Clinical Trial: Targeting Anhedonia in Cocaine Use Disorder

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Targeting Anhedonia in Cocaine Use Disorder - Treatment Study

Brief Summary: The purpose of this study is to examine anhedonia as a potential moderator of treatment outcomes for Cocaine Use Disorder (CUD). Specifically, this study will investigate how anhedonia affects outcomes in contingency management (CM) treatment for CUD and whether anhedonia mediates the effects of adjunctive treatment with a dopaminergic (DAergic) drug, d-amphetamine, on outcomes in CM for CUD, as well as investigate the contribution of anhedonia to overall CUD severity.

Detailed Summary:

Recent research suggests that anhedonia is a key neurobehavioral dysfunction in Cocaine Use Disorder (CUD) that contributes to treatment outcomes. Anhedonia, defined here as lack of interest or pleasure in non-drug rewards, is frequently found in CUD and is related to neural deficits, such as low striatal dopamine and deficient activation to non-drug rewards in mesocortical circuits. Interestingly, not all individuals in CUD have these deficits. Preliminary data suggests that the presence of self-reported anhedonia predicts worse outcome in contingency management (CM) treatment of CUD. Moreover, low baseline dopamine predicts failure to attain abstinence in CM while medications that enhance DA increase CM success rates and responsiveness to rewards.

This study specifically aims to test the contribution of anhedonia to overall CUD severity, the relationship of anhedonia to outcomes in CM treatment, and the mediating role of anhedonia in medication enhancement of CM in CUD. To accomplish these aims, individuals with CUD will be enrolled and will undergo 4 weeks of intensive CM treatment, either with or without treatment with the dopaminergic drug, d-amphetamine. A medication only group will be included to solely measure the effects of d-amphetamine. Anhedonia will be assessed using multi-modal subjective, psychophysiological and behavioral measures of reward functioning at baseline, and each week of treatment. Functional magnetic resonance imaging (fMRI) measures of reward functioning will also be taken at baseline and week 4 in a subset of participants (n = 24)


Sponsor: The University of Texas Health Science Center, Houston

Current Primary Outcome:

  • Number of Participants who were Cocaine Abstinent as Assessed by Urine Screening (Measure of Treatment Efficacy) [ Time Frame: At end of active treatment (Treatment week 4) ]
    Subjects will complete a urine drug screen each visit. Achievement of cocaine abstinence will be defined as two consecutive weeks of cocaine-negative urine samples.
  • Change in Consummatory Reward Composite (Anhedonia) [ Time Frame: Baseline and weeks 1, 2, 3, and 4 of treatment ]
    Principal components analysis will be used to determine whether consummatory anhedonia measures (SHAPS, TEPS-Consummatory, EPRT, Corrugator and Zygomatic EMG) can be reduced into one composite representing consummatory reward functioning. If this is inappropriate, we will use individual measures (see below under "Secondary Outcome Measures") with pessimistic priors to address multiplicity.
  • Change in Motivational Reward Composite (Anhedonia) [ Time Frame: Baseline and weeks 1, 2, 3, and 4 of treatment ]
    Principal components analysis will be used to determine whether motivational anhedonia measures (TEPS-Motivational, EPKT, EEfRT) can be reduced into one composite representing motivational reward functioning. If this is inappropriate, we will use individual measures (see below under "Secondary Outcome Measures") with pessimistic priors to address multiplicity.
  • Change in Reward Learning Composite (Anhedonia) [ Time Frame: Baseline and weeks 1, 2, 3, and 4 of treatment ]
    Principal components analysis will be used to determine whether reward learning measures (PRT

