xml: <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/NCT06030531</url>
    </required_header>
    <id_info>
      <org_study_id>STU00210582</org_study_id>
      <nct_id>NCT06030531</nct_id>
    </id_info>
    <brief_title>Spasticity and Functional Recovery After SCI</brief_title>
    <official_title>Spasticity and Functional Recovery in Humans With Acute to Subacute Spinal Cord Injury.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shirley Ryan AbilityLab</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Shirley Ryan AbilityLab</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Spasticity is one of the most common symptoms manifested in humans with spinal cord injury&#xD;
        (SCI). However, the neural mechanisms underlying the development of spasticity over time&#xD;
        after an acute SCI are not yet understood. Using electrophysiological and imaging techniques&#xD;
        along with traditional measurements of neurological recovery in the acute rehabilitation&#xD;
        setting including physical exam and functional assessments; the investigators aim to examine&#xD;
        the relationship between development of spasticity, residual descending motor pathways and&#xD;
        functional and neurological recovery in humans with SCI from acute to subacute phase&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The purpose of this study is to measure changes to motor-evoked potentials (MEPs) and to&#xD;
        evaluate if the development of spasticity is related to residual descending motor pathways&#xD;
        and to a better neurological recovery and functional improvement in individuals with SCI from&#xD;
        the acute to the subacute phase. The investigators will also test for the presence of&#xD;
        biological markers in the blood that may correlate with levels of spasticity or neurological&#xD;
        recovery and functional improvement, including the presence or absence of neuroplastic&#xD;
        genetic polymorphisms (e.g. BDNF Val66Met polymorphism), as well as circulating levels of&#xD;
        neuroplastic (e.g. BDNF) or inflammatory factors (e.g. interleukins, TNF) that may affect&#xD;
        neuronal growth and functional restoration.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Enrolling by invitation</overall_status>
    <start_date type="Actual">July 1, 2020</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Modified Ashworth scale (MAS)</measure>
      <time_frame>From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)</time_frame>
      <description>This clinical scale will be used by measuring resistance encountered during manual passive muscle stretching using a six-point ordinal scale (0=no increase in tone, 1/+1=slight increase in tone with a catch and release or minimal resistance at the end or less than half of the range of movement, respectively, 2=more marked increased tone through most of the range of movement but affected parts easily moved, 3=considerable increase in tone and passive movement difficultly, and 4=affected parts rigid)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Motor evoked potential (MEP)</measure>
      <time_frame>From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)</time_frame>
      <description>Transcranial magnetic stimulation will be delivered and the coil will be positioned over the vertex and moved around this point to determine the optimal position for eliciting a motor evoked potentials (MEPs) in legs muscles.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>First swing test (FST)</measure>
      <time_frame>From the time of admission to the hospital and enrolled in the study till the time of the discharge (up to 12 weeks)</time_frame>
      <description>We will use the pendulum test to measure muscle tone at the knee by using gravity to provoke muscle stretch reflexes during passive swinging of the lower limb.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)</measure>
      <time_frame>From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)</time_frame>
      <description>At the time of the admission, after obtaining consent, and at the time of discharge, the chart will be reviewed to obtain the ISNCSCI score</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Circulating biomarkers of inflammation and neuroplasticity</measure>
      <time_frame>From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)</time_frame>
      <description>In this study, we will focus on tracking expression of key inflammatory cytokines that have been shown to play a pivotal role in activating the major nuclear factor kappa-B (NF-κB) inflammatory pathway. Specifically, we will characterize serum levels of pro-inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and anti-inflammatory marker interleukin-10 (IL-10). We will also measure levels of circulating neuroplasticity marker Brain-derived neurotrophic factor (BDNF)</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">240</enrollment>
    <condition>Acute Spinal Cord Injury</condition>
    <condition>Spinal Cord Injuries</condition>
    <arm_group>
      <arm_group_label>Inpatients</arm_group_label>
      <description>Prospective participants who meet the study inclusion criteria will be identified by bi-weekly chart review of all new admissions to the acute inpatient spinal cord injury unit at the Shirley Ryan AbilityLab (SRAlab).&#xD;
  Eligible patients will be invited to participate by the clinical staff during their first week of admission.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <description>We will enroll non-injured healthy individuals to compare the level of biomarkers</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Measures of spasticity, connectivity and analysis of single nucleotide polymorphisms and biomarkers of inflammation</intervention_name>
      <description>We will test for presence of biological markers in blood that may correlate with levels of spasticity or neurological recovery and functional improvement, including the presence or absence of neuroplastic genetic polymorphisms (e.g. BDNF Val66Met polymorphism), as well as circulating levels of neuroplastic(e.g. BDNF) or inflammatory factors (e.g. interleukins, TNF) that may affect neuronal growth and functional restoration.</description>
      <arm_group_label>Inpatients</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Analysis of biomarkers</intervention_name>
      <description>We will test for the presence of biological markers in the blood to compare the distribution of polymorphisms and biomarkers with the spinal cord injury patient population.</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>Inpatients</arm_group_label>
    </intervention>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        De-identified plasma and DNA extracts will be stored in key-lock secured -80 oC freezers in&#xD;
        the Biologics Lab at SRALab until used for experimental purposes. Subjects will have the&#xD;
