START NOW in the Treatment of Opioid Addicted Individuals
Condition: Opioid Use Disorder
MeSH terms: Opioid-Related Disorders
Study type: Interventional

Summary: 
      This investigation involves a partially randomized clinical trial examining the effectiveness
      of combining buprenorphine/naloxone MAT with START NOW, a skills-based psychosocial
      intervention modified specifically for the ambulatory substance use disorder (SUD) patient
      population. START NOW is an integrated evidence-informed model based on an adapted form of
      dialectical behavior therapy (DBT), a type of cognitive behavior therapy (CBT) with promising
      indications for treating SUD as it targets impulsive and self-destructive behaviors.
      Furthermore, START NOW combines CBT, the most widely used evidence-based psychosocial
      intervention for treating mental disorders, with motivational interviewing, which in clinical
      trials has been shown to be an effective technique for engaging patients with SUD. In
      addition to tracking clinical outcomes such as abstinence rates through weekly urine drug
      screens, this investigation will use: clinician assessments of disease severity,
      researcher-evaluated tests of delayed discounting (DD) and demand tasks, and self-report
      surveys assessing impulsivity, aggression, interpersonal skills, and other measures to
      capture the patients' sense of progress in treatment in regards to their substance use,
      health, lifestyle, and community. By using DD and functional magnetic resonance imaging
      (fMRI), the identification of the neural correlates of START NOW treatment response will
      begin to elucidate the mechanisms of START NOW's effects and more. This investigation's
      outcome measures may not only compare the effectiveness between START NOW and
      treatment-as-usual (TAU), but also provide a more realistic, holistic view of patients and
      their well-being throughout the recovery process.

      DD will be performed by both START NOW group members and TAU group members at their group
      therapy meetings as per protocol. Additionally, START NOW group members randomized and
      consented to have an fMRI will also perform DD before the scan is initiated.
    

Detailed description: 
      There is an unmet need for implementing a clinically superior behavioral therapy intervention
      for medication-assisted treatment of opioid use disorder.

      One strategy for fighting the opioid epidemic is to improve treatment and detoxification
      programs. In the United States, the Drug Addiction Treatment Act of 2000 requires that
      physicians combine medication-assisted treatment (MAT) with a behavioral intervention.
      However, there is no clear evidence regarding what form of therapy is most effective when
      coupled with MAT for opioid use disorder (OUD) management.

      This investigation will explore the impact of a novel skills-based psychosocial intervention
      called START NOW, which has been modified for the substance use disorder (SUD) patient
      population. The promising therapeutic potential of START NOW is evident in the growing data
      affirming the program's utility and the psychosocial techniques with substantial supportive
      evidence incorporated into the program. This investigation will attempt to prove through a
      number of clinical and behavioral parameters how START NOW with MAT may be an effective
      treatment program for patients undergoing OUD treatment.

      START NOW is an evidence-informed psychotherapy composed of a total of
      32-skills-based-sessions, originally designed for inmates in correctional systems. A previous
      study of incarcerated individuals found that for each additional session of START NOW
      completed, a 5% reduction in the incident rate of disciplinary reports was noted. In fact,
      individuals with a higher overall security risk score also had a greater reduction in the
      number of disciplinary reports with more sessions attended, suggesting that START NOW is an
      effective behavioral intervention for those who need it most. A follow-up study on these same
      participants concluded that START NOW appears to have a beneficial clinical effect with each
      session completed being associated with a 5% decrease in subsequent psychiatric hospital
      days. Evidence continues to build in support for START NOW as a behavioral intervention as
      its implementation continues to grow. For example, START NOW is currently being used in
      correctional facilities in more than 10 states in the US. Using a randomized, controlled
      trial in Europe, investigators are evaluating START NOW's ability to enhance psychosocial
      adjustment and well-being and to reduce oppositional and aggressive behavior in 128
      institutionalized female adolescents diagnosed with oppositional defiant disorder and/or
      conduct disorder.

