<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/NCT02218203</url>
  </required_header>
  <id_info>
    <org_study_id>RO1NS41503-2</org_study_id>
    <nct_id>NCT02218203</nct_id>
  </id_info>
  <brief_title>Clinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan/Lidocaine Combination Clinical Trial</brief_title>
  <official_title>Clinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan/Lidocaine Combination (Factorial Design) Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Brigham and Women's 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized, placebo-controlled, double-blind 4x4 crossover clinical trial was part of a&#xD;
      larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of&#xD;
      chronic oral (PO) dextromethorphan and intravenous (IV) lidocaine in central neuropathic pain&#xD;
      following spinal cord injury.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This trial has several objectives:&#xD;
&#xD;
      Primary Objective To determine which combination (dose-ratio) of dextromethorphan and&#xD;
      lidocaine provides the best balance of pain reduction and toxicity.&#xD;
&#xD;
      Secondary Objectives include To evaluate the analgesic efficacy of both dextromethorphan and&#xD;
      lidocaine in attenuating pain related to central nervous system sensitization, specifically&#xD;
      spontaneous pain, mechanical allodynia, and hyperalgesia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2003</start_date>
  <completion_date type="Actual">January 2008</completion_date>
  <primary_completion_date type="Actual">January 2008</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change in Peak Pain Intensity</measure>
    <time_frame>30 minutes post-infusion (Cmax)</time_frame>
    <description>Primary outcome was percent change from baseline in mean pain intensity at Cmax (transformed Gracely Scale; 0-35). Higher values on the Gracely scale represent greater pain intensity; the greater the percent change from baseline in mean pain intensity, the bigger the reduction in pain intensity.</description>
  </primary_outcome>
  <number_of_arms>16</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Central Neuropathic Pain</condition>
  <condition>Allodynia</condition>
  <condition>Spinal Cord Injury</condition>
  <arm_group>
    <arm_group_label>Placebo- 0mg/kg Lido</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo in combination with 0mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo - 1mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo in combination with 1mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo - 2mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo in combination with 2mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo - 4mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo in combination with 4mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Dose Dex - 0mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low dose dextromethorphan in combination with 0mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Dose Dex - 1mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low dose dextromethorphan in combination with 1mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Dose Dex - 2mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low dose dextromethorphan in combination with 2mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Dose Dex - 4mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low dose dextromethorphan in combination with 4mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Medium Dose Dex - 0mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Medium dose dextromethorphan in combination with 0mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Medium Dose Dex - 1mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Medium dose dextromethorphan in combination with 1mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Medium Dose Dex - 2mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Medium dose dextromethorphan in combination with 2mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Medium Dose Dex - 4mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Medium dose dextromethorphan in combination with 4mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Dose Dex - 0mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High dose dextromethorphan in combination with 0mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Dose Dex - 1mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High dose dextromethorphan in combination with 1mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Dose Dex - 2mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High dose dextromethorphan in combination with 2mg/kg LBM lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High Dose Dex - 4mg/kg Lido</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High dose dextromethorphan in combination with 4mg/kg LBM lidocaine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dextromethorphan</intervention_name>
    <description>Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)</description>
    <arm_group_label>High Dose Dex - 0mg/kg Lido</arm_group_label>
    <arm_group_label>High Dose Dex - 1mg/kg Lido</arm_group_label>
    <arm_group_label>High Dose Dex - 2mg/kg Lido</arm_group_label>
    <arm_group_label>High Dose Dex - 4mg/kg Lido</arm_group_label>
    <arm_group_label>Low Dose Dex - 0mg/kg Lido</arm_group_label>
    <arm_group_label>Low Dose Dex - 1mg/kg Lido</arm_group_label>
    <arm_group_label>Low Dose Dex - 2mg/kg Lido</arm_group_label>
    <arm_group_label>Low Dose Dex - 4mg/kg Lido</arm_group_label>
    <arm_group_label>Medium Dose Dex - 0mg/kg Lido</arm_group_label>
    <arm_group_label>Medium Dose Dex - 1mg/kg Lido</arm_group_label>
    <arm_group_label>Medium Dose Dex - 2mg/kg Lido</arm_group_label>
    <arm_group_label>Medium Dose Dex - 4mg/kg Lido</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lidocaine</intervention_name>
    <description>0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)</description>
    <arm_group_label>High Dose Dex - 1mg/kg Lido</arm_group_label>
    <arm_group_label>High Dose Dex - 2mg/kg Lido</arm_group_label>
    <arm_group_label>High Dose Dex - 4mg/kg Lido</arm_group_label>
    <arm_group_label>Low Dose Dex - 1mg/kg Lido</arm_group_label>
    <arm_group_label>Low Dose Dex - 2mg/kg Lido</arm_group_label>
    <arm_group_label>Low Dose Dex - 4mg/kg Lido</arm_group_label>
    <arm_group_label>Medium Dose Dex - 1mg/kg Lido</arm_group_label>
    <arm_group_label>Medium Dose Dex - 2mg/kg Lido</arm_group_label>
    <arm_group_label>Medium Dose Dex - 4mg/kg Lido</arm_group_label>
    <arm_group_label>Placebo - 1mg/kg Lido</arm_group_label>
    <arm_group_label>Placebo - 2mg/kg Lido</arm_group_label>
    <arm_group_label>Placebo - 4mg/kg Lido</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (Dextromethorphan)</intervention_name>
    <description>0mg Dextromethorphan</description>
    <arm_group_label>Placebo - 1mg/kg Lido</arm_group_label>
    <arm_group_label>Placebo - 2mg/kg Lido</arm_group_label>
    <arm_group_label>Placebo - 4mg/kg Lido</arm_group_label>
    <arm_group_label>Placebo- 0mg/kg Lido</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (Lidocaine)</intervention_name>
    <description>0mg/kg LBM Lidocaine</description>
    <arm_group_label>High Dose Dex - 0mg/kg Lido</arm_group_label>
    <arm_group_label>Low Dose Dex - 0mg/kg Lido</arm_group_label>
    <arm_group_label>Medium Dose Dex - 0mg/kg Lido</arm_group_label>
    <arm_group_label>Placebo- 0mg/kg Lido</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male or female adults, age 18 to 70 with central neuropathic pain for a&#xD;
             minimum of 3 months following SCI as confirmed by neurologic evaluation, with an&#xD;
             average pain intensity score of at least moderate over at least 50% of the day for the&#xD;
             7 days prior to the screening visit and over the 7 days prior to starting study&#xD;
             medication.&#xD;
&#xD;
          2. Subjects used no medication or a stabilized medication regimen for chronic and&#xD;
             well-controlled medical conditions&#xD;
&#xD;
          3. Serum laboratory examination obtained at study entry:&#xD;
&#xD;
          4. Normal cognitive function.&#xD;
&#xD;
          5. Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnancy or breast-feeding.&#xD;
&#xD;
          2. Renal or hepatic dysfunction.&#xD;
&#xD;
          3. Significant cardiac disease (e.g. MI within 1 year).&#xD;
&#xD;
          4. Signs or symptoms of central neurological disorder, excluding SCI.&#xD;
&#xD;
          5. Severe psychological disorder requiring treatment.&#xD;
&#xD;
          6. History of hypersensitivity or intolerance to dextromethorphan or lidocaine.&#xD;
&#xD;
          7. Participation in a study of an investigational drug or device within 30 days prior to&#xD;
             screening for this study.&#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>Christine N. Sang, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Translational Pain Research, Brigham and Women's Hospital (Disclosure: Patent)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Translational Pain Research, Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.paintrials.org</url>
    <description>Translational Pain Research, Brigham and Women's Hospital</description>
  </link>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>August 13, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <results_first_submitted>March 29, 2017</results_first_submitted>
  <results_first_submitted_qc>March 21, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">March 22, 2018</results_first_posted>
  <last_update_submitted>March 21, 2018</last_update_submitted>
  <last_update_submitted_qc>March 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Christine N. Sang, MD, MPH</investigator_full_name>
    <investigator_title>Director, Translational Pain Research</investigator_title>
  </responsible_party>
  <keyword>chronic pain</keyword>
  <keyword>central neuropathic pain</keyword>
  <keyword>spinal cord injury</keyword>
  <keyword>dextromethorphan</keyword>
  <keyword>lidocaine</keyword>
  <keyword>combination therapy</keyword>
  <keyword>analgesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Injuries</mesh_term>
    <mesh_term>Neuralgia</mesh_term>
    <mesh_term>Hyperalgesia</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lidocaine</mesh_term>
    <mesh_term>Dextromethorphan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment began in March 2003. Subjects were recruited nationally from referring physicians, through advertisements, and through an existing database held by the PI.</recruitment_details>
      <pre_assignment_details>During the screening visit, P450 2D6 phenotype status was determined for each subject to identify dextromethorphan-metabolizing capacity; those who were P450 2D6 poor-metabolizers were excluded. Following screen, subjects entered a dose escalation study to determine their maximum tolerated dose of dextromethorphan, prior to randomization.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Dextromethorphan/Lidocaine Combination Clinical Trial</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Placebo Dex v. 0mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Placebo Dex v. 1mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Placebo Dex v. 2mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Placebo Dex v. 4mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Low Dose Dex v. 0mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Low Dose Dex v. 1mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Low Dose Dex v. 2mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Low Dose Dex v. 4mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Medium Dose Dex v. 0mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Medium Dose Dex v. 1mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Medium Dose Dex v. 2mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Medium Dose Dex v. 4mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>High Dose Dex v. 0mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>High Dose Dex v. 1mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>High Dose Dex v. 2mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>High Dose Dex v. 4mg/km LBM Lidocaine</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26">2 subjects did not complete the placebo, medium dose, and high dose dex/lido combination arms.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Dextromethorphan/Lidocaine Combination Clinical Trial</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="26"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46.84" spread="11.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>North America</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change in Peak Pain Intensity</title>
        <description>Primary outcome was percent change from baseline in mean pain intensity at Cmax (transformed Gracely Scale; 0-35). Higher values on the Gracely scale represent greater pain intensity; the greater the percent change from baseline in mean pain intensity, the bigger the reduction in pain intensity.</description>
        <time_frame>30 minutes post-infusion (Cmax)</time_frame>
        <population>Central neuropathic pain following SCI; we present the primary efficacy endpoint (percent change in peak pain intensity) of this nested IV lidocaine dose-response clinical trial independent of the dextromethorphan doses, because the distribution of the dextromethorphan doses is balanced across the lidocaine treatment arms.</population>
        <group_list>
          <group group_id="O1">
            <title>Dextromethorphan/ 0mg/kg Lidocaine Combination</title>
            <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury. This arm represents an average of all dextromethorphan doses in combination with 0mg/kg Lidocaine.</description>
          </group>
          <group group_id="O2">
            <title>Dextromethorphan/1mg/kg Lidocaine Combination</title>
            <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury. This arm represents an average of all dextromethorphan doses in combination with 1mg/kg Lidocaine.</description>
          </group>
          <group group_id="O3">
            <title>Dextromethorphan/2mg/kg Lidocaine Combination</title>
            <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury. This arm represents an average of all dextromethorphan doses in combination with 2mg/kg Lidocaine.</description>
          </group>
          <group group_id="O4">
            <title>Dextromethorphan/4mg/kg Lidocaine Combination</title>
            <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury. This arm represents an average of all dextromethorphan doses in combination with 4mg/kg Lidocaine.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Peak Pain Intensity</title>
          <description>Primary outcome was percent change from baseline in mean pain intensity at Cmax (transformed Gracely Scale; 0-35). Higher values on the Gracely scale represent greater pain intensity; the greater the percent change from baseline in mean pain intensity, the bigger the reduction in pain intensity.</description>
          <population>Central neuropathic pain following SCI; we present the primary efficacy endpoint (percent change in peak pain intensity) of this nested IV lidocaine dose-response clinical trial independent of the dextromethorphan doses, because the distribution of the dextromethorphan doses is balanced across the lidocaine treatment arms.</population>