        choice to allow researchers approved by this IRB to retain any leftover plasma or DNA extract&#xD;
        taken during the study. These samples will be stored indefinitely and may be used only for&#xD;
        IRB-approved research by IRB-approved researchers and personnel.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Prospective participants who meet the study inclusion criteria will be identified by&#xD;
          bi-weekly chart review ofall new admissions to the acute inpatient spinal cord injury unit&#xD;
          at the Shirley Ryan AbilityLab (SRAlab).Eligible patients will be invited to participate by&#xD;
          the clinical staff during their first week of admission.&#xD;
  &#xD;
          Prospective participants that meet the inclusion criteria for the Control group will be&#xD;
          recruited using various sources including the Shirley Ryan AbilityLab non-patient research&#xD;
          database, participants who have taken part in our earlier studies, word of mouth, people&#xD;
          who work at or visit our center and are interested in research participation.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Individuals with SCI:&#xD;
  &#xD;
          Inclusion criteria:&#xD;
  &#xD;
            -  Male and females 18 years of age or greater&#xD;
  &#xD;
            -  Basic proficiency in English language communication&#xD;
  &#xD;
            -  Are admitted to the Shirley Ryan AbilityLab as a spinal cord injury patient&#xD;
  &#xD;
            -  International Standards for Neurological Classification of Spinal Cord Injury&#xD;
               (ISNCSCI) level above L2&#xD;
  &#xD;
            -  American Spinal Cord Injury Association Impairment Scale (AIS) grades A, B, C, or D&#xD;
  &#xD;
            -  Patients with SCI within the first week of inpatient admission to the Shirley Ryan&#xD;
               AbilityLab after sustaining a SC&#xD;
  &#xD;
          Exclusion criteria:&#xD;
  &#xD;
            -  Under 18 years of age&#xD;
  &#xD;
            -  Severe cognitive impairment that precludes the ability to participate in a&#xD;
               comprehensive physical exam or give verbal consent&#xD;
  &#xD;
            -  ISNCSCI level below L2&#xD;
  &#xD;
            -  People who have sustained SCI &gt;30 days&#xD;
  &#xD;
            -  Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic&#xD;
               disease&#xD;
  &#xD;
            -  Any debilitating disease prior to the SCI that caused exercise intolerance&#xD;
  &#xD;
            -  Premorbid, ongoing major depression or psychosis, altered cognitive status&#xD;
  &#xD;
            -  History of head injury or stroke&#xD;
  &#xD;
            -  Vascular, traumatic, tumoral, infectious, or metabolic lesion of the brain, even&#xD;
               without history of seizure, and without anticonvulsant medication&#xD;
  &#xD;
            -  History of seizures or epilepsy&#xD;
  &#xD;
            -  Ongoing cord compression or a syrinx in the spinal cord or people who suffer from a&#xD;
               spinal cord disease such as spinal stenosis, spina bifida, MS, or herniated disk 13.&#xD;
               Metal plate in skull&#xD;
  &#xD;
            -  Individuals with scalp shrapnel, cochlear implants, or aneurysm clips&#xD;
  &#xD;
            -  Skull fractures, skull deficits or concussion within the last 6 months&#xD;
  &#xD;
            -  Presence of orthoses and presence of spinal precautions or healing incisions that make&#xD;
               the area inaccessible to the testing procedures. This criterion will be applied as&#xD;
               needed for the specific study procedures that may need to access the areas under&#xD;
               restriction.&#xD;
  &#xD;
            -  Formal diagnosis of Post-Traumatic Stress Disorder (PTSD)&#xD;
  &#xD;
          Individuals in the control group:&#xD;
  &#xD;
          Inclusion criteria:&#xD;
  &#xD;
            1. Male and females 18 years of age or greater&#xD;
  &#xD;
            2. Basic proficiency in English language communication&#xD;
  &#xD;
          Exclusion criteria:&#xD;
  &#xD;
            1. Under 18 years of age&#xD;
  &#xD;
            2. Uncontrolled medical problems including pulmonary, cardiovascular, or orthopedic&#xD;
               disease&#xD;
  &#xD;
            3. History of neurological impairment or conditions affecting the Central Nervous System&#xD;
  &#xD;
            4. Premorbid, ongoing major depression or psychosis, altered cognitive status&#xD;
  &#xD;
            5. Pregnancy&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Monica A Perez, PT, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shirley Ryan AbilityLab</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Shirley Ryan AbilityLab</name>
        <address>
          <city>Chicago</city>
          <state>Illinois</state>
          <zip>60611</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>April 7, 2022</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Shirley Ryan AbilityLab</investigator_affiliation>
      <investigator_full_name>Monica Perez</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Spasticity</keyword>
    <keyword>Recovery</keyword>
    <keyword>Bio-markers</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Muscle Spasticity</mesh_term>
      <mesh_term>Spinal Cord Injuries</mesh_term>
      <mesh_term>Wounds and Injuries</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06030531
  org study id: STU00210582
  nct id: NCT06030531
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Spasticity is one of the most common symptoms manifested in humans with spinal cord injury
        (SCI). However, the neural mechanisms underlying the development of spasticity over time
        after an acute SCI are not yet understood. Using electrophysiological and imaging techniques
        along with traditional measurements of neurological recovery in the acute rehabilitation
        setting including physical exam and functional assessments; the investigators aim to examine
        the relationship between development of spasticity, residual descending motor pathways and
        functional and neurological recovery in humans with SCI from acute to subacute phase
  The purpose of this study is to measure changes to motor-evoked potentials (MEPs) and to
        evaluate if the development of spasticity is related to residual descending motor pathways
        and to a better neurological recovery and functional improvement in individuals with SCI from
        the acute to the subacute phase. The investigators will also test for the presence of
        biological markers in the blood that may correlate with levels of spasticity or neurological
        recovery and functional improvement, including the presence or absence of neuroplastic
        genetic polymorphisms (e.g. BDNF Val66Met polymorphism), as well as circulating levels of
        neuroplastic (e.g. BDNF) or inflammatory factors (e.g. interleukins, TNF) that may affect
        neuronal growth and functional restoration.
