<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/NCT03287180</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00093907</org_study_id>
    <secondary_id>1R21DA046738-01</secondary_id>
    <nct_id>NCT03287180</nct_id>
  </id_info>
  <brief_title>Adolescent Community Reinforcement Approach in Combination With Buprenorphine/Naloxone for Severe Opioid Use</brief_title>
  <acronym>A-CRA/MAT</acronym>
  <official_title>Adolescent Community Reinforcement Approach (A-CRA) Implementation in Combination With Buprenorphine/Naloxone for Young Adults Ages 18 to 25 With Severe Opioid Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chestnut Health Systems</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study assesses whether adding a behavioral intervention, known as the Adolescent&#xD;
      Community Reinforcement Approach (A-CRA), to the treatment of individuals already receiving&#xD;
      buprenorphine/naloxone can improve treatment success and retention rates in young adults with&#xD;
      severe opioid use disorder.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Buprenorphine is one of the medication assisted treatments approved by the FDA for opioid use&#xD;
      disorders. Treatment with buprenorphine/naloxone may reduce the risk of opioid overdose and&#xD;
      lower the occurrence of further conditions associated with injection drug use such as&#xD;
      psychiatric disorders, hepatitis C infection, HIV, and high-risk sexual and criminal&#xD;
      behaviors. The study assesses whether adding a behavioral intervention, known as the&#xD;
      Adolescent Community Reinforcement Approach (A-CRA), to the treatment of individuals already&#xD;
      receiving buprenorphine/naloxone can improve treatment success and retention rates in young&#xD;
      adults with severe opioid use disorder.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    unable to enroll any participants&#xD;
  </why_stopped>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Actual">June 9, 2020</completion_date>
  <primary_completion_date type="Actual">June 9, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This 12-week randomized controlled pilot trial will begin by an induction on sublingual buprenorphine/naloxone for all participants who would usually receive buprenorphine based treatment in the clinic. After the two-week induction phase, participants will be randomized into two groups. While continuing buprenorphine/naloxone the experimental group will receive a 12-week course of A-CRA, while the control group will be provided medical management by the prescriber. Medical management is the standard treatment approach for prescribing buprenorphine and covers medication adherence, side effects of the medication, assessment of withdrawal/cravings and dose adjustment as indicated. After completion of the 12-week A-CRA intervention, all individuals will receive weekly medical management sessions until week 24 (6 month follow up).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of opiates-negative urine drug screens over the total number of urine drug screens at each stage</measure>
    <time_frame>Each session (weekly) up to 24 weeks.</time_frame>
    <description>Qualitative urine test for opiates (+/-) will be performed. All presumptive positive assays will be confirmed by Gas Chromatography-Mass Spectrometry. The concentration value must be greater than or equal to the cutoff to be reported as positive. The opiates test results (positive/negative) will be documented. Proportion of opiates-negative urine drug screens over the total number of urine drug screens at each stage will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent of days of opioid use within the past 90 days as indicated by self-report on the Global Appraisal of Individual Needs</measure>
    <time_frame>Pre-treatment (baseline) and post-study intervention (12 weeks visit after completion of A-CRA ), and end of follow-up (24-week visit) .</time_frame>
    <description>The Global Appraisal of Individual Needs is a comprehensive, semi-structured interview measure with established validity and reliability used to identify and address a wide range of psychosocial problems in clinical populations. Average administration time for the GAIN Intake version is 1.5 hours and 45 minutes for the follow-up version. The assessment categories include background, school problems, work problems, physical health, sources of stress, risk behaviors and infectious diseases, mental health, substance use, and crime and violence. Substance use categories document self-reported frequency of substance use within the past 90 days for each substance endorsed (alcohol, opioids, marijuana, and other illicit psychoactive drugs). Individuals are able to say that they do not know, or refuse to answer any questions that they do not want to answer.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Completion of the final phase of treatment defined as final study session (yes/no)</measure>
    <time_frame>24-week visit</time_frame>
    <description>To investigate any difference in treatment retention in the experimental group compared to the control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of clinic visits by patient and any expected joint family member sessions</measure>
