<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/NCT03306615</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00273264</org_study_id>
    <nct_id>NCT03306615</nct_id>
  </id_info>
  <brief_title>Peripheral Modulation of Muscle Stiffness and Spasticity</brief_title>
  <official_title>Peripheral Modulation of Muscle Stiffness and Spasticity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <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>
      This is a single-center, double-blind, randomized, placebo-controlled, sequential Phase II&#xD;
      trial of human recombinant hyaluronidase injections in individuals with post-stroke upper&#xD;
      limb muscle stiffness. The investigators will recruit 50 subjects, 25 males and 25 females,&#xD;
      who will be randomized to receive either hyaluronidase plus saline (treatment arm, n=25) or&#xD;
      normal saline (control arm, n=25) injections (first injection) in Phase 1 of the study over 5&#xD;
      visits that will test all 3 study aims. Then subjects will join the Phase 2 to receive a&#xD;
      second injection, where the treatment arm will receive the placebo and the placebo arm will&#xD;
      receive the treatment. It is expected that approximately 50 participants will be enrolled to&#xD;
      produce 42 evaluable participants. This design will ensure that all subjects receive the drug&#xD;
      treatment, which will facilitate recruitment. The injecting physician, the assessors, and the&#xD;
      patients will be blind to group assignment. Randomization will be initiated by the IDS&#xD;
      pharmacy as per the study statistician. All patients will be assessed at seven visits over 9&#xD;
      weeks of the study: Visit 1 - screening and baseline assessment of aims 1 and 2 (week 1-2);&#xD;
      Visit 2 - pre-injection MRI for aim 3 (week 1-2); Visit 3 - first injection (week 2); Visit 4&#xD;
      - post-injection MRI (week 3-5); Visit 5 - post-injection follow up for aims 1 and 2 (week&#xD;
      3-5); CROSSOVER TO OPPOSITE TREATMENT ARM Visit 6 - Second injection (week 6); Visit 7 -&#xD;
      post-injection follow-up for aims 1 and 2/ final study visit (week 7-9). There will be no MRI&#xD;
      assessment after the second injection as the technique is adequately sensitive to demonstrate&#xD;
      changes with a small sample size. The investigators will follow the patients for&#xD;
      approximately 9 weeks in this study. After obtaining informed consent, subjects will be&#xD;
      screened to ensure that the subjects meet study criteria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. To test the effect of hyaluronidase injections on upper limb outcomes. The investigators&#xD;
           will test the hypothesis that compared to placebo, human recombinant hyaluronidase&#xD;
           injections will increase total passive ROM across the affected shoulder, elbow and&#xD;
           forearm as measured by motion analysis (primary outcome), isometric muscle strength or&#xD;
           force generation capacity using MVC on EMG, reduce upper limb motor impairment as&#xD;
           measured by the Fugl-Meyer (FM) scale, and improve function as measured by the Wolf&#xD;
           Motor Function Test (WMFT).&#xD;
&#xD;
        2. To evaluate the effect of hyaluronidase on neural and non-neural components of muscle&#xD;
           stiffness. The investigators will test the hypothesis that compared to placebo, IM&#xD;
           hyaluronidase will modulate the passive and potentially also the active component of the&#xD;
           stretch reflex, reduce stiffness and improve arm motor control.&#xD;
&#xD;
        3. To determine the effect of hyaluronidase on intramuscular GAG content. The investigators&#xD;
           will test the hypothesis that compared to placebo, IM hyaluronidase will reduce the&#xD;
           T1rho relaxation times in the biceps and triceps muscles of the affected arm.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 11, 2021</start_date>
  <completion_date type="Anticipated">November 16, 2023</completion_date>
  <primary_completion_date type="Anticipated">November 16, 2023</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total upper limb passive range of motion</measure>
    <time_frame>9 weeks</time_frame>
    <description>passive range of motion in shoulder, elbow and forearm joints</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total upper limb active range of motion</measure>
    <time_frame>9 weeks</time_frame>
