<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/NCT02219321</url>
  </required_header>
  <id_info>
    <org_study_id>062014-002</org_study_id>
    <nct_id>NCT02219321</nct_id>
  </id_info>
  <brief_title>Lidocaine Infusion for Chronic Pain in Opioid Dependent Patients</brief_title>
  <official_title>Lidocaine Infusion for Chronic Pain in Opioid Dependent Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prescription drug abuse represents a major healthcare problem, with treatment costs reaching&#xD;
      billions of dollars annually in the United States alone. Today opioids are commonly&#xD;
      prescribed for chronic non-cancer pain and are only partially effective for short-term pain&#xD;
      relief. Whereas opioids are initially part of the solution for pain, it eventually often&#xD;
      turns to be a problem in patient with chronic pain. Long-term treatment with opioids can be&#xD;
      complicated by development of tolerance, dependency, addiction, abnormal pain sensitivity,&#xD;
      hormonal changes, and immune modulation. Unfortunately, the chronic use of anti-inflammatory&#xD;
      drugs is associated with a marked increase in adverse effects.&#xD;
&#xD;
      The purpose of this study is to determine whether systemic administration of lidocaine&#xD;
      provides effective pain relief in opioid dependent chronic pain patients. Investigators&#xD;
      intend to demonstrate that lidocaine infusion can improve pain relief and physical function&#xD;
      in opioid dependent patients, thus improving compliance and patient satisfaction, which may&#xD;
      potentially help wean patients off narcotics. The long-term goal of this proposal is to&#xD;
      decrease opioid dependence in chronic pain patients by using lidocaine infusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is a significant disconnect between the escalating healthcare problem of opioid use for&#xD;
      chronic pain, and the development of novel therapeutic strategies. A plausible strategy is to&#xD;
      interrupt the vicious cycle of pain, inflammation and hyperesthesia is using highly&#xD;
      efficacious non-opioid drugs that do not require chronic administration, such as lidocaine.&#xD;
      Lidocaine is FDA approved local anesthetic, class 2 antiarrhythmic with analgesic,&#xD;
      antihyperalgesic and anti-inflammatory properties without rewarding and addictive properties.&#xD;
      Intravenous lidocaine has been utilized since 1943 for a large spectrum of pain conditions.&#xD;
      Lidocaine also has been shown to significantly reduce circulating inflammatory cytokines&#xD;
      production. Investigators propose that systemic administration of lidocaine will decrease the&#xD;
      intensity, duration of pain in opioid dependent chronic pain patients. The long-term goal of&#xD;
      this proposal is to decrease opioid dependence in chronic pain patients by using lidocaine&#xD;
      infusion. The central hypothesis is that lidocaine infusion decreases the intensity of pain&#xD;
      in opioid dependent chronic pain patients.&#xD;
&#xD;
      Primary outcome: To determine the short-term effect of lidocaine infusion on the intensity of&#xD;
      pain in opioid dependent chronic pain patients.&#xD;
&#xD;
      Secondary outcome1: Determine the duration of pain relief after lidocaine infusion in opioid&#xD;
      dependent chronic pain patients. Investigators hypothesize that lidocaine infusions will have&#xD;
      a long lasting Visual Analog Pain (VAS) score improvement that will extend beyond the time of&#xD;
      infusion.&#xD;
&#xD;
      This intermediate and long-term pain relief will be demonstrated by measuring both VAS pain&#xD;
      scores 3 times a day for 3 weeks and by the reduction in daily opioid use by 25%.&#xD;
&#xD;
      Secondary outcome2: Determine the effect of lidocaine infusion on opioid induced&#xD;
      hyperalgesia. Lidocaine infusion may decrease cytokine levels both acutely after infusion as&#xD;
      compared to baseline, as well as at the end of 1 week after infusion.&#xD;
&#xD;
      STUDY DESIGN AND POPULATION: Forty opioid dependent patients will be randomized in a double&#xD;
      blind parallel placebo control study to investigate the effects of lidocaine on neuropathic&#xD;
      pain. Patients who meet the inclusion criteria will receive Initial laboratory work-up prior&#xD;
      to infusion date. Each patient will receive a Hepatic panel, CBC, and Chemistry and baseline&#xD;
      cytokine levels (IL1b) as well as a baseline Cold Pressor Test (CPT) and then will be&#xD;
      randomized to either receive lidocaine or placebo.&#xD;
&#xD;
      Study Intervention: Lidocaine intravenous 2mg/kg initial bolus over 5 minutes followed by a&#xD;
      continuous intravenous infusion of lidocaine at a rate of 2mg /kg /hour for 4 hours versus&#xD;
      saline of same volume and duration.&#xD;
&#xD;
      Duration of the study: Patient will be followed for 3 weeks after the lidocaine infusion.&#xD;
&#xD;
      Monitoring during infusion: Heart rate, blood pressure, EKG, oxygen saturation, and any&#xD;
      potential side effects as sedation, circumoral numbness, metallic taste in the mouth will be&#xD;
      continuously monitored and recorded every 15 minutes (standard monitoring and recording time&#xD;
      in recovery area) as well as pain scores. After completion of infusion patient will be&#xD;
      further monitored for another 2 hrs and then discharged after meeting standard discharge&#xD;
      criteria according to Aldrete scoring system.&#xD;
&#xD;
      Discharge instruction: Patients will be asked to decrease their daily opioid dose by 25%.&#xD;
      Patients will receive a one-week supply of a short acting opioid as a rescue medication.&#xD;
      Patients will be asked to use the rescue medication if pain is moderate to severe for the&#xD;
      first day after infusion. If no improvement in pain despite allowable short acting medication&#xD;
      as reported on first day post infusion follow up phone call, patient will be asked to resume&#xD;
      their usual long acting opioid dose. Each patient will receive a pain diary sheet where they&#xD;
      will record their daily visual analogue pain scores 3 times a day as well as their daily&#xD;
      opioid dose plus over the counter analgesic requirements as NSAIDS and acetaminophen.&#xD;
      Patients will follow up every week till study completion, where pain diary, over the counter&#xD;
      and rescue pain medications will be assessed.&#xD;
&#xD;
      Outcome Measures:&#xD;
&#xD;
        1. Visual Analog Pain (VAS) Scores&#xD;
&#xD;
        2. Serum interleukin Ib level&#xD;
&#xD;
        3. CPT&#xD;
&#xD;
        4. Daily opioid use&#xD;
&#xD;
      Subject Safety and Data Monitoring:&#xD;
&#xD;
      All subjects will be carefully assessed prior to participation in the studies, including&#xD;
      medical history, laboratory tests, and examination by a board-certified physician (Dr.&#xD;