          <units>percentage change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="26"/>
                <count group_id="O3" value="26"/>
                <count group_id="O4" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.5" spread="0.0049"/>
                    <measurement group_id="O2" value="-7.9" spread="0.0176"/>
                    <measurement group_id="O3" value="-11.2" spread="0.0015"/>
                    <measurement group_id="O4" value="-19.2" spread="0.0226"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>We performed a lidocaine dose response clinical trial nested within a dextromethorphan clinical trial to evaluate a potential interaction between lidocaine dose and dextromethorphan dose (pain intensity; Gracely scale).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>We report the interaction between the lidocaine dose response and dextromethorphan dose response. The type of statistical test was a linear regression model with Chi-square test.</non_inferiority_desc>
            <p_value>0.0322</p_value>
            <method>Pearson's Chi-squared test</method>
            <param_type>Lidocaine dose*dextromethorphan dose</param_type>
            <param_value>0.0042</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.0020</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.0004</ci_lower_limit>
            <ci_upper_limit>0.0081</ci_upper_limit>
            <estimate_desc>The estimated value is an estimated interaction term, and not a P-value.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected from the start of the lidocaine infusion (t=0:00) and recorded for the entire 30 minute infusion (t=0:30)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo Dextromethorphan/0mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E2">
          <title>Placebo Dextromethorphan/1mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E3">
          <title>Placebo Dextromethorphan/2mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E4">
          <title>Placebo Dextromethorphan/4mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E5">
          <title>Low Dose Dextromethorphan/0mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E6">
          <title>Low Dose Dextromethorphan/1mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E7">
          <title>Low Dose Dextromethorphan/2mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E8">
          <title>Low Dose Dextromethorphan/4mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E9">
          <title>Medium Dose Dextromethorphan/0mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E10">
          <title>Medium Dose Dextromethorphan/1mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E11">
          <title>Medium Dose Dextromethorphan/2mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E12">
          <title>Medium Dose Dextromethorphan/4mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E13">
          <title>High Dose Dextromethorphan/0mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E14">
          <title>High Dose Dextromethorphan/1mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E15">
          <title>High Dose Dextromethorphan/2mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
        <group group_id="E16">
          <title>High Dose Dextromethorphan/4mg/kg Lidocaine Combination</title>
          <description>This randomized, placebo-controlled, double-blind 4x4 factorial crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of chronic oral (PO)dextromethorphan (placebo, low dose, medium dose, and high dose) and intravenous (IV) lidocaine (0mg/kg LBM, 1mg/kg LBM, 2mg/kg LBM, and 4mg/kg LBM) in central neuropathic pain following spinal cord injury.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="24"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E6" subjects_affected="7" subjects_at_risk="26"/>
                <counts group_id="E7" subjects_affected="8" subjects_at_risk="26"/>
                <counts group_id="E8" subjects_affected="15" subjects_at_risk="26"/>
                <counts group_id="E9" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E10" subjects_affected="6" subjects_at_risk="24"/>
                <counts group_id="E11" subjects_affected="6" subjects_at_risk="24"/>
                <counts group_id="E12" subjects_affected="15" subjects_at_risk="24"/>
                <counts group_id="E13" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E14" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E15" subjects_affected="6" subjects_at_risk="24"/>
                <counts group_id="E16" subjects_affected="17" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Cramping/Spasms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E8" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E9" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E10" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E11" events="3" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E12" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E13" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E14" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E15" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E16" events="0" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Sedation Complex</sub_title>
