Cognitive Impairment, Substance Abuse, Substance Dependence
Conditions
Keywords
Substance Abuse, Substance Dependence, Cognitive Impairment
Brief summary
The initial phase of substance abuse treatment is a vulnerable period for relapse. Cognitive impairments are common during this phase and may reduce the ability to benefit from other forms of substance abuse and rehabilitation services. The study compares a rehabilitation program that combines work therapy with computer-based cognitive training of attention, memory and executive functions to work therapy alone in a 3 months outpatient substance abuse program. It is hypothesized that cognitive training will increase days of sobriety during the active intervention and better substance abuse outcomes at 6 month follow-up.
Detailed description
This proposal aims to pilot test a cognitive remediation therapy (CRT) combined with work therapy (WT) as an adjunct to the initial phase of outpatient substance abuse treatment. There is ample research evidence of cognitive impairment across substance abuse disorders, particularly in the early phase of recovery. Cognitive impairment has been associated with poorer substance abuse treatment outcomes and may be remediated through programs of exercises that target these impairments. The investigators have previously reported on a model of providing CRT with work therapy (WT) in an outpatient context for people with psychotic disorders, which showed significant improvements in executive function and working memory, and in important functional outcomes such as work performance and sustained work activity. The investigators propose to apply this same approach to a sample of participants recruited from a 30-day residential program for substance abusers who are beginning their recovery. When they are discharged, they will be able to continue WT, which may encourage their engagement in CRT and in substance abuse outpatient services. Our Specific Aims are: 1. Test the feasibility and tolerability of CRT & WT in the early phase of substance abuse treatment. 2. Obtain effect size for CRT & WT compared to WT alone on a primary substance abuse outcome measure (Days of Use) for a future R01 RCT submission. 3. Obtain effect sizes for secondary outcomes (e.g. neurocognition). The investigators propose to accomplish these aims by randomizing 50 participants who wish to receive WT services into two conditions: 25 will be assigned to 15 hours of WT plus 5 hours of CRT each week (CRT+WT) and 25 will be assigned to an active control of 20 hours of WT. The active intervention will be for 13 weeks. CRT will be comprised of a repetitive training on a hierarchy of progressive visual and auditory exercise from Positscience. WT will involve paid work activity in a placement of their choosing on the medical center campus. Participants will be paid the same hourly rate (half federal minimum wage) for their time in CRT and WT. Comprehensive assessments will be performed at intake, 3 months and 6 months. These will include substance abuse, cognitive, and psychosocial outcomes as well as adherence to treatment. During the 3 months of active intervention participants will have weekly observed urine toxicology screens, breathalyzer tests and PDA assessments, as well as monthly work performance evaluations. Data analyses will include random effects regression models, as well as models of moderator and mediator effects on the primary outcome of PDA. If meaningful effects are found, these results will guide a subsequent R01 submission.
Interventions
BEHAVIORALCognitive Training + Work Therapy
Cognitive training for 5 hours per week for 13 weeks and 15 hours of work therapy
BEHAVIORALWork Therapy
20 hours per week of work therapy
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* In the initial phase of treatment for substance abuse or dependence at VACHS. * Fluency in English 6th grade or higher reading level DSM-IV criteria for any current drug use disorder * Willingness to attend follow-up assessments at 13 and 26 weeks * Willingness to submit to observed urine toxicology and breathalyzer screenings
Exclusion criteria
* Untreated psychotic disorder * Current prescribed treatment of opioids or benzodiazepines * Having a legal case that may lead to incarceration during study period * Residential plans that would interfere with participation * Developmental disability or medical illness that may significantly compromise cognition or prevent work activity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Days of Sobriety in First 90 Days | 3 months | Abstinence will be determined by toxicology screening, breathalyzer and substance abuse calendar weekly during 3 months of active intervention. Days of sobriety has a range of 0 to 90 with higher being a better outcome. |
| Days of Use in Prior 30 Days | 30 Days Prior to 6 month follow-up | Days of Use based on Time-Line Follow-back, Toxicology Screen, Breathalyzer, and Chart Review. The range at 6 month follow-up is 0 to 30 days of use with more days being a worse outcome. |
