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Temporally-Resolved Electrophysiology of Acamprosate Treatment of Alcohol Use Disorder

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ClinicalTrials.gov Identifier: NCT06269627
Recruitment Status : Not yet recruiting
First Posted : February 21, 2024
Last Update Posted : April 26, 2024
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute on Alcohol Abuse and Alcoholism (NIAAA) )

Study Description
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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.


Condition or disease Intervention/treatment Phase
Alcohol Use Disorder Drug: Acamprosate calcium Other: Placebo Phase 4

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Temporally-Resolved Electrophysiology of Acamprosate Treatment of Alcohol Use Disorder
Estimated Study Start Date : May 1, 2024
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Active
This arm has participants receiving acamprosate for 21 day as inpatients.
 Drug: Acamprosate calcium
Two 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 Comparator: Placebo
This arm has participants receiving placebo for 21 day as inpatients.
 Other: Placebo
Two 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.


Outcome Measures
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Primary Outcome Measures :
  1. Reduction of beta power [ Time Frame: 21 day period as inpatients ]
    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.


Secondary Outcome Measures :
  1. Promotion of alpha power in active group compared to placebo group. [ Time Frame: 21 day period as inpatients ]
    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.

  2. No change in slow band (delta and theta) power in active group compared to placebo group. [ Time Frame: 21 day period as inpatients ]
    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.

  3. Reduction of theta event-related synchronization in active group compared to placebo group. [ Time Frame: 21 day period as inpatients ]
    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.

  4. Amplification and hastening of P300 in active group compared to placebo group. [ Time Frame: 21 day period as inpatients ]
    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.

  5. Correlation of EEG markers of acamprosate treatment with clinical measures of anxiety and alcohol craving [ Time Frame: 21 day period as inpatients ]
    The above EEG measures that are found to be associated with acamprosate treatment will be tested for correlation with clinical measures of anxiety and alcohol craving.

  6. Correlation of EEG markers of acamprosate treatment with polysomnography markers [ Time Frame: 21 day period as inpatients ]
    The above EEG measures that are found to be associated with acamprosate treatment will be tested for correlation with polysomnography markers such as total sleep time, slow wave sleep duration, sleep efficiency, and total wake duration after sleep onset.

  7. Correlation of polysomnography markers of acamprosate treatment with clinical measures of anxiety and alcohol craving [ Time Frame: 21 day period as inpatients ]
    The above polysomnography measures that are found to be associated with acamprosate treatment will be tested for correlation with clinical measures of anxiety and alcohol craving.


Eligibility Criteria
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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Stated willingness to comply with all required study procedures and availability for the duration of the study.
  4. Diagnosed with moderate to severe alcohol use disorder by a clinician at the time of admission.
  5. Agreement to adhere to Lifestyle Considerations (see below) throughout study duration.

During this study, participants are asked to:

  • Not wear any nicotine patches over the duration of the study visits. Nicotine users must refrain from use at least two hours before the study session commencement.
  • Not consume alcohol which is also a requirement for the NIH Clinical Center as they are inpatients seeking treatment for AUD.
  • If medications corresponding to exclusion from the study are indicated for the care of the participant, the participant will be immediately withdrawn from the study without impacting the financial compensation for participation prior to that indication.

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) at admission 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06269627


Contacts
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Contact: Beth A Lee, R.N. (301) 451-6964 beth.lee@nih.gov
Contact: Reza Momenan, Ph.D. (301) 451-6972 rezam@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Contact: NIH Clinical Center Office of Patient Recruitment (OPR)    800-411-1222 ext TTY dial 711    ccopr@nih.gov   
Sponsors and Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
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Principal Investigator: Reza Momenan, Ph.D. National Institute on Alcohol Abuse and Alcoholism (NIAAA)
More Information
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Additional Information:

Publications:

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Responsible Party: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
ClinicalTrials.gov Identifier: NCT06269627    
Other Study ID Numbers: 10001644
001644-AA
First Posted: February 21, 2024    Key Record Dates
Last Update Posted: April 26, 2024
Last Verified: March 4, 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: .Study participant research data will include but not be limited to cognitive responses, EEG and PSG recordings, and cardiac and ocular activities (electronic data); and clinical and study assessments, and behavioral interviews (paper data). Individual participants and their research data will be identified by a unique study identification number. The key to link participants with their research data will be limited to the participating investigators, including the PI, lead associate investigator, and CNIRC research coordinators. Access to study data will be restricted to authorized personnel. De-identified data may be shared with collaborating researchers for data analysis.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute on Alcohol Abuse and Alcoholism (NIAAA) ):
Multimodal
Neuroscience
Resting State
Event-Related Potentials
 Artificial Intelligence
Machine Learning
ELECTROENCEPHALOGRAPHY
Acamprosate
Additional relevant MeSH terms:
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Alcoholism
Alcohol Drinking
Drinking Behavior
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
 Mental Disorders
Acamprosate
Calcium
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Alcohol Deterrents