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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Donepazil+CRT | Experimental | Donepazil+CRT |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Donepazil | Combination Product | Donepezil: Subjects will take 5 mg/day of donepezil in the evening for first 4 weeks, then 10 mg/day of donepezil in the evening until week 13. Cognitive remediation therapy (CRT): This study employs a computerized program (BrainHQ) for cognitive enhancement. Participants use their program for one hour per session, up to five sessions per week, over 13 weeks (maximum of 65 sessions). They may training on site or at another quiet location of their choice. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Global Index of AUD recovery | 7-point likert scale of recovery | 13 weeks |
| Global Composite T-Score of MCI related neurocognitive measures. | Measures of Learning and memory, delayed recall, working memory and executive. Higher scores indicate better functioning | 13-week |
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| Measure | Description | Time Frame |
|---|---|---|
| Feasibility and Acceptability of Interventions | Adverse events | 13 weeks |
| Adherence to Donepezil | Percentage of Donepezil compliance based on weekly pill counts |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Morris Bell | VA Connecticut Healthcare System | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Connecticut Healthcare System | West Haven | Connecticut | 06516 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29336496 | Result | 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. | |
| 29379114 | Result |
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Only those already identified in HIPAA
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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Open-label single group design
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| 13 weeks |
| Adherence to CRT | Percentage of training sessions completed out of 65 possible sessions | 13 weeks |
| 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. |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |