<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01678833</url>
  </required_header>
  <id_info>
    <org_study_id>999912480</org_study_id>
    <secondary_id>12-DA-N480</secondary_id>
    <nct_id>NCT01678833</nct_id>
  </id_info>
  <brief_title>Understanding Drug Abuse Treatment Outcomes</brief_title>
  <official_title>Neural Mechanistic Explanations for Differential Drug Abuse Treatment Outcomes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Although some treatments for substance abuse are considered effective for some people who are&#xD;
      drug dependent, many others do not benefit as much over time. Researchers are working to find&#xD;
      out what characteristics predict treatment response. They also want to determine how to&#xD;
      design treatments that are more effective for a greater number of substance abusers. This&#xD;
      pilot study involves providing drug addicts with cognitive behavioral therapy (CBT), a&#xD;
      treatment considered to be one of the most effective in reducing substance-abuse, to identify&#xD;
      ways in which the brain works that may predict and explain treatment effects. A comparison&#xD;
      group will be included that receives only standard psychotherapy or talk therapy. This&#xD;
      approach will enable researchers to determine what factors might be interfering with&#xD;
      favorable treatment outcomes and how to refine or develop new treatments that work well for&#xD;
      more people.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      - To identify individual characteristics which predict and explain the effects of CBT in&#xD;
      people with opiate dependence.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Males between 18 and 60 years of age who are dependent on opioids (such as heroin).&#xD;
&#xD;
        -  Participants must be willing to take buprenorphine and receive substance abuse&#xD;
           counseling.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with a physical exam and medical history.&#xD;
&#xD;
        -  Researchers will ask questions about participants ability to cope in certain situations,&#xD;
           along with questions about drug use and lifestyle issues. These questions will be asked&#xD;
           twice, before and after completing treatment.&#xD;
&#xD;
        -  Participants will be placed into one of two groups. One group will have CBT twice a week&#xD;
           for 8 weeks. The other group will have standard counseling twice per week. Both groups&#xD;
           will take buprenorphine as part of the drug abuse treatment.&#xD;
&#xD;
        -  Participants will have other tests during this study. They will have imaging studies to&#xD;
           look at brain function. These studies will test thinking and decision making.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OBJECTIVE:&#xD;
&#xD;
      The primary objective of this pilot study is to collect data for a NIH RO1 grant submission&#xD;
      that aims to elucidate cognitive, emotional regulatory and neurobiological mechanisms that&#xD;
      both moderate and mediate effects of cognitive behavioral therapy (CBT) in individuals with&#xD;
      opiate dependence. CBT has proven moderately effective in treating substance abuse; however,&#xD;
      significant variability in treatment outcomes remains. CBT curricula teach adaptive decision&#xD;
      making and cognitive reappraisal skills to down-regulate emotional responses to drug-related&#xD;
      cues, thereby promoting avoidance of drug use situations. A certain level of cognitive and&#xD;
      emotion regulatory functioning is, however, required for assimilating and executing these&#xD;
      skills which is often deficient in substance abusers. Consequently, many addicts cannot&#xD;
      effectively process and act on CBT curriculum, leading to poor treatment outcomes. Tailoring&#xD;
      interventions requires systematic investigation of neurobiological indicators that interfere&#xD;
      with or promote favorable treatment responsivity.&#xD;
&#xD;
      The small pilot study outlined below will provide the feasibility and supportive data for a&#xD;
      larger effort.&#xD;
&#xD;
      Aim 1: Moderation. Identify baseline ECF and emotion regulatory functions and their neural&#xD;
      substrates that predict treatment variability in the form of: (a) program responsivity (e.g.,&#xD;
      treatment engagement, motivation, social competences) and (b) posttreatment outcomes (e.g.,&#xD;
