<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/NCT03301272</url>
  </required_header>
  <id_info>
    <org_study_id>15-1831</org_study_id>
    <nct_id>NCT03301272</nct_id>
  </id_info>
  <brief_title>Effectiveness of Botox on Reducing Rest Tremor in Parkinson's Disease</brief_title>
  <official_title>Effectiveness of Onabotulinumtoxin A on Reduction of Rest Tremor in Parkinson's Disease: a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Purpose: Rest tremor in Parkinson's disease is notoriously difficult to treat through&#xD;
      pharmacological measures, currently only predictably attenuated by the invasive deep brain&#xD;
      stimulation surgery. The investigators hope to find some predictable and clinically&#xD;
      meaningful attenuation of tremor with targeted use of onabotulinum toxin on muscles involved&#xD;
      in creating the tremor.&#xD;
&#xD;
      Participants: 16 subjects who meet United Kingdom (UK) brain bank criteria for Parkinson's&#xD;
      disease with medically refractory rest tremor of at least 3 cm amplitude.&#xD;
&#xD;
      Procedures (methods): Subjects will be blinded to receive either sham saline injection versus&#xD;
      onabotulinum toxin injections directed to muscle groups felt to be clinically involved in&#xD;
      causing the oscillatory movement of the tremor. Assessment of tremor severity and functional&#xD;
      improvement from baseline after injection will occur within group (i.e. each subject will&#xD;
      serve as their own control).&#xD;
&#xD;
      Hypotheses:&#xD;
&#xD;
      1. (A) Onabotulinumtoxin A significantly attenuates the amplitude of medically-refractory&#xD;
      rest tremor of the upper limb in Parkinson's patients as compared to sham injections; as&#xD;
      measured by reduction in the Movement Disorders Society Unified Parkinson's Disease Rating&#xD;
      Scale (MDS-UPDRS) tremor subscore.&#xD;
&#xD;
      1. (B) Onabotulinumtoxin A significantly improves the limb function of Parkinson's patients&#xD;
      with medically-refractory rest tremor of the upper limb as compared to sham injections; as&#xD;
      measured by an increase in Action Research Arm Test (ARAT) scores.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For purposes of properly identifying muscles intended for injection, a portable&#xD;
      electromyography will be attached to an appropriate gauge electromyography-guided botulinum&#xD;
      toxin needle, which in turn will be used to hear/see motor evoked potentials (MEPs). Subjects&#xD;
      will be asked to activate the muscle while needle is inserted to ensure proper placement of&#xD;
      the needle in the desired muscle prior to injection of study solution.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 22, 2018</start_date>
  <completion_date type="Actual">August 21, 2019</completion_date>
  <primary_completion_date type="Actual">August 21, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>The study will comprise of a double blinded, crossover study where the subjects will serve as their own controls. There will be no medication changes made to Parkinson's disease medications throughout the subjects' participation in the study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Double-blinded study whereby the subject, the movement disorder specialist injecting neurotoxin, and the movement disorder specialist rating the patient will be unaware of the solution injected and/or planned for injection same day. To ensure that the injecting specialist is blinded to the solution, syringes will be premixed by a separate member of the research team and de-identified of any possible labels that would indicate the properties of the solution being administered to the subject.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the MDS-UPDRS Tremor Subscore</measure>
    <time_frame>Prior to onabotulinumtoxinA injection and at 30 days after injection</time_frame>
    <description>The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III's tremor subscore (3.17). The subscale has a 0-4 rating, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Higher MDS-UPDRS scores reflect worse tremor/motor function. Larger differences will infer greater effect size for the intervention. Score drops over time imply improvement in tremor/motor function.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the ARAT Score</measure>
    <time_frame>Prior to onabotulinumtoxinA injection and at 30 days after injection</time_frame>
    <description>The Action Research Arm Test (ARAT) is an evaluated measure to assess specific changes in limb function after neurologic sequelae. It assesses a person's ability to handle objects differing in size, weight and shape and therefore can be considered to be an arm-specific measure of activity limitation. The ARAT is a 19 item measure divided into 4 sub-tests (grasp, grip, pinch, and gross arm movement). Performance on each item is rated on a 4-point ordinal scale: 3: Performs test normally 2: Completes test, but takes abnormally long or has great difficulty 1: Performs test partially 0: Can perform no part of test. The maximum score on the ARAT is 57 points (possible range 0 to 57). Higher ARAT scores reflect greater preservation of function in tested arm. Larger differences will infer greater effect sizes for the intervention. Score drops over time imply worsening limb function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation Between MDS-UPDRS Tremor Subscore and Px1 Tremor Amplitude</measure>
    <time_frame>At Visit 1, prior to 1st injection through Visit 4, 30 days after last injection</time_frame>
    <description>MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used is Part III's tremor subscore 3.17. The subscale has a 0-4 rating: (0=no tremor, 1=&lt;1cm, 2=1-3 cm, 3=3-10 cm, 4=&gt;10cm). Higher scores reflect worse tremor amplitude. Larger differences infer greater effect size. The Px1 is a novel, external measuring device using motion-capture technology to determine the frequency, direction and amplitude of movement between hand joints. Movement is captured without ever applying direct pressure on the limb. Output includes tremor frequency in Hz and distance traveled by a hand joint as compared to other joints on the hand in cm. The largest tremor amplitude measured by Px1 was acquired 3x/visit, values averaged then compared with the amplitude range corresponding to MDS-UPDRS tremor subscore. This process was repeated for all subjects for Visits 1-4 comparing all values using Spearman correlation coefficient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Tremor Amplitude in Centimeters (cm) as Measured by Px1</measure>
    <time_frame>Prior to onabotulinumtoxinA injection and at 30 days after injection</time_frame>
    <description>The Px1 is a novel, external measuring device which uses motion-capture technology to determine the frequency, direction, and amplitude of movement between joints within the hand. Oscillatory movement is captured using a camera system and without ever applying any direct pressure upon the limb. Output includes tremor frequency in (Hertz Hz), and distance traveled by a hand joint as compared to other joints on the hand in centimeters (cm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Tremor Frequency in Hertz (Hz) as Measured by Px1</measure>
    <time_frame>Prior to onabotulinumtoxinA injection and at 30 days after injection</time_frame>
    <description>The Px1 is a novel, external measuring device which uses motion-capture technology to determine the frequency, direction, and amplitude of movement between joints within the hand. Oscillatory movement is captured using a camera system and without ever applying any direct pressure upon the limb. Output includes tremor frequency in (Hertz Hz), and distance traveled by a hand joint as compared to other joints on the hand in centimeters (cm)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Onabotulinumtoxin A Injection, then Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants first receive Onabotulinumtoxin A Injection and following a 3-month washout, they receive Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, then Onabotulinumtoxin A Injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants first receive placebo injection and following a 3-month washout, they receive Onabotulinumtoxin A Injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Onabotulinumtoxin A Injection</intervention_name>
    <description>Reconstituted 10 units/0.1 mL. Administered intramuscular once</description>
    <arm_group_label>Onabotulinumtoxin A Injection, then Placebo</arm_group_label>
    <arm_group_label>Placebo, then Onabotulinumtoxin A Injection</arm_group_label>
    <other_name>Botox</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.</description>
    <arm_group_label>Onabotulinumtoxin A Injection, then Placebo</arm_group_label>
    <arm_group_label>Placebo, then Onabotulinumtoxin A Injection</arm_group_label>
    <other_name>Normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. At least 45 years of age, and no more than 80 years of age.&#xD;
&#xD;
          2. Meet UK Parkinson's disease brain bank diagnostic criteria&#xD;
&#xD;
          3. Have clinical evidence of rest tremor of one or both upper extremities defined as&#xD;
             involuntary, rhythmic oscillations about any joint within the upper extremities&#xD;
&#xD;
          4. Rest tremor amplitude must be at minimum 3 cm as determined by expert opinion by a&#xD;
             movement disorders specialist. Confirmation of amplitude measurement will be obtained&#xD;
             from the Px1 prior to active participation in the study but will not be used for&#xD;
             inclusion/exclusion in study participation.&#xD;
&#xD;
          5. Rest tremor must be historically refractory to at least 2 categories of medications&#xD;
             typically used as anti-parkinsonian agents including levodopa formulations, dopamine&#xD;
             agonists, amantadine, and anticholinergics.&#xD;
&#xD;
          6. Participants must be able to make no changes to their anti-parkinsonian medications&#xD;
             for 150 days (study duration). Ability and safety to do so must also be determined by&#xD;
             the participant's treating physician and confirmed in writing prior to participating.&#xD;
&#xD;
          7. Able to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of having undergone botulinum toxin injections for any other condition&#xD;
             previously&#xD;
&#xD;
          2. Allergy to carbidopa or levodopa.&#xD;
&#xD;
          3. Prescreening Montreal Cognitive Assessment (MoCA) score less than 22&#xD;
&#xD;
          4. Prescreening muscle weakness as determined by Medical Research Council grade less than&#xD;
             5/5 on direct testing in the upper limb afflicted with rest tremor.&#xD;
&#xD;
          5. Pregnancy: documentation of non-pregnancy by urine pregnancy test will be obtained&#xD;
             from all women of child-bearing potential prior to participation&#xD;
&#xD;
          6. Infection at the proposed injection site&#xD;
&#xD;
          7. Those with a pre-existing, concomitant neuromuscular disorder&#xD;
&#xD;
          8. Compromised respiratory function&#xD;
&#xD;
          9. History of having undergone deep brain stimulation surgery for any condition&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel A Roque, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UNC Hospitals Neurology Clinic</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27517</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>September 13, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <results_first_submitted>July 9, 2020</results_first_submitted>
  <results_first_submitted_qc>July 28, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 17, 2020</results_first_posted>
  <last_update_submitted>July 28, 2020</last_update_submitted>
  <last_update_submitted_qc>July 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson, Botox, Tremor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Tremor</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>abobotulinumtoxinA</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 3, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/72/NCT03301272/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>OnabotulinumtoxinA Injection, Then Placebo</title>
          <description>Participants first receive OnabotulinumtoxinA Injection and following a 3-month washout, they receive Placebo&#xD;
OnabotulinumtoxinA Injection: Reconstituted 10 units/0.1 mL. Administered intramuscular once&#xD;
Placebo: 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.</description>
        </group>
        <group group_id="P2">
          <title>Placebo, Then OnabotulinumtoxinA Injection</title>
          <description>Participants first receive placebo injection and following a 3-month washout, they receive Onabotulinumtoxin A Injection.&#xD;
OnabotulinumtoxinA Injection: Reconstituted 10 units/0.1 mL. Administered intramuscular once&#xD;
Placebo: 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention (30 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="9"/>
              </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>
          <title>Washout (90 Days From 1st Intervention)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="9"/>
              </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>
          <title>Second Intervention (30 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="9"/>
              </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>OnabotulinumtoxinA Injection, Then Placebo</title>
          <description>Participants first receive OnabotulinumtoxinA Injection and following a 3-month washout, they receive Placebo&#xD;
OnabotulinumtoxinA Injection: Reconstituted 10 units/0.1 mL. Administered intramuscular once&#xD;
Placebo: 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.</description>
        </group>
        <group group_id="B2">
          <title>Placebo, Then OnabotulinumtoxinA Injection</title>
          <description>Participants first receive placebo injection and following a 3-month washout, they receive OnabotulinumtoxinA Injection.&#xD;
OnabotulinumtoxinA Injection: Reconstituted 10 units/0.1 mL. Administered intramuscular once&#xD;
Placebo: 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.</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="7"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="16"/>
          </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="7"/>
                    <count group_id="B2" value="9"/>
                    <count group_id="B3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65.7" lower_limit="47" upper_limit="79"/>
                    <measurement group_id="B2" value="64.7" lower_limit="49" upper_limit="77"/>
                    <measurement group_id="B3" value="65.5" lower_limit="47" upper_limit="79"/>
                  </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="7"/>
                    <count group_id="B2" value="9"/>
                    <count group_id="B3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="13"/>
                  </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 group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <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>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="7"/>
                    <count group_id="B2" value="9"/>
                    <count group_id="B3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Chosen Limb for Study</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Right Arm</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="7"/>
                    <count group_id="B2" value="9"/>
                    <count group_id="B3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Left Arm</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="7"/>
                    <count group_id="B2" value="9"/>
                    <count group_id="B3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean Number of Parkinson's Medications Failed Prior to Enrollment</title>
          <units>Failed Medications</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="7"/>
                    <count group_id="B2" value="9"/>
                    <count group_id="B3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.29" spread="1.25"/>
                    <measurement group_id="B2" value="3.0" spread="1.22"/>
                    <measurement group_id="B3" value="3.13" spread="1.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Levodopa Equivalent Dosing (LED)</title>
          <description>Levodopa Equivalent Dosing (LED) gives a rough way to compare two Parkinson's medications. All medications for Parkinson's can be compared in level of effect to Levodopa, the most consistently used medication for this disease.</description>
          <units>mg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="7"/>
                    <count group_id="B2" value="9"/>
                    <count group_id="B3" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="98.29" spread="54.10"/>
                    <measurement group_id="B2" value="162.22" spread="103.53"/>
                    <measurement group_id="B3" value="134.25" spread="89.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in the MDS-UPDRS Tremor Subscore</title>
        <description>The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III's tremor subscore (3.17). The subscale has a 0-4 rating, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Higher MDS-UPDRS scores reflect worse tremor/motor function. Larger differences will infer greater effect size for the intervention. Score drops over time imply improvement in tremor/motor function.</description>
        <time_frame>Prior to onabotulinumtoxinA injection and at 30 days after injection</time_frame>
        <population>One participant was unavailable to complete assessment during defined window.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA Injection</title>
            <description>Participants receive OnabotulinumtoxinA Injection.&#xD;
OnabotulinumtoxinA Injection: Reconstituted 10 units/0.1 mL. Administered intramuscular once</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants receive placebo injection.&#xD;
Placebo: 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the MDS-UPDRS Tremor Subscore</title>
          <description>The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III's tremor subscore (3.17). The subscale has a 0-4 rating, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Higher MDS-UPDRS scores reflect worse tremor/motor function. Larger differences will infer greater effect size for the intervention. Score drops over time imply improvement in tremor/motor function.</description>
          <population>One participant was unavailable to complete assessment during defined window.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.25" lower_limit="-0.246" upper_limit="0.746"/>
                    <measurement group_id="O2" value="0.27" lower_limit="-0.342" upper_limit="0.876"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.5</p_value>
            <p_value_desc>The threshold for statistical significance is 0.05</p_value_desc>
            <method>Regression, Linear</method>
            <param_type>Difference in differences</param_type>
            <param_value>0</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the ARAT Score</title>
        <description>The Action Research Arm Test (ARAT) is an evaluated measure to assess specific changes in limb function after neurologic sequelae. It assesses a person's ability to handle objects differing in size, weight and shape and therefore can be considered to be an arm-specific measure of activity limitation. The ARAT is a 19 item measure divided into 4 sub-tests (grasp, grip, pinch, and gross arm movement). Performance on each item is rated on a 4-point ordinal scale: 3: Performs test normally 2: Completes test, but takes abnormally long or has great difficulty 1: Performs test partially 0: Can perform no part of test. The maximum score on the ARAT is 57 points (possible range 0 to 57). Higher ARAT scores reflect greater preservation of function in tested arm. Larger differences will infer greater effect sizes for the intervention. Score drops over time imply worsening limb function.</description>
        <time_frame>Prior to onabotulinumtoxinA injection and at 30 days after injection</time_frame>
        <population>Two participants were unavailable to complete assessments during defined window.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA Injection</title>
            <description>Participants receive OnabotulinumtoxinA Injection.&#xD;
OnabotulinumtoxinA Injection: Reconstituted 10 units/0.1 mL. Administered intramuscular once</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants receive placebo injection.&#xD;
Placebo: 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the ARAT Score</title>
          <description>The Action Research Arm Test (ARAT) is an evaluated measure to assess specific changes in limb function after neurologic sequelae. It assesses a person's ability to handle objects differing in size, weight and shape and therefore can be considered to be an arm-specific measure of activity limitation. The ARAT is a 19 item measure divided into 4 sub-tests (grasp, grip, pinch, and gross arm movement). Performance on each item is rated on a 4-point ordinal scale: 3: Performs test normally 2: Completes test, but takes abnormally long or has great difficulty 1: Performs test partially 0: Can perform no part of test. The maximum score on the ARAT is 57 points (possible range 0 to 57). Higher ARAT scores reflect greater preservation of function in tested arm. Larger differences will infer greater effect sizes for the intervention. Score drops over time imply worsening limb function.</description>
          <population>Two participants were unavailable to complete assessments during defined window.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.67" lower_limit="49.06" upper_limit="58.27"/>
