Drug Use Disorders
Conditions
Keywords
Drug use Disorders, Cognitive Remediation
Brief summary
We are proposing a small randomized clinical trial in which 100 substance users will complete the existing Psychotherapy Development Center (PDC) pretreatment assessment battery as well as a novel battery of assays to evaluate cognitive-affective functioning. After completing pretreatment assessments, participants will be randomized to either a (1) cognitive remediation program (training tasks) specifically designed to address cognitive-affective dysregulation or (2) control tasks (verbal fluency tasks). Tasks will be completed twice per week for 4 weeks, after which assessment batteries will be repeated. Finally, we will evaluate real-world behavior and the durability of the training via a one-month follow-up, which will include assessment of substance use as well as the cognitive-affective battery.
Detailed description
Participants will be 100 individuals (aged 18 to 50) enrolled in outpatient (non- methadone/buprenorphine) treatment for any substance use disorder (other than PCP) at the Substance Abuse Treatment Unit in New Haven. As the goal of this project is to develop interventions that address self-regulation across multiple disorders, we will recruit individuals who have a range of substance use disorders and levels of severity. Our primary Specific Aim will be to evaluate the efficacy of the cognitive-remediation program relative to the control condition control on the indicators of cognitive-affective functioning and substance use, testing the hypothesis that individuals randomized to the cognitive remediation program will demonstrate improved functioning on the cognitive-affective battery as well as reduced real-world substance abuse. We will also explore potential moderators of response to the training, including baseline measures of cognitive-affective function.
Interventions
BEHAVIORALTAU plus Cognitive Remediation Program
Treatment normally received at this clinic that generally includes individual or group sessions and regular urine monitoring PLUS computerized games that focus on cognitive-affective self-regulatory processes.
BEHAVIORALTAU plus Control Tasks
Treatment normally received at this clinic that generally includes individual or group sessions and regular urine monitoring PLUS a series of computerized word games.
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be randomized to either a (1) cognitive remediation program (training tasks) specifically designed to address cognitive-affective dysregulation or (2) control tasks (verbal fluency tasks).
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Meet current DSM-5 criteria for an alcohol, stimulant, cannabis, or opioid use disorder. * Are sufficiently stable for 4 weeks of outpatient treatment. * Are willing to provide locator information. * Are fluent in English and have a 4th grader or higher reading level
Exclusion criteria
* Meet DSM-5 criteria for a bipolar or schizophrenic disorder. * Who have a legal case pending such that incarceration during the 4-week protocol is likely. * Are physically dependent on alcohol, opioids or benzodiazepines or who report recent PCP use. * Have a baseline Shipley estimated IQ less than 70 * Have 3 or more head injuries with loss of consciousness for over 30 minutes or lasting effects * Have a history of chronic illness or neurological disorders (e.g., epilepsy or stroke) that would complicate evaluation of effects of cognitive training
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Stop Signal Reaction Time | Training visit 1 through 4 weeks of training | Improved functioning on cognitive-affective battery: Examining Stop Signal reaction time changed across the 4-week training period. A change score was calculated. A negative number indicates better inhibition over time. |
| Change From Pre-Post in Substance Use | 4 weeks before First Training Session through the 4-week training period | The cube root of the number of days the participant endorsed using their primary substance. The number of days was submitted to a cube root transformation given skewness and a change score was calculated (post minus pre). A negative number indicated decreased substance use over time. |
| Change in Pre-Post Cognitive Affective Battery- Negative Urgency Subscale (Part of the Urgency, Premeditation (Lack of), Perseverance (Lack of), Sensation Seeking, Positive Urgency, Impulsive Behavior Scale) | from the week prior to training to the week after training | Negative urgency (NU) subscale. The scale score range is 11-44. Higher values indicate stronger agreement with this pathway toward impulsivity. A change score was calculated. A negative number indicates less agreement with negative urgency. |
| Change in Experimental Performance-Change in Percentage of Risky Choices Under Risk Condition of the Lottery Task | Training visit 1 through 4 weeks of training | The percent of risky choices per session. This would indicate that the participant selected the lottery option that reflected a riskier bet. A change score was calculated. A negative number indicates improved decision-making (selecting fewer risky options). |
