Alcohol Use Disorder Cognitive Decline
Conditions
Keywords
AUD, Neuropsychology, Cognitive Remediation
Brief summary
Alcohol Use Disorders (AUDs) have a significant public health impact and are highly prevalent in Veterans. Alcohol related brain effects on neurocognition (attention, memory and executive function) reduce ability to benefit from current treatments. These cognitive impairments are especially common in the early phase of recovery, persist over years and get worse with age. Recent research suggests that cognitive remediation therapy (CRT) may improve attention, memory and executive function in other disorders, and the investigators just completed pilot study with AUD Veterans found significantly greater improvements for those receiving CRT. The proposed study examines AUD outcomes and neurocognitive improvements when CRT is combined with a standardized alcohol treatment. The investigators hypothesize that CRT will improve neurocognition and AUD outcomes more than standardized alcohol treatment alone. Findings will determine whether CRT augmentation can benefit Veterans with AUDs.
Detailed description
This study aims to determine whether a combined intervention of cognitive remediation therapy (CRT) and Individual Drug Counseling (IDC) can benefit older Veterans in the initial phase of alcohol abuse treatment by improving abstinence outcomes and neurocognition. Substantial cognitive impairment is associated with alcohol use disorders (AUD), and becomes worse with years of use and the aging processes. In particular, Veterans entering treatment for AUD display cognitive deficits that may reduce their ability to benefit from treatment. While there is considerable variety in the severity and types of cognitive impairment found in newly recovering patients, problems with attention, learning and memory and executive function are common. Since treatment requires that the individual be able to sustain attention, remember what is learned, and apply it to recovery, impaired underlying cognitive processes make successful treatment less likely. Moreover, problems with executive functioning and other pre-frontal cognitive processes have been associated with decreased treatment retention and poorer AUD treatment outcomes. Although cognition can improve with sustained abstinence, it is during the early phase of recovery, when cognition is most impaired, that patients receive the most intensive treatment. AUD is a major cause of suffering and functional disability for older Veterans and a common co-morbidity with other physical and mental disorders. Finding more effective treatments of AUD remains a priority for VA healthcare. The purpose of the proposed study is to learn whether CRT plus IDC, an evidence-based outpatient AUD treatment is more effective than a Game-Play Placebo plus IDC. Game-Play Placebo has been used to provide equipoise between conditions in other CRT studies and in a current CRT study with mTBI Veterans funded by DoD being conducted by the PI. The current study is a randomized controlled trial (RCT) with a target enrollment of 90 Veterans in the initial phase of AUD treatment. The study is sufficiently powered to allow us to fulfill the following aims and test their related hypotheses: Specific Primary Aim # 1: To determine if CRT+IDC is more effective than Game-Play Placebo +IDC in decreasing alcohol use in older Veterans during the 3 month active intervention period. Ho1: CRT+IDC will be more effective than Game-Play Placebo+IDC in reducing heavy drinking days and decreasing days of use as measured by Breathalyzer and Timeline Follow-back Method (TLFB) during the 90 days of active intervention. Secondary Aim #1: To determine if CRT+IDC is more effective than Game-Play Placebo+ IDC in sustaining decreased alcohol use in older Veterans at the end of 6 months (3 months after the active intervention period). Ho2: CRT+IDC will be more effective than Game-Play Placebo+IDC in reducing heavy drinking days and decreasing days of use as measured by Breathalyzer and Timeline Follow-back Method (TLFB) for the 30 days preceding 6 month follow-up. Secondary Aim #2: To determine if the combination of CRT and IDC is more effective than game play placebo and IDC in improving neurocognitive functioning. Ho3: Veterans receiving CRT+IDC will show greater improvement than Veterans receiving Game-Play Placebo+IDC at 3 month follow-up on a global index of neurocognitive function, and on an index of working memory and an index of executive function. Ho4: Differential improvements in neurocognitive function will be sustained at 6 month follow-up.
