COMT Inhibition as a Potential Therapeutic Target Among Individuals With Comorbid Alcohol Use Disorder and Attention-Deficit/Hyperactivity Disorder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 2
- 主要终点
- Change in alcohol-induced stimulation between medication periods
研究概览
简要总结
The purpose of this study is to determine whether the catechol-O-methyltransferase (COMT) inhibitor tolcapone, relative to placebo, affects response to alcohol, decision-making, brain activation associated with alcohol cue reactivity, response inhibition, and selective attention, or alcohol drinking.
详细描述
This study evaluates the effects of an FDA-approved medication called tolcapone in people who have both Alcohol Use Disorder (AUD) and Attention-Deficit/Hyperactivity Disorder (ADHD). The study involves seven visits over a three to four week period, including an assessment visit and two eight-day medication periods during which participants will be assigned to take, in a double-blinded fashion, both tolcapone and a placebo (three visits during each period). During two of these visits, participants will undergo a one-hour MRI scan. Participants must not be seeking treatment for AUD or ADHD and must not be currently taking any psychotropic medications, including stimulant medications for ADHD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder (AUD) and current Attention-Deficit/Hyperactivity Disorder (ADHD), as assessed by the Structured Clinical Interview for DSM-5 (SCID-5) or WHO-ASRS.
- •Currently not engaged in, and does not want treatment for, AUD or ADHD.
- •Currently not taking any medication for AUD or ADHD.
- •Able to read and understand questionnaires and informed consent.
- •Lives within 50 miles of the study site.
排除标准
- •Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
- •Any psychoactive substance use (except nicotine) within the last 30 days, as indicated by self-report and urine drug screen (UDS)
- •Current DSM-5 psychotic, mood, anxiety, obsessive-compulsive, trauma-related, or eating disorder, as assessed by SCID-
- •Current suicidal ideation or homicidal ideation.
- •Current use of any psychoactive medication, as evidenced by self-report and UDS.
- •History of severe alcohol withdrawal (e.g., seizure, delirium tremens), as evidenced by self-report and assessment with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar).
- •Clinically significant medical problems such as cardiovascular, renal, gastrointestinal, or endocrine problems, as evidenced by medical history and physical exam.
- •Past alcohol-related medical illness, such as gastrointestinal bleeding, pancreatitis, or peptic ulcer.
- •Current or past hepatocellular disease, as indicated by verbal report, or elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than the upper limit of the normal range at screening.
- •Females of childbearing potential who are pregnant (by plasma HCG), nursing, or who are not using a reliable form of contraception.
- •Current charges pending for a violent crime (not including DUI-related offenses).
- •Lack of a stable living situation.
- •Presence of ferrous metal in the body, as evidenced by metal screening and self-report.
- •Severe claustrophobia or morbid obesity that preclude placement in the MRI scanner.
- •History of neurological disease or head injury with > 2 minutes of unconsciousness.
研究组 & 干预措施
Tolcapone then Placebo
Participants in this arm will receive tolcapone during the first medication period (1 capsule containing 200 mg tolcapone on study days 1 and 2; 3 capsules containing a total of 600 mg tolcapone on study days 3-8), and placebo during the second medication period (1 capsule on study days 1 and 2; 3 capsules on study days 3-8).
干预措施: Placebo (Drug)
Placebo then Tolcapone
Participants in this arm will receive placebo during the first medication period (1 capsule on study days 1 and 2; 3 capsules on study days 3-8), and tolcapone during the second medication period (1 capsule containing 200 mg tolcapone on study days 1 and 2; 3 capsules containing a total of 600 mg tolcapone on study days 3-8).
干预措施: Placebo (Drug)
Tolcapone then Placebo
Participants in this arm will receive tolcapone during the first medication period (1 capsule containing 200 mg tolcapone on study days 1 and 2; 3 capsules containing a total of 600 mg tolcapone on study days 3-8), and placebo during the second medication period (1 capsule on study days 1 and 2; 3 capsules on study days 3-8).
干预措施: Tolcapone (Drug)
Placebo then Tolcapone
Participants in this arm will receive placebo during the first medication period (1 capsule on study days 1 and 2; 3 capsules on study days 3-8), and tolcapone during the second medication period (1 capsule containing 200 mg tolcapone on study days 1 and 2; 3 capsules containing a total of 600 mg tolcapone on study days 3-8).
干预措施: Tolcapone (Drug)
结局指标
主要结局
Change in alcohol-induced stimulation between medication periods
时间窗: 30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
Biphasic Alcohol Effects Scale stimulation score (range = 0-70; higher scores = more stimulation) after laboratory alcohol administration
Change in subjective response to alcohol between medication periods
时间窗: 30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
Subjective High Assessment Scale (range - 0-130; higher scores = greater intoxication) after laboratory alcohol administration
Change in selective attention-associated brain activation (fMRI) between medication periods
时间窗: 60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
Multi-source interference task BOLD signal to interference trials, relative to control trials
Change in risky decision-making after alcohol administration between medication periods
时间窗: 30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
Balloon Analogue Risk Task adjusted average number of pumps (higher scores = more risky decision-making)
Change in cognitive-control-associated brain activation (fMRI) between medication periods
时间窗: 60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
Stop-signal task blood oxygenation level dependent (BOLD) signal to successful stop trials, relative to unsuccessful stop trials
Change in alcohol cue-elicited brain activation (fMRI) between medication periods
时间窗: 60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
Alcohol cue reactivity task BOLD signal to alcohol cues, relative to neutral beverage cues
次要结局
未报告次要终点