<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/NCT03015246</url>
  </required_header>
  <id_info>
    <org_study_id>BOS-1</org_study_id>
    <nct_id>NCT03015246</nct_id>
  </id_info>
  <brief_title>Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence</brief_title>
  <acronym>BOS</acronym>
  <official_title>Biobehavioral Studies of Opioid Seeking: Effects of Buprenorphine/Naloxone Dose on Experimental Stress Reactivity and Opioid Abstinence</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wayne State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wayne State University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research deals with behaviors that are part of opioid dependence. The purpose is to&#xD;
      study how stress and medication dose can affect opioid drug use.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      If participants meet all the criteria, their involvement in the study (Phases 1 and 2&#xD;
      described below) will last for 10-13 weeks. Participants will be asked to stay at the&#xD;
      research site for a minimum of 2 nights on 4 separate weeks and will have 22 office visits&#xD;
      During that time, participants can't leave the unit unescorted or have visitors.&#xD;
&#xD;
      Participants will receive a medication called Buprenorphine/Naloxone. Buprenorphine/Naloxone&#xD;
      is approved by the Food and Drug Administration (FDA) to treat opioid addiction, and is a&#xD;
      safe and effective alternative to methadone. Participants will receive this medication every&#xD;
      day. When participants are not living on the inpatient unit they will come to the research&#xD;
      clinic every day to receive the medication.&#xD;
&#xD;
      On Day 1, one single 1-mL (0.2 teaspoon) blood sample will be collected to assess the effect&#xD;
      of the Buprenorphine/Naloxone medication dose on gene expression pattern.&#xD;
&#xD;
      On each day of admission (once on weeks 3, 5 and 7), a single 1-mL (0.2 teaspoon) blood&#xD;
      sample will be collected to assess the effect of the buprenorphine/naloxone medication dose&#xD;
      on the participant's gene expression pattern.&#xD;
&#xD;
      On the 8 days while participants are an inpatient they will participate in experimental&#xD;
      sessions that involve drug administration. On some days participants will receive morphine&#xD;
      and on some days participants will receive oral medications called yohimbine and&#xD;
      hydrocortisone that will be used to study stress responses. Each afternoon study staff will&#xD;
      collect one blood sample (10 mL or 2 teaspoons) from a vein in the participant's arm; these&#xD;
      samples will be used to measure biological signals of stress.&#xD;
&#xD;
      At the end of the study participants will be detoxified from the Buprenorphine/Naloxone&#xD;
      medication over a 3-week outpatient period.&#xD;
&#xD;
      Study participants will be scheduled for one separate in-person visit at 1 month after week&#xD;
      11. At this follow-up visit participants will be asked to provide a urine sample and to&#xD;
      complete questionnaires that ask about drug craving and use, withdrawal symptoms, risky&#xD;
      situations for drug use, coping with stress, and consequences experienced from using drugs or&#xD;
      being abstinent.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">August 2020</completion_date>
  <primary_completion_date type="Actual">June 2020</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>Crossover Assignment</intervention_model>
    <intervention_model_description>4x2 within-subject crossover design: 4 medication conditions (morphine first, then 3 doses of buprenorphine/naloxone), crossed with 2 stress conditions (placebo vs. stress [yohimbine + hydrocortisone], nested within medication conditions)</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Medication conditions blinded using different-sized buprenorphine/naloxone sublingual tablets including placebo. Stress conditions blinded using encapsulation of yohimbine/placebo and hydrocortisone/placebo. Only pharmacy aware of drug codes.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Opioid price-inelasticity (economic demand)</measure>
    <time_frame>measured once (end of session) in each of the 8 experimental sessions over 7 weeks</time_frame>
    <description>demand intensity (L) and demand elasticity (a) on hypothetical drug purchasing task</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Opioid Symptom Questionnaire: Agonist symptoms</measure>
    <time_frame>Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.</time_frame>
    <description>Total opioid agonist symptom score (16 items, each scored on 0-4 scale, for a scale score range of 0-64, with higher scores indicating higher opioid agonist symptoms)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Opioid Symptom Questionnaire: Withdrawal symptoms</measure>
    <time_frame>Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.</time_frame>
    <description>Total opioid withdrawal symptom score (16 items, each scored on 0-4 scale, for a scale score range of 0-64, with higher scores indicating higher withdrawal symptoms)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual Analog Scale (VAS) ratings</measure>
    <time_frame>Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.</time_frame>