    <time_frame>2-, 12, and 24-week visits.</time_frame>
    <description>To investigate any difference in treatment retention in the experimental group compared to the control group.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Opioid-Related Disorders</condition>
  <condition>Behavior, Addictive</condition>
  <arm_group>
    <arm_group_label>Experimental group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the experimental group will attend one individual assessment with the study physician for combination of buprenorphine/naloxone 4/1 prescription and urinalysis, along with one weekly Adolescent Community Reinforcement Approach (A-CRA) session (approximately 50 minutes).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in the control condition will attend weekly individual medical management sessions with the MD who will also provide a prescription for a combination of buprenorphine/naloxone 4/1 (approximately 25 minutes in duration).</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Adolescent Community Reinforcement Approach (A-CRA)</intervention_name>
    <description>The A-CRA is a modified version of the Community Reinforcement Approach for adolescents and transitional age youth. The A-CRA treatment protocol consists of nineteen procedures designed to promote positive behavior change directed towards prosocial activities and engagement in the individual's community. A community can include but is not limited to: social and peer activities, family interaction, and work or school environments. Some of the highlighted procedures include relapse prevention, sobriety sampling, problem solving, and communication skills. There are also combined parent/and or couples relationship sessions with the young adult. In the current study, 12-weeks of A-CRA treatment will be provided to the intervention group.</description>
    <arm_group_label>Experimental group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Combination of buprenorphine/naloxone 4/1</intervention_name>
    <description>Buprenorphine is a partial agonist at mu-opioid receptor, an antagonist at kappa-opioid receptor. Naloxone is an antagonist at the mu-opioid receptor. Buprenorphine/naloxone requires the use of an induction to avoid the risk of withdrawal. Participants are instructed not to use opioids for at least 10 hours prior to first dose. Once symptoms of withdrawal score a minimum of 7 on the Clinical Opiate Withdrawal Scale (COWS), the first dose of 4/1 mg will be given. Participants will be monitored for an hour. An additional 4/1 mg dose can be provided to a dose that suppresses withdrawal effects. The physician then provides a prescription for 8/2-16/4 mg for Day 2. Doses can be adjusted with a maximum of total 24/6 mg/day. The target daily dose is 16/4 mg.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Experimental group</arm_group_label>
    <other_name>Suboxone/Narcan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  have met DSM-5 criteria for severe opioid use disorder&#xD;
&#xD;
          -  no sensitivity to buprenorphine or naloxone&#xD;
&#xD;
          -  no further medical/addictive conditions that require immediate medical attention&#xD;
&#xD;
          -  ability to read and provide informed consent&#xD;
&#xD;
          -  intent to remain in the area for the duration of the study&#xD;
&#xD;
          -  able to receive outpatient care&#xD;
&#xD;
          -  agreed to use an acceptable birth control method throughout the duration of this study&#xD;
             (female participants)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  endorsement of imminent and serious suicidality&#xD;
&#xD;
          -  medical conditions that take precedence over the presence of treatment for an&#xD;
             addictive disorder&#xD;
&#xD;
          -  history of an adverse reaction to buprenorphine/naloxone&#xD;
&#xD;
          -  current substance use or psychiatric condition requiring a level of care higher than&#xD;
             outpatient&#xD;
&#xD;
          -  pregnant, nursing or planning pregnancy during the extent of the treatment&#xD;
             trial(female participants)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Justine Welsh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>SOM: Psych: Child Psych - CAMP Emory University</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <reference>
    <citation>Arnett JJ. Emerging adulthood. A theory of development from the late teens through the twenties. Am Psychol. 2000 May;55(5):469-80.</citation>
    <PMID>10842426</PMID>
  </reference>
  <reference>
    <citation>Jones CM, Logan J, Gladden RM, Bohm MK. Vital Signs: Demographic and Substance Use Trends Among Heroin Users - United States, 2002-2013. MMWR Morb Mortal Wkly Rep. 2015 Jul 10;64(26):719-25.</citation>
    <PMID>26158353</PMID>
  </reference>
  <reference>
    <citation>Godley SH, Smith JE, Passetti LL, Subramaniam G. The Adolescent Community Reinforcement Approach (A-CRA) as a model paradigm for the management of adolescents with substance use disorders and co-occurring psychiatric disorders. Subst Abus. 2014;35(4):352-63. doi: 10.1080/08897077.2014.936993.</citation>
    <PMID>25035906</PMID>
