Temporally-Resolved Electrophysiology of Acamprosate Treatment of Alcohol Use Disorder

Overview

Background: Chronic heavy drinking can cause alcohol use disorder (AUD). AUD changes how the brain works. People with AUD may drink compulsively or feel like they cannot control their alcohol use. Acamprosate is an FDA-approved drug that reduces anxiety and craving in some, but not all, people with AUD. Objective: To learn more about how acamprosate affects brain function in people with AUD. Eligibility: People aged 21 to 65 years with moderate to severe AUD. Design: Participants will stay in the clinic for 21 days after a detoxification period of approximately 7 days. Acamprosate is a capsule taken by mouth. Half of participants will take this drug 3 times a day with meals. The other half will take a placebo. The placebo looks like the study drug but does not contain any medicine. Participants will not know which capsules they are taking. Participants will have a procedure called electroencephalography (EEG): A gel will be applied to certain locations on their scalp, and a snug cap will be placed on their head. The cap has sensors with wires. The sensors detect electrical activity in the brain. Participants will lie still and perform 2 tasks: they will look at different shapes and press a button when they see a specific one; and they will listen to tones and press dedicated buttons when they hear the corresponding tones. Participants will have 2 EEGs: 1 on day 2 and 1 on day 23 of their study participation. They may opt to have up to 4 more EEG studies (one on day 13 and one on each of the three follow-up visits) and 2 sleep studies, in which they would have sensors attached to their scalp while they sleep. Participants may have up to three follow-up visits for 6 months.

Study Description: This double-blind placebo-controlled study will focus on electrophysiological changes in brains of alcohol use disorder (AUD)inpatients resulting from a post-withdrawal 21-day acamprosate/placebo treatment. Known and established electroencephalogram (EEG) markers of AUD as well as anxiety and alcohol craving levels will be assessed pre- and post-treatment. We hypothesize that acamprosate normalizes EEG markers associated with AUD beyond placebo, specifically, reduces beta power, increases alpha power, does not change slow band (delta and theta) power in resting EEG; and reduces theta event-related synchronization (ERS), and amplifies and hastens P300 waveforms in event-related potentials (ERPs). Objectives: Primary Objective: To test, via within-subject comparisons, whether a 21-day acamprosate treatment regimen normalizes the EEG of AUD inpatients beyond placebo in reducing beta power, increasing alpha power, and changing slow band (delta and theta) power in resting EEG; and reducing theta event-related synchronization (ERS), and amplifying and hastening P300 waveforms in event-related potentials (ERPs). Secondary Objectives: 1) To correlate EEG changes with clinical changes, such as anxiety and alcohol craving. 2) To determine polysomnographic markers of response to acamprosate. 3) To correlate polysomnographic markers with clinical changes, such as anxiety and alcohol craving. Endpoints: Primary Endpoint: The said markers of EEG power and higher order EEG patterns will be measured before and after the 21-day treatment to compare the active-medication and placebo groups. Secondary Endpoints: 1) Acamprosate-induced changes in EEG power and higher order EEG patterns will be correlated to changes in anxiety and alcohol craving. 2) Acamprosate-induced changes in EEG power will be correlated to changes in polysomnographic markers such as total sleep time, slow wave sleep duration, sleep efficiency, and total wake duration after sleep onset. 3) Changes in polysomnographic markers will be correlated to changes in anxiety and alcohol craving.