  observational model: Case-Control
  time perspective: Prospective
  measure: Modified Ashworth scale (MAS)
  time frame: From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)
  description: This clinical scale will be used by measuring resistance encountered during manual passive muscle stretching using a six-point ordinal scale (0=no increase in tone, 1/+1=slight increase in tone with a catch and release or minimal resistance at the end or less than half of the range of movement, respectively, 2=more marked increased tone through most of the range of movement but affected parts easily moved, 3=considerable increase in tone and passive movement difficultly, and 4=affected parts rigid)
  measure: Motor evoked potential (MEP)
  time frame: From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)
  description: Transcranial magnetic stimulation will be delivered and the coil will be positioned over the vertex and moved around this point to determine the optimal position for eliciting a motor evoked potentials (MEPs) in legs muscles.
  measure: First swing test (FST)
  time frame: From the time of admission to the hospital and enrolled in the study till the time of the discharge (up to 12 weeks)
  description: We will use the pendulum test to measure muscle tone at the knee by using gravity to provoke muscle stretch reflexes during passive swinging of the lower limb.
  measure: International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)
  time frame: From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)
  description: At the time of the admission, after obtaining consent, and at the time of discharge, the chart will be reviewed to obtain the ISNCSCI score
  measure: Circulating biomarkers of inflammation and neuroplasticity
  time frame: From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)
  description: In this study, we will focus on tracking expression of key inflammatory cytokines that have been shown to play a pivotal role in activating the major nuclear factor kappa-B (NF-κB) inflammatory pathway. Specifically, we will characterize serum levels of pro-inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and anti-inflammatory marker interleukin-10 (IL-10). We will also measure levels of circulating neuroplasticity marker Brain-derived neurotrophic factor (BDNF)
  arm group label: Inpatients
  description: Prospective participants who meet the study inclusion criteria will be identified by bi-weekly chart review of all new admissions to the acute inpatient spinal cord injury unit at the Shirley Ryan AbilityLab (SRAlab).
  Eligible patients will be invited to participate by the clinical staff during their first week of admission.
  arm group label: Control group
  description: We will enroll non-injured healthy individuals to compare the level of biomarkers
  intervention type: Other
  intervention name: Measures of spasticity, connectivity and analysis of single nucleotide polymorphisms and biomarkers of inflammation
  description: We will test for presence of biological markers in blood that may correlate with levels of spasticity or neurological recovery and functional improvement, including the presence or absence of neuroplastic genetic polymorphisms (e.g. BDNF Val66Met polymorphism), as well as circulating levels of neuroplastic(e.g. BDNF) or inflammatory factors (e.g. interleukins, TNF) that may affect neuronal growth and functional restoration.
  arm group label: Inpatients
  intervention type: Other
  intervention name: Analysis of biomarkers
  description: We will test for the presence of biological markers in the blood to compare the distribution of polymorphisms and biomarkers with the spinal cord injury patient population.
  arm group label: Control group
  arm group label: Inpatients
  De-identified plasma and DNA extracts will be stored in key-lock secured -80 oC freezers in
        the Biologics Lab at SRALab until used for experimental purposes. Subjects will have the
        choice to allow researchers approved by this IRB to retain any leftover plasma or DNA extract
        taken during the study. These samples will be stored indefinitely and may be used only for
        IRB-approved research by IRB-approved researchers and personnel.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Monica A Perez, PT, PhD
  role: Principal Investigator
  affiliation: Shirley Ryan AbilityLab
  facility: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Shirley Ryan AbilityLab
  investigator full name: Monica Perez
  investigator title: Principal Investigator
  mesh term: Muscle Spasticity
  mesh term: Spinal Cord Injuries
  mesh term: Wounds and Injuries
  sharing ipd: Undecided