<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/NCT03769025</url>
  </required_header>
  <id_info>
    <org_study_id>RODS</org_study_id>
    <secondary_id>5U34DA045177-03</secondary_id>
    <nct_id>NCT03769025</nct_id>
  </id_info>
  <brief_title>Remote Observed Dosing of Suboxone to Improve Clinical Practice</brief_title>
  <official_title>Remote Observed Dosing of Suboxone to Improve Clinical Practice</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</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>
      This is a 15-week, outpatient study of remote observed dosing to improve suboxone compliance&#xD;
      in opiate dependent subjects.The main purpose of this study is to see if watching patients&#xD;
      take their medication will improve treatment of opiate dependence by prompting patients to&#xD;
      take all prescribed doses of Suboxone. Suboxone is approved by the Food and Drug&#xD;
      Administration (FDA) for the treatment of opiate dependence. All patients receive a&#xD;
      smartphone and patients in the intervention (remote observed dosing) group will use the&#xD;
      smartphone to take videos of themselves taking Suboxone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Opioid use disorder (OUD) is a significant public health problem. About 2 million Americans&#xD;
      meet criteria for opioid use disorder involving prescription pain relievers and an additional&#xD;
      591,000 Americans meet criteria for a heroin use disorder. The rise in prescription opioid&#xD;
      use in the US has resulted in a dramatic increase in heroin use, as prescription opioid users&#xD;
      switch to heroin when their access to prescription opioids become less available. Opioids&#xD;
      (including prescription opioids and heroin) killed more than 33,000 people in 2015, more than&#xD;
      any year on record. Nearly half of all opioid overdose deaths involve a prescription opioid.&#xD;
&#xD;
      Buprenorphine, a partial agonist that exerts significant actions at the mu opioid receptor,&#xD;
      has been shown to be effective for the treatment of OUD. Because it is a partial agonist and&#xD;
      not prone to overdose, it is considered to be safe enough to dispense out of a clinician's&#xD;
      office as opposed to an opiate treatment program (OTP). The availability of buprenorphine&#xD;
      treatment outside of an OTP has significantly expanded the availability of effective&#xD;
      treatment for OUD and is associated with reducing disparities related to treatment access.&#xD;
&#xD;
      While initial studies reported little evidence of buprenorphine diversion, more recent&#xD;
      studies have indicated buprenorphine is prone to diversion and poor adherence that can&#xD;
      significantly diminish its safety and efficacy. In these US clinical trials, adequate&#xD;
      adherence to buprenorphine has been shown to occur in fewer than 50% of subjects who are&#xD;
      prescribed the medication. In a trial involving 50 African American subjects with opioid use&#xD;
      disorder participating in office based buprenorphine treatment, it was found that only 48% of&#xD;
      the subjects were adherent to the medication as defined as having 80% or more of their visits&#xD;
      associated with a positive UDS for buprenorphine. In another trial involving 703 subjects&#xD;
      with opioid use disorder only 41% of the subjects took buprenorphine 80% of the days it was&#xD;
      prescribed. Finally in an examination of medical and pharmacy claims data over a year, only&#xD;
      32% of patients participating in office based buprenorphine treatment took buprenorphine on&#xD;
      80% or more days.&#xD;
&#xD;
      Efforts to reduce poor adherence and diversion in buprenorphine maintenance generally include&#xD;
      smaller prescriptions and more frequent office visits. An alternative to frequent face to&#xD;
      face meetings is using smartphone technology to conduct remote observation of dosing (ROD).&#xD;
      In addition, OUD patients have expressed that observed dosing of MMT and flexible dose&#xD;
      prescription regimes play an important role in their treatment. However, there have been no&#xD;
      published studies using ROD to monitor compliance of Suboxone.&#xD;
&#xD;
      Remote Observed Dosing Intervention We conducted a Stage 1B integrated cellphone based&#xD;
      behavioral intervention that visually confirmed medication ingestion, thereby potentially&#xD;
      reducing buprenorphine misuse and diversion and improving medication adherence. Patients with&#xD;
      OUD, who were not currently prescribed buprenorphine, were recruited. All patients received&#xD;
      buprenorphine, a study provided smartphone, weekly Cognitive Behavioral Therapy (CBT), and&#xD;
      twice weekly urine screens. The experimental group video recorded themselves taking the&#xD;
      medication and these videos were automatically sent daily to the clinical research staff who&#xD;
      observed the dosing. This allowed for both the patients and clinical staff to find convenient&#xD;
      times to do the tasks and improved clinic office workflow. The attention control (AC) group&#xD;
      did not record their medication dosing.&#xD;
&#xD;
      Participants and Recruitment Participants and Eligibility. This study involved individuals&#xD;
      with Opioid Use Disorder (OUD) who received three months (12 weeks) of burpenorphine&#xD;
      (Suboxone) (standard dose will be up to 16 mgs/day, adjusted as necessary on an individual&#xD;
      basis).&#xD;
&#xD;
      Procedures: Patient and Clinical Data Collection Screening Procedures, Suboxone Induction and&#xD;
      Randomization. Potential participants will be screened for physical and psychological&#xD;
      appropriateness for inclusion in the study using standard intake procedures. Participants who&#xD;
      are appropriate for the trial will be inducted onto Suboxone using standard office based&#xD;
      induction as described in the ASAM National Practice Guideline for the Use of Medications in&#xD;
      the Treatment of Addiction Involving Opioid Use.&#xD;
&#xD;
      Participants will be randomized into one of two study groups based on proportion of use of&#xD;
      prescription opiates and heroin, gender, and prior Suboxone treatment. Both groups will&#xD;
      receive standard buprenorphine maintenance treatment. Participants will attend study visits&#xD;
      twice weekly for 12 weeks. One group will be assigned to Remote Observed Dosing (ROD) and&#xD;
      will have all of their Suboxone doses remotely observed using procedures described below. The&#xD;
      attention control (AC) group will not have their dosing observed but will send a video&#xD;
      message not associated with dosing to the study team daily matching contact time with the&#xD;
      study team.&#xD;
&#xD;
      Remote Observed Dosing Compliance. During the start-up phase of the project, we will record a&#xD;
      short 5 min instruction video that will be stored on participants' cellphones and on our&#xD;
      study web-site that will detail how to take the dosing video and how to ensure it was&#xD;
      uploaded correctly. Clinical staff and participants will also be able to use a HIPAA&#xD;
      compliant texting service to arrange appointments, send reminders and discuss any study&#xD;
      related issues that arise. Note: Participants in the control condition will be provided with&#xD;
      a list of prompts and asked to pick one prompt daily to record a video on. They will then&#xD;