Interventions
Up to 65 hours of computer based cognitive training of attention, verbal and visual memory, verbal and visual working memory, and executive functions
Sponsors
Study design
Eligibility
Inclusion criteria
* Veterans enrolled in VA AUD treatment as usual and Non-Veteran community members in AUD treatment * Have a primary diagnosis of AUD and are within 30 days of detoxification or last use at time of recruitment
Exclusion criteria
* Other medical illnesses that compromise neurocognition * Active use of prescribed opioids or benzodiazepines that may hinder new learning * Commitment to complete active phase and attend follow-up * No pending incarceration or plans to leave the state
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Days of Heavy Alcohol Use Assessed by Weekly Time Line Follow-back and Breathalyzer | 3 months of active treatment | Heavy alcohol use over 90 days as verified by Time Line Follow-back or breathalyzer findings. Minimum = 0. Maximum = 90. Fewer days is better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days of Heavy Alcohol Use Assessed by Weekly Time Line Follow-back and Breathalyzer | 30 days preceding 6 month follow-up, 3 months after active treatment. | Days of heavy drinking days over 30 days adjusted for baseline 30 Day heavy drinking days prior to randomization. Minimum = 0. Maximum = 30. Fewer days is better. |
| Penn Alcohol Craving Scale | 6 month follow-up | Changes in self-ratings of alcohol craving from baseline to 6 months. Minimum score = 0. Maximum score = 30. Lower is better. |
| Neurocognitive Composite Score (Average of T-scores for Measures of Attention, Processing Speed, Memory, Delayed Recall, Executive Function) | Baseline to 6 months | Changes from baseline on Neurocognitive Composite Score Minimum score = 30; Mean = 50 indicates the population mean with a standard deviation of 10; Maximum score = 70. Higher is better. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CRT+IDC Cognitive Remediation Therapy for 13 weeks plus Individual Drug Counseling
Cognitive Remediation Training: Up to 65 hours of computer based cognitive training of attention, verbal and visual memory, verbal and visual working memory, and executive functions | 29 |
| Computer Game Play+IDC Computer arcade games for 13 weeks plus Individual Drug Counseling
Cognitive Remediation Training: Up to 65 hours of computer based cognitive training of attention, verbal and visual memory, verbal and visual working memory, and executive functions | 30 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 13 Week | Lost to Follow-up | 7 | 14 |
| 13 Week | Withdrawal by Subject | 1 | 0 |
| 26 Week | Lost to Follow-up | 5 | 4 |
Baseline characteristics
| Characteristic | Computer Game Play+IDC | CRT+IDC | Total |
|---|---|---|---|
| Age, Continuous | 54.60 years STANDARD_DEVIATION 10.07 | 56.79 years STANDARD_DEVIATION 9.41 | 55.68 years STANDARD_DEVIATION 9.73 |
| Alcohol Use Days in Last 30 Days | 3.07 Days STANDARD_DEVIATION 4.93 | 5.25 Days STANDARD_DEVIATION 7.87 | 4.14 Days STANDARD_DEVIATION 6.57 |
| Alcohol Use Days in Last 90 Days | 32.24 Days STANDARD_DEVIATION 23.92 | 39.39 Days STANDARD_DEVIATION 27.13 | 35.75 Days STANDARD_DEVIATION 25.57 |
| Education (years) | 13.27 years STANDARD_DEVIATION 1.95 | 13.31 years STANDARD_DEVIATION 1.76 | 13.29 years STANDARD_DEVIATION 1.84 |
| Lifetime Months of Alcohol Use | 436.71 Months STANDARD_DEVIATION 141.51 | 474.07 Months STANDARD_DEVIATION 190 | 455.39 Months STANDARD_DEVIATION 165.76 |
| Overall Neurocognitive Composite Score | 44.3 T Scores STANDARD_DEVIATION 6.4 | 45.6 T Scores STANDARD_DEVIATION 4.8 | 44.95 T Scores STANDARD_DEVIATION 5.6 |
| Polysubstance Use Days in the Last 30 Days | .42 Days STANDARD_DEVIATION 1.41 | .73 Days STANDARD_DEVIATION 2.6 | .57 Days STANDARD_DEVIATION 2.05 |
| Polysubstance Use Days in the Last 90 Days | 6.79 Days STANDARD_DEVIATION 18.31 | 6.22 Days STANDARD_DEVIATION 16.47 | 6.51 Days STANDARD_DEVIATION 17.39 |
| Premorbid IQ Estimate (WTAR) | 98.93 units on a scale STANDARD_DEVIATION 13.3 | 100.28 units on a scale STANDARD_DEVIATION 12.6 | 99.61 units on a scale STANDARD_DEVIATION 12.95 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 10 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 18 Participants | 19 Participants | 37 Participants |
| Region of Enrollment United States | 30 Participants | 29 Participants | 59 Participants |
| Service Connected Disability (Yes) | 9 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 29 Participants | 25 Participants | 54 Participants |
| Social Security Disability Income (Yes) | 6 Participants | 10 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 30 |
| other Total, other adverse events | 0 / 29 | 1 / 30 |
| serious Total, serious adverse events | 0 / 29 | 0 / 30 |
Outcome results
Days of Heavy Alcohol Use Assessed by Weekly Time Line Follow-back and Breathalyzer
Heavy alcohol use over 90 days as verified by Time Line Follow-back or breathalyzer findings. Minimum = 0. Maximum = 90. Fewer days is better.