| Change in Experimental Performance- Change in Percentage of Ambiguous Choices Under 24% Ambiguity in Lottery Task | Training visit 1 through 4 weeks of training | Percent of choices the participant made that reflected selecting the ambiguous option. A change score was calculated. A negative number reflects improved decision-making (selecting more safe options). |
| Change in Experimental Performance- Paced Auditory Serial Addition Test (PASAT) | from the week prior to training (pre) to the week after training (post) | Estimated change in percentage of trial attempts on round 3 of the PASAT. A positive number reflects more trial attempts in the third round of PASAT. |
| Change in Pre-Post Cognitive Affective Battery: Digit Backwards | from the week prior to training (pre) to the week after training (post) | Score on digit backwards. Fourteen strings of varying lengths (2 to 7 digits) are presented. A participant receives a point for each string they correctly repeat backwards. Range 0-14 points. Change score was calculated-positive values indicate improved working memory over time. |
| Change in Pre-Post Cognitive Affective Battery: Breath Holding | from the week prior to training (pre) to the week after training (post) | Negative emotionality-distress tolerance as measured by the difference between when the participant says they are uncomfortable and when they let go of holding their breath. Measured in seconds (this was natural log-transformed due to skewness for analyses). Positive change indicates improved distress tolerance over time. |
| Change in Pre-Post Cognitive Affective Battery: Perceived Stress Scale | from the week prior to training (pre) to the week after training (post) | Negative emotionality-perceived stress. The total score ranges from 0-4. Higher scores indicate a higher level of perceived stress. A change score was calculated. Negative change indicates an improvement (reduction in perceived stress) over time. |
| Change in Pre-Post Cognitive Affective Battery: Delay Discounting | from the week prior to training (pre) to the week after training (post) | Incentive salience- delay discounting. Five-Trial Adjusting-Delay Discounting Task (Koffarnus & Bickel, 2014) is a 5-item behavioral assessment used to estimate the extent to which individuals prefer smaller immediate rewards over larger delayed rewards. A discount rate (ln (k)) is calculated for each time the measure is used. Discount rates for the 5- trial delay task were calculated by taking the inverse of the obtained Effective Delay 50 value, which is equivalent to the value of k, when fitted to this singular point. Ln(k) is the natural log of the discount rate. A change score was calculated. Negative change indicates improved decision-making |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TAU Plus Cognitive Remediation Program Treatment normally received at this clinic that generally includes individual or group sessions and regular urine monitoring PLUS computerized games that focus on learning and decision making.
TAU plus Cognitive Remediation Program: Treatment normally received at this clinic that generally includes individual or group sessions and regular urine monitoring PLUS computerized games that focus on cognitive-affective self-regulatory processes. | 22 |
| TAU Plus Control Tasks Treatment normally received at this clinic that generally includes individual or group sessions and regular urine monitoring PLUS a series of computerized word games.
TAU plus Control Tasks: Treatment normally received at this clinic that generally includes individual or group sessions and regular urine monitoring PLUS a series of computerized word games. | 24 |
| Total | 46 |
Baseline characteristics
| Characteristic | TAU Plus Cognitive Remediation Program | TAU Plus Control Tasks | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 24 Participants | 46 Participants |
| Age, Continuous | 34.9 years STANDARD_DEVIATION 8.1 | 32.4 years STANDARD_DEVIATION 8.6 | 33.6 years STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 5 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 19 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) White | 12 Participants | 17 Participants | 29 Participants |
| Region of Enrollment United States | 22 participants | 24 participants | 46 participants |
| Sex: Female, Male Female | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 24 |
| other Total, other adverse events | 0 / 22 | 0 / 24 |
| serious Total, serious adverse events | 2 / 22 | 1 / 24 |
Outcome results
Primary
Change From Pre-Post in Substance Use
The cube root of the number of days the participant endorsed using their primary substance. The number of days was submitted to a cube root transformation given skewness and a change score was calculated (post minus pre). A negative number indicated decreased substance use over time.
