<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/NCT04473950</url>
  </required_header>
  <id_info>
    <org_study_id>Z-1902</org_study_id>
    <nct_id>NCT04473950</nct_id>
  </id_info>
  <brief_title>The Effect of Chronic Pain on Delay Discounting in Methadone Patients</brief_title>
  <official_title>The Effect of Chronic Pain on Delay Discounting in Methadone Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The epidemic of opioid overdose deaths continues to rise, killing more persons in 2017 than&#xD;
      HIV/AIDS at the height of that epidemic. Medication assisted treatment, including methadone&#xD;
      and buprenorphine, is the standard of care for the treatment of opioid use disorder (OUD).&#xD;
      However, chronic pain can reduce treatment efficacy during medication assisted treatment and&#xD;
      is associated with illicit substance relapse, dropout, and subsequent overdose. Mechanisms by&#xD;
      which chronic pain may influence the impulsive decision making (e.g., drug relapse) in&#xD;
      persons with OUD have not been well characterized. A better understanding is needed of&#xD;
      decision-making in this population. Two factors that can influence decisions to use drugs are&#xD;
      impulsivity and acute opioid withdrawal. This proposal will test how chronic pain is&#xD;
      associated with increases in impulsive decision making in OUD, whether impulsive decision&#xD;
      making is greater when undergoing opioid withdrawal, and how catastrophizing may modify the&#xD;
      association between withdrawal and impulsive decision making in patients with chronic pain&#xD;
      and OUD. An ideal population for this developmental research project are methadone maintained&#xD;
      patients, who show high treatment attendance rates and will therefore assure study efficiency&#xD;
      and reliable completion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an outpatient Phase 1 clinical trial investigating the effect of naloxone&#xD;
      precipitated withdrawal on delay discounting. Eligible participants will undergo two&#xD;
      experimental sessions presented in random order. One session will involve the measurement of&#xD;
      delay discounting 30 minutes after double-blind intramuscular (IM) administration of placebo&#xD;
      (normal saline) and the other will have the exact same procedures performed after&#xD;
      double-blind IM administration of naloxone (0.1 mg). Injections will occur 2 hours after&#xD;
      methadone dosing (peak levels). Study sessions will last 2 hours and involve pain and opioid&#xD;
      withdrawal measures assessed at baseline and 15 minute intervals after injections. The&#xD;
      participant should be back to baseline and free of withdrawal by the end of the study&#xD;
      session. Sessions will occur at least 48 hours apart.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The COVID-19 Pandemic prevented us from meeting target goals.&#xD;
  </why_stopped>
  <start_date type="Actual">January 8, 2020</start_date>
  <completion_date type="Actual">October 6, 2022</completion_date>
  <primary_completion_date type="Actual">October 6, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This proposal is a randomized double-blind placebo controlled Phase 1 clinical trial / human laboratory study</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>The participant, investigator, medical personnel administering study drug, and outcomes assessor will be blinded to drug being administered.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Delay discounting of money rate (k)</measure>
    <time_frame>k will be calculated from the same series of discounting questions that will be asked once each session at approcimately 30 minutes after study IM medication administration.</time_frame>
    <description>Delay discounting is the relative preference for smaller sooner over larger later rewards, an aspect of impulsivity. Most individuals would prefer an immediate $100 over $100 delayed by 1 year. However, when faced with the choice between receiving $95 now versus $100 in 1 year, preferences for the delayed reward may increase. By assessing such choices across multiple delays, delay discounting quantifies the devaluation of rewards over time, which allows for an index of overall discounting rate (k).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Study Session Peak Pain Visual Analog Scale (VAS)</measure>
    <time_frame>Peak Pain VAS will be the highest rating during each 2 hour study session.</time_frame>
    <description>Current pain level rated on 0-100 VAS. This is the validated pain scale typically used by clinicians in an outpatient or inpatient clinical visit to represent current level of pain. Higher ratings indicate worse pain severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Clinical Opiate Withdrawal Scale (COWS) Rating</measure>
    <time_frame>Peak COWS rating will be the highest rating during each 2 hour study session.</time_frame>
    <description>The COWS is an 11-item validated clinician administered scale that quantifies level of opioid withdrawal. The range of scores is 0-48, with higher scores indicating greater withdrawal severity. The peak COWS rating will be the highest measurement in the session after study drug administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Subjective Opiate Withdrawal Scale (SOWS) Rating</measure>
    <time_frame>Peak SOWS rating will be the highest rating during each 2 hour study session.</time_frame>
    <description>The SOWS is a 16 item validated self-administered scale for grading opioid withdrawal symptoms. The range of scores is 0-64, with higher scores indicating greater withdrawal severity. The peak SOWS rating will be the highest measurement in the session after study drug administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Increase from baseline Pupil Diameter</measure>