  </reference>
  <reference>
    <citation>Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003 Apr-Jun;35(2):253-9. doi: 10.1080/02791072.2003.10400007.</citation>
    <PMID>12924748</PMID>
  </reference>
  <reference>
    <citation>Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in Drug and Opioid Overdose Deaths--United States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2016 Jan 1;64(50-51):1378-82. doi: 10.15585/mmwr.mm6450a3.</citation>
    <PMID>26720857</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <last_update_submitted>July 24, 2020</last_update_submitted>
  <last_update_submitted_qc>July 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Justine Welsh</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Adolescent Community Reinforcement Approach</keyword>
  <keyword>A-CRA</keyword>
  <keyword>Opioid-Related Disorders</keyword>
  <keyword>Behavior</keyword>
  <keyword>Psychosocial treatment</keyword>
  <keyword>Pharmacotherapy</keyword>
  <keyword>Randomized controlled</keyword>
  <keyword>Adolescent</keyword>
  <keyword>Young adult</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
    <mesh_term>Behavior, Addictive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Buprenorphine</mesh_term>
    <mesh_term>Buprenorphine, Naloxone Drug Combination</mesh_term>
    <mesh_term>Naloxone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03287180
org study id: IRB00093907
secondary id: 1R21DA046738-01
nct id: NCT03287180
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The study assesses whether adding a behavioral intervention, known as the Adolescent
      Community Reinforcement Approach (A-CRA), to the treatment of individuals already receiving
      buprenorphine/naloxone can improve treatment success and retention rates in young adults with
      severe opioid use disorder.
Buprenorphine is one of the medication assisted treatments approved by the FDA for opioid use
      disorders. Treatment with buprenorphine/naloxone may reduce the risk of opioid overdose and
      lower the occurrence of further conditions associated with injection drug use such as
      psychiatric disorders, hepatitis C infection, HIV, and high-risk sexual and criminal
      behaviors. The study assesses whether adding a behavioral intervention, known as the
      Adolescent Community Reinforcement Approach (A-CRA), to the treatment of individuals already
      receiving buprenorphine/naloxone can improve treatment success and retention rates in young
      adults with severe opioid use disorder.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This 12-week randomized controlled pilot trial will begin by an induction on sublingual buprenorphine/naloxone for all participants who would usually receive buprenorphine based treatment in the clinic. After the two-week induction phase, participants will be randomized into two groups. While continuing buprenorphine/naloxone the experimental group will receive a 12-week course of A-CRA, while the control group will be provided medical management by the prescriber. Medical management is the standard treatment approach for prescribing buprenorphine and covers medication adherence, side effects of the medication, assessment of withdrawal/cravings and dose adjustment as indicated. After completion of the 12-week A-CRA intervention, all individuals will receive weekly medical management sessions until week 24 (6 month follow up).
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of opiates-negative urine drug screens over the total number of urine drug screens at each stage
time frame: Each session (weekly) up to 24 weeks.
description: Qualitative urine test for opiates (+/-) will be performed. All presumptive positive assays will be confirmed by Gas Chromatography-Mass Spectrometry. The concentration value must be greater than or equal to the cutoff to be reported as positive. The opiates test results (positive/negative) will be documented. Proportion of opiates-negative urine drug screens over the total number of urine drug screens at each stage will be reported.
measure: Percent of days of opioid use within the past 90 days as indicated by self-report on the Global Appraisal of Individual Needs
time frame: Pre-treatment (baseline) and post-study intervention (12 weeks visit after completion of A-CRA ), and end of follow-up (24-week visit) .
description: The Global Appraisal of Individual Needs is a comprehensive, semi-structured interview measure with established validity and reliability used to identify and address a wide range of psychosocial problems in clinical populations. Average administration time for the GAIN Intake version is 1.5 hours and 45 minutes for the follow-up version. The assessment categories include background, school problems, work problems, physical health, sources of stress, risk behaviors and infectious diseases, mental health, substance use, and crime and violence. Substance use categories document self-reported frequency of substance use within the past 90 days for each substance endorsed (alcohol, opioids, marijuana, and other illicit psychoactive drugs). Individuals are able to say that they do not know, or refuse to answer any questions that they do not want to answer.