    <description>VAS ratings will measure &quot;liking&quot;, &quot;good drug effect,&quot; &quot;bad drug effect,&quot; &quot;stimulated,&quot; &quot;sedated&quot;, &quot;[preferred opioid] craving&quot;, and &quot;cigarette craving&quot;. Each VAS is scored from 0 (not at all) to 100 (extremely).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Profile of Mood States (POMS)</measure>
    <time_frame>Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.</time_frame>
    <description>72-item POMS questionnaire, which has several subscale scores</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.</time_frame>
    <description>Systolic/diastolic blood pressure (mm Hg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.</time_frame>
    <description>Heart rate (beats/min)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pupil diameter</measure>
    <time_frame>Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.</time_frame>
    <description>Pupil diameter (mm) measured with digital pupillometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma noradrenaline level</measure>
    <time_frame>Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions</time_frame>
    <description>Plasma noradrenaline level (µg/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma BDNF level (µg/ml)</measure>
    <time_frame>Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions</time_frame>
    <description>Plasma brain derived neurotrophic factor level (pg/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma IL-1Ra level (µg/ml)</measure>
    <time_frame>Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions</time_frame>
    <description>Plasma interleukin 1Ra level (pg/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Saliva cortisol level</measure>
    <time_frame>Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline, 1.5, 2, 3 and 4 hours post Yohimbine in each of the 8 experimental sessions.</time_frame>
    <description>Saliva cortisol level (µg/dL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Saliva alpha-amylase level</measure>
    <time_frame>Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline, 1.5, 2, 3 and 4 hours post Yohimbine in each of the 8 experimental sessions.</time_frame>
    <description>Saliva alpha-amylase level (U/dL)</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Heroin Dependence</condition>
  <condition>Opioid Use Disorder</condition>
  <arm_group>
    <arm_group_label>Extended-Release Morphine + placebo stressor</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be maintained on extended-release morphine (dose tailored to the individual, based on pre-experimental opioid use amount), in three divided daily doses. The placebo stressor will be administered on one day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Buprenorphine/Naloxone low dose + placebo stressor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 1.4/0.36 mg/day. The placebo stressor will be administered on one day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Buprenorphine/Naloxone moderate dose + placebo stressor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 4.2/1.08 mg/day. The placebo stressor will be administered on one day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Buprenorphine/Naloxone high dose + placebo stressor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be maintained on Buprenorphine-Naloxone (Zubsolv™) sublingual tablet doses of 12.8/3.16 mg/day. The placebo stressor will be administered on one day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Extended-Release Morphine + active stressor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be maintained on extended-release morphine (dose tailored to the individual, based on pre-experimental opioid use amount), in three divided daily doses. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Buprenorphine/Naloxone low dose + active stressor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 1.4/0.36 mg/day. The placebo stressor will be administered on one day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Buprenorphine/Naloxone moderate dose + active stressor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 4.2/1.08 mg/day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Buprenorphine/Naloxone high dose + active stressor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be maintained on Buprenorphine-Naloxone (Zubsolv™) sublingual tablet doses of 12.8/3.16 mg/day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Extended release morphine</intervention_name>
    <description>Dose (tailored to each participant based on his/her pre-experimental opioid use amount) is administered in 3 divided daily doses.</description>
    <arm_group_label>Extended-Release Morphine + active stressor</arm_group_label>
    <arm_group_label>Extended-Release Morphine + placebo stressor</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Buprenorphine/Naloxone low dose</intervention_name>
    <description>Buprenorphine/Naloxone dose of 1.4/0.36 mg/day</description>
    <arm_group_label>Buprenorphine/Naloxone low dose + active stressor</arm_group_label>
    <arm_group_label>Buprenorphine/Naloxone low dose + placebo stressor</arm_group_label>
    <other_name>Zubsolv™ sublingual tablet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Buprenorphine/Naloxone moderate dose</intervention_name>
    <description>Buprenorphine/Naloxone dose of 4.2/1.08 mg/day</description>
    <arm_group_label>Buprenorphine/Naloxone moderate dose + active stressor</arm_group_label>
    <arm_group_label>Buprenorphine/Naloxone moderate dose + placebo stressor</arm_group_label>
    <other_name>Zubsolv™ sublingual tablet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Buprenorphine/Naloxone high dose</intervention_name>
