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/NCT06020898</url>
    </required_header>
    <id_info>
      <org_study_id>LY2023-138-A</org_study_id>
      <nct_id>NCT06020898</nct_id>
    </id_info>
    <brief_title>Sodium Valproate Improves Clinical Outcomes in Patients With Acute Ischemic Stroke</brief_title>
    <official_title>Sodium Valproate Improves Clinical Outcomes in Patients With Acute Ischemic Stroke: a Pilot Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>RenJi Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>RenJi Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This prospective pilot study is intended to clarify whether the use of sodium valproate in&#xD;
        patients with acute ischemic stroke can improve clinical outcomes, and to explore the&#xD;
        mechanism: whether valproate could increase peripheral anti-inflammatory CD177+ neutrophils&#xD;
        levels.&#xD;
  &#xD;
        Patients with acute ischemic stroke included in the study will be randomly assigned to&#xD;
        low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides&#xD;
        receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium&#xD;
        valproate or normal saline were given intravenously for 3 consecutive days, respectively. The&#xD;
        investigators evaluate whether sodium valproate can improve clinical outcomes and increase&#xD;
        peripheral CD177+ neutrophil levels.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Ischemic stroke is one of the leading causes of disability and mortality worldwide, which&#xD;
        imposes a huge burden on families and society. Currently, the effective treatment strategies&#xD;
        of ischemic stroke are limited. It is of great clinical value and significance to explore&#xD;
        effective neuroprotective medications besides reperfusion therapy.&#xD;
  &#xD;
        Sodium valproate is widely used in clinical practice, and its safety and tolerability has&#xD;
        been confirmed. It is mainly used in the treatment of epilepsy, bipolar disorder, neuropathic&#xD;
        pain and other diseases. In recent years, a number of preclinical studies have found that&#xD;
        valproic acid has a potential neuroprotective effect in acute ischemic brain injury, which&#xD;
        can decrease infarct volume, reduce blood-brain barrier damage, and improve neurological&#xD;
        function. However, the neuroprotective mechanism of sodium valproate has not been fully&#xD;
        revealed, and there is still a lack of clinical studies to clarify the neuroprotective effect&#xD;
        of sodium valproate in patients with ischemic stroke.&#xD;
  &#xD;
        The goal of this study is to test whether sodium valproate could become a new therapeutic&#xD;
        approach to improve the functional outcome after ischemic stroke. This prospective pilot&#xD;
        study is intended to clarify whether the use of sodium valproate in patients with acute&#xD;
        ischemic stroke can improve clinical outcomes, and to explore the mechanism: whether&#xD;
        valproate could increase peripheral anti-inflammatory CD177+ neutrophils levels to reduce&#xD;
        neuroinflammation caused by the infiltrated peripheral immune cells.&#xD;
  &#xD;
        Patients with acute ischemic stroke included in the study will be randomly assigned to&#xD;
        low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides&#xD;
        receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium&#xD;
        valproate or normal saline were given intravenously for 3 consecutive days, respectively. The&#xD;
        investigators evaluate whether sodium valproate can improve clinical outcomes and increase&#xD;
        peripheral CD177+ neutrophil levels.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">April 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2024</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, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Favorable outcome at 90 days (the Modified Rankin Scale (mRS) score≤2)</measure>
      <time_frame>Day 90</time_frame>
      <description>The proportion of patients with favorable outcome, which is defined as the Modified Rankin Scale (mRS) score 0-2.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>The Modified Rankin Scale (mRS) score at 90 days</measure>
      <time_frame>Day 90</time_frame>
      <description>The detailed distribution of Modified Rankin Scale (mRS) score will be recorded. The mRS score ranges from 0 to 5, where high scores mean a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Favorable outcome at 30 days (the Modified Rankin Scale (mRS) score≤2)</measure>
      <time_frame>Day 30</time_frame>
      <description>The proportion of patients with favorable outcome, which is defined as the Modified Rankin Scale (mRS) score 0-2.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The Modified Rankin Scale (mRS) score at 30 days</measure>
      <time_frame>Day 30</time_frame>