      Kandil). Subjects with medical problems that would increase risk for participation will be&#xD;
      excluded from the study.&#xD;
&#xD;
      During the infusion patient's vital signs: heart rate, blood pressure, EKG, oxygen&#xD;
      saturation, and any potential side effects as sedation, circumoral numbness, metallic taste&#xD;
      in the mouth will be continuously monitored and recorded every 15 minutes as well as pain&#xD;
      scores.&#xD;
&#xD;
      All lidocaine/saline infusions will be supervised by Dr. Enas Kandil, an anesthesiologist.&#xD;
      Dr. Kandil or a nurse will be in attendance during throughout the infusion. Heart rate,&#xD;
      including EKG rhythm strip, will be monitored continuously throughout the infusion and blood&#xD;
      pressure will be obtained every 15 minutes and more frequently if indicated. If the&#xD;
      participants' hemodynamics (heart rate, blood pressure) change by more than 20% (typically a&#xD;
      consequence of cardiac arrhythmias) the infusion will be stopped. The more serious toxic&#xD;
      effects of lidocaine (e.g. unconsciousness, confusion, convulsions, respiratory arrest) are&#xD;
      preceded by numbness of the tongue, lightheadedness, visual disturbances and muscle&#xD;
      twitching; infusions will be terminated if the subject reports of any of these latter signs&#xD;
      or symptoms. A checklist of signs and symptoms will be obtained every 15 minutes. Subjects&#xD;
      will be observed for at least two hours (approximately one half-life of lidocaine) following&#xD;
      the cessation of lidocaine (or saline) infusion. Dr. Kandil must approve discharge for all&#xD;
      participants on the infusion study day.&#xD;
&#xD;
      Lidocaine labels carry warnings and precautions for use in patients with various cardiac&#xD;
      conditions, notably conduction abnormalities (e.g., heart block, QT prolongation). Cardiac&#xD;
      conditions will be identified by EKG, medical history and physical exam. Participants with&#xD;
      any medical history of cardiac disease (e.g. myocardial infarction, congestive heart failure,&#xD;
      cardiac arrhythmia) or an abnormal EKG (including any arrhythmia, heart block, QT&#xD;
      prolongation) will be excluded.&#xD;
&#xD;
      Women with a positive pregnancy test or who report unprotected heterosexual sex since their&#xD;
      previous menses will not receive an infusion. Women with a positive pregnancy test will be&#xD;
      referred for appropriate care. Subjects will be observed for at least two hours&#xD;
      (approximately one half-life of lidocaine) following the cessation of lidocaine (or saline)&#xD;
      infusion. All participants will receive a 24-hour call-in number to contact research staff in&#xD;
      the advent of problems.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of Funding&#xD;
  </why_stopped>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">September 20, 2019</completion_date>
  <primary_completion_date type="Actual">May 14, 2015</primary_completion_date>
  <phase>Phase 3</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>Intensity of Pain</measure>
    <time_frame>Immediately after continuous 4-hours Intravenous lidocaine infusion</time_frame>
    <description>Visual Analog Pain Scores on a scale of 0 to 10 (0=no pain and 10=worst pain)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Withdrawal Time (Seconds)</measure>
    <time_frame>Immediately after Lidocaine Infusion</time_frame>
    <description>The time to withdraw at the Cold Pressor Task immediately after 4-hours intravenous continuous lidocaine infusion</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Chronic Pain</condition>
  <arm_group>
    <arm_group_label>Lidocaine infusion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A continuous intravenous infusion of lidocaine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline infusion</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A continuous intravenous infusion of saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lidocaine infusion</intervention_name>
    <description>Lidocaine intravenous 2mg/kg initial bolus over 5 minutes followed by a continuous intravenous infusion of lidocaine at a rate of 2mg /kg /hour for 4 hours</description>
    <arm_group_label>Lidocaine infusion</arm_group_label>
    <other_name>Intravenous lidocaine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline infusion</intervention_name>
    <description>A continuous intravenous infusion of saline at the same volume with lidocaine infusion for 4 hours</description>
    <arm_group_label>Saline infusion</arm_group_label>
    <other_name>Isotonic Sodium Chloride</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-65 years old -Patient currently on stable dose of opioids for more than six&#xD;
             months period -&#xD;
&#xD;
          -  Patients with Chronic uncontrolled neuropathic pain with documented pain score &gt; or =&#xD;
             4 despite opioids&#xD;
&#xD;
          -  Not currently abusing opioids or other illicit drugs as demonstrated by history and&#xD;
             negative urine toxicology screen&#xD;
&#xD;
          -  Patient agrees to come to all follow up visits at 1, 2, and 3 week following infusion&#xD;
&#xD;
          -  Having baseline/screening EKG&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals meeting DSM-V dependence criteria for alcohol, benzodiazepine, CNS&#xD;
             stimulant, marijuana or other drug of abuse.&#xD;
&#xD;
          -  Hepatic dysfunction as determined by history and physical or clinical significant lab.&#xD;
&#xD;
          -  Cardiac arrhythmias including heart block and QT prolongation as determined by history&#xD;
             or baseline EKG.&#xD;
&#xD;
          -  Subject has inability to understand and cooperate with study procedures or provide&#xD;
             informed consent.&#xD;
&#xD;
          -  Subject has history of intolerance or allergic reaction to lidocaine.&#xD;
&#xD;
          -  Subject has history of seizures.&#xD;
&#xD;
          -  Raynaud's disease&#xD;
&#xD;
          -  Renal impairment as determined by clinically significant labs.&#xD;
&#xD;
          -  Women of childbearing age who either have:&#xD;
&#xD;
               1. A positive pregnancy test&#xD;
&#xD;
               2. Unprotected heterosexual sex since their previous menses or;&#xD;
&#xD;
               3. Not currently using and/or willing to use a medically approved form of&#xD;
                  contraception (e.g., birth control pill).&#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>Enas Kandil, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas Southwestern Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-9068</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkland Health Hospital System</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <results_first_submitted>March 13, 2020</results_first_submitted>