    <description>Buprenorphine/Naloxone dose of 12.8/3.16 mg/day</description>
    <arm_group_label>Buprenorphine/Naloxone high dose + active stressor</arm_group_label>
    <arm_group_label>Buprenorphine/Naloxone high dose + placebo stressor</arm_group_label>
    <other_name>Zubsolv™ sublingual tablet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Active stressor</intervention_name>
    <description>Yohimbine hydrochloride 60mg + Hydrocortisone 20mg tablet</description>
    <arm_group_label>Buprenorphine/Naloxone high dose + active stressor</arm_group_label>
    <arm_group_label>Buprenorphine/Naloxone low dose + active stressor</arm_group_label>
    <arm_group_label>Buprenorphine/Naloxone moderate dose + active stressor</arm_group_label>
    <arm_group_label>Extended-Release Morphine + active stressor</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo stressor</intervention_name>
    <description>Lactose</description>
    <arm_group_label>Buprenorphine/Naloxone high dose + placebo stressor</arm_group_label>
    <arm_group_label>Buprenorphine/Naloxone low dose + placebo stressor</arm_group_label>
    <arm_group_label>Buprenorphine/Naloxone moderate dose + placebo stressor</arm_group_label>
    <arm_group_label>Extended-Release Morphine + placebo stressor</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Opioid dependent, as determined by structured clinical interview for DSM-IV (SCID) and&#xD;
             Addiction Severity Index (ASI)&#xD;
&#xD;
          -  Positive urine test for opiates&#xD;
&#xD;
          -  Willing to use an adequate form of contraception for the duration of the study.&#xD;
&#xD;
          -  Reads and writes English&#xD;
&#xD;
          -  Participants must be in generally good health to be eligible. All candidates will&#xD;
             receive a routine medical exam (history and physical) with standard laboratory tests&#xD;
             (including blood and urine samples, EKG, mandatory TB testing, and voluntary HIV&#xD;
             testing).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No candidate who has a current DSM-IV Axis I disorder other than Drug Dependence or a&#xD;
             history of serious psychiatric problems (e.g. psychosis, bipolar or major depression)&#xD;
             will be allowed to participate.&#xD;
&#xD;
          -  Candidates meeting criteria for opioid or nicotine dependence will not be excluded,&#xD;
             but those with other Substance Dependence disorders will be excluded. Those with Abuse&#xD;
             of Alcohol, Cannabis, Cocaine, will not be excluded, but participants must provide an&#xD;
             alcohol free breath specimen.&#xD;
&#xD;
          -  No candidate with medical (neurological, cardiovascular, pulmonary or systemic)&#xD;
             disorders will be allowed to participate. This will be determined with history and&#xD;
             physical exam, standard laboratory testing (blood and urine), EKG, and TB tests (to&#xD;
             avoid transmitting this communicable disease on the residential unit or in the&#xD;
             laboratory).&#xD;
&#xD;
          -  Candidates with evidence of cognitive impairment (based on reading ability and&#xD;
             comprehension, will be excluded.&#xD;
&#xD;
          -  Female candidates who are pregnant (urine pregnancy test), lactating, or not using&#xD;
             adequate birth control methods (self-report) will be excluded.&#xD;
&#xD;
          -  Candidates with injection phobia, or seeking treatment for opioid dependence will be&#xD;
             excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark Greenwald, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wayne State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vince and Associates</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>November 6, 2020</last_update_submitted>
  <last_update_submitted_qc>November 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Wayne State University</investigator_affiliation>
    <investigator_full_name>Mark Greenwald, PhD</investigator_full_name>
    <investigator_title>Professor of Psychiatry and Behavioral Neurosciences; and Director, Substance Abuse Research Division</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
    <mesh_term>Heroin Dependence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Buprenorphine</mesh_term>
    <mesh_term>Buprenorphine, Naloxone Drug Combination</mesh_term>
    <mesh_term>Naloxone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03015246
org study id: BOS-1
nct id: NCT03015246
lead sponsor: 
has dmc: Yes
This research deals with behaviors that are part of opioid dependence. The purpose is to
      study how stress and medication dose can affect opioid drug use.
If participants meet all the criteria, their involvement in the study (Phases 1 and 2
      described below) will last for 10-13 weeks. Participants will be asked to stay at the
      research site for a minimum of 2 nights on 4 separate weeks and will have 22 office visits
      During that time, participants can't leave the unit unescorted or have visitors.

      Participants will receive a medication called Buprenorphine/Naloxone. Buprenorphine/Naloxone
      is approved by the Food and Drug Administration (FDA) to treat opioid addiction, and is a
      safe and effective alternative to methadone. Participants will receive this medication every
      day. When participants are not living on the inpatient unit they will come to the research
      clinic every day to receive the medication.

