<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/NCT03303209</url>
  </required_header>
  <id_info>
    <org_study_id>37179</org_study_id>
    <nct_id>NCT03303209</nct_id>
  </id_info>
  <brief_title>Patient-Centered Opioid Tapering Study</brief_title>
  <official_title>Patient-Centered Opioid Tapering in Outpatients With Chronic Pain and Long-Term Opioid Use</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an observational study of a voluntary opioid tapering protocol conducted in community&#xD;
      outpatients taking long term prescription opioids for chronic pain. Patients who would&#xD;
      otherwise continue with their existing opioid prescriptions were encouraged to participate in&#xD;
      a voluntary opioid taper program. Interested patients were identified by their pain&#xD;
      physician, Dr. Richard Stieg, and then completed an online informed consent document and&#xD;
      baseline self-report assessments including types and doses of opioid medications as well as&#xD;
      demographic and psychosocial measures, clinical and pain characteristics. Patients were&#xD;
      either given or mailed a free copy of a patient book The Opioid-Free Pain Relief Kit, or Less&#xD;
      Pain, Fewer Pills: Avoid the dangers of prescription opioids and gain control over chronic&#xD;
      pain. Over the following weeks and up to 4 months, Dr. Stieg implemented a slow, individually&#xD;
      tailored opioid taper in all patient participants. Follow-up online self-report surveys were&#xD;
      completed at 4 months post enrollment. Opioid dose data were confirmed via medical chart&#xD;
      review, and doses were converted to a standardized morphine equivalent daily dose (MEDD).&#xD;
      Main outcome was change in opioid dose baseline to 4 months. Secondary outcome was change in&#xD;
      pain intensity (numeric rating scale, 0-10) baseline to 4 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Background: An estimated 11 million Americans were prescribed long term opioids&#xD;
      in 2014-up to 4 percent of the entire U.S. adult population. Patients with chronic pain&#xD;
      taking long term opioids are at higher risk for multiple health problems including more&#xD;
      severe pain and addiction, and death from accidental overdose. Opioid related overdoses are&#xD;
      now a leading cause of death in the U.S. Multiple national agencies have called for reduced&#xD;
      opioid prescriptions.&#xD;
&#xD;
      Lower doses of opioids are safer for patients. Patients who take very high dose opioids for&#xD;
      chronic pain (&gt;200 morphine equivalent daily dose; MEDD) are at 3-fold increased risk for&#xD;
      accidental overdose death compared to those on low doses (1). However, the primary patient&#xD;
      concern about reducing opioids is fear of having increased pain. Indeed, evidence is lacking&#xD;
      for how to help real-world patients with chronic pain reduce opioid use while controlling&#xD;
      their pain.&#xD;
&#xD;
      Inpatient studies suggest that pain improves with intensive pain rehabilitation and opioid&#xD;
      cessation (2). interdisciplinary chronic pain rehabilitation combined with opioid cessation&#xD;
      in veterans has been associated with improved indices of psychological and physical function,&#xD;
      as well as significantly reduced pain in those who stop opioids during the program (3).&#xD;
      However, inpatient and intensive opioid reduction programs are costly and unavailable to most&#xD;
      patients. Recently, researchers conducted an outpatient randomized controlled trial comparing&#xD;
      an outpatient opioid tapering program to usual care (4). The tapering program consisted of&#xD;
      psychiatric consultation, opioid dose tapering, and 18 weekly meetings with a physician&#xD;
      assistant to explore motivation for tapering and learn pain self-management skills.&#xD;
&#xD;
      No studies exist to inform best practice on opioid reduction in primary care or outpatient&#xD;
      pain clinics. There is a critical gap in knowledge on how to help community-based (primary&#xD;
      care and pain clinic) outpatients with chronic pain actively reduce opioids while controlling&#xD;
      pain. This project was intended to inform real-world patient care to specifically help&#xD;
      patients with chronic pain taking long term moderate-, high-, and super high-dose opioids&#xD;
      reduce their daily use and associated risks. The goal is to understand whether a simple,&#xD;
      patient-centered opioid taper conducted with limited resources and no interdisciplinary&#xD;
      supportive treatments (e.g., psychology services, physical therapy) could effectively reduce&#xD;
      opioid dose without increasing pain.&#xD;
&#xD;
      Methods&#xD;
&#xD;
      Study Design: A prospective observational study of a voluntary patient-centered opioid&#xD;
      tapering program. The study was conducted in compliance with the Stanford University's&#xD;