    <time_frame>Peak increase from baseline pupil diameter will be the largest increase from baseline pupil diameter measured during each 2 hour study session.</time_frame>
    <description>Pupil diameter (mm) will be measured via digital pupillometer in standard room lighting at baseline and then throughout the study session after study drug administration. The peak increase from baseline value will be the largest increase from baseline pupil diameter measured after study drug administration.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Opioid-use Disorder</condition>
  <condition>Chronic Pain Syndrome</condition>
  <arm_group>
    <arm_group_label>Pain Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with chronic pain who are maintained on methadone for opioid use disorder</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Pain Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients who are maintained on methadone for opioid use disorder but who do not have chronic pain.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Naloxone Hydrochloride</intervention_name>
    <description>An intramuscular (IM) injection of naloxone will be given.</description>
    <arm_group_label>No Pain Group</arm_group_label>
    <arm_group_label>Pain Group</arm_group_label>
    <other_name>Narcan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>An IM injection of 0.9% normal saline will be given.</description>
    <arm_group_label>No Pain Group</arm_group_label>
    <arm_group_label>Pain Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female adults aged 18-65&#xD;
&#xD;
          -  Stable methadone dose (at least 21 days) verified by contacting participant's opioid&#xD;
             treatment program&#xD;
&#xD;
          -  Understand and speak English&#xD;
&#xD;
          -  Urine toxicology screen negative for drugs of abuse and positive for methadone&#xD;
&#xD;
          -  Participants must be without signs of intoxication as evidenced by ability to receive&#xD;
             full dose of methadone prior to research activities.&#xD;
&#xD;
          -  Presence of chronic pain (&gt;3 months) for the Pain group and absence of pain for the No&#xD;
             Pain group.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unstable psychiatric illness as assessed by the Mini International Neuropsychiatric&#xD;
             Interview (e.g. active suicidal ideation, psychosis)&#xD;
&#xD;
          -  Unstable medical illness as assessed by the study's independent medical monitor (e.g.&#xD;
             uncontrolled hypertension, recent myocardial infarction, recent stroke, unstable&#xD;
             angina) that may be affected by precipitated withdrawal&#xD;
&#xD;
          -  Prescription opioid use besides methadone&#xD;
&#xD;
          -  Acute pain process unrelated to chronic pain&#xD;
&#xD;
          -  Women who are pregnant or lactating&#xD;
&#xD;
          -  Known allergy to naloxone&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>D. Andrew Tompkins, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Zuckerberg San Francisco General Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>October 6, 2022</last_update_submitted>
  <last_update_submitted_qc>October 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>delay discounting</keyword>
  <keyword>pain catastrophizing</keyword>
  <keyword>impulsivity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chronic Pain</mesh_term>
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Naloxone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data will be made available to the public through presentation at scientific meetings and research publications in peer-reviewed journals. I have routinely kept an open policy to share data with the scientific and medical community upon request, and this policy will be continued with the present project.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data will become available after publication of the main study results.</ipd_time_frame>
  </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/NCT04473950
org study id: Z-1902
nct id: NCT04473950
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The epidemic of opioid overdose deaths continues to rise, killing more persons in 2017 than
      HIV/AIDS at the height of that epidemic. Medication assisted treatment, including methadone
      and buprenorphine, is the standard of care for the treatment of opioid use disorder (OUD).
      However, chronic pain can reduce treatment efficacy during medication assisted treatment and
      is associated with illicit substance relapse, dropout, and subsequent overdose. Mechanisms by
      which chronic pain may influence the impulsive decision making (e.g., drug relapse) in
      persons with OUD have not been well characterized. A better understanding is needed of
      decision-making in this population. Two factors that can influence decisions to use drugs are
      impulsivity and acute opioid withdrawal. This proposal will test how chronic pain is
      associated with increases in impulsive decision making in OUD, whether impulsive decision
      making is greater when undergoing opioid withdrawal, and how catastrophizing may modify the
      association between withdrawal and impulsive decision making in patients with chronic pain
      and OUD. An ideal population for this developmental research project are methadone maintained
      patients, who show high treatment attendance rates and will therefore assure study efficiency
      and reliable completion.