Time frame: 4 weeks before First Training Session through the 4-week training period
Population: All participants who completed the pre- and post-treatment substance use calendar.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAU Plus Cognitive Remediation Program | Change From Pre-Post in Substance Use | -.34 cube root (number of days) | Standard Error 0.19 |
| TAU Plus Control Tasks | Change From Pre-Post in Substance Use | .19 cube root (number of days) | Standard Error 0.17 |
p-value: 0.04995% CI: [-0.333, 0.184]ANOVA
Primary
Change in Experimental Performance- Change in Percentage of Ambiguous Choices Under 24% Ambiguity in Lottery Task
Percent of choices the participant made that reflected selecting the ambiguous option. A change score was calculated. A negative number reflects improved decision-making (selecting more safe options).
Time frame: Training visit 1 through 4 weeks of training
Population: All participants who completed one or more sessions of the computerized Lottery task. Negative change reflects improved decision-making.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAU Plus Cognitive Remediation Program | Change in Experimental Performance- Change in Percentage of Ambiguous Choices Under 24% Ambiguity in Lottery Task | -1.77 percent of ambiguous choices | Standard Error 0.82 |
p-value: 0.03595% CI: [-3.4, -0.13]Mixed Models Analysis
Primary
Change in Experimental Performance-Change in Percentage of Risky Choices Under Risk Condition of the Lottery Task
The percent of risky choices per session. This would indicate that the participant selected the lottery option that reflected a riskier bet. A change score was calculated. A negative number indicates improved decision-making (selecting fewer risky options).
Time frame: Training visit 1 through 4 weeks of training
Population: All participants who completed one or more sessions of the Lottery Task. Negative change indicated improved decision-making
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAU Plus Cognitive Remediation Program | Change in Experimental Performance-Change in Percentage of Risky Choices Under Risk Condition of the Lottery Task | -1.62 percent of risky choices | Standard Error 0.77 |
p-value: 0.03995% CI: [-3.15, -0.08]Mixed Models Analysis
Primary
Change in Experimental Performance- Paced Auditory Serial Addition Test (PASAT)
Estimated change in percentage of trial attempts on round 3 of the PASAT. A positive number reflects more trial attempts in the third round of PASAT.
Time frame: from the week prior to training (pre) to the week after training (post)
Population: All participants who completed one or more sessions of the computerized PASAT. Positive change reflects improved cognitive-affective functioning (distress tolerance) over time.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAU Plus Cognitive Remediation Program | Change in Experimental Performance- Paced Auditory Serial Addition Test (PASAT) | 4.26 percentage of trials attempted | Standard Error 0.57 |
p-value: <0.00195% CI: [3.12, 5.39]Mixed Models Analysis
Primary
Change in Pre-Post Cognitive Affective Battery: Breath Holding
Negative emotionality-distress tolerance as measured by the difference between when the participant says they are uncomfortable and when they let go of holding their breath. Measured in seconds (this was natural log-transformed due to skewness for analyses). Positive change indicates improved distress tolerance over time.
Time frame: from the week prior to training (pre) to the week after training (post)
Population: All participants who completed the breath holding task for both pre- and post-treatment cognitive-affective battery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAU Plus Cognitive Remediation Program | Change in Pre-Post Cognitive Affective Battery: Breath Holding | .19 ln(seconds) | Standard Error 0.15 |
| TAU Plus Control Tasks | Change in Pre-Post Cognitive Affective Battery: Breath Holding | -.16 ln(seconds) | Standard Error 0.12 |
p-value: 0.07797% CI: [-0.177, 0.214]ANOVA
Primary
Change in Pre-Post Cognitive Affective Battery: Delay Discounting
Incentive salience- delay discounting. Five-Trial Adjusting-Delay Discounting Task (Koffarnus & Bickel, 2014) is a 5-item behavioral assessment used to estimate the extent to which individuals prefer smaller immediate rewards over larger delayed rewards. A discount rate (ln (k)) is calculated for each time the measure is used. Discount rates for the 5- trial delay task were calculated by taking the inverse of the obtained Effective Delay 50 value, which is equivalent to the value of k, when fitted to this singular point. Ln(k) is the natural log of the discount rate. A change score was calculated. Negative change indicates improved decision-making
Time frame: from the week prior to training (pre) to the week after training (post)
Population: All participants who completed the delay discounting task for both pre- and post-treatment cognitive-affective battery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAU Plus Cognitive Remediation Program | Change in Pre-Post Cognitive Affective Battery: Delay Discounting | -.23 ln(k) | Standard Error 0.52 |
| TAU Plus Control Tasks | Change in Pre-Post Cognitive Affective Battery: Delay Discounting | -.76 ln(k) | Standard Error 0.42 |
p-value: 0.43695% CI: [-1.805, 0.742]ANOVA
Primary
Change in Pre-Post Cognitive Affective Battery: Digit Backwards
Score on digit backwards. Fourteen strings of varying lengths (2 to 7 digits) are presented. A participant receives a point for each string they correctly repeat backwards. Range 0-14 points. Change score was calculated-positive values indicate improved working memory over time.