                    <measurement group_id="O2" value="55.47" lower_limit="54.30" upper_limit="56.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Correlation Between MDS-UPDRS Tremor Subscore and Px1 Tremor Amplitude</title>
        <description>MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used is Part III's tremor subscore 3.17. The subscale has a 0-4 rating: (0=no tremor, 1=&lt;1cm, 2=1-3 cm, 3=3-10 cm, 4=&gt;10cm). Higher scores reflect worse tremor amplitude. Larger differences infer greater effect size. The Px1 is a novel, external measuring device using motion-capture technology to determine the frequency, direction and amplitude of movement between hand joints. Movement is captured without ever applying direct pressure on the limb. Output includes tremor frequency in Hz and distance traveled by a hand joint as compared to other joints on the hand in cm. The largest tremor amplitude measured by Px1 was acquired 3x/visit, values averaged then compared with the amplitude range corresponding to MDS-UPDRS tremor subscore. This process was repeated for all subjects for Visits 1-4 comparing all values using Spearman correlation coefficient.</description>
        <time_frame>At Visit 1, prior to 1st injection through Visit 4, 30 days after last injection</time_frame>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA Injection</title>
            <description>Participants receive OnabotulinumtoxinA Injection.&#xD;
OnabotulinumtoxinA Injection: Reconstituted 10 units/0.1 mL. Administered intramuscular once</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants receive placebo injection.&#xD;
Placebo: 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.</description>
          </group>
        </group_list>
        <measure>
          <title>Correlation Between MDS-UPDRS Tremor Subscore and Px1 Tremor Amplitude</title>
          <description>MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used is Part III's tremor subscore 3.17. The subscale has a 0-4 rating: (0=no tremor, 1=&lt;1cm, 2=1-3 cm, 3=3-10 cm, 4=&gt;10cm). Higher scores reflect worse tremor amplitude. Larger differences infer greater effect size. The Px1 is a novel, external measuring device using motion-capture technology to determine the frequency, direction and amplitude of movement between hand joints. Movement is captured without ever applying direct pressure on the limb. Output includes tremor frequency in Hz and distance traveled by a hand joint as compared to other joints on the hand in cm. The largest tremor amplitude measured by Px1 was acquired 3x/visit, values averaged then compared with the amplitude range corresponding to MDS-UPDRS tremor subscore. This process was repeated for all subjects for Visits 1-4 comparing all values using Spearman correlation coefficient.</description>
          <units>Spearman Correlation Coefficient</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6225"/>
                    <measurement group_id="O2" value="0.4354"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Tremor Amplitude in Centimeters (cm) as Measured by Px1</title>
        <description>The Px1 is a novel, external measuring device which uses motion-capture technology to determine the frequency, direction, and amplitude of movement between joints within the hand. Oscillatory movement is captured using a camera system and without ever applying any direct pressure upon the limb. Output includes tremor frequency in (Hertz Hz), and distance traveled by a hand joint as compared to other joints on the hand in centimeters (cm)</description>
        <time_frame>Prior to onabotulinumtoxinA injection and at 30 days after injection</time_frame>
        <population>Given that the Px1 tool was simultaneously undergoing validation during the trial, using the tool to determine the differences in tremor amplitude was deemed inappropriate.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA Injection</title>
            <description>Participants receive OnabotulinumtoxinA Injection.&#xD;
OnabotulinumtoxinA Injection: Reconstituted 10 units/0.1 mL. Administered intramuscular once</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants receive placebo injection.&#xD;
Placebo: 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Tremor Amplitude in Centimeters (cm) as Measured by Px1</title>
          <description>The Px1 is a novel, external measuring device which uses motion-capture technology to determine the frequency, direction, and amplitude of movement between joints within the hand. Oscillatory movement is captured using a camera system and without ever applying any direct pressure upon the limb. Output includes tremor frequency in (Hertz Hz), and distance traveled by a hand joint as compared to other joints on the hand in centimeters (cm)</description>
          <population>Given that the Px1 tool was simultaneously undergoing validation during the trial, using the tool to determine the differences in tremor amplitude was deemed inappropriate.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Tremor Frequency in Hertz (Hz) as Measured by Px1</title>
        <description>The Px1 is a novel, external measuring device which uses motion-capture technology to determine the frequency, direction, and amplitude of movement between joints within the hand. Oscillatory movement is captured using a camera system and without ever applying any direct pressure upon the limb. Output includes tremor frequency in (Hertz Hz), and distance traveled by a hand joint as compared to other joints on the hand in centimeters (cm)</description>
        <time_frame>Prior to onabotulinumtoxinA injection and at 30 days after injection</time_frame>