      follow the same procedures as the experimental condition.&#xD;
&#xD;
      Step 1: Using the study provided smartphone a participant in the experimental condition will&#xD;
      use the front facing camera to record taking their study medication.&#xD;
&#xD;
      Step 2: The participant will remove the day's Suboxone dose from their pill pack, place the&#xD;
      dose (film) under their tongue and remain with their head in view of the camera until the&#xD;
      film dissolves completely. They will then open their mouth, raising their tongue to the roof&#xD;
      to ensure the dosage has been dissolved.&#xD;
&#xD;
      Step 3: The participant will end the recording. The phone will automatically save the video&#xD;
      onto the micro-sd card and the video will be automatically sent to a secure study server.&#xD;
      Once the video is uploaded, a notification message will appear on the participant's phone and&#xD;
      the study team will be notified a video has been uploaded. Each recording is expected to last&#xD;
      approximately 5 minutes. Note: by saving the video on the micro-sd card, we are safeguarding&#xD;
      in the event there is a &quot;bad connection&quot; or &quot;user error&quot; in the video uploading to the&#xD;
      server. Phones will be locked with a passcode and if a phone is lost/stolen, it will be&#xD;
      &quot;wiped&quot; clean remotely. In addition, a Certificate of Confidentiality will be requested for&#xD;
      this research study.&#xD;
&#xD;
      Step 4: Clinical staff will view the video daily. Any instances where the subject moves out&#xD;
      of camera view will be recorded as a day without dosing. If the video is not uploaded and is&#xD;
      not saved on the micro-sd card, it too will be recorded as a day without dosing.&#xD;
&#xD;
      Step 5: Clinical staff and participants will use a HIPAA compliant text messaging service to&#xD;
      communicate. Even though we will train participants on how to take and send dosing videos, we&#xD;
      anticipate there will be a slight learning curve. During this time, clinical staff will&#xD;
      communicate with participants on how to record the dosing.&#xD;
&#xD;
      All patients who are enrolled will receive a smartphone that includes unlimited talk, text&#xD;
      and data. The smartphones will be used to communicate with patients for appointments, make&#xD;
      reminder calls, discuss any study related issues, and to record and send the study videos.&#xD;
      All patients will be instructed on smartphone use, security and on how to use the phones to&#xD;
      record and send the videos to the study team. They will also be instructed about how to take&#xD;
      Suboxone and ROD patients will receive additional training on how to ensure the observed&#xD;
      dosing video is recorded and uploaded correctly.&#xD;
&#xD;
      Suboxone Dosing. After induction, all patients will receive open-label Suboxone for 12 weeks.&#xD;
      Patients in both groups will receive a weeks' worth of Suboxone at each medication management&#xD;
      visit. After the 12 weeks of Suboxone, subjects will be referred to on-going treatment&#xD;
      options in the community or will be tapered from Suboxone if they so desire.&#xD;
&#xD;
      Cognitive Behavioral Relapse Prevention. In addition to study medication, subjects will&#xD;
      participate in weekly, manualized, individual cognitive behavioral relapse prevention&#xD;
      psychotherapy. They will also receive weekly Medication Management (MM), adapted for MAT for&#xD;
      opioid use disorder.&#xD;
&#xD;
      Weekly visits. Patients will be seen twice weekly. For each in-office visit, patients will&#xD;
      provide a urine sample that will be tested for drugs of abuse and for quantitative&#xD;
      buprenorphine and norbuprenorphine levels. At each office visit, patients will also complete&#xD;
      questionnaires on mood, craving and general health. They will be asked about other&#xD;
      medications they are using, about their drug and alcohol use since their last visit, and&#xD;
      about any side effects they may be experiencing. Dosage adjustments will be made as needed at&#xD;
      the discretion of their clinician.&#xD;
&#xD;
      Medication adherence will be monitored by self-report and verified with creatinine normalized&#xD;
      quantitative urinary buprenorphine and norbuprenorphine levels. Urine was chosen as opposed&#xD;
      to blood levels to verify adherence for several reasons. First the high number of samples&#xD;
      needed to verify adherence over the course of a twelve-week trial would present a great&#xD;
      burden to the study patients. Frequent venipunctures can be difficult in patients with opioid&#xD;
      use disorder who have a history of IV use of opioids. Creatinine normalized quantitative&#xD;
      urine medication levels have been used successfully to verify medication adherence in trials&#xD;
      involving both methadone and buprenorphine.&#xD;
&#xD;
      Measures Columbia Suicide Severity Rating Scale (C-SSRS). This is a 5-item scale with&#xD;
      additional questions that may be asked based on the participant's responses to the core&#xD;
      items. This questionnaire will assess both lifetime and recent suicidal ideation and&#xD;
      behavior, including both passive and active thoughts/plans. This data will not be analyzed&#xD;
      but will be included to help ensure the safety of the participants.&#xD;
&#xD;
      Timeline Follow Back Interview (TLFB). (The TLFB is a 15-30 minute, semi-structured interview&#xD;
      adapted by our laboratory to collect information about daily drug, alcohol, and nicotine use.&#xD;
      The TLFB will be given by trained research staff at baseline to cover 3 months immediately&#xD;
      preceding treatment entry and will be updated at each research visit to determine any time&#xD;
      spent in a controlled environment and cocaine, nicotine, and other drug use during the period&#xD;
      since the last visit.&#xD;
&#xD;
      Video Compliance. Submission of videos will be recorded (date and time) and assessed daily&#xD;
      for compliance (ie., taking the medication as prescribed). In addition, videos will be saved&#xD;
      off the micro-sd cards at each office visit.&#xD;
&#xD;
      Laboratory Measurements (in alphabetical order) Pregnancy Testing. Urine pregnancy tests will&#xD;
      be obtained from all women at baseline, week 5, week 9, and end of study.&#xD;
&#xD;
      Quantitative urine buprenorphine and norbuprenorphine levels (using gas chromatography) with&#xD;
      urine creatinine used as a control for urinary concentration will be assessed twice weekly&#xD;
      throughout the trial. Qualitative (emit) urine toxicology for other drugs (benzodiazepines,&#xD;
      barbiturates, opiates, marijuana, methadone, and amphetamine) is done at baseline and weekly&#xD;
      throughout the trial.&#xD;
&#xD;
      DATA ANALYSIS For the ROD group, we will calculate the within-patient proportion of study&#xD;
      days on which video captured adherence, as per protocol. The primary comparison between the&#xD;
      groups will use the creatinine normalized weekly quantitative urine levels for buprenorphine&#xD;
      and norbuprenorphine. The main explanatory variable will be a binary indicator for group (ROD&#xD;
      vs AC). Our primary analyses will examine the two sets of responses (buprenorphine and&#xD;
      norbuprenorphine) separately.&#xD;
&#xD;