      Internal Review Board.&#xD;
&#xD;
      Participants: Adult patients with chronic pain prescribed opioids from a private practice&#xD;
      pain clinic in Colorado were invited by their prescribing physician to participate in a&#xD;
      voluntary opioid tapering program. Patients who expressed interest were called and invited&#xD;
      into the study (note that the study, which involved collecting patient data, is distinct from&#xD;
      the taper program. Patients could taper their opioids without agreeing to be studied).&#xD;
      Inclusion criteria included adults over the age of 18 years, medically diagnosed chronic pain&#xD;
      for at least 6 months, interest in participating in patient-centered opioid tapering, intact&#xD;
      cognitive function, an absence of frank psychological disorder, able to speak/read English,&#xD;
      able to complete online forms, and not being enrolled in a treatment program for substance&#xD;
      use disorder.&#xD;
&#xD;
      Procedure&#xD;
&#xD;
      Patients from a private clinic with chronic pain using daily opioid medications were invited&#xD;
      to participate in a voluntary opioid taper program by their physician. Those who agreed to&#xD;
      participated were enrolled in the weaning program (taper program) with the physician. After&#xD;
      patients provided informed consent, enrolled patients completed a series of online&#xD;
      questionnaires that collect data on demographics, psychosocial factors, and physical,&#xD;
      emotional, and cognitive function, and opioid medications (type and dose) at baseline and at&#xD;
      4-month follow-up. The opioid taper program was not regulated by the study protocol. It was&#xD;
      supervised by the physician, and individually tailored to meet the patient's specific&#xD;
      clinical needs. The goal was to reduce opioid consumption at a comfortable pace (individually&#xD;
      determined) and target cessation at 4 months from the time they enter the weaning program.&#xD;
&#xD;
      Data Collected:&#xD;
&#xD;
      Demographics included age and gender. Clinical variables included opioid medications, length&#xD;
      of time on opioids, pain diagnoses, pain intensity, and marijuana use (yes/no). Opioids were&#xD;
      converted to a Morphine Equivalent Daily Dose (MEDD) using standard procedures. MEDDs were&#xD;
      calculated for baseline and for the 4 month follow-up time point.&#xD;
&#xD;
      Current Medications Pain Catastrophizing Scale PROMIS Global Health Scale PROMIS Fatigue&#xD;
      Scale PROMIS Pain Interference Scale PROMIS Physical Function Scale PROMIS Emotional&#xD;
      Distress-Anxiety Scale PROMIS Depression Scale PROMIS Sleep Disturbance Scale PROMIS Sleep&#xD;
      Interference PROMIS Pain Behavior Scale PROMIS Social Isolation PROMIS Sleep Related&#xD;
      Impairment Scale PROMIS Cognitive Function Scale PROMIS Pain Intensity PROMIS Applied Cog&#xD;
      Abilities Marijuana use (yes/no)&#xD;
&#xD;
      Analytic Plan:&#xD;
&#xD;
      Descriptive statistics will include means, medians, ranges, frequencies and percentiles for&#xD;
      study variables.&#xD;
&#xD;
      For continuous variables: Welch Two Sample, two-sided t-test without assumption of equal&#xD;
      variance will be used.&#xD;
&#xD;
      Polychotomous variables: Pearson's Chi-squared test with Yates' continuity correction. For&#xD;
      cells with small numbers, P value will be simulated with 2000 replications.&#xD;
&#xD;
      PRIMARY OUTCOME:&#xD;
&#xD;
      Assuming the primary outcome MEDD will not be normally distributed, Kruskal-Wallis rank sum&#xD;
      test will be used to compare MEDD at baseline and 16 weeks.&#xD;
&#xD;
      Pain intensity, our secondary outcome will be assessed similarly.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2015</start_date>
  <completion_date type="Actual">August 10, 2017</completion_date>
  <primary_completion_date type="Actual">August 10, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Morphine Equivalent Daily Dose (MEDD) from baseline to 4 months.</measure>
    <time_frame>4 months</time_frame>
    <description>Pre-post MEDD change was calculated</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Pain Intensity from baseline to 4 months</measure>
    <time_frame>4 months</time_frame>
    <description>Pre-post changes in pain intensity (using the 0-10 numeric rating scale) were calculated</description>
  </secondary_outcome>
  <enrollment type="Actual">51</enrollment>
  <condition>Opioid Use</condition>
  <condition>Chronic Pain</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Patient-centered opioid tapering protocol</intervention_name>
    <description>All patients who entered the study agreed to partner with their pain physician on a patient-centered opioid tapering program. The research component of the study was to observe patient response (in terms of change in MEDD and pain intensity) at month 4.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with chronic pain receiving treatment in a community chronic pain clinic who were&#xD;