This is an outpatient Phase 1 clinical trial investigating the effect of naloxone
      precipitated withdrawal on delay discounting. Eligible participants will undergo two
      experimental sessions presented in random order. One session will involve the measurement of
      delay discounting 30 minutes after double-blind intramuscular (IM) administration of placebo
      (normal saline) and the other will have the exact same procedures performed after
      double-blind IM administration of naloxone (0.1 mg). Injections will occur 2 hours after
      methadone dosing (peak levels). Study sessions will last 2 hours and involve pain and opioid
      withdrawal measures assessed at baseline and 15 minute intervals after injections. The
      participant should be back to baseline and free of withdrawal by the end of the study
      session. Sessions will occur at least 48 hours apart.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This proposal is a randomized double-blind placebo controlled Phase 1 clinical trial / human laboratory study
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: The participant, investigator, medical personnel administering study drug, and outcomes assessor will be blinded to drug being administered.
measure: Delay discounting of money rate (k)
time frame: k will be calculated from the same series of discounting questions that will be asked once each session at approcimately 30 minutes after study IM medication administration.
description: Delay discounting is the relative preference for smaller sooner over larger later rewards, an aspect of impulsivity. Most individuals would prefer an immediate $100 over $100 delayed by 1 year. However, when faced with the choice between receiving $95 now versus $100 in 1 year, preferences for the delayed reward may increase. By assessing such choices across multiple delays, delay discounting quantifies the devaluation of rewards over time, which allows for an index of overall discounting rate (k).
measure: Study Session Peak Pain Visual Analog Scale (VAS)
time frame: Peak Pain VAS will be the highest rating during each 2 hour study session.
description: Current pain level rated on 0-100 VAS. This is the validated pain scale typically used by clinicians in an outpatient or inpatient clinical visit to represent current level of pain. Higher ratings indicate worse pain severity.
measure: Peak Clinical Opiate Withdrawal Scale (COWS) Rating
time frame: Peak COWS rating will be the highest rating during each 2 hour study session.
description: The COWS is an 11-item validated clinician administered scale that quantifies level of opioid withdrawal. The range of scores is 0-48, with higher scores indicating greater withdrawal severity. The peak COWS rating will be the highest measurement in the session after study drug administration.
measure: Peak Subjective Opiate Withdrawal Scale (SOWS) Rating
time frame: Peak SOWS rating will be the highest rating during each 2 hour study session.
description: The SOWS is a 16 item validated self-administered scale for grading opioid withdrawal symptoms. The range of scores is 0-64, with higher scores indicating greater withdrawal severity. The peak SOWS rating will be the highest measurement in the session after study drug administration.
measure: Peak Increase from baseline Pupil Diameter
time frame: Peak increase from baseline pupil diameter will be the largest increase from baseline pupil diameter measured during each 2 hour study session.
description: Pupil diameter (mm) will be measured via digital pupillometer in standard room lighting at baseline and then throughout the study session after study drug administration. The peak increase from baseline value will be the largest increase from baseline pupil diameter measured after study drug administration.
arm group label: Pain Group
arm group type: Experimental
description: Patients with chronic pain who are maintained on methadone for opioid use disorder
arm group label: No Pain Group
arm group type: Placebo Comparator
description: Patients who are maintained on methadone for opioid use disorder but who do not have chronic pain.
intervention type: Drug
intervention name: Naloxone Hydrochloride
description: An intramuscular (IM) injection of naloxone will be given.
arm group label: No Pain Group
arm group label: Pain Group
other name: Narcan
intervention type: Drug
intervention name: Placebo
description: An IM injection of 0.9% normal saline will be given.
arm group label: No Pain Group
arm group label: Pain Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: D. Andrew Tompkins, MD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
responsible party type: Sponsor
mesh term: Chronic Pain
mesh term: Opioid-Related Disorders
mesh term: Naloxone
sharing ipd: Yes
ipd description: Data will be made available to the public through presentation at scientific meetings and research publications in peer-reviewed journals. I have routinely kept an open policy to share data with the scientific and medical community upon request, and this policy will be continued with the present project.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data will become available after publication of the main study results.