      Exploratory Aims Rates of illicit opiate use will be compared between the groups using urine&#xD;
      drug screens (UDS) obtained at each visit. A study week will be classified as a &quot;non-use&quot;&#xD;
      week if both UDS tests are available and are negative for opiates and if the participant&#xD;
      self-reports no use; a study week with a positive UDS or a self-report of use will be&#xD;
      classified as a &quot;use&quot; week; study weeks with incomplete data and no test or report of use&#xD;
      will be regarded as missing. The number of non-use weeks will be compared.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2019</start_date>
  <completion_date type="Actual">July 1, 2022</completion_date>
  <primary_completion_date type="Actual">May 31, 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Urinary Buprenorphine Levels</measure>
    <time_frame>12 weeks</time_frame>
    <description>compare the mean urinary buprenorphine level obtained over 12 weeks between the two groups</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent of Urine Positive Drug Screens</measure>
    <time_frame>12 weeks</time_frame>
    <description>Percent of urine drug screens positive for opiates</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Opioid-use Disorder</condition>
  <condition>Opioid Dependence</condition>
  <condition>Opiate Dependence</condition>
  <arm_group>
    <arm_group_label>Remote Observed Dosing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One group will be assigned to Remote Observed Dosing (ROD) and will have all of their Suboxone® doses remotely observed. The intervention is remote observed dosing</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Attention Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The attention control (AC) group will not have their dosing observed but will send a text message confirming they have taken their study medication to the study team daily matching contact with the study team. Text message confirming that they have taken their study medication is the intervention</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Suboxone Remote Observed Dosing</intervention_name>
    <description>The remote observed dosing group will use the provided smartphone to video record themselves taking their Suboxone dose each day</description>
    <arm_group_label>Remote Observed Dosing</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Suboxone Attention Control</intervention_name>
    <description>Attention control group will send a text message daily confirming that they have taken their Suboxone dose</description>
    <arm_group_label>Attention Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Voluntarily provide written informed consent prior to the conduct of any study-related&#xD;
             procedure&#xD;
&#xD;
          -  Male, female, or transgender&#xD;
&#xD;
          -  18 - 45 years of age&#xD;
&#xD;
          -  Meet DSM 5 criteria for opioid use disorder moderate to severe&#xD;
&#xD;
          -  Women of childbearing potential must use a reliable means of contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current diagnosis of AIDS&#xD;
&#xD;
          -  Participation in buprenorphine maintenance treatment within the past 3 months&#xD;
&#xD;
          -  Presence of AST and/or ALT equal to or &gt; 3X upper limit of normal&#xD;
&#xD;
          -  Total bilirubin equal to or &gt; 1.5X upper limit of normal and/or estimated creatinine&#xD;
             clearance &lt; 60ml/min&#xD;
&#xD;
          -  Current diagnosis of pain requiring opioids&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Previous hypersensitivity or allergy to buprenorphine&#xD;
&#xD;
          -  Current use of agents metabolized through CYP 3A4 such as azole antifungals (e.g.&#xD;
             ketoconazole), macrolide antibiotics (e.g. erythromycin), and protease inhibitors&#xD;
             (e.g. ritonavir, indinavir, saquinavir)&#xD;
&#xD;
          -  Meet DSM - 5 criteria for current use disorder for any psychoactive substances other&#xD;
             than opioids, marijuana, cocaine or nicotine (e.g. alcohol, sedatives)&#xD;
&#xD;
          -  Current use of benzodiazepines&#xD;
&#xD;
          -  Significant medical or psychiatric symptoms or dementia which in the opinion of the&#xD;
             investigators would preclude compliance with the protocol, adequate cooperation in the&#xD;
             study, or obtaining informed consent&#xD;
&#xD;
          -  Concurrent medical conditions (such as severe respiratory insufficiency) that may&#xD;
             prevent the patient from safely participating in the study; and/or any pending legal&#xD;
             action that could prohibit participation and/or compliance in study procedures&#xD;
&#xD;
          -  Unwilling to accept or use alternative transportation (i.e. public transportation,&#xD;
             taxi services, etc.) instead of driving self to appointments during Suboxone Induction&#xD;
&#xD;
          -  Living in unstable housing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kyle Kampman, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Brenda Curtis, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennsylvania Treatment Research Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <results_first_submitted>July 23, 2023</results_first_submitted>
  <results_first_submitted_qc>July 25, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 27, 2023</results_first_posted>
  <last_update_submitted>July 25, 2023</last_update_submitted>
  <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pennsylvania</investigator_affiliation>
    <investigator_full_name>Kyle Kampman</investigator_full_name>
    <investigator_title>Medical Director</investigator_title>
  </responsible_party>
  <keyword>remote observed dosing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Buprenorphine, Naloxone Drug Combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 16, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/25/NCT03769025/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Remote Observed Dosing</title>
          <description>One group will be assigned to Remote Observed Dosing (ROD) and will have all of their Suboxone® doses remotely observed. The intervention is remote observed dosing&#xD;
Suboxone Remote Observed Dosing: The remote observed dosing group will use the provided smartphone to video record themselves taking their Suboxone dose each day</description>
        </group>
        <group group_id="P2">
          <title>Attention Control</title>
          <description>The attention control (AC) group will not have their dosing observed but will send a text message confirming they have taken their study medication to the study team daily matching contact with the study team. Text message confirming that they have taken their study medication is the intervention&#xD;
Suboxone Attention Control: Attention control group will send a text message daily confirming that they have taken their Suboxone dose</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Remote Observed Dosing</title>
          <description>One group will be assigned to Remote Observed Dosing (ROD) and will have all of their Suboxone® doses remotely observed. The intervention is remote observed dosing&#xD;
Suboxone Remote Observed Dosing: The remote observed dosing group will use the provided smartphone to video record themselves taking their Suboxone dose each day</description>
        </group>
        <group group_id="B2">
          <title>Attention Control</title>