      Investigators hypothesize that OUD patients who complete START NOW group therapy will show a
      statistically greater reduction in impulsivity, delay discounting, and illicit drug use
      compared to the OUD patients who complete the treatment-as-usual (TAU) because of START NOW's
      integrated model of care. For example, START NOW combines CBT, the most widely used
      evidence-based psychosocial intervention for treating mental disorders, with motivational
      interviewing, which in clinical trials has been shown to be an effective conjunction
      intervention for SUD. START NOW exercises psychosocial techniques similar to dialectical
      behavior therapy (DBT), a type of cognitive behavior therapy (CBT) with promising indications
      for treating SUD because it targets impulsive and self-destructive behaviors. A currently
      unpublished pilot study using START NOW in an office-based outpatient treatment setting with
      OUD yielded patient satisfaction data and detailed feedback; this data is being used to guide
      the modification process of START NOW's materials and delivery so that START NOW is more
      culturally sensitive and appropriate for the SUD patient population. This proposed
      investigation will use the revised START NOW participant workbooks and real-life exercises
      adapted specifically for SUD.

      Investigators believe that START NOW possesses many components that make it a particularly
      useful behavioral intervention for SUD. For example, the program is divided into four units,
      and Unit 1, while teaching focusing skills and functional analysis of behavior skills, tries
      to teach individuals how to develop self-control, cope with stressors, and become ready for
      change. Unit 2 focuses on understanding and coping with feelings and emotions. Unit 3 aims to
      teach individuals how to build positive relationships with others. Finally, Unit 4 focuses on
      setting and reaching personal goals. Investigators hypothesize that using START NOW's
      manual-guided approach will confer improved executive functioning skills and decreased
      delayed discounting, which will ultimately yield better clinical outcomes. This will be the
      first investigation evaluating an adapted START NOW for treating OUD with
      buprenorphine/naloxone MAT in the outpatient setting. The study aims to provide clinical
      utility for healthcare professionals in the field of addiction medicine and contributions to
      the understanding of addiction biology.

      Delayed discounting may be a useful biomarker for tracking and predicting clinical outcomes
      for patients undergoing rehabilitation Delayed discounting (DD) is a behavioral marker for
      impulsive decision-making and devaluation of delayed rewards. This investigation will use
      delayed discounting as an objective measure of cognitive executive functioning of its study
      participants before, during, and after treatment. Furthermore, we will compare DD values to
      clinical outcomes, clinician assessments, and self-report assessments in order to see if
      there is a correlation between all of these measures.

      Opiate addiction has consistently been found to correlate with delay discounting, especially
      during periods of active addiction and especially amongst intravenous heroin users. However,
      methadone treatment, even when it resulted in the avoidance of relapse or other drug use, did
      not significantly improve delay discounting, when compared to the treatment condition in
      which participants continued to abuse substances. The authors of this study suggest that this
      may be due to patients receiving effective drug treatment that does not involve prolonged
      substitution therapy may be forced to develop better self-control skills to remain abstinent.
      In a comparison between buprenorphine and methadone, a 2012 study found buprenorphine has a
      number of advantages over methadone for use in MAT. While methadone is a full agonist of
      opioid receptors, buprenorphine is a weak partial agonist, especially at the mμ opioid
      receptor, thereby causing less analgesia and euphoria.

      Investigators hypothesize that methadone, as a full agonist more prone to inducing euphoria
      and thereby enabling drug abuse, may prevent the improvement in cognitive executive functions
      theorized to be impaired by substance dependence. Moreover, the unique pharmacokinetics and
      pharmacodynamics profiles of buprenorphine may allow for more stable disease control, reduced
      harmful behavior, and thus improvements in cognitive executive functions (namely DD) for
      individuals undergoing concomitant buprenorphine MAT and an effective psychosocial
      intervention such as START NOW. Furthermore, previous studies found that DD decreases in
      individuals completing treatment for opioid dependence with buprenorphine MAT, but they
      failed to find any relationship between DD measures and abstinence outcomes.

