<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/NCT02192398</url>
  </required_header>
  <id_info>
    <org_study_id>2014P-001377</org_study_id>
    <secondary_id>1R01DA036564-01</secondary_id>
    <nct_id>NCT02192398</nct_id>
  </id_info>
  <brief_title>Effect of Guanfacine on the Reversal of Opioid-induced Hyperalgesia (OIH)</brief_title>
  <official_title>Effect of Guanfacine on the Reversal of Opioid-induced Hyperalgesia (OIH)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Combination of guanfacine with opioid medication as a standard treatment for chronic pain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This aim proposes that guanfacine would be a useful drug to reverse Opioid-Induced&#xD;
      Hyperalgesia (OIH) when combined with opioids in chronic pain management.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Actual">December 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quantitative Sensory Testing (QST)</measure>
    <time_frame>4 weeks</time_frame>
    <description>Quantitative Sensory Testing (QST) results will be used to compare the 3 treatment groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heat Pain Threshold</measure>
    <time_frame>4 weeks</time_frame>
    <description>Subjects will be measured for their heat pain threshold using QST. The testing will be done at 3 of the 4 visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heat Pain Tolerance</measure>
    <time_frame>4 weeks</time_frame>
    <description>Subjects will be measured for their heat pain tolerance using QST. The testing will be done at 3 of the 4 visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Temporal Pain Summation</measure>
    <time_frame>4 weeks</time_frame>
    <description>Subjects will be measured for their temporal pain summation using QST. The testing will be done at 3 of the 4 visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Detecting Diffuse Noxious Inhibitory Control (DNIC)</measure>
    <time_frame>4 weeks</time_frame>
    <description>Subjects will be measured for their Diffuse Noxious Inhibitory Control (DNIC). The testing will be done at 3 of the 4 visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heat Sensation</measure>
    <time_frame>4 weeks</time_frame>
    <description>Subjects will be measured for their heat sensation using QST. The testing will be done at 3 of the 4 visits.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Chronic Pain</condition>
  <arm_group>
    <arm_group_label>Guanfacine (2mg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will be randomized into 1 of the following 3 treatment groups:&#xD;
guanfacine (2mg)&#xD;
guanfacine (1mg)&#xD;
placebo&#xD;
Subjects will be instructed to take one capsule in the evening for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Guanfacine (1mg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will be randomized into 1 of the following 3 treatment groups:&#xD;
guanfacine (2mg)&#xD;
guanfacine (1mg)&#xD;
placebo&#xD;
Subjects will be instructed to take one capsule in the evening for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will be randomized into 1 of the following 3 treatment groups:&#xD;
guanfacine (2mg)&#xD;
guanfacine (1mg)&#xD;
placebo&#xD;
Subjects will be instructed to take one capsule in the evening for 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Guanfacine</intervention_name>
    <description>Subjects will be randomized into 1 of the following 3 treatment groups:&#xD;
guanfacine (2mg)&#xD;
guanfacine (1mg)&#xD;
placebo&#xD;
To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 4 weeks of drug treatment (guanfacine or placebo).</description>
    <arm_group_label>Guanfacine (1mg)</arm_group_label>
    <arm_group_label>Guanfacine (2mg)</arm_group_label>
    <other_name>Tenex, Intuniv</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects will be randomized into 1 of the following 3 treatment groups:&#xD;
guanfacine (2mg)&#xD;
guanfacine (1mg)&#xD;
placebo To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 4 weeks of drug treatment (guanfacine or placebo).</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo, sugar pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  18-65 years old&#xD;
&#xD;
          -  Chronic neck or back pain condition for at least 6 months&#xD;
&#xD;
          -  VAS score of 4-8, despite opioid therapy&#xD;
&#xD;
          -  On a stable morphine equivalent dose of at least 60mg/day and ≤ 240mg/day for at least&#xD;
             3 months&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Has taken Methadone, Suboxone, Fentanyl, and/or Tramadol in the last six (6) months&#xD;
&#xD;
          -  Has taken guanfacine (or other alpha-2AR agonists) in the last six (6) months&#xD;
&#xD;
          -  Changes to current or adding new pain treatment while enrolled in the study (i.e.&#xD;
             opiates, epidural steroid injection) will be reviewed by the study physician&#xD;
&#xD;
          -  Unable to independently provide informed written consent&#xD;
&#xD;
          -  Sensory deficits at site of QST, such as peripheral neuropathy&#xD;
&#xD;
          -  Intolerable allergies or has had a severe adverse reaction to study medication (i.e.&#xD;
             guanfacine, lactose, vitamin B2 a.k.a. riboflavin)&#xD;
&#xD;
          -  Takes vitamin B2 &gt; 1.6mg/day during the study&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Pending litigation related to neck or back pain&#xD;
&#xD;
          -  Diagnosed with Raynaud's syndrome&#xD;
&#xD;
          -  Has other chronic pain conditions such as fibromyalgia or joint osteoarthritis that&#xD;
             are predominant over back and neck pain with regard to its intensity (VAS)&#xD;
&#xD;
          -  Has known pre-existing severe cardiovascular disease (i.e. arrhythmia - prolonged QT&#xD;
             interval &gt; 440ms), cerebrovascular disease/accident (i.e., stroke), hepatic or renal&#xD;
             impairment, CNS condition, metabolic condition, or history of syncope&#xD;
&#xD;
          -  Hypotension (SBP &lt; 90 mmHg and DBP &lt; 60 mmHg for female or SBP &lt; 100 mmHg and DBP &lt; 60&#xD;
             mmHg for male; measured while in a sitting position) will be reviewed by a study&#xD;