          <description>The attention control (AC) group will not have their dosing observed but will send a text message confirming they have taken their study medication to the study team daily matching contact with the study team. Text message confirming that they have taken their study medication is the intervention&#xD;
Suboxone Attention Control: Attention control group will send a text message daily confirming that they have taken their Suboxone dose</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
            <count group_id="B2" value="8"/>
            <count group_id="B3" value="16"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34" spread="5.1"/>
                    <measurement group_id="B2" value="34" spread="8.4"/>
                    <measurement group_id="B3" value="34" spread="6.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Urinary Buprenorphine Levels</title>
        <description>compare the mean urinary buprenorphine level obtained over 12 weeks between the two groups</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Remote Observed Dosing</title>
            <description>One group will be assigned to Remote Observed Dosing (ROD) and will have all of their Suboxone® doses remotely observed. The intervention is remote observed dosing&#xD;
Suboxone Remote Observed Dosing: The remote observed dosing group will use the provided smartphone to video record themselves taking their Suboxone dose each day</description>
          </group>
          <group group_id="O2">
            <title>Attention Control</title>
            <description>The attention control (AC) group will not have their dosing observed but will send a text message confirming they have taken their study medication to the study team daily matching contact with the study team. Text message confirming that they have taken their study medication is the intervention&#xD;
Suboxone Attention Control: Attention control group will send a text message daily confirming that they have taken their Suboxone dose</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Urinary Buprenorphine Levels</title>
          <description>compare the mean urinary buprenorphine level obtained over 12 weeks between the two groups</description>
          <units>ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="861" spread="1656"/>
                    <measurement group_id="O2" value="287" spread="253"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.1</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Urine Positive Drug Screens</title>
        <description>Percent of urine drug screens positive for opiates</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Remote Observed Dosing</title>
            <description>One group will be assigned to Remote Observed Dosing (ROD) and will have all of their Suboxone® doses remotely observed. The intervention is remote observed dosing&#xD;
Suboxone Remote Observed Dosing: The remote observed dosing group will use the provided smartphone to video record themselves taking their Suboxone dose each day</description>
          </group>
          <group group_id="O2">
            <title>Attention Control</title>
            <description>The attention control (AC) group will not have their dosing observed but will send a text message confirming they have taken their study medication to the study team daily matching contact with the study team. Text message confirming that they have taken their study medication is the intervention&#xD;
Suboxone Attention Control: Attention control group will send a text message daily confirming that they have taken their Suboxone dose</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Urine Positive Drug Screens</title>
          <description>Percent of urine drug screens positive for opiates</description>
          <units>percent of urine positive drug screens</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".3" spread=".36"/>
                    <measurement group_id="O2" value=".29" spread=".49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.959</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 week</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Remote Observed Dosing</title>
          <description>One group will be assigned to Remote Observed Dosing (ROD) and will have all of their Suboxone® doses remotely observed. The intervention is remote observed dosing&#xD;
Suboxone Remote Observed Dosing: The remote observed dosing group will use the provided smartphone to video record themselves taking their Suboxone dose each day</description>
        </group>
        <group group_id="E2">
          <title>Attention Control</title>
          <description>The attention control (AC) group will not have their dosing observed but will send a text message confirming they have taken their study medication to the study team daily matching contact with the study team. Text message confirming that they have taken their study medication is the intervention&#xD;
Suboxone Attention Control: Attention control group will send a text message daily confirming that they have taken their Suboxone dose</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 10.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>nephrolithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 10.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>drug withdrawal</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>upper respiratory infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>arthralgias</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>flushing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>edema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>skin infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This trial was intended to be a preliminary trial and involved a small number of subjects. Results should be interpreted accordingly.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Kyle M Kampman MD Principal Investigator</name_or_title>
      <organization>Perelman School of Medicine</organization>
      <phone>215 746 2764</phone>
      <email>kampman@pennmedicine.upenn.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03769025
org study id: RODS
secondary id: 5U34DA045177-03
nct id: NCT03769025
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a 15-week, outpatient study of remote observed dosing to improve suboxone compliance
      in opiate dependent subjects.The main purpose of this study is to see if watching patients
      take their medication will improve treatment of opiate dependence by prompting patients to
      take all prescribed doses of Suboxone. Suboxone is approved by the Food and Drug
      Administration (FDA) for the treatment of opiate dependence. All patients receive a
      smartphone and patients in the intervention (remote observed dosing) group will use the
      smartphone to take videos of themselves taking Suboxone.
Opioid use disorder (OUD) is a significant public health problem. About 2 million Americans
      meet criteria for opioid use disorder involving prescription pain relievers and an additional
      591,000 Americans meet criteria for a heroin use disorder. The rise in prescription opioid
      use in the US has resulted in a dramatic increase in heroin use, as prescription opioid users
      switch to heroin when their access to prescription opioids become less available. Opioids
      (including prescription opioids and heroin) killed more than 33,000 people in 2015, more than
      any year on record. Nearly half of all opioid overdose deaths involve a prescription opioid.