| Weeks of Sobriety | 26 weeks | 0 to 26 Weeks. Higher number of Weeks is better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Verbal and Visual Working Memory | Baseline, 3 Month, 6 Months | WAIS Digit Span and Wechsler Memory Scale (WMS) Spatial Span. T Scores are averaged. T Scores range from 30 to 80 with a mean of 50. Higher scores are better. |
| Attention Index | Baseline, 3 month and 6 month follow-up | Index comprised on Trails A and Continuous Performance Test. T scores for the assessments are averaged. T scores range from 30 to 80 with a mean of 50. Higher scores are better. |
| Global Index | Baseline, 3 Months, 6 Months | Comprised of the average of 5 Index T Scores (Attention, Processing Speed, Visual and Verbal Memory and Learning, Working Memory and Executive Function). T Scores range from 30 to 80 with a mean of 50. Higher scores are better. |
| Executive Function | Baseline, 3 Months, 6 Months | Mazes, Wisconsin Card Sorting Task (WCST) Perseverative Error, Non-Perseverative Error, Conceptual Level. T Scores for each variable were averaged together. T Scores have a range of 30 to 80 with a mean of 50. Higher scores are better. |
| Processing Speed Index | Baseline, 3 Months, 6 Months | Wechsler Adult Intelligence Scale (WAIS) Digit Coding and Symbol Search. T scores for the assessments are averaged. T scores range from 30 to 80 with a mean of 50. Higher scores are better. |
| Verbal and Visual Learning and Memory | Baseline, 3 Months, 6 Months | Brief Visual-Spatial Memory Test (BVMT) and Hopkins Verbal Learning and Memory Test (HVLT). Total Score T Scores for tests were averaged. T score range is 30 to 80 with a mean of 50. Higher scores are better. |
Countries
United States
Participant flow
Recruitment details
Recruitment was by referral from clinicians at VA Substance Abuse program including a 21 day substance abuse day program and a 30 day residential program. Recruitment began in January 2011 and was completed in March 2014.
Pre-assignment details
Following informed consent, participants completed baseline assessments and their VA medical record was reviewed to determine whether they met inclusion/exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Cognitive Training + Work Therapy Cognitive Training using auditory and visual Positscience software 5 hours/per week for 13 weeks.
Work Therapy for 15 hours per week at half minimum wage doing entry level duties at medical center job sites, supervised by regular medical center staff.
Cognitive Training + Work Therapy: Cognitive training for 5 hours per week for 13 weeks and 15 hours of work therapy | 24 |
| Work Therapy Only Same work therapy but for 20 hours per week.
Work Therapy: 20 hours per week of work therapy | 24 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Cognitive Training + Work Therapy | Work Therapy Only | Total |
|---|---|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 9.7 | 53.8 years STANDARD_DEVIATION 7.4 | 52.55 years STANDARD_DEVIATION 8.55 |
| Axis 1 Primary Diagnosis Alcohol Use Disorder | 13 participants | 15 participants | 28 participants |
| Axis 1 Primary Diagnosis Cocaine | 3 participants | 7 participants | 10 participants |
| Axis 1 Primary Diagnosis Opiods | 6 participants | 0 participants | 6 participants |
| Axis 1 Primary Diagnosis Other | 2 participants | 2 participants | 4 participants |
| Disability (SSDI or VA Service Connected) No | 22 participants | 21 participants | 43 participants |
| Disability (SSDI or VA Service Connected) Yes | 2 participants | 3 participants | 5 participants |
| Education | 13.2 years STANDARD_DEVIATION 1.6 | 12.21 years STANDARD_DEVIATION 1.5 | 12.71 years STANDARD_DEVIATION 1.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 24 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Felony Convictions No | 13 participants | 12 participants | 25 participants |
| Felony Convictions Yes | 11 participants | 12 participants | 23 participants |
| Global Assessment of Function (GAF) | 45.17 units on a scale STANDARD_DEVIATION 3.6 | 47.67 units on a scale STANDARD_DEVIATION 5.9 | 46.42 units on a scale STANDARD_DEVIATION 4.75 |
| Marital Status Divorced/Widowed | 16 participants | 10 participants | 26 participants |
| Marital Status Married | 3 participants | 6 participants | 9 participants |
| Marital Status Never Married | 5 participants | 8 participants | 13 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 13 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 22 Participants | 23 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Days of Sobriety in First 90 Days
Abstinence will be determined by toxicology screening, breathalyzer and substance abuse calendar weekly during 3 months of active intervention. Days of sobriety has a range of 0 to 90 with higher being a better outcome.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Training + Work Therapy | Days of Sobriety in First 90 Days | 87.3 Days of Sobriety | Standard Deviation 7.8 |
| Work Therapy Only | Days of Sobriety in First 90 Days | 84.64 Days of Sobriety | Standard Deviation 18.2 |
Comparison: t-test for equality of meansp-value: 0.5595% CI: [-11.57, 6.25]t-test, 2 sided
Primary
Days of Use in Prior 30 Days
Days of Use based on Time-Line Follow-back, Toxicology Screen, Breathalyzer, and Chart Review. The range at 6 month follow-up is 0 to 30 days of use with more days being a worse outcome.
