Donepezil and Cognitive Training for Alcohol Use Disorder (AUD)

NCT05042102 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: GY00105R01AA029075
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the project is to evaluate whether donepezil + cognitive remediation therapy is superior to placebo in reducing heavy drinking in patients with alcohol use disorder in a double-blind, placebo-controlled trial.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (1)

• Heavy drinking days

  Heavy drinking days as measured by weekly Time Line Follow Back (TLFB)

  13 weeks of active intervention

Secondary Outcomes (1)

• Global neurocognitive functioning

  At 7 weeks and at 13 weeks

Study Arms (4)

Donepezil + Cognitive remediation therapy (CRT)

EXPERIMENTAL

Subjects in this arm will receive (1) donepezil and (2) cognitive remediation therapy (CRT). Subjects will take 5 mg/day of oral donepezil in the evening for the first 4 weeks, then 10 mg/day of oral donepezil in the evening until week 13.

Combination Product: Donepezil + Cognitive remediation therapy (CRT)

Donepezil + Placebo CRT

EXPERIMENTAL

Subjects in this arm will receive (1) donepezil and (2) placebo CRT. Subjects will take 5 mg/day of oral donepezil in the evening for the first 4 weeks, then 10 mg/day of oral donepezil in the evening until week 13.

Combination Product: Donepezil + Placebo CRT

Placebo medication + Cognitive remediation therapy (CRT)

EXPERIMENTAL

Subjects in this arm will receive (1) placebo medication and (2) cognitive remediation therapy (CRT). Subjects will take placebo oral medication in the evening for the first 4 weeks, then placebo oral medication in the evening until week 13.

Combination Product: Placebo medication + Cognitive remediation therapy (CRT)

Placebo medication + Placebo CRT

EXPERIMENTAL

Subjects in this arm will receive (1) placebo medication and (2) placebo CRT. Subjects will take placebo oral medication in the evening for the first 4 weeks, then placebo oral medication in the evening until week 13.

Combination Product: Placebo medication + Placebo CRT

Interventions

Donepezil + Cognitive remediation therapy (CRT) COMBINATION_PRODUCT

Subjects in this arm will receive (1) donepezil and (2) cognitive remediation therapy (CRT). Subjects will take 5 mg/day of oral donepezil in the evening for the first 4 weeks, then 10 mg/day of oral donepezil in the evening until week 13.

Donepezil + Cognitive remediation therapy (CRT)

Donepezil + Placebo CRT COMBINATION_PRODUCT

Subjects in this arm will receive (1) donepezil and (2) placebo CRT. Subjects will take 5 mg/day of oral donepezil in the evening for the first 4 weeks, then 10 mg/day of oral donepezil in the evening until week 13.

Donepezil + Placebo CRT

Placebo medication + Cognitive remediation therapy (CRT) COMBINATION_PRODUCT

Subjects in this arm will receive (1) placebo medication and (2) cognitive remediation therapy (CRT). Subjects will take placebo oral medication in the evening for the first 4 weeks, then placebo oral medication in the evening until week 13.

Placebo medication + Cognitive remediation therapy (CRT)

Placebo medication + Placebo CRT COMBINATION_PRODUCT

Subjects in this arm will receive (1) placebo medication and (2) placebo CRT. Subjects will take placebo oral medication in the evening for the first 4 weeks, then placebo oral medication in the evening until week 13.

Placebo medication + Placebo CRT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females 18-80 years of age
• Fluency in English and a 6th grade or higher reading level
• Meets the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for a current alcohol use disorder (subjects should have a primary alcohol use disorder \[AUD\] diagnosis, but may have concurrent occasional use of other substances)
• Last alcohol use and at least one heavy drinking day within the past 30 days
• Willingness to attend follow-up assessments at 13 weeks
• Willingness to submit to Urine Toxicology screenings

You may not qualify if:

• Lifetime diagnosis of a psychotic disorder, not induced by drug use
• Current treatment with opioids or benzodiazepines, which may affect new learning
• Involvement in a legal case that may lead to incarceration during the study period
• Residential plans that would interfere with participation
• Medical illness that may significantly compromise cognition (e.g., Parkinson's, Alzheimer's, Huntington's chorea, moderate or greater TBI)
• An uncorrected sensory impairment (hearing or sight) that would seriously interfere with cognitive training
• Pre-morbid intelligence quotient (IQ) estimate below 70
• Unstable housing or lack of commitment to staying within a geographic area that would make follow-up unlikely
• Unwillingness to provide contact information of someone who can help study staff contact the subjects in the event that study staff are unable to maintain contact directly
• Allergy to donepezil
• Unstable cardiovascular disease or unstable medical condition-clinically determined by a physician
• Imminent suicidal or homicidal risk
• Pregnant or nursing women, positive pregnancy test, or inadequate birth control methods in women of childbearing potential

Sponsors & Collaborators

• VA Connecticut Healthcare System: lead
• Yale University: collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

RECRUITING

Related Publications (1)

• Yoon G, Sofuoglu M, Petrakis IL, Pittman B, Bell MD. The combination of donepezil and cognitive training for improving treatment outcomes for alcohol use disorder: Design of a randomized controlled trial. Contemp Clin Trials. 2024 Oct;145:107657. doi: 10.1016/j.cct.2024.107657. Epub 2024 Aug 5.

  PMID: 39111388 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• Gihyun Yoon, MD

  Yale University, VA Connecticut Healthcare System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gihyun Yoon, MD

CONTACT

203-932-5711; gihyun.yoon@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: September 13, 2021
• Study Start: August 8, 2022
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)