      Buprenorphine, a partial agonist that exerts significant actions at the mu opioid receptor,
      has been shown to be effective for the treatment of OUD. Because it is a partial agonist and
      not prone to overdose, it is considered to be safe enough to dispense out of a clinician's
      office as opposed to an opiate treatment program (OTP). The availability of buprenorphine
      treatment outside of an OTP has significantly expanded the availability of effective
      treatment for OUD and is associated with reducing disparities related to treatment access.

      While initial studies reported little evidence of buprenorphine diversion, more recent
      studies have indicated buprenorphine is prone to diversion and poor adherence that can
      significantly diminish its safety and efficacy. In these US clinical trials, adequate
      adherence to buprenorphine has been shown to occur in fewer than 50% of subjects who are
      prescribed the medication. In a trial involving 50 African American subjects with opioid use
      disorder participating in office based buprenorphine treatment, it was found that only 48% of
      the subjects were adherent to the medication as defined as having 80% or more of their visits
      associated with a positive UDS for buprenorphine. In another trial involving 703 subjects
      with opioid use disorder only 41% of the subjects took buprenorphine 80% of the days it was
      prescribed. Finally in an examination of medical and pharmacy claims data over a year, only
      32% of patients participating in office based buprenorphine treatment took buprenorphine on
      80% or more days.

