<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/NCT03249558</url>
  </required_header>
  <id_info>
    <org_study_id>2017P001589</org_study_id>
    <nct_id>NCT03249558</nct_id>
  </id_info>
  <brief_title>Effect of Combined Morphine and Duloxetine on Chronic Pain</brief_title>
  <acronym>Duloxetine</acronym>
  <official_title>Effect of Combined Morphine and Duloxetine on Chronic Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A double-blind, randomized, and placebo-controlled clinical study examining whether&#xD;
      duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), could enhance opioid&#xD;
      analgesia and reduce overall opioid use. Positive outcomes will help improve the overall&#xD;
      effectiveness of clinical opioid therapy and reduce unnecessary opioid dose escalation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 12, 2018</start_date>
  <completion_date type="Actual">April 5, 2022</completion_date>
  <primary_completion_date type="Actual">April 5, 2022</primary_completion_date>
  <phase>Phase 4</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>Other</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Opioid Dose</measure>
    <time_frame>10 weeks</time_frame>
    <description>The investigators will compare overall opioid dose between the morphine/duloxetine group and the morphine/placebo group and compare rescue dose among all three groups.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Visual Analog Scale (VAS)</measure>
    <time_frame>10 weeks</time_frame>
    <description>To examine changes in VAS scores and to determine total versus rescue opioid use after each treatment</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">81</enrollment>
  <condition>Chronic Low Back Pain</condition>
  <condition>Chronic Neck Pain</condition>
  <arm_group>
    <arm_group_label>Morphine, Duloxetine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and 60 mg of duloxetine capsules.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Morphine, Placebo Duloxetine</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and placebo duloxetine capsules.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Morphine, Duloxetine</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will take placebo morphine capsules and 60 mg of duloxetine capsules.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.</description>
    <arm_group_label>Morphine, Duloxetine</arm_group_label>
    <arm_group_label>Morphine, Placebo Duloxetine</arm_group_label>
    <other_name>Morphine Sulfate Contin, Morphine Sulfate Instant Release</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Duloxetine</intervention_name>
    <description>Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.</description>
    <arm_group_label>Morphine, Duloxetine</arm_group_label>
    <arm_group_label>Placebo Morphine, Duloxetine</arm_group_label>
    <other_name>Cymbalta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.</description>
    <arm_group_label>Morphine, Placebo Duloxetine</arm_group_label>
    <arm_group_label>Placebo Morphine, Duloxetine</arm_group_label>
    <other_name>Sugar pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is 18-70 years old.&#xD;
&#xD;
          2. Subject has chronic neck or back pain for at least 3 months.&#xD;
&#xD;
          3. Subject has a VAS ≥ 5.&#xD;
&#xD;
          4. Has not taken duloxetine in the last 3 months.&#xD;
&#xD;
          5. Has not taken an opioid in the last 3 months, but has taken one in the past without&#xD;
             sufficient pain control OR has never taken opioids but has failed at 3 (or more)&#xD;
             non-opioid treatments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has major psychiatric disorders requiring recent hospitalization (within 3&#xD;
             months) such as major depression, bipolar disorder, schizophrenia, anxiety disorder,&#xD;
             or psychotic disorder.&#xD;
&#xD;
          2. Subject is using illicit drugs detected by urine toxicology/drug screen.&#xD;
&#xD;
          3. Subject is pregnant or lactating/breast feeding.&#xD;
&#xD;
          4. Subject is allergic to morphine or duloxetine.&#xD;
&#xD;
          5. Subject is on an antidepressant including serotonin-norepinephrine reuptake inhibitors&#xD;
             (SNRI), selective serotonin reuptake inhibitor (SSRI), tricyclic antidepressant.&#xD;
&#xD;
          6. Subject has a history of suicidal attempts or current suicidal ideation.&#xD;
&#xD;
          7. Subject takes monoamine oxidase inhibitors, antipsychotics, triptan drugs such as&#xD;
             sumatriptan, lithium, linezolid, tramadol (Ultram), St. John's Wort, central nervous&#xD;
             system (CNS) stimulants such as amphetamine, methylphenidate, methamphetamine,&#xD;
             phentermine, diethylpropion, sibutramine, cocaine, or thioridazine.&#xD;
&#xD;
          8. Subject has uncontrolled narrow-angle glaucoma.&#xD;
&#xD;
          9. Subject has sensory deficits on arms or Raynaud's Syndrome.&#xD;
&#xD;
         10. Subject has a pending litigation related to chronic pain condition.&#xD;
&#xD;
         11. Subject is on methadone or suboxone treatment for addiction.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jianren Mao, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Karina de Sousa</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>August 23, 2022</last_update_submitted>
  <last_update_submitted_qc>August 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Jianren Mao, MD, PhD</investigator_full_name>
    <investigator_title>Vice Chair for Research; Chief, Division of Pain Medicine; Director, MGH Center for Translational Pain Research</investigator_title>
  </responsible_party>
  <keyword>Pain</keyword>
  <keyword>Pain Management</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Low Back Pain</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
    <mesh_term>Neck Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</mesh_term>
    <mesh_term>Duloxetine Hydrochloride</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/NCT03249558
org study id: 2017P001589
nct id: NCT03249558
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
A double-blind, randomized, and placebo-controlled clinical study examining whether
      duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), could enhance opioid
      analgesia and reduce overall opioid use. Positive outcomes will help improve the overall
      effectiveness of clinical opioid therapy and reduce unnecessary opioid dose escalation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Triple (Participant, Care Provider, Investigator)
measure: Overall Opioid Dose
time frame: 10 weeks
description: The investigators will compare overall opioid dose between the morphine/duloxetine group and the morphine/placebo group and compare rescue dose among all three groups.
measure: Visual Analog Scale (VAS)
time frame: 10 weeks
description: To examine changes in VAS scores and to determine total versus rescue opioid use after each treatment
arm group label: Morphine, Duloxetine
arm group type: Active Comparator
description: Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and 60 mg of duloxetine capsules.
arm group label: Morphine, Placebo Duloxetine
arm group type: Placebo Comparator
description: Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and placebo duloxetine capsules.
arm group label: Placebo Morphine, Duloxetine
arm group type: Placebo Comparator
description: Subjects will take placebo morphine capsules and 60 mg of duloxetine capsules.
intervention type: Drug
intervention name: Morphine
description: Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.
arm group label: Morphine, Duloxetine
arm group label: Morphine, Placebo Duloxetine
other name: Morphine Sulfate Contin, Morphine Sulfate Instant Release
intervention type: Drug
intervention name: Duloxetine
description: Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.
arm group label: Morphine, Duloxetine
arm group label: Placebo Morphine, Duloxetine
other name: Cymbalta
intervention type: Drug
intervention name: Placebo
description: Subjects will be randomized into one of the treatment groups and will follow the assigned medication schedule for 10 weeks. Quantitative Sensory Testing (QST) will be performed on the subjects to compare pain threshold, pain tolerance, and wind up.
arm group label: Morphine, Placebo Duloxetine
arm group label: Placebo Morphine, Duloxetine
other name: Sugar pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jianren Mao, MD, PhD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Jianren Mao, MD, PhD
investigator title: Vice Chair for Research; Chief, Division of Pain Medicine; Director, MGH Center for Translational Pain Research
mesh term: Low Back Pain
mesh term: Chronic Pain
mesh term: Neck Pain
mesh term: Morphine
mesh term: Duloxetine Hydrochloride
sharing ipd: No