      substance use frequency, days of continuous abstinence). Functional magnetic resonance&#xD;
      imaging (fMRI) will be used during performance of tasks that measure ECF (decision-making;&#xD;
      inhibitory control) and cognitive reappraisal of emotional cues to investigate the&#xD;
      neuromodulatory role of PFC regions (e.g., OFC, ACC) on emotion (e.g., amygdala) and reward&#xD;
      (e.g., ventral striatum) structures and autonomic activity.&#xD;
&#xD;
      Aim 2: Mediation. Determine whether change in these neurocognitive functions in response to&#xD;
      CBT mediate intervention effects. Evidence suggests that CBT alters PFC and limbic function;&#xD;
      such changes are associated with clinical outcomes in depression and anxiety. Similarly, in&#xD;
      drug abusers, we predict treatment response will be associated with changes in neural&#xD;
      activation patterns, ECF, and emotional regulation, and that little to no change will occur&#xD;
      in those with relatively poorer outcomes.&#xD;
&#xD;
      Study Population: Participants will be 18 primary opioid dependent individuals between the&#xD;
      ages of 18 and 60. These individuals will either be enrolled in NIDA Protocol 09-DA-N020,&#xD;
      (Dr. Kenzie Preston, PI) or patients at the University of Maryland Medical Center outpatient&#xD;
      substance abuse clinics (i.e., Alcohol and Drug Abuse Program (ADAP) or Outpatient Addiction&#xD;
      Treatment Service (OATS) and are receiving buprenorphine.&#xD;
&#xD;
      DESIGN:&#xD;
&#xD;
      Study participants visit their treatment facility daily for buprenorphine and receive&#xD;
      standard counseling as part of Protocol 09-DA-N020 or their treatment protocol at ADAP or&#xD;
&#xD;
      OATS. They will be screened by MMG for eligibility into the present study then randomly&#xD;
      assigned to a TAU control group or a CBT group. This study consists of 3 assessment time&#xD;
      points (baseline, midway, post-treatment) and 16 bi-weekly counseling visits (CBT or standard&#xD;
      TAU counseling). Baseline assessments will consist of functional magnetic resonance imaging&#xD;
      (fMRI) during performance of decision making, inhibitory control and emotional regulatory&#xD;
      tasks. Questionnaires will be used to evaluate historical and current drug use, background&#xD;
      and psychological traits, and other relevant factors. Those in the TAU group visit their&#xD;
      treatment facility routinely for buprenorphine and standard counseling but will not receive&#xD;
      CBT. The CBT group participants will undergo 8 weeks of CBT in the&#xD;
&#xD;
      Archway Clinic twice a week provided by a CBT clinician from Mountain Manor Treatment&#xD;
&#xD;
      Center who will be supervised by Dr. Marc Fishman, treatment director at MMTC; this CBT&#xD;
      counseling will be in place of the TAU counseling they would be receiving as part of the&#xD;
      parent protocol. Midway through CBT/TAU counseling, participants in this pilot study will be&#xD;
      evaluated outside the scanner with the same cognitive tasks used in the scanner and&#xD;
      questionnaires from baseline. After treatment completion, they will receive a post-treatment&#xD;
      fMRI scan where they will perform the same tasks and questionnaires. Also, we will&#xD;
      preliminarily assess mediation by examining variability in level of responsivity within the&#xD;
      treatment group to determine whether this outcome is related to functional baseline&#xD;
      characteristics and change over time. Expectations are that baseline features will predict&#xD;
      intervention response and that these same characteristics will change over time in response&#xD;
      to intervention in those with favorable outcomes.&#xD;
&#xD;
      OUTCOME MEASURES:&#xD;
&#xD;
      The focus of our outcome evaluation will be use of opioid (e.g., frequency, days of&#xD;
      continuous abstinence, etc.), coping strategies, and change in lifestyle measures (e.g.,&#xD;
      employment, relationships, behavioral problems, treatment engagement).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 19, 2012</start_date>
  <completion_date>March 7, 2016</completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The focus of our outcome evaluation will be use of opioid (e.g., frequency, days of continuous abstinence, etc.), coping strategies, and change in lifestyle measures (e.g., employment, relationships, behavioral problems, treatment engagement).</measure>
