<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/NCT02247063</url>
  </required_header>
  <id_info>
    <org_study_id>70766</org_study_id>
    <nct_id>NCT02247063</nct_id>
  </id_info>
  <brief_title>Motor Cortex as a Research &amp; Therapeutic Target in TMD</brief_title>
  <official_title>Motor Cortex as a Research and Therapeutic Target in TMD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are doing a study to learn about the effects of a type of low-energy&#xD;
      non-surgical electrical brain stimulation (HD-tDCS) on chronic pain in people's jaw joints.&#xD;
      Disorders in these joints are called temporomandibular joint disorders, or TMD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic temporomandibular joint disorders (TMD) represent clinical problems in which&#xD;
      empirical treatments offer uncertain relief for a large number of patients. Many conventional&#xD;
      therapies are ineffectual, leading to persistent treatment failure and/or poor&#xD;
      iatrogenic-induced results; which raises the possibility that the cause for their pain&#xD;
      endurance may also lie in the brain milieu. Although MRI-based techniques have provided&#xD;
      insights into some neuroplastic mechanisms of TMD in humans, many questions regarding its&#xD;
      molecular mechanisms in vivo are still unanswered. First, how are endogenous μ-opioid&#xD;
      mechanisms in the brain, known to be centrally involved in pain regulation, affected by acute&#xD;
      and chronic TMD pain? Second, how can they be directly modulated to provide analgesic effect&#xD;
      on pain measures? Finally, what are the neuroplastic effects in the brain after continuous&#xD;
      modulation of those molecular mechanisms? The understanding of these processes is crucial to&#xD;
      determine the mechanisms engaged in the persistence and, most important, the alleviation of&#xD;
      TMD.&#xD;
&#xD;
      Preliminary studies from our center, using positron emission tomography (PET) with [11C]&#xD;
      carfentanil, a selective radiotracer for mu-opioid receptor (muOR), have demonstrated that&#xD;
      there is a decrease in μOR availability (non-displaceable binding potential -BPND) in key&#xD;
      pain-related structures in the brains of chronic trigeminal pain patients, which correlated&#xD;
      with their clinical pain measures. We propose to demonstrate that acute (masseteric pain&#xD;
      challenge) and chronic clinical pain measures in TMD patients are correlated with μ-opioid&#xD;
      receptor (µOR) non-displaceable binding potential (BPND) in the thalamus and other&#xD;
      pain-related regions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2013</start_date>
  <completion_date type="Actual">January 2014</completion_date>
  <primary_completion_date type="Actual">January 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Pain Relief as Measured by Visual Analog Scale (VAS) Decrease of 50% or Greater From Baseline</measure>
    <time_frame>Post tDCS sessions compared to baseline (one week)</time_frame>
    <description>Self-reported VAS from 0 (no pain) to 10 (worst possible pain)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Pain Relief as Measured by Visual Analog Scale (VAS) Decrease of 50% or Greater From Baseline</measure>
    <time_frame>One month after tDCS sessions compared to baseline (6 weeks)</time_frame>
    <description>Self-reported VAS from 0 (no pain) to 10 (worst possible pain)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Temporomandibular Joint Disorders</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>The subjects in the placebo arm will participate in 5 daily M1 High-Definition Transcranial Direct Current Stimulation (HD-tDCS) sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Current will be applied only for 30 seconds - this is a reliable method of sham stimulation (Gandiga et al., 2006) as sensations arising from tDCS treatment occur only at the beginning of application.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects in the experimental arm will participate in 5 daily sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Then 2mA of transcranial direct current stimulation will be applied for 20 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>High-Definition Transcranial Direct Current Stimulation (HD-tDCS)</intervention_name>
    <description>HD-tDCS is a non-invasive brain neuromodulatory method for M1 that involves sending a weak electrical current into your brain.</description>
    <arm_group_label>Experimental</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Daily chronic TMD pain and dysfunction for at least one year (Research Diagnostic&#xD;
             Criteria for Temporomandibular Disorders (RDC/TMD) Axis I Group I: Myofascial pain&#xD;
             diagnosis[15]) not adequately controlled by previous conventional therapies (TMJ&#xD;
             open-surgery naïve) for more than&#xD;
&#xD;
             1 year&#xD;
&#xD;
          -  Self-reported pain score of at least 3 on a 0-10 scale in spite of existing treatment&#xD;
             in the two weeks preceding the onset of the study&#xD;
&#xD;
          -  Taking stable doses of medications for at least 4 weeks (if taking medications), and&#xD;
             willing to limit the introduction of new medications for chronic TMD symptoms during&#xD;
             the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pain not primarily due to TMD&#xD;
&#xD;
          -  History or current evidence of a psychotic disorder (e.g. schizophrenia) or substance&#xD;
             abuse by DSM-IV criteria; bipolar or severe major depression&#xD;
&#xD;
          -  History of neurological disorder (e.g. epilepsy, stroke, neuropathy, neuropathic pain)&#xD;
&#xD;
          -  Any severe clinical condition that in the opinion of the principal investigator&#xD;
             interferes with the study&#xD;
&#xD;
          -  Pregnant or expecting to become pregnant during the study&#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>Alexandre FM DaSilva, DDS, DMedSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 23, 2014</study_first_posted>
  <results_first_submitted>November 8, 2017</results_first_submitted>
  <results_first_submitted_qc>November 8, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 6, 2017</results_first_posted>
  <last_update_submitted>March 23, 2020</last_update_submitted>
  <last_update_submitted_qc>March 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Alexandre DaSilva, DDS, DMedSc</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Joint Diseases</mesh_term>
    <mesh_term>Temporomandibular Joint Disorders</mesh_term>
    <mesh_term>Temporomandibular Joint Dysfunction Syndrome</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>The subjects in the placebo arm will participate in 5 daily M1 High-Definition Transcranial Direct Current Stimulation (HD-tDCS) sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Current will be applied only for 30 seconds - this is a reliable method of sham stimulation (Gandiga et al., 2006) as sensations arising from tDCS treatment occur only at the beginning of application.&#xD;
High-Definition Transcranial Direct Current Stimulation (HD-tDCS): HD-tDCS is a non-invasive brain neuromodulatory method for M1that involves sending a weak electrical current into your brain.</description>
        </group>
        <group group_id="P2">
          <title>Experimental</title>
          <description>The subjects in the experimental arm will participate in 5 daily sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Then 2mA of transcranial direct current stimulation will be applied for 20 minutes.&#xD;
High-Definition Transcranial Direct Current Stimulation (HD-tDCS): HD-tDCS is a non-invasive brain neuromodulatory method for M1that involves sending a weak electrical current into your brain.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
              </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>Placebo</title>
          <description>The subjects in the placebo arm will participate in 5 daily M1 High-Definition Transcranial Direct Current Stimulation (HD-tDCS) sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Current will be applied only for 30 seconds - this is a reliable method of sham stimulation (Gandiga et al., 2006) as sensations arising from tDCS treatment occur only at the beginning of application.&#xD;
High-Definition Transcranial Direct Current Stimulation (HD-tDCS): HD-tDCS is a non-invasive brain neuromodulatory method for M1that involves sending a weak electrical current into your brain.</description>
        </group>
        <group group_id="B2">
          <title>Experimental</title>
          <description>The subjects in the experimental arm will participate in 5 daily sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Then 2mA of transcranial direct current stimulation will be applied for 20 minutes.&#xD;
High-Definition Transcranial Direct Current Stimulation (HD-tDCS): HD-tDCS is a non-invasive brain neuromodulatory method for M1that involves sending a weak electrical current into your brain.</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="12"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="24"/>
          </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="35.6" spread="16.7"/>
                    <measurement group_id="B2" value="34.8" spread="13.7"/>
                    <measurement group_id="B3" value="35.2" spread="15.0"/>
                  </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="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Pain Relief as Measured by Visual Analog Scale (VAS) Decrease of 50% or Greater From Baseline</title>
        <description>Self-reported VAS from 0 (no pain) to 10 (worst possible pain)</description>
        <time_frame>Post tDCS sessions compared to baseline (one week)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>The subjects in the placebo arm will participate in 5 daily M1 High-Definition Transcranial Direct Current Stimulation (HD-tDCS) sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Current will be applied only for 30 seconds - this is a reliable method of sham stimulation (Gandiga et al., 2006) as sensations arising from tDCS treatment occur only at the beginning of application.&#xD;
High-Definition Transcranial Direct Current Stimulation (HD-tDCS): HD-tDCS is a non-invasive brain neuromodulatory method for M1that involves sending a weak electrical current into your brain.</description>
          </group>
          <group group_id="O2">
            <title>Experimental</title>
            <description>The subjects in the experimental arm will participate in 5 daily sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Then 2mA of transcranial direct current stimulation will be applied for 20 minutes.&#xD;
High-Definition Transcranial Direct Current Stimulation (HD-tDCS): HD-tDCS is a non-invasive brain neuromodulatory method for M1that involves sending a weak electrical current into your brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Pain Relief as Measured by Visual Analog Scale (VAS) Decrease of 50% or Greater From Baseline</title>
          <description>Self-reported VAS from 0 (no pain) to 10 (worst possible pain)</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Pain Relief as Measured by Visual Analog Scale (VAS) Decrease of 50% or Greater From Baseline</title>
        <description>Self-reported VAS from 0 (no pain) to 10 (worst possible pain)</description>
        <time_frame>One month after tDCS sessions compared to baseline (6 weeks)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>The subjects in the placebo arm will participate in 5 daily M1 High-Definition Transcranial Direct Current Stimulation (HD-tDCS) sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Current will be applied only for 30 seconds - this is a reliable method of sham stimulation (Gandiga et al., 2006) as sensations arising from tDCS treatment occur only at the beginning of application.&#xD;
High-Definition Transcranial Direct Current Stimulation (HD-tDCS): HD-tDCS is a non-invasive brain neuromodulatory method for M1that involves sending a weak electrical current into your brain.</description>
          </group>
          <group group_id="O2">
            <title>Experimental</title>
            <description>The subjects in the experimental arm will participate in 5 daily sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Then 2mA of transcranial direct current stimulation will be applied for 20 minutes.&#xD;
High-Definition Transcranial Direct Current Stimulation (HD-tDCS): HD-tDCS is a non-invasive brain neuromodulatory method for M1that involves sending a weak electrical current into your brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Pain Relief as Measured by Visual Analog Scale (VAS) Decrease of 50% or Greater From Baseline</title>
          <description>Self-reported VAS from 0 (no pain) to 10 (worst possible pain)</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>5 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>The subjects in the placebo arm will participate in 5 daily M1 High-Definition Transcranial Direct Current Stimulation (HD-tDCS) sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Current will be applied only for 30 seconds - this is a reliable method of sham stimulation (Gandiga et al., 2006) as sensations arising from tDCS treatment occur only at the beginning of application.&#xD;
High-Definition Transcranial Direct Current Stimulation (HD-tDCS): HD-tDCS is a non-invasive brain neuromodulatory method for M1that involves sending a weak electrical current into your brain.</description>
        </group>
        <group group_id="E2">
          <title>Experimental</title>
          <description>The subjects in the experimental arm will participate in 5 daily sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Then 2mA of transcranial direct current stimulation will be applied for 20 minutes.&#xD;
High-Definition Transcranial Direct Current Stimulation (HD-tDCS): HD-tDCS is a non-invasive brain neuromodulatory method for M1that involves sending a weak electrical current into your brain.</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="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Scalp Pain</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Scalp Burn (Sensation)</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Tingling</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Skin Redness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sleepiness</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Trouble Concentrating</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Mood Change</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="12"/>
              </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>Thiago Nascimento</name_or_title>
      <organization>University of Michigan</organization>
      <phone>734-615-9390</phone>
      <email>Nasci@umich.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/NCT02247063
org study id: 70766
nct id: NCT02247063
lead sponsor: 
has dmc: No
The investigators are doing a study to learn about the effects of a type of low-energy
      non-surgical electrical brain stimulation (HD-tDCS) on chronic pain in people's jaw joints.
      Disorders in these joints are called temporomandibular joint disorders, or TMD.
Chronic temporomandibular joint disorders (TMD) represent clinical problems in which
      empirical treatments offer uncertain relief for a large number of patients. Many conventional
      therapies are ineffectual, leading to persistent treatment failure and/or poor
      iatrogenic-induced results; which raises the possibility that the cause for their pain
      endurance may also lie in the brain milieu. Although MRI-based techniques have provided
      insights into some neuroplastic mechanisms of TMD in humans, many questions regarding its
      molecular mechanisms in vivo are still unanswered. First, how are endogenous μ-opioid
      mechanisms in the brain, known to be centrally involved in pain regulation, affected by acute
      and chronic TMD pain? Second, how can they be directly modulated to provide analgesic effect
      on pain measures? Finally, what are the neuroplastic effects in the brain after continuous
      modulation of those molecular mechanisms? The understanding of these processes is crucial to
      determine the mechanisms engaged in the persistence and, most important, the alleviation of
      TMD.

      Preliminary studies from our center, using positron emission tomography (PET) with [11C]
      carfentanil, a selective radiotracer for mu-opioid receptor (muOR), have demonstrated that
      there is a decrease in μOR availability (non-displaceable binding potential -BPND) in key
      pain-related structures in the brains of chronic trigeminal pain patients, which correlated
      with their clinical pain measures. We propose to demonstrate that acute (masseteric pain
      challenge) and chronic clinical pain measures in TMD patients are correlated with μ-opioid
      receptor (µOR) non-displaceable binding potential (BPND) in the thalamus and other
      pain-related regions.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Number of Participants With Pain Relief as Measured by Visual Analog Scale (VAS) Decrease of 50% or Greater From Baseline
time frame: Post tDCS sessions compared to baseline (one week)
description: Self-reported VAS from 0 (no pain) to 10 (worst possible pain)
measure: Number of Participants With Pain Relief as Measured by Visual Analog Scale (VAS) Decrease of 50% or Greater From Baseline
time frame: One month after tDCS sessions compared to baseline (6 weeks)
description: Self-reported VAS from 0 (no pain) to 10 (worst possible pain)
arm group label: Placebo
arm group type: Sham Comparator
description: The subjects in the placebo arm will participate in 5 daily M1 High-Definition Transcranial Direct Current Stimulation (HD-tDCS) sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Current will be applied only for 30 seconds - this is a reliable method of sham stimulation (Gandiga et al., 2006) as sensations arising from tDCS treatment occur only at the beginning of application.
arm group label: Experimental
arm group type: Experimental
description: The subjects in the experimental arm will participate in 5 daily sessions. During each session, a modular EEG recording cap will be placed on the subject's head and the anodal electrode will be placed on the motor cortex contralateral to the worst TMD pain side (C3). Then 2mA of transcranial direct current stimulation will be applied for 20 minutes.
intervention type: Device
intervention name: High-Definition Transcranial Direct Current Stimulation (HD-tDCS)
description: HD-tDCS is a non-invasive brain neuromodulatory method for M1 that involves sending a weak electrical current into your brain.
arm group label: Experimental
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Alexandre FM DaSilva, DDS, DMedSc
role: Principal Investigator
affiliation: University of Michigan
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Alexandre DaSilva, DDS, DMedSc
investigator title: Associate Professor
mesh term: Joint Diseases
mesh term: Temporomandibular Joint Disorders
mesh term: Temporomandibular Joint Dysfunction Syndrome
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 