        also taking long term prescription opioids were invited by their prescribing physician to&#xD;
        participate in patient-centered, voluntary opioid tapering.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Over age 18&#xD;
&#xD;
          -  Chronic pain&#xD;
&#xD;
          -  Chronic daily opioids&#xD;
&#xD;
          -  Wish to reduce opioid dose&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not able to communicate in English&#xD;
&#xD;
          -  Not able to complete electronic questionnaires&#xD;
&#xD;
          -  No major cognitive impairment&#xD;
&#xD;
          -  Not actively engaged in treatment for substance use disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Beth Darnall, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <reference>
    <citation>Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011 Apr 11;171(7):686-91. doi: 10.1001/archinternmed.2011.117.</citation>
    <PMID>21482846</PMID>
  </reference>
  <reference>
    <citation>Crisostomo RA, Schmidt JE, Hooten WM, Kerkvliet JL, Townsend CO, Bruce BK. Withdrawal of analgesic medication for chronic low-back pain patients: improvement in outcomes of multidisciplinary rehabilitation regardless of surgical history. Am J Phys Med Rehabil. 2008 Jul;87(7):527-36. doi: 10.1097/PHM.0b013e31817c124f.</citation>
    <PMID>18574345</PMID>
  </reference>
  <reference>
    <citation>Murphy JL, Clark ME, Banou E. Opioid cessation and multidimensional outcomes after interdisciplinary chronic pain treatment. Clin J Pain. 2013 Feb;29(2):109-17. doi: 10.1097/AJP.0b013e3182579935.</citation>
    <PMID>22751033</PMID>
  </reference>
  <reference>
    <citation>Sullivan MD, Turner JA, DiLodovico C, D'Appollonio A, Stephens K, Chan YF. Prescription Opioid Taper Support for Outpatients With Chronic Pain: A Randomized Controlled Trial. J Pain. 2017 Mar;18(3):308-318. doi: 10.1016/j.jpain.2016.11.003. Epub 2016 Nov 28.</citation>
    <PMID>27908840</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>October 2, 2017</study_first_submitted>
  <study_first_submitted_qc>October 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 5, 2017</study_first_posted>
  <last_update_submitted>October 4, 2017</last_update_submitted>
  <last_update_submitted_qc>October 4, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Beth Darnall</investigator_full_name>
    <investigator_title>Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>opioid</keyword>
  <keyword>opioids</keyword>
  <keyword>taper</keyword>
  <keyword>chronic pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Analgesics, Opioid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>We have no plan in place; however data may be shared upon request.</ipd_description>
  </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/NCT03303209
org study id: 37179
nct id: NCT03303209
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is an observational study of a voluntary opioid tapering protocol conducted in community
      outpatients taking long term prescription opioids for chronic pain. Patients who would
      otherwise continue with their existing opioid prescriptions were encouraged to participate in
      a voluntary opioid taper program. Interested patients were identified by their pain
      physician, Dr. Richard Stieg, and then completed an online informed consent document and
      baseline self-report assessments including types and doses of opioid medications as well as
      demographic and psychosocial measures, clinical and pain characteristics. Patients were
      either given or mailed a free copy of a patient book The Opioid-Free Pain Relief Kit, or Less
      Pain, Fewer Pills: Avoid the dangers of prescription opioids and gain control over chronic
      pain. Over the following weeks and up to 4 months, Dr. Stieg implemented a slow, individually
      tailored opioid taper in all patient participants. Follow-up online self-report surveys were
      completed at 4 months post enrollment. Opioid dose data were confirmed via medical chart
      review, and doses were converted to a standardized morphine equivalent daily dose (MEDD).
      Main outcome was change in opioid dose baseline to 4 months. Secondary outcome was change in
      pain intensity (numeric rating scale, 0-10) baseline to 4 months.
Background: Background: An estimated 11 million Americans were prescribed long term opioids
      in 2014-up to 4 percent of the entire U.S. adult population. Patients with chronic pain
      taking long term opioids are at higher risk for multiple health problems including more
      severe pain and addiction, and death from accidental overdose. Opioid related overdoses are
      now a leading cause of death in the U.S. Multiple national agencies have called for reduced
      opioid prescriptions.