        <population>Given that the Px1 tool was simultaneously undergoing validation during the trial, using the tool to determine the differences in tremor frequency was deemed inappropriate.</population>
        <group_list>
          <group group_id="O1">
            <title>OnabotulinumtoxinA Injection</title>
            <description>Participants receive OnabotulinumtoxinA Injection.&#xD;
OnabotulinumtoxinA Injection: Reconstituted 10 units/0.1 mL. Administered intramuscular once</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants receive placebo injection.&#xD;
Placebo: 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Tremor Frequency in Hertz (Hz) as Measured by Px1</title>
          <description>The Px1 is a novel, external measuring device which uses motion-capture technology to determine the frequency, direction, and amplitude of movement between joints within the hand. Oscillatory movement is captured using a camera system and without ever applying any direct pressure upon the limb. Output includes tremor frequency in (Hertz Hz), and distance traveled by a hand joint as compared to other joints on the hand in centimeters (cm)</description>
          <population>Given that the Px1 tool was simultaneously undergoing validation during the trial, using the tool to determine the differences in tremor frequency was deemed inappropriate.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were included starting with the Screening Visit up to and including Visit 5, a total of approximately 150 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Onabotulinumtoxin A Injection</title>
          <description>Participants receive Onabotulinumtoxin A Injection.&#xD;
OnabotulinumtoxinA Injection: Reconstituted 10 units/0.1 mL. Administered intramuscular once</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants receive placebo injection.&#xD;
Placebo: 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.</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="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="6" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Pain of Injected Limb</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Weakness of Injected Limb</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </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>Daniel Roque, MD</name_or_title>
      <organization>University of North Carolina at Chapel Hill</organization>
      <phone>919-966-8178</phone>
      <email>droque@neurology.unc.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/NCT03301272
org study id: 15-1831
nct id: NCT03301272
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Purpose: Rest tremor in Parkinson's disease is notoriously difficult to treat through
      pharmacological measures, currently only predictably attenuated by the invasive deep brain
      stimulation surgery. The investigators hope to find some predictable and clinically
      meaningful attenuation of tremor with targeted use of onabotulinum toxin on muscles involved
      in creating the tremor.

      Participants: 16 subjects who meet United Kingdom (UK) brain bank criteria for Parkinson's
      disease with medically refractory rest tremor of at least 3 cm amplitude.

      Procedures (methods): Subjects will be blinded to receive either sham saline injection versus
      onabotulinum toxin injections directed to muscle groups felt to be clinically involved in
      causing the oscillatory movement of the tremor. Assessment of tremor severity and functional
      improvement from baseline after injection will occur within group (i.e. each subject will
      serve as their own control).

      Hypotheses:

      1. (A) Onabotulinumtoxin A significantly attenuates the amplitude of medically-refractory
      rest tremor of the upper limb in Parkinson's patients as compared to sham injections; as
      measured by reduction in the Movement Disorders Society Unified Parkinson's Disease Rating
      Scale (MDS-UPDRS) tremor subscore.

      1. (B) Onabotulinumtoxin A significantly improves the limb function of Parkinson's patients
      with medically-refractory rest tremor of the upper limb as compared to sham injections; as
      measured by an increase in Action Research Arm Test (ARAT) scores.
For purposes of properly identifying muscles intended for injection, a portable
      electromyography will be attached to an appropriate gauge electromyography-guided botulinum
      toxin needle, which in turn will be used to hear/see motor evoked potentials (MEPs). Subjects
      will be asked to activate the muscle while needle is inserted to ensure proper placement of
      the needle in the desired muscle prior to injection of study solution.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The study will comprise of a double blinded, crossover study where the subjects will serve as their own controls. There will be no medication changes made to Parkinson's disease medications throughout the subjects' participation in the study.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Double-blinded study whereby the subject, the movement disorder specialist injecting neurotoxin, and the movement disorder specialist rating the patient will be unaware of the solution injected and/or planned for injection same day. To ensure that the injecting specialist is blinded to the solution, syringes will be premixed by a separate member of the research team and de-identified of any possible labels that would indicate the properties of the solution being administered to the subject.
