Neurocognitive Factors in Substance Use Treatment Response: The Ways of Rewarding Abstinence Project (WRAP)

Electrophysiological Predictors and Indicators of Contingency Management Treatment Response

The proposed work will investigate changes in brain signaling and cognitive functioning that support recovery from addiction, as well as use of pretreatment neurocognitive functioning to inform substance use treatment planning. Substance use disorders are prevalent amongst Veterans. Cocaine addiction, in particular, has been shown to complicate treatment of other high priority behavioral health problems in the Veteran population (e.g., PTSD, opioid addiction). While there are currently no approved medications to support recovery from cocaine addiction, research indicates that Contingency Management (CM) - a behavioral intervention for cocaine users - can be effective. However, individual responses are variable and long-term benefits are limited. This CDA will test a new model of how CM works by examining brain-based predictors and indicators of treatment response. Results will have immediate implications for measurement-based implementation of existing CM variants within the VA, supporting access to the version of CM that is best aligned with each Veteran's needs.

Study Overview

• Status: Completed
• Conditions: Cocaine Use Disorder
• Intervention / Treatment: Behavioral: Prize-Based Contingency Management; Behavioral: Treatment As Usual Outpatient Substance Use Treatment

Detailed Description

Electrophysiological methods, including event-related potential and functional connectivity approaches, have potential to clarify mechanisms of substance use treatment response and characterize individual differences therein. Veterans are disproportionately affected by disorders of addiction, of which cocaine use disorder (CUD) is particularly problematic due to high relapse rates and the absence of approved pharmacotherapy options. Behavioral interventions for CUD have therefore become an important focus and Contingency Management (CM) has emerged as the best-supported approach. CM involves reinforcing cocaine abstinence (established through objective testing) with reliable, short-term reward, such as chances to win prizes (i.e., Prize-Based CM or PBCM). Given robust empirical support, nationwide dissemination of PBCM has been supported by a VHA initiative since 2011. However, PBCM response rates are variable and long-term benefits are limited - problems magnified by the cost of implementation with respect to staffing and prizes. Measurement-based approaches to PBCM implementation have promise to improve the effectiveness and efficiency of CM programming but have not yet been investigated within the VA or considered in relation to promising neuromarkers. Importantly, two versions of PBCM are already utilized at VA sites and may differentially benefit individuals with distinct neurocognitive profiles. Specifically, VA PBCM programs employ either abstract (voucher prize) or concrete (tangible prize) incentives, the latter of which may more effectively incentivize abstinence in Veterans with poor future-oriented thinking and planning ability. While selection between existing PBCM variants currently reflects practical considerations only, pretreatment neurocognitive functioning could meaningfully and realistically inform clinical decision-making in this regard.

This project aims to advance measurement-based implementation of CM by testing a novel neurocognitive model with immediate implications for the use of abstract versus concrete PBCM incentives within the VA. Specifically, the future-minded decision-making (FMDM) model posits that CM scaffolds future-oriented goal representation and self-control to support abstinence during in the moment use-related decision-making. For individuals with greater FMDM impairment, concrete, readily-accessible incentives may be more effective than abstract voucher-based rewards (which require future-oriented thinking and planning to acquire value). To test this model, neurocognitive substrates of FMDM will be examined as predictors of differential treatment response in voucher (VoucherPBCM) versus tangible prize (TangiblePBCM) versions of PBCM. Treatment-related change in neural and cognitive-behavioral correlates of FMDM will also be evaluated in PBCM-adherent versus non-adherent subgroups. Veterans with CUD will be allocated to VoucherPBCM or TangiblePBCM conditions and followed for a 12-week treatment interval. Pre- and post-treatment electroencephalography (EEG) and cognitive-behavioral assessments will be used to measure FMDM-related constructs (working memory, self-control, future-oriented decision-making, future reward representation) and related neuromarkers. These measures will be investigated as predictors of differential treatment response in VoucherPBCM versus TangiblePBCM, as well as maintenance of gains during a post-treatment follow-up period. Change in FMDM-related neural and cognitive measures over the course of treatment will also be evaluated for evidence of neuroadaptation (e.g., changes in functional connectivity) and enhancement of FMDM function through PBCM. Taken together, results of the current research project will represent a first step toward precision implementation of CM within the VA.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15240
      • VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Military Veterans
• DSM-5 Criteria for Cocaine Use Disorder (Mild, Moderate, or Severe)
• Cocaine Use Within Past 60 Days
• Stated Goal of Cocaine Abstinence or Reduced Cocaine Use
• Normal or Corrected-to-Normal Vision
• Average or Corrected Hearing

Exclusion Criteria:

• History of Severe Traumatic Brain Injury, Seizure Disorder, or other Neurological Illness
• Severe or Unstable Medical or Psychiatric Condition
• Pregnant or Lactating Women
• Moderate-to-Severe Neurocognitive Impairment per Medical Record, SLUMS < 21, or Mini MoCA < 11
• In Ongoing Residential Treatment or Imminently Expected to Enter Residential Treatment During the Study Interval at Time of Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tangible Prize-Based Contingency Management (TangiblePBCM); For participants assigned to TangiblePBCM, prize draws resulting in one or more small, large, or jumbo wins will result in access to a prize cabinet stocked with small, medium, large, and jumbo financial incentive items. Medium incentive items are included for selection in the event that a patient draws several small prize slips on the same day and are considered equivalent to 4 small prizes. Selection of specific prize items will be informed by patient preference and items will be restocked at least every 2 weeks. The prize cabinet will be open during TangiblePBCM sessions such that prize items are readily visible. Selection of prizes, maintenance of the prize cabinet, and policies regarding prize redemption will follow published guidance on administration of TangiblePBCM within the context of research protocols.	Behavioral: Prize-Based Contingency Management; Participants assigned to Prize-based Contingency Management (PBCM) conditions will receive PBCM as an adjunct to TAU. PBCM will involve twice weekly one-on-one sessions with a provider for 12-weeks. During each session, a urine specimen provided by the patient will be tested for cocaine using a point-of-care dip-test. Results of point-of-care testing will be shared with the patient and negative results will be reinforced with draws from a fish bowl containing 500 paper slips, 250 of which award small, large, or jumbo prizes (remaining slips deliver words of encouragement). Patients will be reinforced with a single prize draw for their first negative specimen; an additional prize draw will be added for each consecutive negative result (up to 8 prize draws per session). Abstinence-contingent prize draws will be reset to one upon either a positive test result or unexcused, missed appointment.; Behavioral: Treatment As Usual Outpatient Substance Use Treatment; All participants will receive treatment as usual outpatient substance use services during the 12-week treatment interval. TAU will specifically entail recommended participation in at least two outpatient group and/or individual psychotherapy encounters per week within the Center for Treatment of Addictive Disorders (CTAD) at VA Pittsburgh Healthcare System. Participants will additionally continue any previously prescribed pharmacotherapy for substance use and/or other mental health conditions, if applicable.
Experimental: Voucher Prize-Based Contingency Management (VoucherPBCM); For participants assigned to VoucherPBCM, prize draws resulting in one or more small, large, or jumbo wins will be reinforced with VA Canteen vouchers in the specified incentive range (i.e., small, large, or jumbo).	Behavioral: Prize-Based Contingency Management; Participants assigned to Prize-based Contingency Management (PBCM) conditions will receive PBCM as an adjunct to TAU. PBCM will involve twice weekly one-on-one sessions with a provider for 12-weeks. During each session, a urine specimen provided by the patient will be tested for cocaine using a point-of-care dip-test. Results of point-of-care testing will be shared with the patient and negative results will be reinforced with draws from a fish bowl containing 500 paper slips, 250 of which award small, large, or jumbo prizes (remaining slips deliver words of encouragement). Patients will be reinforced with a single prize draw for their first negative specimen; an additional prize draw will be added for each consecutive negative result (up to 8 prize draws per session). Abstinence-contingent prize draws will be reset to one upon either a positive test result or unexcused, missed appointment.; Behavioral: Treatment As Usual Outpatient Substance Use Treatment; All participants will receive treatment as usual outpatient substance use services during the 12-week treatment interval. TAU will specifically entail recommended participation in at least two outpatient group and/or individual psychotherapy encounters per week within the Center for Treatment of Addictive Disorders (CTAD) at VA Pittsburgh Healthcare System. Participants will additionally continue any previously prescribed pharmacotherapy for substance use and/or other mental health conditions, if applicable.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% Cocaine-Negative Urine Specimens Per Participant	Percentage of cocaine-negative urine specimens during the 12-week treatment interval out of the total number possible, computed on a per-participant basis. The denominator was adjusted for participants for whom a full course of treatment could not be delivered due to suspension of face-to-face research activities during the COVID-19 pandemic. Denominators were similarly adjusted for 2 TAU participants who withdrew from the study during the 12-week treatment interval. Descriptive statistics represent the mean and standard deviation of the per-participant percentage of cocaine-negative urine specimens, computed across participants within each arm.	12-Week Treatment Interval
Longest Duration of Cocaine Abstinence (LDCA)	Longest period of objectively-verified abstinence from cocaine during treatment. It is noted that two TAU participants withdrew during the 12-week treatment interval. For these participants, the LDCA was computed for the pre-withdrawal period only.	12-Week Treatment Interval