measure: Completion of the final phase of treatment defined as final study session (yes/no)
time frame: 24-week visit
description: To investigate any difference in treatment retention in the experimental group compared to the control group.
measure: Number of clinic visits by patient and any expected joint family member sessions
time frame: 2-, 12, and 24-week visits.
description: To investigate any difference in treatment retention in the experimental group compared to the control group.
arm group label: Experimental group
arm group type: Experimental
description: Participants in the experimental group will attend one individual assessment with the study physician for combination of buprenorphine/naloxone 4/1 prescription and urinalysis, along with one weekly Adolescent Community Reinforcement Approach (A-CRA) session (approximately 50 minutes).
arm group label: Control group
arm group type: Active Comparator
description: Participants in the control condition will attend weekly individual medical management sessions with the MD who will also provide a prescription for a combination of buprenorphine/naloxone 4/1 (approximately 25 minutes in duration).
intervention type: Behavioral
intervention name: Adolescent Community Reinforcement Approach (A-CRA)
description: The A-CRA is a modified version of the Community Reinforcement Approach for adolescents and transitional age youth. The A-CRA treatment protocol consists of nineteen procedures designed to promote positive behavior change directed towards prosocial activities and engagement in the individual's community. A community can include but is not limited to: social and peer activities, family interaction, and work or school environments. Some of the highlighted procedures include relapse prevention, sobriety sampling, problem solving, and communication skills. There are also combined parent/and or couples relationship sessions with the young adult. In the current study, 12-weeks of A-CRA treatment will be provided to the intervention group.
arm group label: Experimental group
intervention type: Other
intervention name: Combination of buprenorphine/naloxone 4/1
description: Buprenorphine is a partial agonist at mu-opioid receptor, an antagonist at kappa-opioid receptor. Naloxone is an antagonist at the mu-opioid receptor. Buprenorphine/naloxone requires the use of an induction to avoid the risk of withdrawal. Participants are instructed not to use opioids for at least 10 hours prior to first dose. Once symptoms of withdrawal score a minimum of 7 on the Clinical Opiate Withdrawal Scale (COWS), the first dose of 4/1 mg will be given. Participants will be monitored for an hour. An additional 4/1 mg dose can be provided to a dose that suppresses withdrawal effects. The physician then provides a prescription for 8/2-16/4 mg for Day 2. Doses can be adjusted with a maximum of total 24/6 mg/day. The target daily dose is 16/4 mg.
arm group label: Control group
arm group label: Experimental group
other name: Suboxone/Narcan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 25 Years
healthy volunteers: No
last name: Justine Welsh, MD
role: Principal Investigator
affiliation: SOM: Psych: Child Psych - CAMP Emory University
country: United States
citation: Arnett JJ. Emerging adulthood. A theory of development from the late teens through the twenties. Am Psychol. 2000 May;55(5):469-80.
PMID: 10842426
citation: Jones CM, Logan J, Gladden RM, Bohm MK. Vital Signs: Demographic and Substance Use Trends Among Heroin Users - United States, 2002-2013. MMWR Morb Mortal Wkly Rep. 2015 Jul 10;64(26):719-25.
PMID: 26158353
citation: Godley SH, Smith JE, Passetti LL, Subramaniam G. The Adolescent Community Reinforcement Approach (A-CRA) as a model paradigm for the management of adolescents with substance use disorders and co-occurring psychiatric disorders. Subst Abus. 2014;35(4):352-63. doi: 10.1080/08897077.2014.936993.
PMID: 25035906
citation: Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003 Apr-Jun;35(2):253-9. doi: 10.1080/02791072.2003.10400007.
PMID: 12924748
citation: Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in Drug and Opioid Overdose Deaths--United States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2016 Jan 1;64(50-51):1378-82. doi: 10.15585/mmwr.mm6450a3.
PMID: 26720857
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Justine Welsh
investigator title: Assistant Professor
mesh term: Opioid-Related Disorders
mesh term: Behavior, Addictive
mesh term: Buprenorphine
mesh term: Buprenorphine, Naloxone Drug Combination
mesh term: Naloxone
sharing ipd: Undecided