The Effects of the Histamine-3 Receptor Inverse Agonist Pitolisant on Alcohol Self-Administration in Heavy Drinkers
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Alcohol Consumption (BAC): Observation Period, Minute 20
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This study is double-blind. Medications are over-encapsulated.
入排标准
- 年龄范围
- 21 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •21-55 years of age
- •Able to verify age with a state or federal picture identification
- •Exceeds safe weekly drinking limits during the 28 days prior to consent (average of 14 drinks for women or 21 drinks for men per week)
- •Reports at least one episode of binge drinking (>3 drinks for women, >4 drinks for men) in the 28 days prior consent.
- •Meets DSM-5 criteria for mild alcohol use disorder or greater severity.
- •Has a smartphone to complete medication exposure period study assessments.
排除标准
- •Seeking treatment for alcohol problems
- •Clinical Institute Withdrawal Assessment at ≥10
- •DSM-5 diagnosis of current major depression, bipolar disorder, schizophrenia, bulimia/anorexia, dementia, insomnia disorder or a substance use disorder other than alcohol, nicotine, marijuana or caffeine
- •If female, pregnant, nursing, have plans to become pregnant
- •If female, does not agree to use an accepted form of birth control
- •Has a medical contraindication to the use of pitolisant
- •Has medical or mental condition for which further alcohol exposure at the planned dose range would be contraindicated
- •Current risk of suicidality (MINI suicidality score greater than 8 (low risk) or Yes to the ideation question #4 of the C-SSRS)
- •BMI is greater than 40 or less than 18
- •Impaired renal function (GFR <80 mL/min)
- •Have a history of any clinically significant renal or hepatic disease
- •Child-Pugh Score equal to or greater than Class B (evaluated based on presence or absence of encephalopathy and ascites, INR, bilirubin, and albumin) [https://www.mdcalc.com/child-pugh-score-cirrhosis-mortality]
- •Have a clinically significant ECG as determined by the investigator or abnormal ECG heart rate (<45 or >100 bpm) or QTc interval corrected for heart rate using the Fridericia formula (QTcF) > 450 msec
- •Have a history of cardiac arrhythmias or who for other reasons are at risk for developing Torsade de Pointes including those with bradycardia, hypokalemia, and congenital QT interval prolongation
- •Has received alcohol counseling or other non-pharmacologic intervention to treat AUD in the past 90 days
- •Has taken medications that are used to treat AUD in the past 90 days
- •Has urine toxicology results positive for cocaine, opioids, amphetamines, buprenorphine, methadone, methamphetamines, oxycontin, barbiturates, or benzodiazepines.
- •Subject is taking a medication which will significantly alter drug metabolism (e.g., strong CYP2D6 inhibitors, strong CYP3A4 inducers, or H1 receptor antagonists that cross the blood barrier (e.g. diphenhydramine or meclizine).
- •Subject is known to be a poor CYP2D6 metabolizer.
- •Subject is unable to comfortably abstain from nicotine for a period of 8 hours.
- •Has Chronic Obstructive Pulmonary Disease (COPD), history of solid organ transplant, sickle cell disease, severe heart disease or other health condition for which exposure to COVID-19 represents an unreasonable risk as determined by the study staff physician using accepted COVID-19 guidance (e.g. Centers for Disease Control, etc.).
研究组 & 干预措施
Pitolisant
Subjects will take an 8.9 mg dose (two 4.45 mg pills) of pitolisant once per day on day 1 through 4. On day 5, 8.9 mg will be taken in front of staff prior to an alcohol self administration trial.
干预措施: Pitolisant (Drug)
Placebo
Subjects will take an placebo once per day on day 1 through 4. On day 5, a placebo will be taken in front of staff prior to an alcohol self administration trial.
干预措施: Placebo (Drug)
结局指标
主要结局
Alcohol Consumption (BAC): Observation Period, Minute 20
时间窗: 1 minute
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Alcohol Consumption in Alcohol Self-Administration Trials
时间窗: 2.6 hours
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.
Alcohol Consumption (BAC): Observation Period, Minute 10
时间窗: 1 minute
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable
Alcohol Consumption (BAC): Observation Period, Minute 40
时间窗: 1 minute
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Alcohol Consumption (BAC): Self-administration Block 2, Minute 60
时间窗: 1 minute
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Alcohol Consumption (BAC): Observation Period, Minute 30
时间窗: 1 minute
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Alcohol Consumption (BAC): Self-administration Block 1, Minute 30
时间窗: 1 minute
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Alcohol Consumption (BAC): Self-administration Block 2, Minute 30
时间窗: 1 minute
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
Alcohol Consumption (BAC): Self-administration Block 1, Minute 60
时间窗: 1 minute
Alcohol consumption will be measured throughout the study by their Blood Alcohol Content (BAC) measured by a breathalyzer test. Lower BACs are favorable.
次要结局
- Alcohol-induced Stimulation: Observation Period, Minute 30(1 minute)
- Alcohol-induced Stimulation: Self-Administration Block 1, Minute 30(1 minute)
- Alcohol-induced Stimulation: Self-Administration Block 2, Minute 60(1 minute)
- Alcohol-induced Sedation: Self-administration Block 2, Minute 30(1 minute)
- Alcohol Consumption During the 12-day Drug Exposure(12 days)
- Alcohol-induced Stimulation: Observation Period, Minute 20(1 minute)
- Alcohol-induced Sedation: Observation Period, Minute 20(1 minute)
- Alcohol-induced Sedation: Observation Period, Minute 40(1 minute)
- Alcohol-induced Sedation: Self-Administration Block 1, Minute 30(1 minute)
- Alcohol Craving: Observation Period, Minute 30(1 minute)
- Alcohol Craving: Self-administration Block 2, Minute 60(1 minute)
- Alcohol Craving During 12-day Drug Exposure(12 days)
- Alcohol-induced Stimulation: Observation Period, Minute 10(1 minute)
- Alcohol-induced Stimulation: Self-Administration Block 2, Minute 30(1 minute)
- Alcohol-induced Sedation: Self-administration Block 1, Minute 60(1 minute)
- Alcohol Craving: Self-administration Block 1, Minute 30(1 minute)
- Alcohol Craving: Self-administration Block 2, Minute 30(1 minute)
- Alcohol-induced Stimulation: Observation Period, Minute 40(1 minute)
- Alcohol-induced Stimulation: Self-Administration Block 1, Minute 60(1 minute)
- Alcohol-induced Sedation: Observation Period, Minute 10(1 minute)
- Alcohol-induced Sedation: Observation Period, Minute 30(1 minute)
- Alcohol Craving: Observation Period, Minute 10(1 minute)
- Alcohol Urge: Self-administration Block 1, Minute 30(1 minute)
- Alcohol Urge: Self-administration Block 1, Minute 60(1 minute)
- Alcohol Urge: Self-administration Block 2, Minute 60(1 minute)
- Alcohol Craving: Observation Period, Minute 20(1 minute)
- Alcohol Craving: Self-administration Block 1, Minute 60(1 minute)
- Alcohol-induced Sedation: Self-administration Block 2, Minute 60(1 minute)
- Alcohol Urge: Self-administration Block 2, Minute 30(1 minute)
- Alcohol Craving: Observation Period, Minute 40(1 minute)