    <description>active range of motion in shoulder, elbow and forearm joints</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in upper limb Fugl-Meyer Assessment Score</measure>
    <time_frame>9 weeks</time_frame>
    <description>measures motor impairment in the affected upper limb, Score range is 0-66, and a higher score indicates a better outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Wolf-Motor Function Test (WMFT) Score</measure>
    <time_frame>9 weeks</time_frame>
    <description>Measures upper extremity function following stroke, Includes 6 items, with a 0-5 score range for each item, and a higher score indicates a better outcome</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Muscle Spasticity</condition>
  <arm_group>
    <arm_group_label>Treatment Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hyaluronidase plus saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal Saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hyaluronidase</intervention_name>
    <description>HYLENEX recombinant, diluted with 0.9% Sodium Chloride Injection</description>
    <arm_group_label>Treatment Arm</arm_group_label>
    <other_name>Hylenex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>0.9% Sodium Chloride Injection</description>
    <arm_group_label>Control Arm</arm_group_label>
    <other_name>Normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ischemic or hemorrhagic stroke 6-120 months prior&#xD;
&#xD;
          -  Moderately-severe muscle stiffness&#xD;
&#xD;
          -  Lack of full passive and active range of motion in at least 2/4 areas (shoulder,&#xD;
             elbow, forearm, wrist) in the hemiparetic upper limb;&#xD;
&#xD;
          -  Willingness to have MRI, complete all clinical assessments, and comply with study&#xD;
             protocols;&#xD;
&#xD;
          -  Ability to give informed consent and HIPPA certifications; and&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  treatment of spasticity with Botulinum toxin or intrathecal baclofen within the past&#xD;
             six months, phenol injections within the past 12 months, or ongoing adjustment of&#xD;
             anti-spastic medications;&#xD;
&#xD;
          -  other neurologic condition that may affect motor response (e.g., Parkinson's disease,&#xD;
             ALS, MS);&#xD;
&#xD;
          -  clinically significant cognitive dysfunction with score &lt;24 on Folstein's Mini Mental&#xD;
             Status Examination or depression with score &gt;10 on the PHQ-9;&#xD;
&#xD;
          -  pregnancy;&#xD;
&#xD;
          -  known hypersensitivity to hyaluronidase;&#xD;
&#xD;
          -  claustrophobia;&#xD;
&#xD;
          -  standard contraindications for MRI&#xD;
&#xD;
          -  Any condition that will preclude the patient from completing the protocol as&#xD;
             determined by the PI&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pablo Celnik, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Layla Murray, BA</last_name>
    <phone>410-955-1347</phone>
    <email>lmurra41@jhu.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Matthew Bird, MA</last_name>
    <phone>4109551381</phone>
    <email>mbird6@jhmi.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Paria Arfa Fatollahkhani, MD, M.Sc.</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21231</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paria Arfa Fatollahkhani, MD, MSc</last_name>
      <email>parfafa1@jhmi.edu</email>
    </contact>
    <contact_backup>
      <last_name>Matthew Bird, MA</last_name>
      <phone>410-955-1381</phone>
      <email>mbird6@jhmi.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Pablo Celnik, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>October 3, 2017</study_first_submitted>
  <study_first_submitted_qc>October 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>October 28, 2022</last_update_submitted>
  <last_update_submitted_qc>October 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Muscle Stiffness</keyword>
  <keyword>Muscle Spasticity</keyword>
  <keyword>Stroke</keyword>
  <keyword>Cerebral Palsy</keyword>
  <keyword>Hyperreflexia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Spasticity</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03306615
org study id: IRB00273264
nct id: NCT03306615
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a single-center, double-blind, randomized, placebo-controlled, sequential Phase II
      trial of human recombinant hyaluronidase injections in individuals with post-stroke upper
      limb muscle stiffness. The investigators will recruit 50 subjects, 25 males and 25 females,