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Treatment Effectiveness Score [ Time Frame: At end of active treatment (Treatment week 4) ]
      Subjects will complete a urine drug screen each visit. The Treatment Effectiveness Score is defined as the total number of cocaine negative urines across treatment.
    • Consummatory Reward as Assessed by The Emotional Picture Rating Task (EPRT) [ Time Frame: Baseline and weeks 1, 2, 3, and 4 of treatment ]
      The Emotional Picture Rating Task (EPRT) is a behavioral measure of consummatory reward where participants are asked to report positive, negative and aroused feelings while viewing emotional pictures. Valence and arousal ratings of positive pictures are the outcomes.
    • Motivational Reward as Assessed by the Emotional Picture Keypress Task (EPKT) [ Time Frame: Baseline and weeks 1, 2, 3, and 4 of treatment ]
      The Emotional Picture Key-press Task (EPKT) is a measure of motivational reward in which participants expend effort via key-pressing to extend or reduce viewing times for emotional pictures. Key-pressing to extend time viewing positive pictures is the outcome.
    • Motivational Reward as Assessed by the Effort Expenditure for Rewards Task (EEfRT) [ Time Frame: Baseline and weeks 1, 2, 3, and 4 of treatment ]
      The Effort Expenditure for Rewards Task (EEfRT) is a measure of motivational reward where, on each trial, participants choose between a "hard task" requiring many key-presses but worth more money and an "easy task" requiring few key-presses but worth less money. Percent of hard task choices is the outcome.
    • Consummatory Reward as Assessed by the Snaith-Hamilton Pleasure Scale (SHAPS) Score [ Time Frame: Baseline and weeks 1, 2, 3, and 4 of treatment ]
      The Snaith-Hamilton Pleasure Scale (SHAPS) is a measure of consummatory reward consisting of 14 hedonic capacity statements (e.g. "I would enjoy my favorite television program"). The sum of these scores is the outcome.
    • Consummatory Reward as Assessed by the Temporal Experience of Pleasure Scale (TEPS) [ Time Frame: Baseline and weeks 1, 2, 3, and 4 of treatment ]
      The Temporal Experience of Pleasure Scale (TEPS) contains 18 statements measuring both motivational and consummatory experiences of reward. Half of those statements comprise a subscale for consummatory reward, which is the outcome.
    • Motivational Reward as Assessed by the Temporal Experience of Pleasure Scale (TEPS) Motivational Score [ Time Frame: Baseline and weeks 1, 2, 3, and 4 of treatment ]
      The Temporal Experience of Pleasure Scale (TEPS) contains 18 statements measuring both motivational and consummatory experiences of reward. Half of those statements comprise a subscale for consummatory reward, which is the outcome.
    • Reward Learning as Assessed by the Probabilistic Classification Task (PCT) [ Time Frame: Baseline and weeks 1, 2, 3, and 4 of treatment ]
      The Probabilistic Classification Task is a measure of reward learning in which participants repeatedly guess whether an image belongs to Category A or B. For half of stimuli from each category, correct answers are rewarded with points (no change for incorrect) and for the other half incorrect guesses are punished with point removal (no change for correct). Learning rates for rewarded stimuli are the outcome.
    • Reward Learning as Assessed by the Probabilistic Reward Task (PRT) [ Time Frame: Baseline and weeks 1, 2, 3, and 4 of treatment ]
      The Probabilistic Reward Task (PRT) is a measure of reward learning consisting of trials in which participants must identify whether a cartoon face has a short or long mouth over a brief presentation. Correct identification of one category (short or long) is rewarded more often. Response bias for the rewarded category is the outcome.
    • Change in Consummatory Reward Activity as Assessed by fMRI [ Time Frame: Measured 2 times (Baseline and week 4 of treatment) ]
      Consummatory reward will be measured by activity in nucleus accumbens and ventral pallidum and psychophysiological from nucleus accumbens to ventral pallidum, orbitofrontal cortex and rostral anterior cingulate cortex during reward/positive pictures vs. non-reward/neutral pictures during the Emotional Picture fMRI Task and the delay portions of Monetary Incentive Delay Task. Note: fMRI data will be collected in only 24 participants (12 in CM/Placebo arm and 12 in CM/Sustained Release-Amphetamine arm)
    • Change in Motivational Reward Activity as Assessed by fMRI [ Time Frame: Measured 2 times (Baseline and week 4 of treatment) ]
      Motivational reward will be measured by activity in nucleus accumbens, and psychophysiological interactions from accumbens to ventromedial prefrontal cortex, accumbens and amygdala during anticipation of reward vs. non-reward during the anticipation phases of the Monetary Incentive Delay Task. Note: fMRI data will be collected in only 24 participants

      Original Secondary Outcome: Same as current

      Information By: The University of Texas Health Science Center, Houston

      Dates:
      Date Received: May 6, 2016
      Date Started: May 2016
      Date Completion: April 2021
      Last Updated: May 11, 2016
      Last Verified: May 2016