  </primary_outcome>
  <enrollment type="Actual">7</enrollment>
  <condition>Drug Abuse/Dependence</condition>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
        Participants will be eligible for inclusion in the study if they meet the following&#xD;
        criteria:&#xD;
&#xD;
          1. Right-handed individuals between the ages of 18 and 60;&#xD;
&#xD;
          2. Good physical condition;&#xD;
&#xD;
          3. Participating and receiving buprenorphine treatment in protocol 09-DA-N020, a study&#xD;
             being conducted in the NIDA Intramural Archway Clinic (Dr. Kenzie Preston, PI) in&#xD;
             Baltimore, MD OR at outpatient treatment facilities at UMMC (ADAP or OATS);&#xD;
&#xD;
          4. Heroin or other opioid dependent;&#xD;
&#xD;
          5. Suitable for MRI scanning;&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        Participants will be excluded from this study if they:&#xD;
&#xD;
          1. History of neurological illnesses including but not limited to CVA, CNS tumor, head&#xD;
             trauma, MS or other demyelinating diseases, epilepsy, movement disorders, or migraine&#xD;
             in treatment.&#xD;
&#xD;
          2. Are HIV infected.&#xD;
&#xD;
          3. Have deep vein thrombosis (DVT): Assessment tool: self report during H&amp;P of&#xD;
             thrombosis, family history of thrombosis, or a medical condition that may lead to a&#xD;
             hypercoagulable state Rationale: Lying still for an hour (plus the mock scanning&#xD;
             session) may be a risk for the development of DVT in persons with certain medical&#xD;
             conditions. As such, persons with will be excluded.&#xD;
&#xD;
          4. Have current suicidal ideation.&#xD;
&#xD;
          5. Are unable to undergo MRI scanning due to metallic devices in the body including&#xD;
             dental braces, claustrophobia or body morphometry.&#xD;
&#xD;
          6. Are currently using respiratory, cardiovascular or anticonvulsant medications that may&#xD;
             interfere with the BOLD MRI signal.&#xD;
&#xD;
          7. Cognitively impaired;&#xD;
&#xD;
          8. Continued noncompliance (after the 3rd time) with respect to testing positive for&#xD;
             illicit drugs or reporting caffeine use in the past 12 hours or alcohol use in the&#xD;
             past 24 hours when they visit for their scanning sessions will lead to discontinuing&#xD;
             their participation in the #480 protocol.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elliot Stein, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute on Drug Abuse (NIDA)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institute on Drug Abuse</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Apodaca TR, Miller WR. A meta-analysis of the effectiveness of bibliotherapy for alcohol problems. J Clin Psychol. 2003 Mar;59(3):289-304. doi: 10.1002/jclp.10130.</citation>
    <PMID>12579546</PMID>
  </reference>
  <reference>
    <citation>Aharonovich E, Hasin DS, Brooks AC, Liu X, Bisaga A, Nunes EV. Cognitive deficits predict low treatment retention in cocaine dependent patients. Drug Alcohol Depend. 2006 Feb 28;81(3):313-22. doi: 10.1016/j.drugalcdep.2005.08.003. Epub 2005 Sep 19.</citation>
    <PMID>16171953</PMID>
  </reference>
  <reference>
    <citation>Aharonovich E, Brooks AC, Nunes EV, Hasin DS. Cognitive deficits in marijuana users: Effects on motivational enhancement therapy plus cognitive behavioral therapy treatment outcome. Drug Alcohol Depend. 2008 Jun 1;95(3):279-83. doi: 10.1016/j.drugalcdep.2008.01.009. Epub 2008 Mar 7.</citation>
    <PMID>18329188</PMID>
  </reference>
  <verification_date>March 7, 2016</verification_date>
  <study_first_submitted>August 31, 2012</study_first_submitted>
  <study_first_submitted_qc>August 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2012</study_first_posted>
  <last_update_submitted>April 4, 2018</last_update_submitted>
  <last_update_submitted_qc>April 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug Abuse/Dependence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Substance-Related Disorders</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01678833
org study id: 999912480
secondary id: 12-DA-N480
nct id: NCT01678833
lead sponsor: 
Background:

      Although some treatments for substance abuse are considered effective for some people who are
      drug dependent, many others do not benefit as much over time. Researchers are working to find
      out what characteristics predict treatment response. They also want to determine how to
      design treatments that are more effective for a greater number of substance abusers. This
      pilot study involves providing drug addicts with cognitive behavioral therapy (CBT), a
      treatment considered to be one of the most effective in reducing substance-abuse, to identify
      ways in which the brain works that may predict and explain treatment effects. A comparison
      group will be included that receives only standard psychotherapy or talk therapy. This
      approach will enable researchers to determine what factors might be interfering with
      favorable treatment outcomes and how to refine or develop new treatments that work well for
      more people.

      Objectives:

      - To identify individual characteristics which predict and explain the effects of CBT in
      people with opiate dependence.

      Eligibility:

        -  Males between 18 and 60 years of age who are dependent on opioids (such as heroin).

        -  Participants must be willing to take buprenorphine and receive substance abuse
           counseling.

      Design:

        -  Participants will be screened with a physical exam and medical history.

        -  Researchers will ask questions about participants ability to cope in certain situations,
           along with questions about drug use and lifestyle issues. These questions will be asked
           twice, before and after completing treatment.

        -  Participants will be placed into one of two groups. One group will have CBT twice a week
           for 8 weeks. The other group will have standard counseling twice per week. Both groups
           will take buprenorphine as part of the drug abuse treatment.

        -  Participants will have other tests during this study. They will have imaging studies to
           look at brain function. These studies will test thinking and decision making.
OBJECTIVE:

      The primary objective of this pilot study is to collect data for a NIH RO1 grant submission
      that aims to elucidate cognitive, emotional regulatory and neurobiological mechanisms that
      both moderate and mediate effects of cognitive behavioral therapy (CBT) in individuals with
      opiate dependence. CBT has proven moderately effective in treating substance abuse; however,
      significant variability in treatment outcomes remains. CBT curricula teach adaptive decision
      making and cognitive reappraisal skills to down-regulate emotional responses to drug-related
      cues, thereby promoting avoidance of drug use situations. A certain level of cognitive and
      emotion regulatory functioning is, however, required for assimilating and executing these
      skills which is often deficient in substance abusers. Consequently, many addicts cannot
      effectively process and act on CBT curriculum, leading to poor treatment outcomes. Tailoring
      interventions requires systematic investigation of neurobiological indicators that interfere
      with or promote favorable treatment responsivity.

      The small pilot study outlined below will provide the feasibility and supportive data for a
      larger effort.

      Aim 1: Moderation. Identify baseline ECF and emotion regulatory functions and their neural
      substrates that predict treatment variability in the form of: (a) program responsivity (e.g.,
      treatment engagement, motivation, social competences) and (b) posttreatment outcomes (e.g.,
      substance use frequency, days of continuous abstinence). Functional magnetic resonance
      imaging (fMRI) will be used during performance of tasks that measure ECF (decision-making;
      inhibitory control) and cognitive reappraisal of emotional cues to investigate the
      neuromodulatory role of PFC regions (e.g., OFC, ACC) on emotion (e.g., amygdala) and reward
      (e.g., ventral striatum) structures and autonomic activity.

      Aim 2: Mediation. Determine whether change in these neurocognitive functions in response to
      CBT mediate intervention effects. Evidence suggests that CBT alters PFC and limbic function;
      such changes are associated with clinical outcomes in depression and anxiety. Similarly, in
      drug abusers, we predict treatment response will be associated with changes in neural
      activation patterns, ECF, and emotional regulation, and that little to no change will occur
      in those with relatively poorer outcomes.