                <description>Dizziness, blurry vision, interference with ability to drive/alertness, etc.</description>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E2" events="7" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E3" events="7" subjects_affected="5" subjects_at_risk="24"/>
                <counts group_id="E4" events="15" subjects_affected="7" subjects_at_risk="24"/>
                <counts group_id="E5" events="7" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E6" events="10" subjects_affected="7" subjects_at_risk="26"/>
                <counts group_id="E7" events="16" subjects_affected="7" subjects_at_risk="26"/>
                <counts group_id="E8" events="36" subjects_affected="14" subjects_at_risk="26"/>
                <counts group_id="E9" events="6" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E10" events="12" subjects_affected="5" subjects_at_risk="24"/>
                <counts group_id="E11" events="8" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E12" events="28" subjects_affected="14" subjects_at_risk="24"/>
                <counts group_id="E13" events="6" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E14" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E15" events="14" subjects_affected="6" subjects_at_risk="24"/>
                <counts group_id="E16" events="38" subjects_affected="16" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E8" events="5" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E9" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E10" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E11" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E12" events="3" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E13" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E14" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E15" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E16" events="4" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Euphoria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E8" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E9" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E10" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E11" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E12" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E13" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E14" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E15" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E16" events="2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Parathesias</sub_title>
                <description>Numbness, tingling, burning</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E4" events="5" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E6" events="3" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E7" events="4" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E8" events="8" subjects_affected="5" subjects_at_risk="26"/>
                <counts group_id="E9" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E10" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E11" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E12" events="8" subjects_affected="7" subjects_at_risk="24"/>
                <counts group_id="E13" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E14" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E15" events="3" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E16" events="10" subjects_affected="7" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Christine N. Sang, MD, MPH</name_or_title>
      <organization>Translational Pain Research, Brigham and Women's Hospital</organization>
      <phone>617-525-7246</phone>
      <email>paintrials@partners.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02218203
org study id: RO1NS41503-2
nct id: NCT02218203
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This randomized, placebo-controlled, double-blind 4x4 crossover clinical trial was part of a
      larger NIH-funded study to evaluate the analgesic efficacy of multiple dose-combinations of
      chronic oral (PO) dextromethorphan and intravenous (IV) lidocaine in central neuropathic pain
      following spinal cord injury.
This trial has several objectives:

      Primary Objective To determine which combination (dose-ratio) of dextromethorphan and
      lidocaine provides the best balance of pain reduction and toxicity.

      Secondary Objectives include To evaluate the analgesic efficacy of both dextromethorphan and
      lidocaine in attenuating pain related to central nervous system sensitization, specifically
      spontaneous pain, mechanical allodynia, and hyperalgesia.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percent Change in Peak Pain Intensity
time frame: 30 minutes post-infusion (Cmax)
