Clinical trial NCT04318639: The Combination of Donepezil and Cognitive Training for Treating Alcohol Use Disorder
Official title: The Combination of Donepezil and Cognitive Training for Treating Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Alcohol Use Disorder
Mild Cognitive Impairment
Keywords: Alcohol Use Disorder
Mild Cognitive Impairment
Cognitive Remediation Therapy
Donepezil
Recovery
Lead sponsor: VA Connecticut Healthcare System
Sponsor class: FED
First posted: 2020-03-24
Enrollment: 15
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label single group design
Primary purpose: TREATMENT

Brief summary: This is an open label feasibility trial to learn whether the combination of donepezil and cognitive remediation therapy (Donepezil + CRT) may improve neurocognitive functioning and decreasing alcohol use in Veterans with alcohol use disorder who have mild cognitive impairment (AUD-MCI). The study will determine the acceptability and adherence to treatment and preliminary evidence for efficacy. The study will recruit 15 newly recovering Veterans individuals with AUD-MCI for a 13-week, open-label, single-arm pilot study with sobriety and cognitive assessments at baseline and at 13-week follow-up.

Detailed description: Donepezil is FDA approved for treatment of dementia and recent animal studies have suggested that it may reduce craving in rat models of alcohol use disorder. Investigators' previous studies of cognitive remediation therapy (CRT) with work therapy have shown efficacy with newly recovering Veterans with AUD compared with work therapy alone. The current study combines Donepezil and CRT in an open-label trial to learn whether the combination of Donepezil + CRT may improve neurocognitive functioning and decrease alcohol use in Veterans with alcohol use disorder who have mild cognitive impairment (AUD-MCI). The study will determine the acceptability and adherence to treatment and provide preliminary evidence for efficacy. The study will recruit 15 newly recovering Veterans individuals with AUD-MCI for a 13-week, open-label, single-arm pilot study with sobriety and cognitive assessments at baseline and at 13-week follow-up. Primary outcome variables will be a Clinical Global Index of AUD recovery and a Global Cognitive Composite of MCI related neurocognitive assessment.

Eligibility criteria: Inclusion Criteria:

* Males and females 21-80 years of age
* Fluency in English and a 6th grade or higher reading level
* Meets DSM-V criteria for a current Alcohol Use Disorder
* Referred for the study within 30 days of detoxification or last substance use according to medical records
* Willingness to attend follow-up assessments at 13 weeks
* Willingness to submit to Breathalyzer screenings and Urine Toxicology screenings.
* Meets MCI criteria with greater than 1.5 SD below pre-morbid IQ estimate or 1.5 SD below standard norms on at least 1 key neurocognitive MCI related variable (Learning and Memory, Delayed Recall, Executive Function, Working Memory).

Exclusion Criteria:

* Lifetime diagnosis of a psychotic disorder, not induced by drug use.
* Current prescribed treatment of opioids or benzodiazepines, which may affect new learning Involvement in a legal case that may lead to incarceration during 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 IQ estimate below 70.
* Unstable housing or lack of commitment to staying within a geographic area that would make follow-up possible.
* Unwillingness to provide contact information of someone who can help study staff contact the participant 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.

Primary outcomes:
measure: Clinical Global Index of AUD recovery
timeFrame: 13 weeks
measure: Global Composite T-Score of MCI related neurocognitive measures.
timeFrame: 13-week
Secondary outcomes:
Other outcomes:
measure: Feasibility and Acceptability of Interventions
timeFrame: 13 weeks
measure: Adherence to Donepezil
timeFrame: 13 weeks
measure: Adherence to CRT
timeFrame: 13 weeks
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
Study officials:
affiliation: VA Connecticut Healthcare System
name: Morris Bell
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mulholland PJ, Teppen TL, Miller KM, Sexton HG, Pandey SC, Swartzwelder HS. Donepezil Reverses Dendritic Spine Morphology Adaptations and Fmr1 Epigenetic Modifications in Hippocampus of Adult Rats After Adolescent Alcohol Exposure. Alcohol Clin Exp Res. 2018 Apr;42(4):706-717. doi: 10.1111/acer.13599. Epub 2018 Feb 15.
citation: Bell MD, Laws H, Pittman B, Johannesen JK. Comparison of focused cognitive training and portable "brain-games" on functional outcomes for vocational rehabilitation participants. Sci Rep. 2018 Jan 29;8(1):1779. doi: 10.1038/s41598-018-20094-w.