      While DD might be a stable trait in some individuals, a technology of behavior that
      manipulates DD may not only impact DD but also reduce the impulsive choices that comprise
      behavioral patterns of addiction and poor health-decision-making. Studies have successfully
      shown reduced delay discounting (DD) when targeting cognitive skills such as learning to
      activate one's working memory for longer periods. The clinical trial proposed by this
      investigation not only utilizes MAT and START NOW as a unique approach for not only treating
      OUD and developing effective clinical practices, but also aims to enhance the understanding
      of DD in addiction treatment outcomes. Showing a correlation between DD and opioid addiction
      may enable clinicians and researchers alike with the ability to predict treatment success and
      to use DD as a biomarker for OUD disease regression or relapse.

      DD will be measured in both groups during the appointed time at the designated group
      sessions. Those in the START NOW group that have been randomized to have the fMRI will also
      perform DD before their fMRI scan.

      Neural correlates will be studied from before and after the START NOW treatment begins.
      Neural correlates in the TAU group will be not studied. The identification of the neural
      correlates of START NOW treatment response may lead to a number of potential future
      directions. First, understanding who is most likely to respond to treatment may help target
      treatment efforts. Second, this information will help elucidate the mechanisms of START NOW
      effects, allowing for refining and further development of the treatment approach. Third,
      future efforts could use knowledge gained in this proposal to directly target behavior change
      with techniques such as transcranial magnetic stimulation or real-time fMRI biofeedback. All
      of the information obtained through this investigation's outcome measures may help in the
      development of a superior behavioral intervention for OUD and improve our understanding of
      addiction biology.

      For participants in the START NOW group, those that are eligible and interested will be
      randomized to have an fMRI or not. Only 20 participants will complete the fMRI. These
      participants will perform delayed discounting tasks in fMRI sessions before and after
      behavioral intervention. Investigators expect the neural correlates of delayed discounting to
      predict START NOW treatment success. Depending on the results, the fMRI component of this
      investigation may elucidate the mechanisms of START NOW's effects, help create a model for
      predicting treatment success, or provide information on how to better target behavior change.
      Neural correlates will only be studied in the START NOW group, comparing before and after the
      treatment begins.

      Beyond capturing a participant's drug use and clinical disease course, this study aims to
      capture participants' personal satisfaction with one's livelihood and other measures to
      effectively compare START NOW with TAU. Moreover, investigators hypothesize that in the
      best-case scenario, individuals who maintain their sobriety, regardless of the behavioral
      treatment intervention they receive, will show improvements in other aspects of their lives.
      For example, individuals who remain sober throughout treatment (clean urine drug screens)
      will also show: decrease disease severity (CGI-S), increased disease improvement (CGI-I),
      reduced impulsivity (BIS), decreased aggression (AGQ), and fewer interpersonal problems
      (IIP). With all of these measures, investigators hope to offer a more compassionate,
      comprehensive view-one that extends beyond the disease and diagnosis-of the whole patient.

      Data Analysis For Specific Aim 1, the differences between START NOW and TAU utilizing an
      intent-to-treat model with a regression statistical approach will be evaluated. The specific
      regression model will be determined by the distribution of the data. For Specific Aim 2 and
      3, self-assessment by the participants between START NOW and TAU will be compared in the
      stated domains using an analysis of variance model (ANOVA). For Specific Aim 4, neural
      correlates associated with delay discounting task performance will be compared between
      groups. For Specific Aim 5, variance / co-variance matrixes of SNAP compared to the BIS, AGQ,
      and IPP will be looked at to determine the factor structure and correlation between the
      instruments.

      Investigators hypothesize that activation of valuation networks (e.g., dopaminergic networks
      connecting midbrain to frontal cortices) will predict and change in response to START NOW
      treatment success.
    

Intervention name(s): START NOW Group
Intervention type(s): Behavioral
Intervention description(s): START NOW psychotherapy is a CBT, DBT and skills-based intervention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: START NOW group psychotherapy versus Treatment-as-Usual group psychotherapy in OUD individuals in an OBOT program
Masking: Single (Outcomes Assessor)
Primary purpose: Health Services Research