      Efforts to reduce poor adherence and diversion in buprenorphine maintenance generally include
      smaller prescriptions and more frequent office visits. An alternative to frequent face to
      face meetings is using smartphone technology to conduct remote observation of dosing (ROD).
      In addition, OUD patients have expressed that observed dosing of MMT and flexible dose
      prescription regimes play an important role in their treatment. However, there have been no
      published studies using ROD to monitor compliance of Suboxone.

      Remote Observed Dosing Intervention We conducted a Stage 1B integrated cellphone based
      behavioral intervention that visually confirmed medication ingestion, thereby potentially
      reducing buprenorphine misuse and diversion and improving medication adherence. Patients with
      OUD, who were not currently prescribed buprenorphine, were recruited. All patients received
      buprenorphine, a study provided smartphone, weekly Cognitive Behavioral Therapy (CBT), and
      twice weekly urine screens. The experimental group video recorded themselves taking the
      medication and these videos were automatically sent daily to the clinical research staff who
      observed the dosing. This allowed for both the patients and clinical staff to find convenient
      times to do the tasks and improved clinic office workflow. The attention control (AC) group
      did not record their medication dosing.

      Participants and Recruitment Participants and Eligibility. This study involved individuals
      with Opioid Use Disorder (OUD) who received three months (12 weeks) of burpenorphine
      (Suboxone) (standard dose will be up to 16 mgs/day, adjusted as necessary on an individual
      basis).