             physician&#xD;
&#xD;
          -  Bradycardia (resting heart rate &lt; 60 bpm) will be reviewed by a study physician&#xD;
&#xD;
          -  Subjects are on antihypertensive drugs (e.g., a beta-blocker) that result in&#xD;
             hypotension and/or bradycardia as defined above&#xD;
&#xD;
          -  Tests positive for illicit drugs, marijuana, or non-prescribed drugs&#xD;
&#xD;
          -  Major psychiatric disorders that required hospitalization in the past 6 months such&#xD;
             as: major depression, bipolar disorder, schizophrenia, anxiety disorder, or psychotic&#xD;
             disorders&#xD;
&#xD;
          -  Currently in a treatment program for alcohol or drug abuse, or currently on methadone&#xD;
             or buprenorphine (i.e. suboxone, subutex) for treatment of addiction, or currently&#xD;
             prescribed stimulants for treatment of ADHD&#xD;
&#xD;
          -  History of substance or alcohol abuse (meets DSM IV criteria) per medical record or&#xD;
             subject admission&#xD;
&#xD;
          -  Subjects are on medications that serve as CYP3A4/5 inhibitors or CYP3A4 inducers&#xD;
             including, but are not limited to, valproic acid, macrolide antibiotics, antifungal&#xD;
             drugs, St. John wort, ACE inhibitors, nefazodone (antidepressant), calcium channel&#xD;
             blockers, H2-receptor antagonists, anti-HIV or AIDS drugs, and antiepileptic drugs&#xD;
&#xD;
          -  Subjects are on medications that are ligands for alpha2-adrenergic receptors including&#xD;
             antipsychotic drugs (e.g. clozapine) and tricyclic or tetracyclic antidepressants&#xD;
             (e.g. imipramine, mirtazapine, mianserin). Any medications taken by a subject at the&#xD;
             enrollment will be reviewed regarding their compatibility with guanfacine as well as&#xD;
             possible confounding side effects. Subjects will be allowed to take non-opioid pain&#xD;
             medications except for gabapentinoids and amitriptyline/nortriptyline as far as such&#xD;
             medications do not have incompatibility with guanfacine.&#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>Jianren Mao, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>MGH Center for Translational Pain Research</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>March 2023</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 16, 2014</study_first_posted>
  <last_update_submitted>March 13, 2023</last_update_submitted>
  <last_update_submitted_qc>March 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2023</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>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Pain</keyword>
  <keyword>Pain management</keyword>
  <keyword>Neck</keyword>
  <keyword>Back</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperalgesia</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Guanfacine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02192398
org study id: 2014P-001377
secondary id: 1R01DA036564-01
nct id: NCT02192398
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Combination of guanfacine with opioid medication as a standard treatment for chronic pain.
This aim proposes that guanfacine would be a useful drug to reverse Opioid-Induced
      Hyperalgesia (OIH) when combined with opioids in chronic pain management.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Quantitative Sensory Testing (QST)
time frame: 4 weeks
description: Quantitative Sensory Testing (QST) results will be used to compare the 3 treatment groups.
measure: Heat Pain Threshold
time frame: 4 weeks
description: Subjects will be measured for their heat pain threshold using QST. The testing will be done at 3 of the 4 visits.
measure: Heat Pain Tolerance
time frame: 4 weeks
description: Subjects will be measured for their heat pain tolerance using QST. The testing will be done at 3 of the 4 visits.
measure: Temporal Pain Summation
time frame: 4 weeks
description: Subjects will be measured for their temporal pain summation using QST. The testing will be done at 3 of the 4 visits.
measure: Detecting Diffuse Noxious Inhibitory Control (DNIC)
time frame: 4 weeks
description: Subjects will be measured for their Diffuse Noxious Inhibitory Control (DNIC). The testing will be done at 3 of the 4 visits.
measure: Heat Sensation
time frame: 4 weeks
description: Subjects will be measured for their heat sensation using QST. The testing will be done at 3 of the 4 visits.
arm group label: Guanfacine (2mg)
arm group type: Active Comparator
description: Subjects will be randomized into 1 of the following 3 treatment groups:
guanfacine (2mg)
guanfacine (1mg)
placebo
Subjects will be instructed to take one capsule in the evening for 4 weeks.
arm group label: Guanfacine (1mg)
arm group type: Active Comparator
description: Subjects will be randomized into 1 of the following 3 treatment groups:
guanfacine (2mg)
guanfacine (1mg)
placebo
Subjects will be instructed to take one capsule in the evening for 4 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects will be randomized into 1 of the following 3 treatment groups:
guanfacine (2mg)
guanfacine (1mg)
placebo
Subjects will be instructed to take one capsule in the evening for 4 weeks.
intervention type: Drug
intervention name: Guanfacine
description: Subjects will be randomized into 1 of the following 3 treatment groups:
guanfacine (2mg)
guanfacine (1mg)
placebo
To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 4 weeks of drug treatment (guanfacine or placebo).
arm group label: Guanfacine (1mg)
arm group label: Guanfacine (2mg)
other name: Tenex, Intuniv
intervention type: Drug
intervention name: Placebo
description: Subjects will be randomized into 1 of the following 3 treatment groups:
guanfacine (2mg)
guanfacine (1mg)
placebo To compare pain threshold, pain tolerance, and wind up, as measured by QST, throughout 4 weeks of drug treatment (guanfacine or placebo).
arm group label: Placebo
other name: Placebo, sugar pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Jianren Mao, M.D., Ph.D.
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: Principal Investigator
mesh term: Hyperalgesia
mesh term: Chronic Pain
mesh term: Guanfacine