      Study Population: Participants will be 18 primary opioid dependent individuals between the
      ages of 18 and 60. These individuals will either be enrolled in NIDA Protocol 09-DA-N020,
      (Dr. Kenzie Preston, PI) or patients at the University of Maryland Medical Center outpatient
      substance abuse clinics (i.e., Alcohol and Drug Abuse Program (ADAP) or Outpatient Addiction
      Treatment Service (OATS) and are receiving buprenorphine.

      DESIGN:

      Study participants visit their treatment facility daily for buprenorphine and receive
      standard counseling as part of Protocol 09-DA-N020 or their treatment protocol at ADAP or

      OATS. They will be screened by MMG for eligibility into the present study then randomly
      assigned to a TAU control group or a CBT group. This study consists of 3 assessment time
      points (baseline, midway, post-treatment) and 16 bi-weekly counseling visits (CBT or standard
      TAU counseling). Baseline assessments will consist of functional magnetic resonance imaging
      (fMRI) during performance of decision making, inhibitory control and emotional regulatory
      tasks. Questionnaires will be used to evaluate historical and current drug use, background
      and psychological traits, and other relevant factors. Those in the TAU group visit their
      treatment facility routinely for buprenorphine and standard counseling but will not receive
      CBT. The CBT group participants will undergo 8 weeks of CBT in the

      Archway Clinic twice a week provided by a CBT clinician from Mountain Manor Treatment

      Center who will be supervised by Dr. Marc Fishman, treatment director at MMTC; this CBT
      counseling will be in place of the TAU counseling they would be receiving as part of the
      parent protocol. Midway through CBT/TAU counseling, participants in this pilot study will be
      evaluated outside the scanner with the same cognitive tasks used in the scanner and
      questionnaires from baseline. After treatment completion, they will receive a post-treatment
      fMRI scan where they will perform the same tasks and questionnaires. Also, we will
      preliminarily assess mediation by examining variability in level of responsivity within the
      treatment group to determine whether this outcome is related to functional baseline
      characteristics and change over time. Expectations are that baseline features will predict
      intervention response and that these same characteristics will change over time in response
      to intervention in those with favorable outcomes.

      OUTCOME MEASURES:

      The focus of our outcome evaluation will be use of opioid (e.g., frequency, days of
      continuous abstinence, etc.), coping strategies, and change in lifestyle measures (e.g.,
      employment, relationships, behavioral problems, treatment engagement).
time perspective: Other
measure: The focus of our outcome evaluation will be use of opioid (e.g., frequency, days of continuous abstinence, etc.), coping strategies, and change in lifestyle measures (e.g., employment, relationships, behavioral problems, treatment engagement).
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Elliot Stein, Ph.D.
role: Principal Investigator
affiliation: National Institute on Drug Abuse (NIDA)
facility: 
facility: 
country: United States
citation: Apodaca TR, Miller WR. A meta-analysis of the effectiveness of bibliotherapy for alcohol problems. J Clin Psychol. 2003 Mar;59(3):289-304. doi: 10.1002/jclp.10130.
PMID: 12579546
citation: Aharonovich E, Hasin DS, Brooks AC, Liu X, Bisaga A, Nunes EV. Cognitive deficits predict low treatment retention in cocaine dependent patients. Drug Alcohol Depend. 2006 Feb 28;81(3):313-22. doi: 10.1016/j.drugalcdep.2005.08.003. Epub 2005 Sep 19.
PMID: 16171953
citation: Aharonovich E, Brooks AC, Nunes EV, Hasin DS. Cognitive deficits in marijuana users: Effects on motivational enhancement therapy plus cognitive behavioral therapy treatment outcome. Drug Alcohol Depend. 2008 Jun 1;95(3):279-83. doi: 10.1016/j.drugalcdep.2008.01.009. Epub 2008 Mar 7.
PMID: 18329188
responsible party type: Sponsor
mesh term: Substance-Related Disorders