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.
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.
Enrolled in NIAAA natural history protocol 14-AA-0181.
Admitted to alcohol treatment program of NIAAA with moderate to severe alcohol use disorder by a clinician at the time of admission.
Determination by the attending physician or licensed practitioner caring for the patient that the patient's current clinical status is stable enough to provide informed consent for research.
Use of naltrexone, disulfiram, benzodiazepines (except Oxazepam), antiepileptic compounds, antidepressants, neuroleptics, or acamprosate within a time sufficient for the medication to be eliminated from the body (five half-lives from last use).
Pregnancy at admission (negative urine pregnancy test required).
History of head trauma associated with an unconscious state lasting more than 30 minutes, persistent sequelae, and/or cranial surgery.
History of epilepsy.
Parallel
Acamprosate calcium
DrugTwo oral capsules (packaged as one) containing 666 mg of acamprosate calcium will be given three times a day (total daily dose: 1998 mg/day) for a total of 21 days.
Placebo
Other interventionTwo oral capsules (packaged as one) containing 666 mg of inactive substance (e.g., sugar) will be given three times a day (total daily dose: 1998 mg/day) for a total of 21 days.
Reduction of beta power
Spectral power of EEG signals will be calculated in the beta frequency band (beta power). We expect a reduction of beta power to be greater in participants receiving acamprosate for 21 days than participants receiving placebo.
Promotion of alpha power in active group compared to placebo group.
Spectral power of EEG signals will be calculated in the alpha frequency band (alpha power). We expect a promotion of alpha power to be greater in participants receiving acamprosate for 21 days than participants receiving placebo.
No change in slow band (delta and theta) power in active group compared to placebo group.
Spectral power of EEG signals will be calculated in the delta and theta frequency bands (slow band power). We do not expect a significant difference in change in slow band power between the active and placebo groups over the course of 21 days.
Reduction of theta event-related synchronization in active group compared to placebo group.
Immediate brain activity, recorded via EEG, in response to task-related stimuli is termed as event-related potentials (ERPs). Spectral power of such ERPs in theta frequency band is called theta event-related synchronization (ERS).We expect a reduction of theta ERS to be greater in participants receiving acamprosate for 21 days than participants receiving placebo.
Amplification and hastening of P300 in active group compared to placebo group.
Immediate brain activity, recorded via EEG, in response to task-related stimuli is termed as event-related potentials (ERPs). These ERPs have stereotypical peaks, e.g., P300. We expect amplification and hastening of P300 peaks in ERPs among participants receiving acamprosate for 21 days in comparison to participants receiving placebo.
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