      Procedures: Patient and Clinical Data Collection Screening Procedures, Suboxone Induction and
      Randomization. Potential participants will be screened for physical and psychological
      appropriateness for inclusion in the study using standard intake procedures. Participants who
      are appropriate for the trial will be inducted onto Suboxone using standard office based
      induction as described in the ASAM National Practice Guideline for the Use of Medications in
      the Treatment of Addiction Involving Opioid Use.

      Participants will be randomized into one of two study groups based on proportion of use of
      prescription opiates and heroin, gender, and prior Suboxone treatment. Both groups will
      receive standard buprenorphine maintenance treatment. Participants will attend study visits
      twice weekly for 12 weeks. One group will be assigned to Remote Observed Dosing (ROD) and
      will have all of their Suboxone doses remotely observed using procedures described below. The
      attention control (AC) group will not have their dosing observed but will send a video
      message not associated with dosing to the study team daily matching contact time with the
      study team.

      Remote Observed Dosing Compliance. During the start-up phase of the project, we will record a
      short 5 min instruction video that will be stored on participants' cellphones and on our
      study web-site that will detail how to take the dosing video and how to ensure it was
      uploaded correctly. Clinical staff and participants will also be able to use a HIPAA
      compliant texting service to arrange appointments, send reminders and discuss any study
      related issues that arise. Note: Participants in the control condition will be provided with
      a list of prompts and asked to pick one prompt daily to record a video on. They will then
      follow the same procedures as the experimental condition.

      Step 1: Using the study provided smartphone a participant in the experimental condition will
      use the front facing camera to record taking their study medication.

      Step 2: The participant will remove the day's Suboxone dose from their pill pack, place the
      dose (film) under their tongue and remain with their head in view of the camera until the
      film dissolves completely. They will then open their mouth, raising their tongue to the roof
      to ensure the dosage has been dissolved.

      Step 3: The participant will end the recording. The phone will automatically save the video
      onto the micro-sd card and the video will be automatically sent to a secure study server.
      Once the video is uploaded, a notification message will appear on the participant's phone and
      the study team will be notified a video has been uploaded. Each recording is expected to last
      approximately 5 minutes. Note: by saving the video on the micro-sd card, we are safeguarding
      in the event there is a "bad connection" or "user error" in the video uploading to the
      server. Phones will be locked with a passcode and if a phone is lost/stolen, it will be
      "wiped" clean remotely. In addition, a Certificate of Confidentiality will be requested for
      this research study.

      Step 4: Clinical staff will view the video daily. Any instances where the subject moves out
      of camera view will be recorded as a day without dosing. If the video is not uploaded and is
      not saved on the micro-sd card, it too will be recorded as a day without dosing.

      Step 5: Clinical staff and participants will use a HIPAA compliant text messaging service to
      communicate. Even though we will train participants on how to take and send dosing videos, we
      anticipate there will be a slight learning curve. During this time, clinical staff will
      communicate with participants on how to record the dosing.

      All patients who are enrolled will receive a smartphone that includes unlimited talk, text
      and data. The smartphones will be used to communicate with patients for appointments, make
      reminder calls, discuss any study related issues, and to record and send the study videos.
      All patients will be instructed on smartphone use, security and on how to use the phones to
      record and send the videos to the study team. They will also be instructed about how to take
      Suboxone and ROD patients will receive additional training on how to ensure the observed
      dosing video is recorded and uploaded correctly.

      Suboxone Dosing. After induction, all patients will receive open-label Suboxone for 12 weeks.
      Patients in both groups will receive a weeks' worth of Suboxone at each medication management
      visit. After the 12 weeks of Suboxone, subjects will be referred to on-going treatment
      options in the community or will be tapered from Suboxone if they so desire.

      Cognitive Behavioral Relapse Prevention. In addition to study medication, subjects will
      participate in weekly, manualized, individual cognitive behavioral relapse prevention
      psychotherapy. They will also receive weekly Medication Management (MM), adapted for MAT for
      opioid use disorder.

      Weekly visits. Patients will be seen twice weekly. For each in-office visit, patients will
      provide a urine sample that will be tested for drugs of abuse and for quantitative
      buprenorphine and norbuprenorphine levels. At each office visit, patients will also complete
      questionnaires on mood, craving and general health. They will be asked about other
      medications they are using, about their drug and alcohol use since their last visit, and
      about any side effects they may be experiencing. Dosage adjustments will be made as needed at
      the discretion of their clinician.

