The Combination of Donepezil and Cognitive Training for Treating Alcohol Use Disorder
Primary Purpose
Alcohol Use Disorder, Mild Cognitive Impairment
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Donepazil
Sponsored by
About this trial
This is an interventional treatment trial for Alcohol Use Disorder focused on measuring Alcohol Use Disorder, Mild Cognitive Impairment, Cognitive Remediation Therapy, Donepezil, Recovery
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.
Sites / Locations
- VA Connecticut Healthcare System
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Donepazil+CRT
Arm Description
Donepazil+CRT
Outcomes
Primary Outcome Measures
Clinical Global Index of AUD recovery
7-point likert scale of recovery
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
Secondary Outcome Measures
Full Information
NCT ID
NCT04318639
First Posted
March 16, 2020
Last Updated
March 19, 2020
Sponsor
VA Connecticut Healthcare System
1. Study Identification
Unique Protocol Identification Number
NCT04318639
Brief Title
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
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
August 17, 2018 (Actual)
Primary Completion Date
December 31, 2019 (Actual)
Study Completion Date
December 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
VA Connecticut Healthcare System
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorder, Mild Cognitive Impairment
Keywords
Alcohol Use Disorder, Mild Cognitive Impairment, Cognitive Remediation Therapy, Donepezil, Recovery
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Open-label single group design
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Donepazil+CRT
Arm Type
Experimental
Arm Description
Donepazil+CRT
Intervention Type
Combination Product
Intervention Name(s)
Donepazil
Other Intervention Name(s)
Cognitive Remediation Therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Clinical Global Index of AUD recovery
Description
7-point likert scale of recovery
Time Frame
13 weeks
Title
Global Composite T-Score of MCI related neurocognitive measures.
Description
Measures of Learning and memory, delayed recall, working memory and executive. Higher scores indicate better functioning
Time Frame
13-week
Other Pre-specified Outcome Measures:
Title
Feasibility and Acceptability of Interventions
Description
Adverse events
Time Frame
13 weeks
Title
Adherence to Donepezil
Description
Percentage of Donepezil compliance based on weekly pill counts
Time Frame
13 weeks
Title
Adherence to CRT
Description
Percentage of training sessions completed out of 65 possible sessions
Time Frame
13 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morris Bell
Organizational Affiliation
VA Connecticut Healthcare System
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Connecticut Healthcare System
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Only those already identified in HIPAA
Citations:
PubMed Identifier
29336496
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.
Results Reference
result
PubMed Identifier
29379114
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.
Results Reference
result
Learn more about this trial
The Combination of Donepezil and Cognitive Training for Treating Alcohol Use Disorder
We'll reach out to this number within 24 hrs