      On Day 1, one single 1-mL (0.2 teaspoon) blood sample will be collected to assess the effect
      of the Buprenorphine/Naloxone medication dose on gene expression pattern.

      On each day of admission (once on weeks 3, 5 and 7), a single 1-mL (0.2 teaspoon) blood
      sample will be collected to assess the effect of the buprenorphine/naloxone medication dose
      on the participant's gene expression pattern.

      On the 8 days while participants are an inpatient they will participate in experimental
      sessions that involve drug administration. On some days participants will receive morphine
      and on some days participants will receive oral medications called yohimbine and
      hydrocortisone that will be used to study stress responses. Each afternoon study staff will
      collect one blood sample (10 mL or 2 teaspoons) from a vein in the participant's arm; these
      samples will be used to measure biological signals of stress.

      At the end of the study participants will be detoxified from the Buprenorphine/Naloxone
      medication over a 3-week outpatient period.

      Study participants will be scheduled for one separate in-person visit at 1 month after week
      11. At this follow-up visit participants will be asked to provide a urine sample and to
      complete questionnaires that ask about drug craving and use, withdrawal symptoms, risky
      situations for drug use, coping with stress, and consequences experienced from using drugs or
      being abstinent.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: 4x2 within-subject crossover design: 4 medication conditions (morphine first, then 3 doses of buprenorphine/naloxone), crossed with 2 stress conditions (placebo vs. stress [yohimbine + hydrocortisone], nested within medication conditions)
primary purpose: Basic Science
masking: Double (Participant, Outcomes Assessor)
masking description: Medication conditions blinded using different-sized buprenorphine/naloxone sublingual tablets including placebo. Stress conditions blinded using encapsulation of yohimbine/placebo and hydrocortisone/placebo. Only pharmacy aware of drug codes.
measure: Opioid price-inelasticity (economic demand)
time frame: measured once (end of session) in each of the 8 experimental sessions over 7 weeks
description: demand intensity (L) and demand elasticity (a) on hypothetical drug purchasing task
measure: Opioid Symptom Questionnaire: Agonist symptoms
time frame: Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.
description: Total opioid agonist symptom score (16 items, each scored on 0-4 scale, for a scale score range of 0-64, with higher scores indicating higher opioid agonist symptoms)
measure: Opioid Symptom Questionnaire: Withdrawal symptoms
time frame: Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.
description: Total opioid withdrawal symptom score (16 items, each scored on 0-4 scale, for a scale score range of 0-64, with higher scores indicating higher withdrawal symptoms)
measure: Visual Analog Scale (VAS) ratings
time frame: Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.
description: VAS ratings will measure "liking", "good drug effect," "bad drug effect," "stimulated," "sedated", "[preferred opioid] craving", and "cigarette craving". Each VAS is scored from 0 (not at all) to 100 (extremely).
measure: Profile of Mood States (POMS)
time frame: Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.
description: 72-item POMS questionnaire, which has several subscale scores
measure: Blood pressure
time frame: Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.
description: Systolic/diastolic blood pressure (mm Hg)
measure: Heart rate
time frame: Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.
description: Heart rate (beats/min)
measure: Pupil diameter
time frame: Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline 0930, 1030, 1145, 1230, 1300, 1330, 1400, 1430, 1500, and 1600.
description: Pupil diameter (mm) measured with digital pupillometer
measure: Plasma noradrenaline level
time frame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions
description: Plasma noradrenaline level (µg/ml)
measure: Plasma BDNF level (µg/ml)
time frame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions
description: Plasma brain derived neurotrophic factor level (pg/ml)
measure: Plasma IL-1Ra level (µg/ml)
time frame: Measured once per session at 2-hours post Yohimbine in each of the 8 experimental sessions
description: Plasma interleukin 1Ra level (pg/ml)
measure: Saliva cortisol level
time frame: Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline, 1.5, 2, 3 and 4 hours post Yohimbine in each of the 8 experimental sessions.
description: Saliva cortisol level (µg/dL)
measure: Saliva alpha-amylase level
time frame: Within-session change is being assessed, in each of 8 sessions over 7 weeks. Within-session measurements at baseline, 1.5, 2, 3 and 4 hours post Yohimbine in each of the 8 experimental sessions.