description: Primary outcome was percent change from baseline in mean pain intensity at Cmax (transformed Gracely Scale; 0-35). Higher values on the Gracely scale represent greater pain intensity; the greater the percent change from baseline in mean pain intensity, the bigger the reduction in pain intensity.
arm group label: Placebo- 0mg/kg Lido
arm group type: Placebo Comparator
description: Placebo in combination with 0mg/kg LBM lidocaine
arm group label: Placebo - 1mg/kg Lido
arm group type: Experimental
description: Placebo in combination with 1mg/kg LBM lidocaine
arm group label: Placebo - 2mg/kg Lido
arm group type: Experimental
description: Placebo in combination with 2mg/kg LBM lidocaine
arm group label: Placebo - 4mg/kg Lido
arm group type: Experimental
description: Placebo in combination with 4mg/kg LBM lidocaine
arm group label: Low Dose Dex - 0mg/kg Lido
arm group type: Experimental
description: Low dose dextromethorphan in combination with 0mg/kg LBM lidocaine
arm group label: Low Dose Dex - 1mg/kg Lido
arm group type: Experimental
description: Low dose dextromethorphan in combination with 1mg/kg LBM lidocaine
arm group label: Low Dose Dex - 2mg/kg Lido
arm group type: Experimental
description: Low dose dextromethorphan in combination with 2mg/kg LBM lidocaine
arm group label: Low Dose Dex - 4mg/kg Lido
arm group type: Experimental
description: Low dose dextromethorphan in combination with 4mg/kg LBM lidocaine
arm group label: Medium Dose Dex - 0mg/kg Lido
arm group type: Experimental
description: Medium dose dextromethorphan in combination with 0mg/kg LBM lidocaine
arm group label: Medium Dose Dex - 1mg/kg Lido
arm group type: Experimental
description: Medium dose dextromethorphan in combination with 1mg/kg LBM lidocaine
arm group label: Medium Dose Dex - 2mg/kg Lido
arm group type: Experimental
description: Medium dose dextromethorphan in combination with 2mg/kg LBM lidocaine
arm group label: Medium Dose Dex - 4mg/kg Lido
arm group type: Experimental
description: Medium dose dextromethorphan in combination with 4mg/kg LBM lidocaine
arm group label: High Dose Dex - 0mg/kg Lido
arm group type: Experimental
description: High dose dextromethorphan in combination with 0mg/kg LBM lidocaine
arm group label: High Dose Dex - 1mg/kg Lido
arm group type: Experimental
description: High dose dextromethorphan in combination with 1mg/kg LBM lidocaine
arm group label: High Dose Dex - 2mg/kg Lido
arm group type: Experimental
description: High dose dextromethorphan in combination with 2mg/kg LBM lidocaine
arm group label: High Dose Dex - 4mg/kg Lido
arm group type: Experimental
description: High dose dextromethorphan in combination with 4mg/kg LBM lidocaine
intervention type: Drug
intervention name: Dextromethorphan
description: Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
arm group label: High Dose Dex - 0mg/kg Lido
arm group label: High Dose Dex - 1mg/kg Lido
arm group label: High Dose Dex - 2mg/kg Lido
arm group label: High Dose Dex - 4mg/kg Lido
arm group label: Low Dose Dex - 0mg/kg Lido
arm group label: Low Dose Dex - 1mg/kg Lido
arm group label: Low Dose Dex - 2mg/kg Lido
arm group label: Low Dose Dex - 4mg/kg Lido
arm group label: Medium Dose Dex - 0mg/kg Lido
arm group label: Medium Dose Dex - 1mg/kg Lido
arm group label: Medium Dose Dex - 2mg/kg Lido
arm group label: Medium Dose Dex - 4mg/kg Lido
intervention type: Drug
intervention name: Lidocaine
description: 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)
arm group label: High Dose Dex - 1mg/kg Lido
arm group label: High Dose Dex - 2mg/kg Lido
arm group label: High Dose Dex - 4mg/kg Lido
arm group label: Low Dose Dex - 1mg/kg Lido
arm group label: Low Dose Dex - 2mg/kg Lido
arm group label: Low Dose Dex - 4mg/kg Lido
arm group label: Medium Dose Dex - 1mg/kg Lido
arm group label: Medium Dose Dex - 2mg/kg Lido
arm group label: Medium Dose Dex - 4mg/kg Lido
arm group label: Placebo - 1mg/kg Lido
arm group label: Placebo - 2mg/kg Lido
arm group label: Placebo - 4mg/kg Lido
intervention type: Drug
intervention name: Placebo (Dextromethorphan)
description: 0mg Dextromethorphan
arm group label: Placebo - 1mg/kg Lido
arm group label: Placebo - 2mg/kg Lido
arm group label: Placebo - 4mg/kg Lido
arm group label: Placebo- 0mg/kg Lido
intervention type: Drug
intervention name: Placebo (Lidocaine)
description: 0mg/kg LBM Lidocaine
arm group label: High Dose Dex - 0mg/kg Lido
arm group label: Low Dose Dex - 0mg/kg Lido
arm group label: Medium Dose Dex - 0mg/kg Lido
arm group label: Placebo- 0mg/kg Lido
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Christine N. Sang, MD, MPH
role: Principal Investigator
affiliation: Translational Pain Research, Brigham and Women's Hospital (Disclosure: Patent)
facility: 
country: United States
url: http://www.paintrials.org
description: Translational Pain Research, Brigham and Women's Hospital
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Christine N. Sang, MD, MPH
investigator title: Director, Translational Pain Research
mesh term: Spinal Cord Injuries
mesh term: Neuralgia
mesh term: Hyperalgesia
mesh term: Wounds and Injuries
mesh term: Lidocaine
mesh term: Dextromethorphan
sharing ipd: Undecided
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 