Time frame: 30 Days Prior to 6 month follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Training + Work Therapy | Days of Use in Prior 30 Days | 4.35 Days of Use | Standard Deviation 9.44 |
| Work Therapy Only | Days of Use in Prior 30 Days | 1.86 Days of Use | Standard Deviation 5.96 |
p-value: <0.3195% CI: [-7.36, 2.39]t-test, 2 sided
Primary
Weeks of Sobriety
0 to 26 Weeks. Higher number of Weeks is better.
Time frame: 26 weeks
Population: 1 additional participant in Work Therapy Only had missing data for this variable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Training + Work Therapy | Weeks of Sobriety | 23.80 Weeks | Standard Deviation 2.8 |
| Work Therapy Only | Weeks of Sobriety | 23.95 Weeks | Standard Deviation 3.25 |
p-value: 0.8795% CI: [-1.77, 2.08]t-test, 2 sided
Secondary
Attention Index
Index comprised on Trails A and Continuous Performance Test. T scores for the assessments are averaged. T scores range from 30 to 80 with a mean of 50. Higher scores are better.
Time frame: Baseline, 3 month and 6 month follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Training + Work Therapy | Attention Index | Baseline | 48.08 T Scores | Standard Deviation 8.26 |
| Cognitive Training + Work Therapy | Attention Index | 3 Month | 48.17 T Scores | Standard Deviation 8.74 |
| Cognitive Training + Work Therapy | Attention Index | 6 Month | 50.36 T Scores | Standard Deviation 10.14 |
| Work Therapy Only | Attention Index | Baseline | 41.79 T Scores | Standard Deviation 8.87 |
| Work Therapy Only | Attention Index | 3 Month | 43.19 T Scores | Standard Deviation 9.54 |
| Work Therapy Only | Attention Index | 6 Month | 43.55 T Scores | Standard Deviation 10.24 |
Comparison: F Test (df = 1,39.32), Type III Fixed Effects for Time X Conditionp-value: 0.8695% CI: [-1.73, 2.05]Mixed Models Analysis
Secondary
Executive Function
Mazes, Wisconsin Card Sorting Task (WCST) Perseverative Error, Non-Perseverative Error, Conceptual Level. T Scores for each variable were averaged together. T Scores have a range of 30 to 80 with a mean of 50. Higher scores are better.
Time frame: Baseline, 3 Months, 6 Months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Training + Work Therapy | Executive Function | Baseline | 45.11 T Scores | Standard Deviation 6.75 |
| Cognitive Training + Work Therapy | Executive Function | 3 Month | 48.8 T Scores | Standard Deviation 8.4 |
| Cognitive Training + Work Therapy | Executive Function | 6 Month | 49.53 T Scores | Standard Deviation 9.8 |
| Work Therapy Only | Executive Function | Baseline | 42.59 T Scores | Standard Deviation 7.72 |
| Work Therapy Only | Executive Function | 3 Month | 43.26 T Scores | Standard Deviation 8.7 |
| Work Therapy Only | Executive Function | 6 Month | 43.8 T Scores | Standard Deviation 8.3 |
Comparison: Type III Fixed Effects Time X Condition F Test (df = 1,37.8)p-value: 0.0395% CI: [0.169, 3.93]Mixed Models Analysis
Secondary
Global Index
Comprised of the average of 5 Index T Scores (Attention, Processing Speed, Visual and Verbal Memory and Learning, Working Memory and Executive Function). T Scores range from 30 to 80 with a mean of 50. Higher scores are better.
