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

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ClinicalTrials.gov Identifier: NCT03799341
Recruitment Status : Not yet recruiting
First Posted : January 10, 2019
Last Update Posted : January 14, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cocaine Use Disorder Behavioral: Prize-Based Contingency Management Behavioral: Treatment As Usual Outpatient Substance Use Treatment Not Applicable

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 relative to treatment-as-usual (TAU) care. Veterans with CUD will be allocated to VoucherPBCM, TangiblePBCM, or TAU 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  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomly assigned to receive: (1) 12 weeks of TangiblePBCM (n = 70), (2) 12 weeks of VoucherPBCM (n = 70), or (3) 12 weeks of TAU (n = 40). CM recipients will also be followed for 6 months post treatment. The proposed design enables evaluation of CM outcome predictors within 140 CM recipients - both with respect to initial treatment response and longer term (6 month) outcomes. Predictors of treatment response, can also be evaluated within the whole sample (n = 180) to determine general versus CM-specific individual difference factors of relevance to treatment response. All participants will receive a Baseline Assessment prior to the 12 Week Treatment interval, as well as a Follow-up Assessment at the conclusion of this period. Data from Baseline and Follow-up Assessments will enable longitudinal analysis of treatment-related change in EEG and cognitive-behavioral measures in TangiblePBCM, VoucherPBCM, and TAU.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Electrophysiological Predictors and Indicators of Contingency Management Treatment Response
Estimated Study Start Date : April 1, 2019
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : March 31, 2023

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.

Active Comparator: Treatment As Usual (TAU)
Participants in all arms will be engaged with TAU outpatient substance use services and will be recommended to participate in at least two outpatient group and/or individual psychotherapy encounters per week. Participants assigned to the TAU only arm will be asked to engage with recommended outpatient treatment services for 12-weeks (as described above) but will not receive adjunctive PBCM during this time period. Participants in the TAU arm will additionally be asked to provide urine specimens on a twice-weekly basis for lab-based urinalysis. However, these participants will not interact with a CM provider or receive contingent reinforcement based on urinalysis results.
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.




Primary Outcome Measures :
  1. % Cocaine-Negative Urine Specimens [ Time Frame: 12-Week Treatment Interval ]
    Proportion of urine specimens provided during the 12-week treatment interval that test negative for cocaine.

  2. Longest Duration of Cocaine Abstinence [ Time Frame: 12-Week Treatment Interval ]
    Longest period of objectively verified abstinence from cocaine during treatment.


Secondary Outcome Measures :
  1. % Contingency Management (CM) Sessions Attended (CM Groups Only) [ Time Frame: 12-Week Treatment Interval ]
    Proportion of CM treatment sessions attended.

  2. Total Non-CM Treatment Encounters [ Time Frame: 12-Week Treatment Interval ]
    Number of non-CM treatment encounters during treatment (documented in chart and/or self-reported)

  3. % Self-Reported Cocaine-Abstinent Days During Treatment [ Time Frame: 12-Week Treatment Interval ]
    Proportion of self-reported cocaine-abstinent days during the 12-week treatment interval.

  4. % Self-Reported Drug- and Alcohol-Abstinent Days During Treatment [ Time Frame: 12-Week Treatment Interval ]
    Proportion of self-reported drug- and alcohol-abstinent days during the 12-week treatment interval.

  5. % Self-Reported Stimulant-Abstinent Days at Post-Treatment (CM Groups Only) [ Time Frame: 6 Month Post-Treatment Interval ]
    Proportion of self-reported stimulant-abstinent days during the 6 month post-treatment interval.

  6. % Self-Reported Drug- and Alcohol-Abstinent Days at Post-Treatment (CM Groups Only) [ Time Frame: 6 Month Post-Treatment Interval ]
    Proportion of self-reported drug- and alcohol-abstinent days during the 6 month post-treatment interval.


Other Outcome Measures:
  1. Pre- to Post-Treatment Change in Theta Synchronization [ Time Frame: 12-Week Treatment Interval ]
    Treatment-related change in theta synchronization between anterior cingulate cortex and lateral prefrontal cortex during high conflict events in the Parametric Conflict Flankers task.

  2. Pre- to Post-Treatment Change in Executive Working Memory [ Time Frame: 12-Week Treatment Interval ]
    Treatment-related change in Brown-Peterson working memory scores. 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.

  3. Pre- to Post-Treatment Change in Episodic Future Thinking Effect (Delay Discounting) [ Time Frame: 12-Week Treatment Interval ]
    Treatment-related change in the difference in delay discounting slopes (ln(k)) estimated for discounting conditions with and without personally meaningful event tags.

  4. Pre- to Post-Treatment Change Spontaneous Eyeblink Rate [ Time Frame: 12-Week Treatment Interval ]
    Treatment-related change in spontaneous eyeblink rate at rest.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 or SLUMS < 21
  • In Ongoing Residential Treatment or Imminently Expected to Enter Residential Treatment During the Study Interval at Time of Screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03799341


Contacts
Contact: Andrea Ortiz, BA (412) 360-2379 andrea.ortiz5@va.gov

Locations
United States, Pennsylvania
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15240
Contact: Sarah E Forster, PhD    412-360-2365    Sarah.Forster2@va.gov   
Principal Investigator: Sarah E. Forster, PhD         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
Principal Investigator: Sarah E. Forster, PhD VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03799341     History of Changes
Other Study ID Numbers: NURA-002-18S
CX001807-01A1 ( Other Grant/Funding Number: VA CSR&D )
First Posted: January 10, 2019    Key Record Dates
Last Update Posted: January 14, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Keywords provided by VA Office of Research and Development:
Cocaine-Related Disorders
Contingency Management
Reward
Choice Behavior
Executive Function
Precision Medicine
Evidence-Based Practice
Prospective Thinking
Electroencephalography
Event-Related Potentials
Functional Connectivity