      Lower doses of opioids are safer for patients. Patients who take very high dose opioids for
      chronic pain (>200 morphine equivalent daily dose; MEDD) are at 3-fold increased risk for
      accidental overdose death compared to those on low doses (1). However, the primary patient
      concern about reducing opioids is fear of having increased pain. Indeed, evidence is lacking
      for how to help real-world patients with chronic pain reduce opioid use while controlling
      their pain.

      Inpatient studies suggest that pain improves with intensive pain rehabilitation and opioid
      cessation (2). interdisciplinary chronic pain rehabilitation combined with opioid cessation
      in veterans has been associated with improved indices of psychological and physical function,
      as well as significantly reduced pain in those who stop opioids during the program (3).
      However, inpatient and intensive opioid reduction programs are costly and unavailable to most
      patients. Recently, researchers conducted an outpatient randomized controlled trial comparing
      an outpatient opioid tapering program to usual care (4). The tapering program consisted of
      psychiatric consultation, opioid dose tapering, and 18 weekly meetings with a physician
      assistant to explore motivation for tapering and learn pain self-management skills.

      No studies exist to inform best practice on opioid reduction in primary care or outpatient
      pain clinics. There is a critical gap in knowledge on how to help community-based (primary
      care and pain clinic) outpatients with chronic pain actively reduce opioids while controlling
      pain. This project was intended to inform real-world patient care to specifically help
      patients with chronic pain taking long term moderate-, high-, and super high-dose opioids
      reduce their daily use and associated risks. The goal is to understand whether a simple,
      patient-centered opioid taper conducted with limited resources and no interdisciplinary
      supportive treatments (e.g., psychology services, physical therapy) could effectively reduce
      opioid dose without increasing pain.

      Methods

      Study Design: A prospective observational study of a voluntary patient-centered opioid
      tapering program. The study was conducted in compliance with the Stanford University's
      Internal Review Board.

      Participants: Adult patients with chronic pain prescribed opioids from a private practice
      pain clinic in Colorado were invited by their prescribing physician to participate in a
      voluntary opioid tapering program. Patients who expressed interest were called and invited
      into the study (note that the study, which involved collecting patient data, is distinct from
      the taper program. Patients could taper their opioids without agreeing to be studied).
      Inclusion criteria included adults over the age of 18 years, medically diagnosed chronic pain
      for at least 6 months, interest in participating in patient-centered opioid tapering, intact
      cognitive function, an absence of frank psychological disorder, able to speak/read English,
      able to complete online forms, and not being enrolled in a treatment program for substance
      use disorder.

      Procedure

      Patients from a private clinic with chronic pain using daily opioid medications were invited
      to participate in a voluntary opioid taper program by their physician. Those who agreed to
      participated were enrolled in the weaning program (taper program) with the physician. After
      patients provided informed consent, enrolled patients completed a series of online
      questionnaires that collect data on demographics, psychosocial factors, and physical,
      emotional, and cognitive function, and opioid medications (type and dose) at baseline and at
      4-month follow-up. The opioid taper program was not regulated by the study protocol. It was
      supervised by the physician, and individually tailored to meet the patient's specific
      clinical needs. The goal was to reduce opioid consumption at a comfortable pace (individually
      determined) and target cessation at 4 months from the time they enter the weaning program.