Time frame: Baseline, 3 Months, 6 Months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Training + Work Therapy | Global Index | Intake | 45.23 T Scores | Standard Deviation 5.36 |
| Cognitive Training + Work Therapy | Global Index | 3 Months | 46.63 T Scores | Standard Deviation 7.55 |
| Cognitive Training + Work Therapy | Global Index | 6 Months | 47.95 T Scores | Standard Deviation 7.95 |
| Work Therapy Only | Global Index | 6 Months | 43.05 T Scores | Standard Deviation 7.68 |
| Work Therapy Only | Global Index | Intake | 41.25 T Scores | Standard Deviation 7.54 |
| Work Therapy Only | Global Index | 3 Months | 41.86 T Scores | Standard Deviation 7.66 |
Comparison: Type III Fixed Effects for Time X Condition F Test (df = 1,39.8)p-value: 0.1795% CI: [-1.73, 9.46]Mixed Models Analysis
Secondary
Processing Speed Index
Wechsler Adult Intelligence Scale (WAIS) Digit Coding and Symbol Search. T scores for the assessments are averaged. T scores range from 30 to 80 with a mean of 50. Higher scores are better.
Time frame: Baseline, 3 Months, 6 Months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Training + Work Therapy | Processing Speed Index | Baseline | 49.42 T Scores | Standard Deviation 7.46 |
| Cognitive Training + Work Therapy | Processing Speed Index | 3 Months | 49.61 T Scores | Standard Deviation 9.04 |
| Cognitive Training + Work Therapy | Processing Speed Index | 6 Months | 50.42 T Scores | Standard Deviation 9.39 |
| Work Therapy Only | Processing Speed Index | Baseline | 45.06 T Scores | Standard Deviation 9.14 |
| Work Therapy Only | Processing Speed Index | 3 Months | 45.57 T Scores | Standard Deviation 10.03 |
| Work Therapy Only | Processing Speed Index | 6 Months | 46.90 T Scores | Standard Deviation 9.54 |
Comparison: Type III Fixed Effects for Time X Condition F Test (df = 1,36.86)p-value: 0.6795% CI: [-2.07, 1.33]Mixed Models Analysis
Secondary
Verbal and Visual Learning and Memory
Brief Visual-Spatial Memory Test (BVMT) and Hopkins Verbal Learning and Memory Test (HVLT). Total Score T Scores for tests were averaged. T score range is 30 to 80 with a mean of 50. Higher scores are better.
Time frame: Baseline, 3 Months, 6 Months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Training + Work Therapy | Verbal and Visual Learning and Memory | Baseline | 38.13 T Scores | Standard Deviation 9.39 |
| Cognitive Training + Work Therapy | Verbal and Visual Learning and Memory | 3 Months | 40.48 T Scores | Standard Deviation 8.3 |
| Cognitive Training + Work Therapy | Verbal and Visual Learning and Memory | 6 Months | 39.5 T Scores | Standard Deviation 11.3 |
| Work Therapy Only | Verbal and Visual Learning and Memory | Baseline | 33.5 T Scores | Standard Deviation 10.89 |
| Work Therapy Only | Verbal and Visual Learning and Memory | 3 Months | 36.67 T Scores | Standard Deviation 11.1 |
| Work Therapy Only | Verbal and Visual Learning and Memory | 6 Months | 38.3 T Scores | Standard Deviation 9.9 |
Comparison: Type III Fixed Effects for Time X Condition, F Test F (df = 1,42.4)p-value: 0.595% CI: [-1.67, 0.83]Mixed Models Analysis
Secondary
Verbal and Visual Working Memory
WAIS Digit Span and Wechsler Memory Scale (WMS) Spatial Span. T Scores are averaged. T Scores range from 30 to 80 with a mean of 50. Higher scores are better.
Time frame: Baseline, 3 Month, 6 Months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Training + Work Therapy | Verbal and Visual Working Memory | Baseline | 45.43 T Scores | Standard Deviation 6.26 |
| Cognitive Training + Work Therapy | Verbal and Visual Working Memory | 3 Month | 46.25 T Scores | Standard Deviation 12.1 |
| Cognitive Training + Work Therapy | Verbal and Visual Working Memory | 6 Month | 50.00 T Scores | Standard Deviation 9.37 |
| Work Therapy Only | Verbal and Visual Working Memory | Baseline | 43.25 T Scores | Standard Deviation 8.49 |
| Work Therapy Only | Verbal and Visual Working Memory | 3 Month | 40.62 T Scores | Standard Deviation 7.5 |
| Work Therapy Only | Verbal and Visual Working Memory | 6 Month | 42.62 T Scores | Standard Deviation 9.3 |
Comparison: Type III Fixed Effects Time X Condition F Test (df = 1,70.15)p-value: 0.00895% CI: [0.32, 2.01]Mixed Models Analysis