Donepezil and Cognitive Training for Alcohol Use Disorder (AUD)

The Combination of Donepezil and Cognitive Training for Treating Alcohol Use Disorder

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.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Combination product: Donepezil + Cognitive remediation therapy (CRT); Combination product: Donepezil + Placebo CRT; Combination product: Placebo medication + Cognitive remediation therapy (CRT); Combination product: Placebo medication + Placebo CRT

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gihyun Yoon, MD; Phone Number: 7421 203-932-5711; Email: gihyun.yoon@yale.edu

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Recruiting
      • VA Connecticut Healthcare System
      • Contact: Gihyun Yoon, MD; Phone Number: 7421 203-932-5711; Email: gihyun.yoon@yale.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Combination product: 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.
Experimental: 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.	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.
Experimental: 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.	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.
Experimental: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heavy drinking days	Heavy drinking days as measured by weekly Time Line Follow Back (TLFB)	13 weeks of active intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global neurocognitive functioning	Global neurocognitive functioning on a global index of neurocognitive function	At 7 weeks and at 13 weeks

Collaborators and Investigators

• Sponsor: VA Connecticut Healthcare System
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); Yale University
• Investigators: Principal Investigator: Gihyun Yoon, MD, Yale University, VA Connecticut Healthcare System

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2022
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: September 3, 2021
• First Submitted That Met QC Criteria: September 3, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: GY0010; 5R01AA029075 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No