description: Saliva alpha-amylase level (U/dL)
arm group label: Extended-Release Morphine + placebo stressor
arm group type: Placebo Comparator
description: Participants will be maintained on extended-release morphine (dose tailored to the individual, based on pre-experimental opioid use amount), in three divided daily doses. The placebo stressor will be administered on one day.
arm group label: Buprenorphine/Naloxone low dose + placebo stressor
arm group type: Experimental
description: Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 1.4/0.36 mg/day. The placebo stressor will be administered on one day.
arm group label: Buprenorphine/Naloxone moderate dose + placebo stressor
arm group type: Experimental
description: Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 4.2/1.08 mg/day. The placebo stressor will be administered on one day.
arm group label: Buprenorphine/Naloxone high dose + placebo stressor
arm group type: Experimental
description: Participants will be maintained on Buprenorphine-Naloxone (Zubsolv™) sublingual tablet doses of 12.8/3.16 mg/day. The placebo stressor will be administered on one day.
arm group label: Extended-Release Morphine + active stressor
arm group type: Experimental
description: Participants will be maintained on extended-release morphine (dose tailored to the individual, based on pre-experimental opioid use amount), in three divided daily doses. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
arm group label: Buprenorphine/Naloxone low dose + active stressor
arm group type: Experimental
description: Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 1.4/0.36 mg/day. The placebo stressor will be administered on one day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
arm group label: Buprenorphine/Naloxone moderate dose + active stressor
arm group type: Experimental
description: Participants will be maintained on Buprenorphine/Naloxone (Zubsolv™) sublingual tablet doses of 4.2/1.08 mg/day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
arm group label: Buprenorphine/Naloxone high dose + active stressor
arm group type: Experimental
description: Participants will be maintained on Buprenorphine-Naloxone (Zubsolv™) sublingual tablet doses of 12.8/3.16 mg/day. Yohimbine 60mg powder + Hydrocortisone (Cortef™) 20mg tablet administered on one day.
intervention type: Drug
intervention name: Extended release morphine
description: Dose (tailored to each participant based on his/her pre-experimental opioid use amount) is administered in 3 divided daily doses.
arm group label: Extended-Release Morphine + active stressor
arm group label: Extended-Release Morphine + placebo stressor
intervention type: Drug
intervention name: Buprenorphine/Naloxone low dose
description: Buprenorphine/Naloxone dose of 1.4/0.36 mg/day
arm group label: Buprenorphine/Naloxone low dose + active stressor
arm group label: Buprenorphine/Naloxone low dose + placebo stressor
other name: Zubsolv™ sublingual tablet
intervention type: Drug
intervention name: Buprenorphine/Naloxone moderate dose
description: Buprenorphine/Naloxone dose of 4.2/1.08 mg/day
arm group label: Buprenorphine/Naloxone moderate dose + active stressor
arm group label: Buprenorphine/Naloxone moderate dose + placebo stressor
other name: Zubsolv™ sublingual tablet
intervention type: Drug
intervention name: Buprenorphine/Naloxone high dose
description: Buprenorphine/Naloxone dose of 12.8/3.16 mg/day
arm group label: Buprenorphine/Naloxone high dose + active stressor
arm group label: Buprenorphine/Naloxone high dose + placebo stressor
other name: Zubsolv™ sublingual tablet
intervention type: Drug
intervention name: Active stressor
description: Yohimbine hydrochloride 60mg + Hydrocortisone 20mg tablet
arm group label: Buprenorphine/Naloxone high dose + active stressor
arm group label: Buprenorphine/Naloxone low dose + active stressor
arm group label: Buprenorphine/Naloxone moderate dose + active stressor
arm group label: Extended-Release Morphine + active stressor
intervention type: Drug
intervention name: Placebo stressor
description: Lactose
arm group label: Buprenorphine/Naloxone high dose + placebo stressor
arm group label: Buprenorphine/Naloxone low dose + placebo stressor
arm group label: Buprenorphine/Naloxone moderate dose + placebo stressor
arm group label: Extended-Release Morphine + placebo stressor
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Mark Greenwald, PhD
role: Principal Investigator
affiliation: Wayne State University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Wayne State University
investigator full name: Mark Greenwald, PhD
investigator title: Professor of Psychiatry and Behavioral Neurosciences; and Director, Substance Abuse Research Division
mesh term: Opioid-Related Disorders
mesh term: Heroin Dependence
mesh term: Morphine
mesh term: Buprenorphine
mesh term: Buprenorphine, Naloxone Drug Combination
mesh term: Naloxone
sharing ipd: No