Time frame: from the week prior to training (pre) to the week after training (post)
Population: All participants who completed the digit backwards for both pre- and post-treatment cognitive-affective battery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAU Plus Cognitive Remediation Program | Change in Pre-Post Cognitive Affective Battery: Digit Backwards | 2.08 scores on scale | Standard Error 0.62 |
| TAU Plus Control Tasks | Change in Pre-Post Cognitive Affective Battery: Digit Backwards | -.21 scores on scale | Standard Error 0.51 |
p-value: 0.00895% CI: [0.111, 1.755]ANOVA
Primary
Change in Pre-Post Cognitive Affective Battery- Negative Urgency Subscale (Part of the Urgency, Premeditation (Lack of), Perseverance (Lack of), Sensation Seeking, Positive Urgency, Impulsive Behavior Scale)
Negative urgency (NU) subscale. The scale score range is 11-44. Higher values indicate stronger agreement with this pathway toward impulsivity. A change score was calculated. A negative number indicates less agreement with negative urgency.
Time frame: from the week prior to training to the week after training
Population: All participants who completed the UPPS-NU for both pre- and post-treatment cognitive-affective battery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAU Plus Cognitive Remediation Program | Change in Pre-Post Cognitive Affective Battery- Negative Urgency Subscale (Part of the Urgency, Premeditation (Lack of), Perseverance (Lack of), Sensation Seeking, Positive Urgency, Impulsive Behavior Scale) | -3.13 score on scale | Standard Error 1.57 |
| TAU Plus Control Tasks | Change in Pre-Post Cognitive Affective Battery- Negative Urgency Subscale (Part of the Urgency, Premeditation (Lack of), Perseverance (Lack of), Sensation Seeking, Positive Urgency, Impulsive Behavior Scale) | -.70 score on scale | Standard Error 1.27 |
p-value: 0.23695% CI: [-3.965, 0.136]ANOVA
Primary
Change in Pre-Post Cognitive Affective Battery: Perceived Stress Scale
Negative emotionality-perceived stress. The total score ranges from 0-4. Higher scores indicate a higher level of perceived stress. A change score was calculated. Negative change indicates an improvement (reduction in perceived stress) over time.
Time frame: from the week prior to training (pre) to the week after training (post)
Population: All participants who completed the perceived stress scale (PSS) for both pre- and post-treatment cognitive-affective battery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAU Plus Cognitive Remediation Program | Change in Pre-Post Cognitive Affective Battery: Perceived Stress Scale | -.53 scores on scale | Standard Error 1.38 |
| TAU Plus Control Tasks | Change in Pre-Post Cognitive Affective Battery: Perceived Stress Scale | -1.61 scores on scale | Standard Error 1.11 |
p-value: 0.54795% CI: [-4.822, 2.895]ANOVA
Primary
Change in Stop Signal Reaction Time
Improved functioning on cognitive-affective battery: Examining Stop Signal reaction time changed across the 4-week training period. A change score was calculated. A negative number indicates better inhibition over time.
Time frame: Training visit 1 through 4 weeks of training
Population: All participants who completed one or more sessions of the computerized Stop Signal task. Negative change reflects improved inhibition over time.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAU Plus Cognitive Remediation Program | Change in Stop Signal Reaction Time | -8.62 ms | Standard Error 2.79 |
p-value: 0.00395% CI: [-14.17, -3.06]Mixed Models Analysis