measure: Change in the MDS-UPDRS Tremor Subscore
time frame: Prior to onabotulinumtoxinA injection and at 30 days after injection
description: The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III's tremor subscore (3.17). The subscale has a 0-4 rating, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Higher MDS-UPDRS scores reflect worse tremor/motor function. Larger differences will infer greater effect size for the intervention. Score drops over time imply improvement in tremor/motor function.
measure: Change in the ARAT Score
time frame: Prior to onabotulinumtoxinA injection and at 30 days after injection
description: The Action Research Arm Test (ARAT) is an evaluated measure to assess specific changes in limb function after neurologic sequelae. It assesses a person's ability to handle objects differing in size, weight and shape and therefore can be considered to be an arm-specific measure of activity limitation. The ARAT is a 19 item measure divided into 4 sub-tests (grasp, grip, pinch, and gross arm movement). Performance on each item is rated on a 4-point ordinal scale: 3: Performs test normally 2: Completes test, but takes abnormally long or has great difficulty 1: Performs test partially 0: Can perform no part of test. The maximum score on the ARAT is 57 points (possible range 0 to 57). Higher ARAT scores reflect greater preservation of function in tested arm. Larger differences will infer greater effect sizes for the intervention. Score drops over time imply worsening limb function.
measure: Correlation Between MDS-UPDRS Tremor Subscore and Px1 Tremor Amplitude
time frame: At Visit 1, prior to 1st injection through Visit 4, 30 days after last injection
description: MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used is Part III's tremor subscore 3.17. The subscale has a 0-4 rating: (0=no tremor, 1=<1cm, 2=1-3 cm, 3=3-10 cm, 4=>10cm). Higher scores reflect worse tremor amplitude. Larger differences infer greater effect size. The Px1 is a novel, external measuring device using motion-capture technology to determine the frequency, direction and amplitude of movement between hand joints. Movement is captured without ever applying direct pressure on the limb. Output includes tremor frequency in Hz and distance traveled by a hand joint as compared to other joints on the hand in cm. The largest tremor amplitude measured by Px1 was acquired 3x/visit, values averaged then compared with the amplitude range corresponding to MDS-UPDRS tremor subscore. This process was repeated for all subjects for Visits 1-4 comparing all values using Spearman correlation coefficient.
measure: Change in Tremor Amplitude in Centimeters (cm) as Measured by Px1
time frame: Prior to onabotulinumtoxinA injection and at 30 days after injection
description: The Px1 is a novel, external measuring device which uses motion-capture technology to determine the frequency, direction, and amplitude of movement between joints within the hand. Oscillatory movement is captured using a camera system and without ever applying any direct pressure upon the limb. Output includes tremor frequency in (Hertz Hz), and distance traveled by a hand joint as compared to other joints on the hand in centimeters (cm)
measure: Change in Tremor Frequency in Hertz (Hz) as Measured by Px1
time frame: Prior to onabotulinumtoxinA injection and at 30 days after injection
description: The Px1 is a novel, external measuring device which uses motion-capture technology to determine the frequency, direction, and amplitude of movement between joints within the hand. Oscillatory movement is captured using a camera system and without ever applying any direct pressure upon the limb. Output includes tremor frequency in (Hertz Hz), and distance traveled by a hand joint as compared to other joints on the hand in centimeters (cm)
arm group label: Onabotulinumtoxin A Injection, then Placebo
arm group type: Experimental
description: Participants first receive Onabotulinumtoxin A Injection and following a 3-month washout, they receive Placebo
arm group label: Placebo, then Onabotulinumtoxin A Injection
arm group type: Experimental
description: Participants first receive placebo injection and following a 3-month washout, they receive Onabotulinumtoxin A Injection.
intervention type: Drug
intervention name: Onabotulinumtoxin A Injection
description: Reconstituted 10 units/0.1 mL. Administered intramuscular once
arm group label: Onabotulinumtoxin A Injection, then Placebo
arm group label: Placebo, then Onabotulinumtoxin A Injection
other name: Botox
intervention type: Other
intervention name: Placebo
description: 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.
arm group label: Onabotulinumtoxin A Injection, then Placebo
arm group label: Placebo, then Onabotulinumtoxin A Injection
other name: Normal saline
criteria: 
gender: All
minimum age: 45 Years
maximum age: 80 Years
healthy volunteers: No
last name: Daniel A Roque, MD
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
facility: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Tremor
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 