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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 : May 14, 2024
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute on Alcohol Abuse and Alcoholism (NIAAA) )

Tracking Information
First Submitted Date  ICMJE February 17, 2024
First Posted Date  ICMJE February 21, 2024
Last Update Posted Date May 14, 2024
Estimated Study Start Date  ICMJE May 19, 2024
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 17, 2024)		 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2024)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Temporally-Resolved Electrophysiology of Acamprosate Treatment of Alcohol Use Disorder
Official Title  ICMJE Temporally-Resolved Electrophysiology of Acamprosate Treatment of Alcohol Use Disorder
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Alcohol Use Disorder
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • Active Comparator: Active
    This arm has participants receiving acamprosate for 21 day as inpatients.
    Intervention: Drug: Acamprosate calcium
  • Placebo Comparator: Placebo
    This arm has participants receiving placebo for 21 day as inpatients.
    Intervention: Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 17, 2024)		 48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2026
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Beth A Lee, R.N. (301) 451-6964 beth.lee@nih.gov
Contact: Reza Momenan, Ph.D. (301) 451-6972 rezam@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT06269627
Other Study ID Numbers  ICMJE 10001644
001644-AA
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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.
Current Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute on Alcohol Abuse and Alcoholism (NIAAA) )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Reza Momenan, Ph.D. National Institute on Alcohol Abuse and Alcoholism (NIAAA)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date March 4, 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP