<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/NCT03302741</url>
  </required_header>
  <id_info>
    <org_study_id>HSC-MS-17-0174</org_study_id>
    <nct_id>NCT03302741</nct_id>
  </id_info>
  <brief_title>Imaging of 3D Innervation Zone Distribution in Spastic Muscles From High-density Surface EMG Recordings</brief_title>
  <official_title>Imaging of 3D Innervation Zone Distribution in Spastic Muscles From High-density Surface</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Health Science Center, Houston</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Houston</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Texas Health Science Center, Houston</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate if it is possible to use a new 3D imaging method to&#xD;
      guide Botulinum neurotoxin (BTX) injection for muscle spasticity management after stroke.&#xD;
      This imaging method is called three dimensional innervation zone imaging, or 3DIZI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 21, 2017</start_date>
  <completion_date type="Actual">November 18, 2019</completion_date>
  <primary_completion_date type="Actual">November 18, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Spasticity as Assessed by Reflex Torque of Elbow Flexors</measure>
    <time_frame>baseline (1 day prior to BTX injection)</time_frame>
    <description>Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Spasticity as Assessed by Reflex Torque of Elbow Flexors</measure>
    <time_frame>3 weeks after BTX injection</time_frame>
    <description>Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Spasticity as Assessed by Reflex Torque of Elbow Flexors</measure>
    <time_frame>3 months after BTX injection</time_frame>
    <description>Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Spasticity as Assessed by the Modified Ashworth Scale (MAS)</measure>
    <time_frame>baseline (1 day prior to BTX injection)</time_frame>
    <description>The following modified Ashworth scale (MAS) will be used for spasticity assessment:&#xD;
0 -No increase in muscle tone;&#xD;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;&#xD;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spasticity as Assessed by the Modified Ashworth Scale (MAS)</measure>
    <time_frame>3 weeks after BTX injection</time_frame>
    <description>The following modified Ashworth scale (MAS) will be used for spasticity assessment:&#xD;
0 -No increase in muscle tone;&#xD;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;&#xD;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spasticity as Assessed by the Modified Ashworth Scale (MAS)</measure>
    <time_frame>3 months after BTX injection</time_frame>
    <description>The following modified Ashworth scale (MAS) will be used for spasticity assessment:&#xD;
0 -No increase in muscle tone;&#xD;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;&#xD;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Spasticity</condition>
  <arm_group>
    <arm_group_label>Standard BTX injection (ultrasound guided)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3-dimensional innervation zone (3DIZ) guided injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Botulinum neurotoxin (BTX)</intervention_name>
    <description>Each patient will receive BTX injections in 2 sites. 100 units at double dilution will be injected at each site.</description>
    <arm_group_label>3-dimensional innervation zone (3DIZ) guided injection</arm_group_label>
    <arm_group_label>Standard BTX injection (ultrasound guided)</arm_group_label>
    <other_name>Botox</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Physical Therapy</intervention_name>
    <description>Standard physical therapy will be ordered to both groups as part of standard of care for patients after BTX injections to maximize the outcomes.</description>
    <arm_group_label>3-dimensional innervation zone (3DIZ) guided injection</arm_group_label>
    <arm_group_label>Standard BTX injection (ultrasound guided)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Standard BTX injection (ultrasound guided)</intervention_name>
    <description>For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the innervation zones (IZs) of the entire muscle.</description>
    <arm_group_label>Standard BTX injection (ultrasound guided)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>3-dimensional innervation zone (3DIZ) guided injection</intervention_name>
    <description>Simultaneous surface EMG and intramuscular EMG measurements will be acquired from the spastic biceps of the patients. Patients will be seated comfortably on a height-adjustable chair. The arm to be tested will be secured firmly on a customized apparatus with the elbow joint at approximately 90° of flexion and the shoulder at approximately 45° of abduction and 30° of flexion. The 128-channel unipolar surface EMG signals will be recorded with 2 flexible 2-dimensional 64-channel surface electrode array. A coating fine wire electrode will be inserted into the mid-axial section of the biceps to record bipolar intramuscular EMG signals. Ultrasound scan will be performed on the biceps to identify the location of the inserted wire electrode. Patients will be asked to contract their impaired biceps to perform maximum voluntary contraction of elbow flexion against the vertical plates 3 times.</description>
    <arm_group_label>3-dimensional innervation zone (3DIZ) guided injection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  a history of not more than one stroke which occurred at least 6 months prior to study&#xD;
             enrollment;&#xD;
&#xD;
          -  elbow flexor spasticity rated at 2 or 3 on Modified Ashworth scale (MAS);&#xD;
&#xD;
          -  receiving repeated botulinum toxin injection every 3-4 months;&#xD;
&#xD;
          -  absence of excessive pain in the paretic upper limb;&#xD;
&#xD;
          -  capacity to provide informed consent, with Mini-Mental State Examination (MMSE) must&#xD;
             be 25 or higher;&#xD;
&#xD;
        The following modified Ashworth scale (MAS) will be used for spasticity assessment:&#xD;
&#xD;
        0 -No increase in muscle tone; 1 -Slight increase in muscle tone, manifested by a catch and&#xD;
        release or by minimal resistance at the end of the range of motion when the affected&#xD;
        part(s) is moved in flexion or extension; 1+ -Slight increase in muscle tone, manifested by&#xD;
        a catch, followed by minimal resistance throughout the remainder (less than half) of the&#xD;
        ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s)&#xD;
        easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4&#xD;
        -Affected part(s) rigid in flexion or extension.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  recent botulinum toxin injection &lt; 4 months;&#xD;
&#xD;
          -  recent changes in antispastic medications &lt;3 weeks (i.e., the antispastic medication&#xD;
             regime is not stable;&#xD;
&#xD;
          -  Changes in antispastic medications (such as baclofen, tizanidine, dantrolene etc)&#xD;
             during the followup research visits. (NOTE: it is clinically rare for patients who&#xD;
             receive repeated injections to change their antispastic medications);&#xD;
&#xD;
          -  history of spinal cord injury or traumatic brain damage;&#xD;
&#xD;
          -  history of serious medical illness such as cardiovascular or pulmonary complications;&#xD;
&#xD;
          -  any condition that, in the judgment of a physician, would prevent the person from&#xD;
             participating.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sheng Li, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Texas Health Science Center, Houston</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>70030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>October 1, 2017</study_first_submitted>
  <study_first_submitted_qc>October 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 5, 2017</study_first_posted>
  <results_first_submitted>October 13, 2020</results_first_submitted>
  <results_first_submitted_qc>October 13, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 5, 2020</results_first_posted>
  <last_update_submitted>October 13, 2020</last_update_submitted>
  <last_update_submitted_qc>October 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Texas Health Science Center, Houston</investigator_affiliation>
    <investigator_full_name>Sheng Li</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>stroke</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Spasticity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins</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>March 21, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT03302741/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Standard BTX Injection (Ultrasound Guided)</title>
          <description>For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.</description>
        </group>
        <group group_id="P2">
          <title>3-dimensional Innervation Zone (3DIZ) Guided Injection</title>
          <description>In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.</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 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="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Standard BTX Injection (Ultrasound Guided)</title>
          <description>For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.</description>
        </group>
        <group group_id="B2">
          <title>3-dimensional Innervation Zone (3DIZ) Guided Injection</title>
          <description>In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.</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="8"/>
            <count group_id="B3" value="15"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.43" spread="11.91"/>
                    <measurement group_id="B2" value="52.75" spread="11.90"/>
                    <measurement group_id="B3" value="54.00" spread="11.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <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_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Spasticity as Assessed by Reflex Torque of Elbow Flexors</title>
        <description>Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.</description>
        <time_frame>baseline (1 day prior to BTX injection)</time_frame>
        <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard BTX Injection (Ultrasound Guided)</title>
            <description>For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.</description>
          </group>
          <group group_id="O2">
            <title>3-dimensional Innervation Zone (3DIZ) Guided Injection</title>
            <description>In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Spasticity as Assessed by Reflex Torque of Elbow Flexors</title>
          <description>Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.</description>
          <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
          <units>Newton meter (n-m)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>reflex torque at 50˚/sec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.32" spread="1.73"/>
                    <measurement group_id="O2" value="2.04" spread="1.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>reflex torque 100˚/sec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.41" spread="2.35"/>
                    <measurement group_id="O2" value="3.11" spread="1.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Spasticity as Assessed by Reflex Torque of Elbow Flexors</title>
        <description>Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.</description>
        <time_frame>3 weeks after BTX injection</time_frame>
        <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard BTX Injection (Ultrasound Guided)</title>
            <description>For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.</description>
          </group>
          <group group_id="O2">
            <title>3-dimensional Innervation Zone (3DIZ) Guided Injection</title>
            <description>In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Spasticity as Assessed by Reflex Torque of Elbow Flexors</title>
          <description>Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.</description>
          <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
          <units>Newton meter (n-m)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>reflex torque at 50˚/sec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.22" spread="1.21"/>
                    <measurement group_id="O2" value="1.47" spread="0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>reflex torque at 100˚/sec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.64" spread="1.69"/>
                    <measurement group_id="O2" value="2.14" spread="1.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Spasticity as Assessed by Reflex Torque of Elbow Flexors</title>
        <description>Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.</description>
        <time_frame>3 months after BTX injection</time_frame>
        <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard BTX Injection (Ultrasound Guided)</title>
            <description>For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.</description>
          </group>
          <group group_id="O2">
            <title>3-dimensional Innervation Zone (3DIZ) Guided Injection</title>
            <description>In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Spasticity as Assessed by Reflex Torque of Elbow Flexors</title>
          <description>Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.</description>
          <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
          <units>Newton meter (n-m)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>reflex torque at 50˚/sec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.71" spread="2.12"/>
                    <measurement group_id="O2" value="1.89" spread="0.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>reflex torque at 100˚/sec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.29" spread="2.57"/>
                    <measurement group_id="O2" value="2.85" spread="1.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Spasticity as Assessed by the Modified Ashworth Scale (MAS)</title>
        <description>The following modified Ashworth scale (MAS) will be used for spasticity assessment:&#xD;
0 -No increase in muscle tone;&#xD;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;&#xD;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.</description>
        <time_frame>baseline (1 day prior to BTX injection)</time_frame>
        <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard BTX Injection (Ultrasound Guided)</title>
            <description>For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.</description>
          </group>
          <group group_id="O2">
            <title>3-dimensional Innervation Zone (3DIZ) Guided Injection</title>
            <description>In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Spasticity as Assessed by the Modified Ashworth Scale (MAS)</title>
          <description>The following modified Ashworth scale (MAS) will be used for spasticity assessment:&#xD;
0 -No increase in muscle tone;&#xD;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;&#xD;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.</description>
          <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1+</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Spasticity as Assessed by the Modified Ashworth Scale (MAS)</title>
        <description>The following modified Ashworth scale (MAS) will be used for spasticity assessment:&#xD;
0 -No increase in muscle tone;&#xD;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;&#xD;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.</description>
        <time_frame>3 weeks after BTX injection</time_frame>
        <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard BTX Injection (Ultrasound Guided)</title>
            <description>For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.</description>
          </group>
          <group group_id="O2">
            <title>3-dimensional Innervation Zone (3DIZ) Guided Injection</title>
            <description>In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Spasticity as Assessed by the Modified Ashworth Scale (MAS)</title>
          <description>The following modified Ashworth scale (MAS) will be used for spasticity assessment:&#xD;
0 -No increase in muscle tone;&#xD;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;&#xD;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.</description>
          <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1+</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Spasticity as Assessed by the Modified Ashworth Scale (MAS)</title>
        <description>The following modified Ashworth scale (MAS) will be used for spasticity assessment:&#xD;
0 -No increase in muscle tone;&#xD;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;&#xD;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.</description>
        <time_frame>3 months after BTX injection</time_frame>
        <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard BTX Injection (Ultrasound Guided)</title>
            <description>For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.</description>
          </group>
          <group group_id="O2">
            <title>3-dimensional Innervation Zone (3DIZ) Guided Injection</title>
            <description>In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Spasticity as Assessed by the Modified Ashworth Scale (MAS)</title>
          <description>The following modified Ashworth scale (MAS) will be used for spasticity assessment:&#xD;
0 -No increase in muscle tone;&#xD;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;&#xD;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.</description>
          <population>Data for 1 in each arm was not analyzed because these participants only completed one out of three sessions.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1+</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Standard BTX Injection (Ultrasound Guided)</title>
          <description>For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.</description>
        </group>
        <group group_id="E2">
          <title>3-dimensional Innervation Zone (3DIZ) Guided Injection</title>
          <description>In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.</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="7"/>
                <counts group_id="E2" 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="7"/>
                <counts group_id="E2" 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="7"/>
                <counts group_id="E2" 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>Sheng Li, MD, PhD</name_or_title>
      <organization>The University of Texas Health Science Center at Houston</organization>
      <phone>713-797-7125</phone>
      <email>sheng.li@uth.tmc.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/NCT03302741
org study id: HSC-MS-17-0174
nct id: NCT03302741
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: Yes
is us export: No
The purpose of this study is to evaluate if it is possible to use a new 3D imaging method to
      guide Botulinum neurotoxin (BTX) injection for muscle spasticity management after stroke.
      This imaging method is called three dimensional innervation zone imaging, or 3DIZI.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Spasticity as Assessed by Reflex Torque of Elbow Flexors
time frame: baseline (1 day prior to BTX injection)
description: Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.
measure: Spasticity as Assessed by Reflex Torque of Elbow Flexors
time frame: 3 weeks after BTX injection
description: Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.
measure: Spasticity as Assessed by Reflex Torque of Elbow Flexors
time frame: 3 months after BTX injection
description: Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.
measure: Spasticity as Assessed by the Modified Ashworth Scale (MAS)
time frame: baseline (1 day prior to BTX injection)
description: The following modified Ashworth scale (MAS) will be used for spasticity assessment:
0 -No increase in muscle tone;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.
measure: Spasticity as Assessed by the Modified Ashworth Scale (MAS)
time frame: 3 weeks after BTX injection
description: The following modified Ashworth scale (MAS) will be used for spasticity assessment:
0 -No increase in muscle tone;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.
measure: Spasticity as Assessed by the Modified Ashworth Scale (MAS)
time frame: 3 months after BTX injection
description: The following modified Ashworth scale (MAS) will be used for spasticity assessment:
0 -No increase in muscle tone;
1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension;
1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.
arm group label: Standard BTX injection (ultrasound guided)
arm group type: Active Comparator
description: For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.
arm group label: 3-dimensional innervation zone (3DIZ) guided injection
arm group type: Experimental
description: In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.
intervention type: Drug
intervention name: Botulinum neurotoxin (BTX)
description: Each patient will receive BTX injections in 2 sites. 100 units at double dilution will be injected at each site.
arm group label: 3-dimensional innervation zone (3DIZ) guided injection
arm group label: Standard BTX injection (ultrasound guided)
other name: Botox
intervention type: Other
intervention name: Physical Therapy
description: Standard physical therapy will be ordered to both groups as part of standard of care for patients after BTX injections to maximize the outcomes.
arm group label: 3-dimensional innervation zone (3DIZ) guided injection
arm group label: Standard BTX injection (ultrasound guided)
intervention type: Device
intervention name: Standard BTX injection (ultrasound guided)
description: For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the innervation zones (IZs) of the entire muscle.
arm group label: Standard BTX injection (ultrasound guided)
intervention type: Device
intervention name: 3-dimensional innervation zone (3DIZ) guided injection
description: Simultaneous surface EMG and intramuscular EMG measurements will be acquired from the spastic biceps of the patients. Patients will be seated comfortably on a height-adjustable chair. The arm to be tested will be secured firmly on a customized apparatus with the elbow joint at approximately 90° of flexion and the shoulder at approximately 45° of abduction and 30° of flexion. The 128-channel unipolar surface EMG signals will be recorded with 2 flexible 2-dimensional 64-channel surface electrode array. A coating fine wire electrode will be inserted into the mid-axial section of the biceps to record bipolar intramuscular EMG signals. Ultrasound scan will be performed on the biceps to identify the location of the inserted wire electrode. Patients will be asked to contract their impaired biceps to perform maximum voluntary contraction of elbow flexion against the vertical plates 3 times.
arm group label: 3-dimensional innervation zone (3DIZ) guided injection
criteria: 
gender: All
minimum age: 21 Years
maximum age: 75 Years
healthy volunteers: No
last name: Sheng Li, MD, PhD
role: Principal Investigator
affiliation: The University of Texas Health Science Center, Houston
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The University of Texas Health Science Center, Houston
investigator full name: Sheng Li
investigator title: Professor
mesh term: Muscle Spasticity
mesh term: Botulinum Toxins
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 