Time frame: 3 months of active treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT+IDC | Days of Heavy Alcohol Use Assessed by Weekly Time Line Follow-back and Breathalyzer | 5.49 Days | Standard Deviation 10.85 |
| Computer Game Play+IDC | Days of Heavy Alcohol Use Assessed by Weekly Time Line Follow-back and Breathalyzer | 3.0 Days | Standard Deviation 5.89 |
Days of Heavy Alcohol Use Assessed by Weekly Time Line Follow-back and Breathalyzer
Days of heavy drinking days over 30 days adjusted for baseline 30 Day heavy drinking days prior to randomization. Minimum = 0. Maximum = 30. Fewer days is better.
Time frame: 30 days preceding 6 month follow-up, 3 months after active treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CRT+IDC | Days of Heavy Alcohol Use Assessed by Weekly Time Line Follow-back and Breathalyzer | 1.67 units on a scale (Number of Days) | Standard Error 1.21 |
| Computer Game Play+IDC | Days of Heavy Alcohol Use Assessed by Weekly Time Line Follow-back and Breathalyzer | 1.51 units on a scale (Number of Days) | Standard Error 1.11 |
Neurocognitive Composite Score (Average of T-scores for Measures of Attention, Processing Speed, Memory, Delayed Recall, Executive Function)
Changes from baseline on Neurocognitive Composite Score Minimum score = 30; Mean = 50 indicates the population mean with a standard deviation of 10; Maximum score = 70. Higher is better.
Time frame: Baseline to 6 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CRT+IDC | Neurocognitive Composite Score (Average of T-scores for Measures of Attention, Processing Speed, Memory, Delayed Recall, Executive Function) | 48.15 score on a scale (T scores) | Standard Error 1.08 |
| Computer Game Play+IDC | Neurocognitive Composite Score (Average of T-scores for Measures of Attention, Processing Speed, Memory, Delayed Recall, Executive Function) | 46.70 score on a scale (T scores) | Standard Error 1.08 |
Penn Alcohol Craving Scale
Changes in self-ratings of alcohol craving from baseline to 6 months. Minimum score = 0. Maximum score = 30. Lower is better.
Time frame: 6 month follow-up
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CRT+IDC | Penn Alcohol Craving Scale | 3.94 score on a scale | Standard Error 1.45 |
| Computer Game Play+IDC | Penn Alcohol Craving Scale | 4.59 score on a scale | Standard Error 1.68 |
Clinical Global Index at 6 Months
Clinical Global Index Scale (1 to 7) with 1 being full recovery and total abstinence. Scores 3 and below represent good recovery. Lower scores are better.
Time frame: 6 months after randomization
Population: Data was extracted from VA medical records and there were many participants who did not have sufficient information in their chart
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CRT+IDC | Clinical Global Index at 6 Months | 3.00 units on a scale | Standard Error 1.91 |
| Computer Game Play+IDC | Clinical Global Index at 6 Months | 3.28 units on a scale | Standard Error 2.35 |