesses the participant's urge for an alcoholic drink at the time the questionnaire is completed, Questions are in the form of a 7-point Likert scale (from strongly disagree to strongly agree) and participants select the extent to which they disagree or agree with the 8 statements relating to desire to drink, expectation of a desired outcome from drinking, and inability to avoid drinking if alcohol was available. The minimum AUQ score is 8 and the maximum score is 56. Lower AUQ scores are associated with less urge for an alcoholic drink, and therefore more favorable.
Time frame: 1 minute
Alcohol Craving: Observation Period, Minute 10
Alcohol craving will be measured by self report with the Visual Analog Scale (VAS). The VAS is a straight line with one end meaning no alcohol craving (score of 0) and the other end meaning intense alcohol craving (score of 100). The Participant marks a point on the line that matches their amount of alcohol craving. Lower VAS score is favorable.
Time frame: 1 minute
Alcohol Craving: Observation Period, Minute 20
Alcohol craving will be measured by self report with the Visual Analog Scale (VAS). The VAS is a straight line with one end meaning no alcohol craving (score of 0) and the other end meaning intense alcohol craving (score of 100). The Participant marks a point on the line that matches their amount of alcohol craving. Lower VAS score is favorable.
Time frame: 1 minute
Alcohol Craving: Observation Period, Minute 30
Alcohol craving will be measured by self report with the Visual Analog Scale (VAS). The VAS is a straight line with one end meaning no alcohol craving (score of 0) and the other end meaning intense alcohol craving (score of 100). The Participant marks a point on the line that matches their amount of alcohol craving. Lower VAS score is favorable.
Time frame: 1 minute
Alcohol Craving: Observation Period, Minute 40
Alcohol craving will be measured by self report with the Visual Analog Scale (VAS). The VAS is a straight line with one end meaning no alcohol craving (score of 0) and the other end meaning intense alcohol craving (score of 100). The Participant marks a point on the line that matches their amount of alcohol craving. Lower VAS score is favorable.
Time frame: 1 minute
Alcohol Craving: Self-administration Block 1, Minute 30
Alcohol craving will be measured by self report with the Visual Analog Scale (VAS). The VAS is a straight line with one end meaning no alcohol craving (score of 0) and the other end meaning intense alcohol craving (score of 100). The Participant marks a point on the line that matches their amount of alcohol craving. Lower VAS score is favorable.
Time frame: 1 minute
Alcohol Craving: Self-administration Block 1, Minute 60
Alcohol craving will be measured by self report with the Visual Analog Scale (VAS). The VAS is a straight line with one end meaning no alcohol craving (score of 0) and the other end meaning intense alcohol craving (score of 100). The Participant marks a point on the line that matches their amount of alcohol craving. Lower VAS score is favorable.
Time frame: 1 minute
Alcohol Craving: Self-administration Block 2, Minute 30
Alcohol craving will be measured by self report with the Visual Analog Scale (VAS). The VAS is a straight line with one end meaning no alcohol craving (score of 0) and the other end meaning intense alcohol craving (score of 100). The Participant marks a point on the line that matches their amount of alcohol craving. Lower VAS score is favorable.
Time frame: 1 minute
Alcohol Craving: Self-administration Block 2, Minute 60
Alcohol craving will be measured by self report with the Visual Analog Scale (VAS). The VAS is a straight line with one end meaning no alcohol craving (score of 0) and the other end meaning intense alcohol craving (score of 100). The Participant marks a point on the line that matches their amount of alcohol craving. Lower VAS score is favorable.
Time frame: 1 minute