Donepezil and Cognitive Training for Alcohol Use Disorder (AUD)

NCT ID: NCT05042102

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-08
• Study Completion Date: 2027-05-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Donepezil + Cognitive remediation therapy (CRT)

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.

Group Type: EXPERIMENTAL

Donepezil + Cognitive remediation therapy (CRT)

Intervention Type: 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 + Placebo CRT

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.

Group Type: EXPERIMENTAL

Donepezil + Placebo CRT

Intervention Type: 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.

Placebo medication + Cognitive remediation therapy (CRT)

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.

Group Type: EXPERIMENTAL

Placebo medication + Cognitive remediation therapy (CRT)

Intervention Type: 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 + Placebo CRT

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.

Group Type: EXPERIMENTAL

Placebo medication + Placebo CRT

Intervention Type: 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.

Interventions

Donepezil + Cognitive remediation therapy (CRT)

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.

Intervention Type: COMBINATION_PRODUCT

Donepezil + Placebo CRT

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.

Intervention Type: COMBINATION_PRODUCT

Placebo medication + Cognitive remediation therapy (CRT)

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.

Intervention Type: COMBINATION_PRODUCT

Placebo medication + Placebo CRT

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.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

1. Males and females 18-80 years of age

2. Fluency in English and a 6th grade or higher reading level

3. 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)

4. Last alcohol use and at least one heavy drinking day within the past 30 days

5. Willingness to attend follow-up assessments at 13 weeks

6. Willingness to submit to Urine Toxicology screenings

Exclusion Criteria

1. Lifetime diagnosis of a psychotic disorder, not induced by drug use

2. Current treatment with opioids or benzodiazepines, which may affect new learning

3. Involvement in a legal case that may lead to incarceration during the study period

4. Residential plans that would interfere with participation

5. Medical illness that may significantly compromise cognition (e.g., Parkinson's, Alzheimer's, Huntington's chorea, moderate or greater TBI)

6. An uncorrected sensory impairment (hearing or sight) that would seriously interfere with cognitive training

7. Pre-morbid intelligence quotient (IQ) estimate below 70

8. Unstable housing or lack of commitment to staying within a geographic area that would make follow-up unlikely

9. 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

10. Allergy to donepezil

11. Unstable cardiovascular disease or unstable medical condition-clinically determined by a physician

12. Imminent suicidal or homicidal risk

13. Pregnant or nursing women, positive pregnancy test, or inadequate birth control methods in women of childbearing potential

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

VA Connecticut Healthcare System

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gihyun Yoon, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University, VA Connecticut Healthcare System

Locations

VA Connecticut Healthcare System

West Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Gihyun Yoon, MD

Role: CONTACT

gihyun.yoon@yale.edu

203-932-5711 ext. 7421

Facility Contacts

Gihyun Yoon, MD

Role: primary

gihyun.yoon@yale.edu

203-932-5711 ext. 7421

References

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.

Reference Type: DERIVED

PMID: 39111388 (View on PubMed)

Other Identifiers

5R01AA029075

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GY0010

Identifier Type: -

Identifier Source: org_study_id