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% Contingency Management (CM) Sessions Attended Per Participant (CM Groups Only)	Percentage of CM treatment sessions attended out of the total number possible, computed on a per-participant basis. The denominator was adjusted for participants for whom a full course of treatment could not be delivered due to suspension of face-to-face research activities during the COVID-19 pandemic. Descriptive statistics represent the mean and standard deviation of the per-participant percentage of CM sessions attended, computed across participants within each arm.	12-Week Treatment Interval
Total Non-CM Treatment Encounters Per Participant	Number of non-CM, recovery-oriented treatment encounters during the 12-week treatment interval, computed on a per-participant basis. Encounters were documented in the electronic health record (VA encounters) and/or self-reported (non-VA encounters, including interactions with mutual support communities). Because this measure reflects the absolute number of non-CM treatment encounters per participant, only individuals with complete data for the 12-week period were included.	12-Week Treatment Interval
% Self-Reported Cocaine-Abstinent Days During Treatment	Percentage of self-reported cocaine-abstinent days during the 12-week treatment interval, computed on a per-participant basis. Only participants with complete self-report data for the full treatment interval were included.	12-Week Treatment Interval
% Self-Reported Drug- and Alcohol-Abstinent Days During Treatment	Percentage of self-reported drug and alcohol-abstinent days during the 12-week treatment interval, computed on a per-participant basis. Only participants with complete self-report data for the full treatment interval were included.	12-Week Treatment Interval
% Self-Reported Stimulant-Abstinent Days at Post-Treatment (CM Groups Only)	Percentage of self-reported stimulant-abstinent days during the 6 month post-treatment interval. For participants without complete data for the full 6-month post-treatment interval, the percentage of self-reported stimulant-abstinent days was computed based on the total number of days for which self-report data were available.	6 Month Post-Treatment Interval
% Self-Reported Drug- and Alcohol-Abstinent Days at Post-Treatment (CM Groups Only)	Percentage of self-reported drug- and alcohol-abstinent days during the 6 month post-treatment interval. For participants without complete data for the full 6-month post-treatment interval, the percentage of self-reported stimulant-abstinent days was computed based on the total number of days for which self-report data were available.	6 Month Post-Treatment Interval

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Control-related Theta Synchronization From Baseline to Post-Treatment	Theta synchronization between anterior cingulate cortex (Cz) and lateral prefrontal cortex (F3, F4, FC5, FC6) was measured to assess differences in functional connectivity between baseline and post-treatment (i.e., follow-up assessment conducted after the conclusion of the 12-week treatment interval) for high versus low conflict events. At each timepoint, phase locking value (PLV) was computed for 4 electrode pairs (Cz-F3, Cz-F4, Cz-FC5, Cz-FC6) across 3 stimulus conditions ranging from low to high conflict (Congruent, Intermediate-Incongruent, High-Incongruent) and for high-conflict error versus low-conflict correct responses in the Parametric Conflict Flankers task. A wavelet transformation isolated theta activity, and PLV was derived from normalized complex wavelet phases. PLV quantifies trial-to-trial phase synchrony (0-1), with 1 representing perfect synchrony. Descriptive data reported below represent the average PLV across the 4 electrode pairs.	Baseline and Post-Treatment Follow-up
Difference in Executive Working Memory From Baseline to Post-Treatment	Difference in Brown-Peterson working memory scores between baseline and post-treatment (i.e., follow-up assessment conducted after the conclusion of the 12-week treatment interval). We will specifically use a modified Brown-Peterson test (Auditory Consonant Trigrams) for which both age- and Veteran-specific norms exist. Summary scores for this measure (including 9-, 18-, and 36-second delay conditions) can range from 0-45, with higher scores indicating improved executive working memory performance.	Baseline and Post-Treatment Follow-up
Difference in Episodic Future Thinking Effect on Delay Discounting From Baseline to Post-Treatment	Delay discounting was quantified using the hyperbolic discounting parameter (k), estimated separately for the Episodic Future Thinking (EFT) condition-with personally meaningful event tags anchoring delayed rewards-and the Standard condition without such tags. Values of k were natural log-transformed (ln(k)), with higher ln(k) indicating steeper discounting of delayed rewards, reflecting greater devaluation of future outcomes and a stronger preference for immediate gratification.	Baseline and Post-Treatment Follow-up

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Sarah E. Forster, PhD, VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): October 31, 2023
• Study Completion (Actual): April 12, 2024

Study Registration Dates

• First Submitted: January 7, 2019
• First Submitted That Met QC Criteria: January 7, 2019
• First Posted (Actual): January 10, 2019

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Executive Function; Precision Medicine; Contingency Management; Reward; Electroencephalography; Evidence-Based Practice; Event-Related Potentials; Choice Behavior; Functional Connectivity; Cocaine-Related Disorders; Prospective Thinking
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Cocaine-Related Disorders; Therapeutics
• Other Study ID Numbers: NURA-002-18S; CX001807-01A1 (Other Grant/Funding Number: VA CSR&D)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: If possible, a de-identified, anonymized dataset will be created and shared. However, specific arrangements for sharing have not yet been made and options for data sharing (for example, the availability of data repositories for electroencephalographic data files), as well as VA policies regarding data sharing may change over the course of the study. A detailed plan for data sharing will be developed and approved upon completion of data collection.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No