Clinical trial NCT06269627: Temporally-Resolved Electrophysiology of Acamprosate Treatment of Alcohol Use Disorder
Official title: Temporally-Resolved Electrophysiology of Acamprosate Treatment of Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Alcohol Use Disorder
Keywords: Multimodal
Neuroscience
Resting State
Event-Related Potentials
Artificial Intelligence
Machine Learning
ELECTROENCEPHALOGRAPHY
Acamprosate
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2024-02-21
Enrollment: 48
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: * INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Age 21-65. In younger participants, the central nervous system has not sufficiently developed, whereas in older participants, degenerative changes may confound the studied measures. Moreover, the minimum legal drinking age is 21 years.
2. Enrolled in NIAAA natural history protocol 14-AA-0181.
3. Admitted to alcohol treatment program of NIAAA\* with moderate to severe alcohol use disorder by a clinician at the time of admission.

   * The determination of the severity of AUD is via Structured Clinical Interview for DSM-5 after particpant s enrollment.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Use of naltrexone, disulfiram, benzodiazepines (except Oxazepam), antiepileptic compounds, antidepressants, or neuroleptics currently or within the last 4 weeks.

   Individuals treated with acamprosate in the last 4 weeks would also be excluded.
2. Pregnancy at admission (negative urine pregnancy test required).
3. History of head trauma associated with an unconscious state lasting more than 30 minutes, persistent sequelae, and/or cranial surgery.
4. History of epilepsy.
5. History of non-substance related psychotic disorders.
6. Contraindications for acamprosate (previously exhibited hypersensitivity to acamprosate calcium or any of its compounds; and/or severe renal impairment, manifested as creatinine clearance \<= 30 mL/min).
7. Positive screens for alcohol or any illicit drugs (except THC) after admission and alcohol detoxification via breathanalysis and urine drug screen.
8. Current Clinical Institute Withdrawal Assessment (CIWA-Ar) score greater than or equal to 8. The participant can enroll in the study once their CIWA-Ar score drops below 8.

Primary outcomes:
measure: Reduction of beta power
timeFrame: 21 day period as inpatients
Secondary outcomes:
measure: Promotion of alpha power in active group compared to placebo group.
timeFrame: 21 day period as inpatients
measure: No change in slow band (delta and theta) power in active group compared to placebo group.
timeFrame: 21 day period as inpatients
measure: Reduction of theta event-related synchronization in active group compared to placebo group.
timeFrame: 21 day period as inpatients
measure: Amplification and hastening of P300 in active group compared to placebo group.
timeFrame: 21 day period as inpatients
measure: Correlation of EEG markers of acamprosate treatment with clinical measures of anxiety and alcohol craving
timeFrame: 21 day period as inpatients
measure: Correlation of EEG markers of acamprosate treatment with polysomnography markers
timeFrame: 21 day period as inpatients
measure: Correlation of polysomnography markers of acamprosate treatment with clinical measures of anxiety and alcohol craving
timeFrame: 21 day period as inpatients
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: Abdolreza Momenan, Ph.D.
role: PRINCIPAL_INVESTIGATOR
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