  <results_first_submitted_qc>March 13, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 25, 2020</results_first_posted>
  <last_update_submitted>March 13, 2020</last_update_submitted>
  <last_update_submitted_qc>March 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Enas Kandil</investigator_full_name>
    <investigator_title>Asistant Professor</investigator_title>
  </responsible_party>
  <keyword>Pain, Opioid dependence, Lidocaine infusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lidocaine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Lidocaine Infusion</title>
          <description>A continuous intravenous infusion of lidocaine&#xD;
Lidocaine infusion: Lidocaine intravenous 2mg/kg initial bolus over 5 minutes followed by a continuous intravenous infusion of lidocaine at a rate of 2mg /kg /hour for 4 hours</description>
        </group>
        <group group_id="P2">
          <title>Saline Infusion</title>
          <description>A continuous intravenous infusion of saline&#xD;
Saline infusion: A continuous intravenous infusion of saline at the same volume with lidocaine infusion for 4 hours</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lidocaine Infusion</title>
          <description>A continuous intravenous infusion of lidocaine&#xD;
Lidocaine infusion: Lidocaine intravenous 2mg/kg initial bolus over 5 minutes followed by a continuous intravenous infusion of lidocaine at a rate of 2mg /kg /hour for 4 hours</description>
        </group>
        <group group_id="B2">
          <title>Saline Infusion</title>
          <description>A continuous intravenous infusion of saline&#xD;
Saline infusion: A continuous intravenous infusion of saline at the same volume with lidocaine infusion for 4 hours</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="3"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51" lower_limit="51" upper_limit="51"/>
                    <measurement group_id="B2" value="57" lower_limit="50" upper_limit="64"/>
                    <measurement group_id="B3" value="55" lower_limit="50" upper_limit="64"/>
                  </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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </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>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Intensity of Pain</title>
        <description>Visual Analog Pain Scores on a scale of 0 to 10 (0=no pain and 10=worst pain)</description>
        <time_frame>Immediately after continuous 4-hours Intravenous lidocaine infusion</time_frame>
        <population>Chronic pain patients with opioid precription</population>
        <group_list>
          <group group_id="O1">
            <title>Lidocaine Infusion</title>
            <description>A continuous intravenous infusion of lidocaine&#xD;
Lidocaine infusion: Lidocaine intravenous 2mg/kg initial bolus over 5 minutes followed by a continuous intravenous infusion of lidocaine at a rate of 2mg /kg /hour for 4 hours</description>
          </group>
          <group group_id="O2">
            <title>Saline Infusion</title>
            <description>A continuous intravenous infusion of saline&#xD;
Saline infusion: A continuous intravenous infusion of saline at the same volume with lidocaine infusion for 4 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Intensity of Pain</title>
          <description>Visual Analog Pain Scores on a scale of 0 to 10 (0=no pain and 10=worst pain)</description>
          <population>Chronic pain patients with opioid precription</population>
          <units>units on a scale 0 to 10</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" lower_limit="7" upper_limit="8"/>
                    <measurement group_id="O2" value="3" lower_limit="0" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Withdrawal Time (Seconds)</title>
        <description>The time to withdraw at the Cold Pressor Task immediately after 4-hours intravenous continuous lidocaine infusion</description>
        <time_frame>Immediately after Lidocaine Infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lidocaine Infusion</title>
            <description>A continuous intravenous infusion of lidocaine&#xD;
Lidocaine infusion: Lidocaine intravenous 2mg/kg initial bolus over 5 minutes followed by a continuous intravenous infusion of lidocaine at a rate of 2mg /kg /hour for 4 hours</description>
          </group>
          <group group_id="O2">
            <title>Saline Infusion</title>
            <description>A continuous intravenous infusion of saline&#xD;
Saline infusion: A continuous intravenous infusion of saline at the same volume with lidocaine infusion for 4 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Withdrawal Time (Seconds)</title>
          <description>The time to withdraw at the Cold Pressor Task immediately after 4-hours intravenous continuous lidocaine infusion</description>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61" lower_limit="61" upper_limit="61"/>
                    <measurement group_id="O2" value="41.5" lower_limit="24" upper_limit="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events data were collected during lidocaine infusion and 2 hours immediately after the infusion and during 3-weeks follow-up period</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Lidocaine Infusion</title>
          <description>A continuous intravenous infusion of lidocaine&#xD;
Lidocaine infusion: Lidocaine intravenous 2mg/kg initial bolus over 5 minutes followed by a continuous intravenous infusion of lidocaine at a rate of 2mg /kg /hour for 4 hours</description>
        </group>
        <group group_id="E2">
          <title>Saline Infusion</title>
          <description>A continuous intravenous infusion of saline&#xD;
Saline infusion: A continuous intravenous infusion of saline at the same volume with lidocaine infusion for 4 hours</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="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Enas Kandil</name_or_title>
      <organization>University of Texas Southwestern Medical Center</organization>
      <phone>214-648 ext 9374</phone>
      <email>Enas.Kandil@UTSouthwestern.edu</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/NCT02219321
org study id: 062014-002
nct id: NCT02219321
lead sponsor: 
has dmc: Yes
Prescription drug abuse represents a major healthcare problem, with treatment costs reaching
      billions of dollars annually in the United States alone. Today opioids are commonly
      prescribed for chronic non-cancer pain and are only partially effective for short-term pain
      relief. Whereas opioids are initially part of the solution for pain, it eventually often
      turns to be a problem in patient with chronic pain. Long-term treatment with opioids can be
      complicated by development of tolerance, dependency, addiction, abnormal pain sensitivity,
      hormonal changes, and immune modulation. Unfortunately, the chronic use of anti-inflammatory
      drugs is associated with a marked increase in adverse effects.

      The purpose of this study is to determine whether systemic administration of lidocaine
      provides effective pain relief in opioid dependent chronic pain patients. Investigators
      intend to demonstrate that lidocaine infusion can improve pain relief and physical function
      in opioid dependent patients, thus improving compliance and patient satisfaction, which may
      potentially help wean patients off narcotics. The long-term goal of this proposal is to
      decrease opioid dependence in chronic pain patients by using lidocaine infusion.
There is a significant disconnect between the escalating healthcare problem of opioid use for
      chronic pain, and the development of novel therapeutic strategies. A plausible strategy is to
      interrupt the vicious cycle of pain, inflammation and hyperesthesia is using highly
      efficacious non-opioid drugs that do not require chronic administration, such as lidocaine.
      Lidocaine is FDA approved local anesthetic, class 2 antiarrhythmic with analgesic,
      antihyperalgesic and anti-inflammatory properties without rewarding and addictive properties.
      Intravenous lidocaine has been utilized since 1943 for a large spectrum of pain conditions.
      Lidocaine also has been shown to significantly reduce circulating inflammatory cytokines
      production. Investigators propose that systemic administration of lidocaine will decrease the
      intensity, duration of pain in opioid dependent chronic pain patients. The long-term goal of
      this proposal is to decrease opioid dependence in chronic pain patients by using lidocaine
      infusion. The central hypothesis is that lidocaine infusion decreases the intensity of pain
      in opioid dependent chronic pain patients.

      Primary outcome: To determine the short-term effect of lidocaine infusion on the intensity of
      pain in opioid dependent chronic pain patients.

      Secondary outcome1: Determine the duration of pain relief after lidocaine infusion in opioid
      dependent chronic pain patients. Investigators hypothesize that lidocaine infusions will have
      a long lasting Visual Analog Pain (VAS) score improvement that will extend beyond the time of
      infusion.

      This intermediate and long-term pain relief will be demonstrated by measuring both VAS pain
      scores 3 times a day for 3 weeks and by the reduction in daily opioid use by 25%.

      Secondary outcome2: Determine the effect of lidocaine infusion on opioid induced
      hyperalgesia. Lidocaine infusion may decrease cytokine levels both acutely after infusion as
      compared to baseline, as well as at the end of 1 week after infusion.

      STUDY DESIGN AND POPULATION: Forty opioid dependent patients will be randomized in a double
      blind parallel placebo control study to investigate the effects of lidocaine on neuropathic
      pain. Patients who meet the inclusion criteria will receive Initial laboratory work-up prior
      to infusion date. Each patient will receive a Hepatic panel, CBC, and Chemistry and baseline
      cytokine levels (IL1b) as well as a baseline Cold Pressor Test (CPT) and then will be
      randomized to either receive lidocaine or placebo.

      Study Intervention: Lidocaine intravenous 2mg/kg initial bolus over 5 minutes followed by a
      continuous intravenous infusion of lidocaine at a rate of 2mg /kg /hour for 4 hours versus
      saline of same volume and duration.

      Duration of the study: Patient will be followed for 3 weeks after the lidocaine infusion.

      Monitoring during infusion: Heart rate, blood pressure, EKG, oxygen saturation, and any
      potential side effects as sedation, circumoral numbness, metallic taste in the mouth will be
      continuously monitored and recorded every 15 minutes (standard monitoring and recording time
      in recovery area) as well as pain scores. After completion of infusion patient will be
      further monitored for another 2 hrs and then discharged after meeting standard discharge
      criteria according to Aldrete scoring system.