      Data Collected:

      Demographics included age and gender. Clinical variables included opioid medications, length
      of time on opioids, pain diagnoses, pain intensity, and marijuana use (yes/no). Opioids were
      converted to a Morphine Equivalent Daily Dose (MEDD) using standard procedures. MEDDs were
      calculated for baseline and for the 4 month follow-up time point.

      Current Medications Pain Catastrophizing Scale PROMIS Global Health Scale PROMIS Fatigue
      Scale PROMIS Pain Interference Scale PROMIS Physical Function Scale PROMIS Emotional
      Distress-Anxiety Scale PROMIS Depression Scale PROMIS Sleep Disturbance Scale PROMIS Sleep
      Interference PROMIS Pain Behavior Scale PROMIS Social Isolation PROMIS Sleep Related
      Impairment Scale PROMIS Cognitive Function Scale PROMIS Pain Intensity PROMIS Applied Cog
      Abilities Marijuana use (yes/no)

      Analytic Plan:

      Descriptive statistics will include means, medians, ranges, frequencies and percentiles for
      study variables.

      For continuous variables: Welch Two Sample, two-sided t-test without assumption of equal
      variance will be used.

      Polychotomous variables: Pearson's Chi-squared test with Yates' continuity correction. For
      cells with small numbers, P value will be simulated with 2000 replications.

      PRIMARY OUTCOME:

      Assuming the primary outcome MEDD will not be normally distributed, Kruskal-Wallis rank sum
      test will be used to compare MEDD at baseline and 16 weeks.

      Pain intensity, our secondary outcome will be assessed similarly.
observational model: Cohort
time perspective: Prospective
measure: Change in Morphine Equivalent Daily Dose (MEDD) from baseline to 4 months.
time frame: 4 months
description: Pre-post MEDD change was calculated
measure: Change in Pain Intensity from baseline to 4 months
time frame: 4 months
description: Pre-post changes in pain intensity (using the 0-10 numeric rating scale) were calculated
intervention type: Other
intervention name: Patient-centered opioid tapering protocol
description: All patients who entered the study agreed to partner with their pain physician on a patient-centered opioid tapering program. The research component of the study was to observe patient response (in terms of change in MEDD and pain intensity) at month 4.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
last name: Beth Darnall, PhD
role: Principal Investigator
affiliation: Stanford University
citation: Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011 Apr 11;171(7):686-91. doi: 10.1001/archinternmed.2011.117.
PMID: 21482846
citation: Crisostomo RA, Schmidt JE, Hooten WM, Kerkvliet JL, Townsend CO, Bruce BK. Withdrawal of analgesic medication for chronic low-back pain patients: improvement in outcomes of multidisciplinary rehabilitation regardless of surgical history. Am J Phys Med Rehabil. 2008 Jul;87(7):527-36. doi: 10.1097/PHM.0b013e31817c124f.
PMID: 18574345
citation: Murphy JL, Clark ME, Banou E. Opioid cessation and multidimensional outcomes after interdisciplinary chronic pain treatment. Clin J Pain. 2013 Feb;29(2):109-17. doi: 10.1097/AJP.0b013e3182579935.
PMID: 22751033
citation: Sullivan MD, Turner JA, DiLodovico C, D'Appollonio A, Stephens K, Chan YF. Prescription Opioid Taper Support for Outpatients With Chronic Pain: A Randomized Controlled Trial. J Pain. 2017 Mar;18(3):308-318. doi: 10.1016/j.jpain.2016.11.003. Epub 2016 Nov 28.
PMID: 27908840
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Beth Darnall
investigator title: Clinical Professor
mesh term: Chronic Pain
mesh term: Analgesics, Opioid
sharing ipd: No
ipd description: We have no plan in place; however data may be shared upon request.