      who will be randomized to receive either hyaluronidase plus saline (treatment arm, n=25) or
      normal saline (control arm, n=25) injections (first injection) in Phase 1 of the study over 5
      visits that will test all 3 study aims. Then subjects will join the Phase 2 to receive a
      second injection, where the treatment arm will receive the placebo and the placebo arm will
      receive the treatment. It is expected that approximately 50 participants will be enrolled to
      produce 42 evaluable participants. This design will ensure that all subjects receive the drug
      treatment, which will facilitate recruitment. The injecting physician, the assessors, and the
      patients will be blind to group assignment. Randomization will be initiated by the IDS
      pharmacy as per the study statistician. All patients will be assessed at seven visits over 9
      weeks of the study: Visit 1 - screening and baseline assessment of aims 1 and 2 (week 1-2);
      Visit 2 - pre-injection MRI for aim 3 (week 1-2); Visit 3 - first injection (week 2); Visit 4
      - post-injection MRI (week 3-5); Visit 5 - post-injection follow up for aims 1 and 2 (week
      3-5); CROSSOVER TO OPPOSITE TREATMENT ARM Visit 6 - Second injection (week 6); Visit 7 -
      post-injection follow-up for aims 1 and 2/ final study visit (week 7-9). There will be no MRI
      assessment after the second injection as the technique is adequately sensitive to demonstrate
      changes with a small sample size. The investigators will follow the patients for
      approximately 9 weeks in this study. After obtaining informed consent, subjects will be
      screened to ensure that the subjects meet study criteria.
1. To test the effect of hyaluronidase injections on upper limb outcomes. The investigators
           will test the hypothesis that compared to placebo, human recombinant hyaluronidase
           injections will increase total passive ROM across the affected shoulder, elbow and
           forearm as measured by motion analysis (primary outcome), isometric muscle strength or
           force generation capacity using MVC on EMG, reduce upper limb motor impairment as
           measured by the Fugl-Meyer (FM) scale, and improve function as measured by the Wolf
           Motor Function Test (WMFT).

        2. To evaluate the effect of hyaluronidase on neural and non-neural components of muscle
           stiffness. The investigators will test the hypothesis that compared to placebo, IM
           hyaluronidase will modulate the passive and potentially also the active component of the
           stretch reflex, reduce stiffness and improve arm motor control.

        3. To determine the effect of hyaluronidase on intramuscular GAG content. The investigators
           will test the hypothesis that compared to placebo, IM hyaluronidase will reduce the
           T1rho relaxation times in the biceps and triceps muscles of the affected arm.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Total upper limb passive range of motion
time frame: 9 weeks
description: passive range of motion in shoulder, elbow and forearm joints
measure: Total upper limb active range of motion
time frame: 9 weeks
description: active range of motion in shoulder, elbow and forearm joints
measure: Change in upper limb Fugl-Meyer Assessment Score
time frame: 9 weeks
description: measures motor impairment in the affected upper limb, Score range is 0-66, and a higher score indicates a better outcome
measure: Change in Wolf-Motor Function Test (WMFT) Score
time frame: 9 weeks
description: Measures upper extremity function following stroke, Includes 6 items, with a 0-5 score range for each item, and a higher score indicates a better outcome
arm group label: Treatment Arm
arm group type: Experimental
description: Hyaluronidase plus saline
arm group label: Control Arm
arm group type: Placebo Comparator
description: Normal Saline
intervention type: Drug
intervention name: Hyaluronidase
description: HYLENEX recombinant, diluted with 0.9% Sodium Chloride Injection
arm group label: Treatment Arm
other name: Hylenex
intervention type: Drug
intervention name: Placebo
description: 0.9% Sodium Chloride Injection
arm group label: Control Arm
other name: Normal saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pablo Celnik, MD
role: Principal Investigator
affiliation: Johns Hopkins University
last name: Layla Murray, BA
phone: 410-955-1347
email: lmurra41@jhu.edu
last name: Matthew Bird, MA
phone: 4109551381
email: mbird6@jhmi.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Muscle Spasticity