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

Mild Cognitive Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04318639
• Other study ID #: MB0020
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 17, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: March 2020
• Source: VA Connecticut Healthcare System
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• Cognitive Dysfunction
• Disease
• Mild Cognitive Impairment

Intervention

Combination Product:
• Donepazil
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.

Locations

Country	Name	City	State
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
VA Connecticut Healthcare System

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Feasibility and Acceptability of Interventions	Adverse events	13 weeks
Other	Adherence to Donepezil	Percentage of Donepezil compliance based on weekly pill counts	13 weeks
Other	Adherence to CRT	Percentage of training sessions completed out of 65 possible sessions	13 weeks
Primary	Clinical Global Index of AUD recovery	7-point likert scale of recovery	13 weeks
Primary	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