<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/NCT03249779</url>
  </required_header>
  <id_info>
    <org_study_id>16-005286</org_study_id>
    <nct_id>NCT03249779</nct_id>
  </id_info>
  <brief_title>Treatment of RLS/WED Symptoms Through Sensory Counter-stimulation</brief_title>
  <acronym>RLS/WED</acronym>
  <official_title>Electrical Stimulation Via the Scrambler Device as a Treatment for Restless Legs Syndrome/Willis Ekbom Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate, in a pilot fashion, efficacy and tolerability of electrical counter-stimulation&#xD;
      using the Scrambler device in alleviating uncomfortable sensations and urge to move in&#xD;
      patients with restless legs syndrome/Willis Ekbom Disease (RLS/WED).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of up to 10 eligible subjects will be recruited who have been diagnosed with chronic&#xD;
      RLS/WED (Restless legs syndrome/ Willis Ekbom Disease) in the Mayo Clinic Center for Sleep&#xD;
      Medicine. Subjects must experience daily symptoms and must typically be symptomatic during&#xD;
      the timeframe in which Scrambler Therapy will be utilized (12-5 PM). Each patient will&#xD;
      complete the International Restless Legs Syndrome Rating Scale (IRLS), a validated scale&#xD;
      which assesses severity of RLS symptoms16 at baseline (pre-treatment) and before and directly&#xD;
      after each session of Scrambler Therapy.&#xD;
&#xD;
      Patients will receive Scrambler Therapy on a daily basis for up to 10 consecutive weekdays.&#xD;
      Electrodes will be placed proximal to the area of RLS symptomatology, with gradual downward&#xD;
      localization until the entire area of RLS symptoms has been treated. Treatment will initially&#xD;
      take place on one leg. Treatments will be administered by a technician trained in using the&#xD;
      Scrambler device. A physician or nurse (with familiarity of Scrambler therapy) will be&#xD;
      available throughout each treatment session.&#xD;
&#xD;
      Patients will complete questionnaires regarding discomfort or other side effects encountered&#xD;
      during or after treatment. Patients will also complete surveys assessing for any changes&#xD;
      (benefits or worsening) in RLS symptomatology between treatments.&#xD;
&#xD;
      Patients will be monitored for any adverse events associated with the study procedures. Any&#xD;
      reported adverse events will be expediently classified by the study group as to severity&#xD;
      level, whether it relates to the treatments in the study protocol, and whether the event was&#xD;
      expected or unexpected. This information will allow determination of whether or not the&#xD;
      adverse event should be reported as an expedited report or part of the routinely reported&#xD;
      outcomes data. All adverse events which meet criteria for expedited reporting will be&#xD;
      reported to the institutional IRB as well as external agencies as required.&#xD;
&#xD;
      If there is no evidence of clinical benefit with the first 2-4 patients, then further&#xD;
      patients may not be recruited.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">June 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in International Restless Legs Syndrome Rating Scale (IRLS)</measure>
    <time_frame>baseline, 2 weeks</time_frame>
    <description>The International Restless Legs Syndrome Rating Scale (IRLS) questionnaire will be used for this purpose.&#xD;
The IRLS is a validated patient-reported outcome measure to accurately assess disease severity of restless legs syndrome. It has questions on the primary features of restless legs syndrome, along with intensity and frequency, associated sleep problems. For this study subjects were asked to answer 10 questions on how often they experienced each symptom, using a score of 0-4, 0 being &quot;None&quot; and 4 being &quot;Very severe.&quot; Answers from these questions were combined to provide a total Restless Legs Syndrome score (for a total possible range of 0-40) for each patient at each visit. Lower scores reflected fewer symptoms and higher scores reflected more symptoms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in International Restless Legs Syndrome Rating Scale (IRLS)</measure>
    <time_frame>baseline, 1 week post treatment (approximately 3 weeks)</time_frame>
    <description>The International Restless Legs Syndrome Rating Scale (IRLS) questionnaire will be used for this purpose.&#xD;
The IRLS is a validated patient-reported outcome measure to accurately assess disease severity of restless legs syndrome. It has questions on the primary features of restless legs syndrome, along with intensity and frequency, associated sleep problems. For this study subjects were asked to answer 10 questions on how often they experienced each symptom, using a score of 0-4, 0 being &quot;None&quot; and 4 being &quot;Very severe.&quot; Answers from these questions were combined to provide a total Restless Legs Syndrome score (for a total possible range of 0-40) for each patient at each visit. Lower scores reflected fewer symptoms and higher scores reflected more symptoms.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Restless Legs Syndrome</condition>
  <condition>Willis-Ekbom Disease</condition>
  <arm_group>
    <arm_group_label>Scrambler</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants will receive electrical stimulation applied to the lower extremities using the Scrambler.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Scrambler</intervention_name>
    <description>Scrambler Therapy is a specific form of electrical stimulation which has also been utilized in chronic neurogenic pain11. This modality of therapy differs from TENS in that the goal is to mediate the patient's perception of pain, rather than masking the peripheral pain signal. The results of this modality of treatment may be longer-lasting than TENS, presumably via reduction in central signal generation. Scrambler therapy works through C fibers to retrain the peripheral sensation in the area being treated. Further description of this technology is available at: International Patent PCT/IT2007/000647 and U.S. Patent No. 8,380,317. Literature search does not yield prior studies regarding efficacy of Scrambler therapy in treating RLS</description>
    <arm_group_label>Scrambler</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients age 18 and over diagnosed with RLS/WED by a board certified&#xD;
             sleep medicine physician within the Mayo Clinic Center for Sleep Medicine.&#xD;
&#xD;
          -  Patients must have moderate to severe symptoms which have been present for ≥ 3 months.&#xD;
             Patients must endorse discomfort as part of their typical RLS/WED symptomatology.&#xD;
&#xD;
          -  Patients must experience daily symptoms and must experience daily symptoms during&#xD;
             afternoon hours (12-5 PM)&#xD;
&#xD;
          -  Patients on no medications for RLS/WED, or those who have refractory symptoms despite&#xD;
             RLS/WED medications will be enrolled. Patients on alpha-2-delta ligands (pregabalin,&#xD;
             gabapentin) will be asked to discontinue these medications two weeks prior to starting&#xD;
             treatments and remain off these medications throughout the study protocol.&#xD;
&#xD;
          -  Informed consent to participate in this study needs to be obtained&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Research authorization not provided&#xD;
&#xD;
          -  Patients who are asymptomatic (either by verbal report or completion of severity&#xD;
             scale) at time of initiation of Scrambler Therapy treatment&#xD;
&#xD;
          -  Patients who have made changes in medication regimen during the 2 weeks prior to study&#xD;
             initiation (including initiation of iron supplementation)&#xD;
&#xD;
          -  Prior use of Scrambler Therapy&#xD;
&#xD;
          -  Pregnant or Nursing Patients&#xD;
&#xD;
          -  Patients with implantable drug delivery systems, heart stents, or metal implants&#xD;
             (including pacemakers and defibrillators)&#xD;
&#xD;
          -  Patients with history of epilepsy or other medical conditions that in the opinion of&#xD;
             the investigators should be excluded&#xD;
&#xD;
          -  Patients with skin conditions or wounds in or around the area of electrode application&#xD;
             (lower extremities)&#xD;
&#xD;
          -  Patients treated with alpha-2 delta ligands (gabapentin, pregabalin), who cannot&#xD;
             discontinue the medications as above&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Melissa Lipford, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <results_first_submitted>April 25, 2019</results_first_submitted>
  <results_first_submitted_qc>August 13, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">September 4, 2019</results_first_posted>
  <last_update_submitted>August 13, 2019</last_update_submitted>
  <last_update_submitted_qc>August 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Melissa Lipford</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psychomotor Agitation</mesh_term>
    <mesh_term>Restless Legs Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 10, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT03249779/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Scrambler</title>
          <description>All participants will receive electrical stimulation applied to the lower extremities using the Scrambler.&#xD;
Scrambler: Scrambler Therapy is a specific form of electrical stimulation which has also been utilized in chronic neurogenic pain11. This modality of therapy differs from TENS in that the goal is to mediate the patient's perception of pain, rather than masking the peripheral pain signal. The results of this modality of treatment may be longer-lasting than TENS, presumably via reduction in central signal generation. Scrambler therapy works through C fibers to retrain the peripheral sensation in the area being treated. Further description of this technology is available at: International Patent PCT/IT2007/000647 and U.S. Patent No. 8,380,317. Literature search does not yield prior studies regarding efficacy of Scrambler therapy in treating RLS</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </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>Scrambler</title>
          <description>All participants will receive electrical stimulation applied to the lower extremities using the Scrambler.&#xD;
Scrambler: Scrambler Therapy is a specific form of electrical stimulation which has also been utilized in chronic neurogenic pain11. This modality of therapy differs from TENS in that the goal is to mediate the patient's perception of pain, rather than masking the peripheral pain signal. The results of this modality of treatment may be longer-lasting than TENS, presumably via reduction in central signal generation. Scrambler therapy works through C fibers to retrain the peripheral sensation in the area being treated. Further description of this technology is available at: International Patent PCT/IT2007/000647 and U.S. Patent No. 8,380,317. Literature search does not yield prior studies regarding efficacy of Scrambler therapy in treating RLS</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="71" lower_limit="51" upper_limit="87"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in International Restless Legs Syndrome Rating Scale (IRLS)</title>
        <description>The International Restless Legs Syndrome Rating Scale (IRLS) questionnaire will be used for this purpose.&#xD;
The IRLS is a validated patient-reported outcome measure to accurately assess disease severity of restless legs syndrome. It has questions on the primary features of restless legs syndrome, along with intensity and frequency, associated sleep problems. For this study subjects were asked to answer 10 questions on how often they experienced each symptom, using a score of 0-4, 0 being &quot;None&quot; and 4 being &quot;Very severe.&quot; Answers from these questions were combined to provide a total Restless Legs Syndrome score (for a total possible range of 0-40) for each patient at each visit. Lower scores reflected fewer symptoms and higher scores reflected more symptoms.</description>
        <time_frame>baseline, 2 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Scrambler</title>
            <description>All participants will receive electrical stimulation applied to the lower extremities using the Scrambler.&#xD;
Scrambler: Scrambler Therapy is a specific form of electrical stimulation which has also been utilized in chronic neurogenic pain11. This modality of therapy differs from TENS in that the goal is to mediate the patient's perception of pain, rather than masking the peripheral pain signal. The results of this modality of treatment may be longer-lasting than TENS, presumably via reduction in central signal generation. Scrambler therapy works through C fibers to retrain the peripheral sensation in the area being treated. Further description of this technology is available at: International Patent PCT/IT2007/000647 and U.S. Patent No. 8,380,317. Literature search does not yield prior studies regarding efficacy of Scrambler therapy in treating RLS</description>
          </group>
        </group_list>
        <measure>
          <title>Change in International Restless Legs Syndrome Rating Scale (IRLS)</title>
          <description>The International Restless Legs Syndrome Rating Scale (IRLS) questionnaire will be used for this purpose.&#xD;
The IRLS is a validated patient-reported outcome measure to accurately assess disease severity of restless legs syndrome. It has questions on the primary features of restless legs syndrome, along with intensity and frequency, associated sleep problems. For this study subjects were asked to answer 10 questions on how often they experienced each symptom, using a score of 0-4, 0 being &quot;None&quot; and 4 being &quot;Very severe.&quot; Answers from these questions were combined to provide a total Restless Legs Syndrome score (for a total possible range of 0-40) for each patient at each visit. Lower scores reflected fewer symptoms and higher scores reflected more symptoms.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.5" spread="8.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0396</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in International Restless Legs Syndrome Rating Scale (IRLS)</title>
        <description>The International Restless Legs Syndrome Rating Scale (IRLS) questionnaire will be used for this purpose.&#xD;
The IRLS is a validated patient-reported outcome measure to accurately assess disease severity of restless legs syndrome. It has questions on the primary features of restless legs syndrome, along with intensity and frequency, associated sleep problems. For this study subjects were asked to answer 10 questions on how often they experienced each symptom, using a score of 0-4, 0 being &quot;None&quot; and 4 being &quot;Very severe.&quot; Answers from these questions were combined to provide a total Restless Legs Syndrome score (for a total possible range of 0-40) for each patient at each visit. Lower scores reflected fewer symptoms and higher scores reflected more symptoms.</description>
        <time_frame>baseline, 1 week post treatment (approximately 3 weeks)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Scrambler</title>
            <description>All participants will receive electrical stimulation applied to the lower extremities using the Scrambler.&#xD;
Scrambler: Scrambler Therapy is a specific form of electrical stimulation which has also been utilized in chronic neurogenic pain11. This modality of therapy differs from TENS in that the goal is to mediate the patient's perception of pain, rather than masking the peripheral pain signal. The results of this modality of treatment may be longer-lasting than TENS, presumably via reduction in central signal generation. Scrambler therapy works through C fibers to retrain the peripheral sensation in the area being treated. Further description of this technology is available at: International Patent PCT/IT2007/000647 and U.S. Patent No. 8,380,317. Literature search does not yield prior studies regarding efficacy of Scrambler therapy in treating RLS</description>
          </group>
        </group_list>
        <measure>
          <title>Change in International Restless Legs Syndrome Rating Scale (IRLS)</title>
          <description>The International Restless Legs Syndrome Rating Scale (IRLS) questionnaire will be used for this purpose.&#xD;
The IRLS is a validated patient-reported outcome measure to accurately assess disease severity of restless legs syndrome. It has questions on the primary features of restless legs syndrome, along with intensity and frequency, associated sleep problems. For this study subjects were asked to answer 10 questions on how often they experienced each symptom, using a score of 0-4, 0 being &quot;None&quot; and 4 being &quot;Very severe.&quot; Answers from these questions were combined to provide a total Restless Legs Syndrome score (for a total possible range of 0-40) for each patient at each visit. Lower scores reflected fewer symptoms and higher scores reflected more symptoms.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.25" spread="11.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1330</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events were collected from baseline through 1 week post treatment, approximately 3 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Scrambler</title>
          <description>All participants will receive electrical stimulation applied to the lower extremities using the Scrambler.&#xD;
Scrambler: Scrambler Therapy is a specific form of electrical stimulation which has also been utilized in chronic neurogenic pain11. This modality of therapy differs from TENS in that the goal is to mediate the patient's perception of pain, rather than masking the peripheral pain signal. The results of this modality of treatment may be longer-lasting than TENS, presumably via reduction in central signal generation. Scrambler therapy works through C fibers to retrain the peripheral sensation in the area being treated. Further description of this technology is available at: International Patent PCT/IT2007/000647 and U.S. Patent No. 8,380,317. Literature search does not yield prior studies regarding efficacy of Scrambler therapy in treating RLS</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="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
              </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="8"/>
              </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>Melissa C. Lipford, M.D.</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-255-9230</phone>
      <email>Lipford.Melissa@mayo.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/NCT03249779
org study id: 16-005286
nct id: NCT03249779
lead sponsor: 
has dmc: No
To evaluate, in a pilot fashion, efficacy and tolerability of electrical counter-stimulation
      using the Scrambler device in alleviating uncomfortable sensations and urge to move in
      patients with restless legs syndrome/Willis Ekbom Disease (RLS/WED).
A total of up to 10 eligible subjects will be recruited who have been diagnosed with chronic
      RLS/WED (Restless legs syndrome/ Willis Ekbom Disease) in the Mayo Clinic Center for Sleep
      Medicine. Subjects must experience daily symptoms and must typically be symptomatic during
      the timeframe in which Scrambler Therapy will be utilized (12-5 PM). Each patient will
      complete the International Restless Legs Syndrome Rating Scale (IRLS), a validated scale
      which assesses severity of RLS symptoms16 at baseline (pre-treatment) and before and directly
      after each session of Scrambler Therapy.

      Patients will receive Scrambler Therapy on a daily basis for up to 10 consecutive weekdays.
      Electrodes will be placed proximal to the area of RLS symptomatology, with gradual downward
      localization until the entire area of RLS symptoms has been treated. Treatment will initially
      take place on one leg. Treatments will be administered by a technician trained in using the
      Scrambler device. A physician or nurse (with familiarity of Scrambler therapy) will be
      available throughout each treatment session.

      Patients will complete questionnaires regarding discomfort or other side effects encountered
      during or after treatment. Patients will also complete surveys assessing for any changes
      (benefits or worsening) in RLS symptomatology between treatments.

      Patients will be monitored for any adverse events associated with the study procedures. Any
      reported adverse events will be expediently classified by the study group as to severity
      level, whether it relates to the treatments in the study protocol, and whether the event was
      expected or unexpected. This information will allow determination of whether or not the
      adverse event should be reported as an expedited report or part of the routinely reported
      outcomes data. All adverse events which meet criteria for expedited reporting will be
      reported to the institutional IRB as well as external agencies as required.

      If there is no evidence of clinical benefit with the first 2-4 patients, then further
      patients may not be recruited.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in International Restless Legs Syndrome Rating Scale (IRLS)
time frame: baseline, 2 weeks
description: The International Restless Legs Syndrome Rating Scale (IRLS) questionnaire will be used for this purpose.
The IRLS is a validated patient-reported outcome measure to accurately assess disease severity of restless legs syndrome. It has questions on the primary features of restless legs syndrome, along with intensity and frequency, associated sleep problems. For this study subjects were asked to answer 10 questions on how often they experienced each symptom, using a score of 0-4, 0 being "None" and 4 being "Very severe." Answers from these questions were combined to provide a total Restless Legs Syndrome score (for a total possible range of 0-40) for each patient at each visit. Lower scores reflected fewer symptoms and higher scores reflected more symptoms.
measure: Change in International Restless Legs Syndrome Rating Scale (IRLS)
time frame: baseline, 1 week post treatment (approximately 3 weeks)
description: The International Restless Legs Syndrome Rating Scale (IRLS) questionnaire will be used for this purpose.
The IRLS is a validated patient-reported outcome measure to accurately assess disease severity of restless legs syndrome. It has questions on the primary features of restless legs syndrome, along with intensity and frequency, associated sleep problems. For this study subjects were asked to answer 10 questions on how often they experienced each symptom, using a score of 0-4, 0 being "None" and 4 being "Very severe." Answers from these questions were combined to provide a total Restless Legs Syndrome score (for a total possible range of 0-40) for each patient at each visit. Lower scores reflected fewer symptoms and higher scores reflected more symptoms.
arm group label: Scrambler
arm group type: Experimental
description: All participants will receive electrical stimulation applied to the lower extremities using the Scrambler.
intervention type: Device
intervention name: Scrambler
description: Scrambler Therapy is a specific form of electrical stimulation which has also been utilized in chronic neurogenic pain11. This modality of therapy differs from TENS in that the goal is to mediate the patient's perception of pain, rather than masking the peripheral pain signal. The results of this modality of treatment may be longer-lasting than TENS, presumably via reduction in central signal generation. Scrambler therapy works through C fibers to retrain the peripheral sensation in the area being treated. Further description of this technology is available at: International Patent PCT/IT2007/000647 and U.S. Patent No. 8,380,317. Literature search does not yield prior studies regarding efficacy of Scrambler therapy in treating RLS
arm group label: Scrambler
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Melissa Lipford, MD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Melissa Lipford
investigator title: MD
mesh term: Psychomotor Agitation
mesh term: Restless Legs Syndrome
mesh term: Syndrome
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 