      Medication adherence will be monitored by self-report and verified with creatinine normalized
      quantitative urinary buprenorphine and norbuprenorphine levels. Urine was chosen as opposed
      to blood levels to verify adherence for several reasons. First the high number of samples
      needed to verify adherence over the course of a twelve-week trial would present a great
      burden to the study patients. Frequent venipunctures can be difficult in patients with opioid
      use disorder who have a history of IV use of opioids. Creatinine normalized quantitative
      urine medication levels have been used successfully to verify medication adherence in trials
      involving both methadone and buprenorphine.

      Measures Columbia Suicide Severity Rating Scale (C-SSRS). This is a 5-item scale with
      additional questions that may be asked based on the participant's responses to the core
      items. This questionnaire will assess both lifetime and recent suicidal ideation and
      behavior, including both passive and active thoughts/plans. This data will not be analyzed
      but will be included to help ensure the safety of the participants.

      Timeline Follow Back Interview (TLFB). (The TLFB is a 15-30 minute, semi-structured interview
      adapted by our laboratory to collect information about daily drug, alcohol, and nicotine use.
      The TLFB will be given by trained research staff at baseline to cover 3 months immediately
      preceding treatment entry and will be updated at each research visit to determine any time
      spent in a controlled environment and cocaine, nicotine, and other drug use during the period
      since the last visit.

      Video Compliance. Submission of videos will be recorded (date and time) and assessed daily
      for compliance (ie., taking the medication as prescribed). In addition, videos will be saved
      off the micro-sd cards at each office visit.

      Laboratory Measurements (in alphabetical order) Pregnancy Testing. Urine pregnancy tests will
      be obtained from all women at baseline, week 5, week 9, and end of study.

      Quantitative urine buprenorphine and norbuprenorphine levels (using gas chromatography) with
      urine creatinine used as a control for urinary concentration will be assessed twice weekly
      throughout the trial. Qualitative (emit) urine toxicology for other drugs (benzodiazepines,
      barbiturates, opiates, marijuana, methadone, and amphetamine) is done at baseline and weekly
      throughout the trial.

      DATA ANALYSIS For the ROD group, we will calculate the within-patient proportion of study
      days on which video captured adherence, as per protocol. The primary comparison between the
      groups will use the creatinine normalized weekly quantitative urine levels for buprenorphine
      and norbuprenorphine. The main explanatory variable will be a binary indicator for group (ROD
      vs AC). Our primary analyses will examine the two sets of responses (buprenorphine and
      norbuprenorphine) separately.

      Exploratory Aims Rates of illicit opiate use will be compared between the groups using urine
      drug screens (UDS) obtained at each visit. A study week will be classified as a "non-use"
      week if both UDS tests are available and are negative for opiates and if the participant
      self-reports no use; a study week with a positive UDS or a self-report of use will be
      classified as a "use" week; study weeks with incomplete data and no test or report of use
      will be regarded as missing. The number of non-use weeks will be compared.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mean Urinary Buprenorphine Levels
time frame: 12 weeks
description: compare the mean urinary buprenorphine level obtained over 12 weeks between the two groups
measure: Percent of Urine Positive Drug Screens
time frame: 12 weeks
description: Percent of urine drug screens positive for opiates
arm group label: Remote Observed Dosing
arm group type: Experimental
description: One group will be assigned to Remote Observed Dosing (ROD) and will have all of their Suboxone® doses remotely observed. The intervention is remote observed dosing
arm group label: Attention Control
arm group type: Active Comparator
description: The attention control (AC) group will not have their dosing observed but will send a text message confirming they have taken their study medication to the study team daily matching contact with the study team. Text message confirming that they have taken their study medication is the intervention
intervention type: Behavioral
intervention name: Suboxone Remote Observed Dosing
description: The remote observed dosing group will use the provided smartphone to video record themselves taking their Suboxone dose each day
arm group label: Remote Observed Dosing
intervention type: Other
intervention name: Suboxone Attention Control
description: Attention control group will send a text message daily confirming that they have taken their Suboxone dose
arm group label: Attention Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Kyle Kampman, MD
role: Study Director
affiliation: University of Pennsylvania
last name: Brenda Curtis, PhD
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pennsylvania
investigator full name: Kyle Kampman
investigator title: Medical Director
mesh term: Opioid-Related Disorders
mesh term: Buprenorphine, Naloxone Drug Combination
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This trial was intended to be a preliminary trial and involved a small number of subjects. Results should be interpreted accordingly.
point of contact: 