Donepezil and Cognitive Training for Alcohol Use Disorder (AUD)

Study Overview
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Brief Summary
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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.

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

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 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 Exclusion criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donepezil + Cognitive remediation therapy (CRT)<br>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)<br>* 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.<br>|
| Experimental: Donepezil + Placebo CRT<br>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<br>* 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.<br>|
| Experimental: Placebo medication + Cognitive remediation therapy (CRT)<br>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)<br>* 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.<br>|
| Experimental: Placebo medication + Placebo CRT<br>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<br>* 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.<br>|

What is the study measuring?
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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 |