      Discharge instruction: Patients will be asked to decrease their daily opioid dose by 25%.
      Patients will receive a one-week supply of a short acting opioid as a rescue medication.
      Patients will be asked to use the rescue medication if pain is moderate to severe for the
      first day after infusion. If no improvement in pain despite allowable short acting medication
      as reported on first day post infusion follow up phone call, patient will be asked to resume
      their usual long acting opioid dose. Each patient will receive a pain diary sheet where they
      will record their daily visual analogue pain scores 3 times a day as well as their daily
      opioid dose plus over the counter analgesic requirements as NSAIDS and acetaminophen.
      Patients will follow up every week till study completion, where pain diary, over the counter
      and rescue pain medications will be assessed.

      Outcome Measures:

        1. Visual Analog Pain (VAS) Scores

        2. Serum interleukin Ib level

        3. CPT

        4. Daily opioid use

      Subject Safety and Data Monitoring:

      All subjects will be carefully assessed prior to participation in the studies, including
      medical history, laboratory tests, and examination by a board-certified physician (Dr.
      Kandil). Subjects with medical problems that would increase risk for participation will be
      excluded from the study.

      During the infusion patient's vital signs: heart rate, blood pressure, EKG, oxygen
      saturation, and any potential side effects as sedation, circumoral numbness, metallic taste
      in the mouth will be continuously monitored and recorded every 15 minutes as well as pain
      scores.

      All lidocaine/saline infusions will be supervised by Dr. Enas Kandil, an anesthesiologist.
      Dr. Kandil or a nurse will be in attendance during throughout the infusion. Heart rate,
      including EKG rhythm strip, will be monitored continuously throughout the infusion and blood
      pressure will be obtained every 15 minutes and more frequently if indicated. If the
      participants' hemodynamics (heart rate, blood pressure) change by more than 20% (typically a
      consequence of cardiac arrhythmias) the infusion will be stopped. The more serious toxic
      effects of lidocaine (e.g. unconsciousness, confusion, convulsions, respiratory arrest) are
      preceded by numbness of the tongue, lightheadedness, visual disturbances and muscle
      twitching; infusions will be terminated if the subject reports of any of these latter signs
      or symptoms. A checklist of signs and symptoms will be obtained every 15 minutes. Subjects
      will be observed for at least two hours (approximately one half-life of lidocaine) following
      the cessation of lidocaine (or saline) infusion. Dr. Kandil must approve discharge for all
      participants on the infusion study day.

      Lidocaine labels carry warnings and precautions for use in patients with various cardiac
      conditions, notably conduction abnormalities (e.g., heart block, QT prolongation). Cardiac
      conditions will be identified by EKG, medical history and physical exam. Participants with
      any medical history of cardiac disease (e.g. myocardial infarction, congestive heart failure,
      cardiac arrhythmia) or an abnormal EKG (including any arrhythmia, heart block, QT
      prolongation) will be excluded.

      Women with a positive pregnancy test or who report unprotected heterosexual sex since their
      previous menses will not receive an infusion. Women with a positive pregnancy test will be
      referred for appropriate care. Subjects will be observed for at least two hours
      (approximately one half-life of lidocaine) following the cessation of lidocaine (or saline)
      infusion. All participants will receive a 24-hour call-in number to contact research staff in
      the advent of problems.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Intensity of Pain
time frame: Immediately after continuous 4-hours Intravenous lidocaine infusion
description: Visual Analog Pain Scores on a scale of 0 to 10 (0=no pain and 10=worst pain)
measure: Withdrawal Time (Seconds)
time frame: Immediately after Lidocaine Infusion
description: The time to withdraw at the Cold Pressor Task immediately after 4-hours intravenous continuous lidocaine infusion
arm group label: Lidocaine infusion
arm group type: Active Comparator
description: A continuous intravenous infusion of lidocaine
arm group label: Saline infusion
arm group type: Placebo Comparator
description: A continuous intravenous infusion of saline
intervention type: Drug
intervention name: Lidocaine infusion
description: Lidocaine intravenous 2mg/kg initial bolus over 5 minutes followed by a continuous intravenous infusion of lidocaine at a rate of 2mg /kg /hour for 4 hours
arm group label: Lidocaine infusion
other name: Intravenous lidocaine
intervention type: Drug
intervention name: Saline infusion
description: A continuous intravenous infusion of saline at the same volume with lidocaine infusion for 4 hours
arm group label: Saline infusion
other name: Isotonic Sodium Chloride
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Enas Kandil, MD
role: Principal Investigator
affiliation: University of Texas Southwestern Medical Center
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Enas Kandil
investigator title: Asistant Professor
mesh term: Chronic Pain
mesh term: Lidocaine
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 