      <description>The detailed distribution of Modified Rankin Scale (mRS) score will be recorded. The mRS score ranges from 0 to 5, where high scores mean a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>NIH Stroke Scale (NIHSS) score at 3 days</measure>
      <time_frame>Day 3</time_frame>
      <description>The NIH Stroke Scale (NIHSS) score ranges from 0 to 42, where high scores mean a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>NIH Stroke Scale (NIHSS) score at 7 days</measure>
      <time_frame>Day 7</time_frame>
      <description>The NIH Stroke Scale (NIHSS) score ranges from 0 to 42, where high scores mean a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes of lesion volume from baseline to day 7</measure>
      <time_frame>Day 7</time_frame>
      <description>The infarct lesion volume will be measures on magnetic resonance imaging DWI and FLAIR.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Length of hospital stay</measure>
      <time_frame>Up to 30 days</time_frame>
      <description>Record the time when patients discharge from hospital.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>The peripheral CD177+ neutrophil levels</measure>
      <time_frame>Day 3 and Day 7</time_frame>
      <description>The CD177+ neutrophil levels in peripheral blood will be evaluated using flow cytometry.</description>
    </other_outcome>
    <other_outcome>
      <measure>The levels of inflammatory cytokines in peripheral blood</measure>
      <time_frame>Day 3 and Day 7</time_frame>
      <description>IL-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12、IL-17A、IFN-α、IFN-γ、TNF-α</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">45</enrollment>
    <condition>Acute Ischemic Stroke</condition>
    <arm_group>
      <arm_group_label>Low-dose sodium valproate group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Within 3 days after admission, 10mg/kg sodium valproate will be given daily. Specifically, sodium valproate will be intravenously infused at the dose of 5mg/kg within 15 minutes, followed by intravenous drip (1mg/kg/h) for 5 hours.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>High-dose sodium valproate group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Within 3 days after admission, 20mg/kg sodium valproate will be given daily. Specifically, sodium valproate will be intravenously infused at the dose of 15mg/kg within 15 minutes, followed by intravenous drip (1mg/kg/h) for 5 hours.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Within 3 days after admission, normal saline will be given daily in the same way.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Sodium valproate</intervention_name>
      <description>Patients with acute ischemic stroke included in the study are randomly assigned to low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium valproate or normal saline were given intravenously for 3 consecutive days, respectively.</description>
      <arm_group_label>High-dose sodium valproate group</arm_group_label>
      <arm_group_label>Low-dose sodium valproate group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Normal saline</intervention_name>
      <description>Patients with acute ischemic stroke included in the study are randomly assigned to low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium valproate or normal saline were given intravenously for 3 consecutive days, respectively.</description>
      <arm_group_label>Placebo group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. 18≤age&lt;75;&#xD;
  &#xD;
            2. Admitted to hospital within 24 hours after the onset of neurological impairment&#xD;
               symptoms and diagnosed as acute ischemic stroke by CT or MRI;&#xD;
  &#xD;
            3. Not suitable for thrombolysis and mechanical thrombectomy, including: contraindication&#xD;
               of thrombolysis, no large vessel occlusion, responsible vessel stenosis &lt;70%;&#xD;
  &#xD;
            4. Give written informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients with mRS ≥ 2 before the disease onset;&#xD;
  &#xD;
            2. Patients with refractory hypertension (SBP&gt;180mmHg or DBP&gt;110mmHg after&#xD;
               antihypertensive treatment);&#xD;
  &#xD;
            3. Patients with history of cerebral hemorrhage, intracranial tumor, cerebral&#xD;
               arteriovenous malformation and aneurysm;&#xD;
  &#xD;
            4. Patients with clear history of brain trauma, intracranial or spinal surgery within 3&#xD;
               months, major surgery or severe physical trauma within 1 month;&#xD;
  &#xD;
            5. Patients with signs of infection before or within 72 hours after admission;&#xD;
  &#xD;
            6. Patients with history of malignancy or autoimmune disease;&#xD;
  &#xD;
            7. Patients using glucocorticoids or other immunosuppressive medications;&#xD;
  &#xD;
            8. Patients with contraindications of the use of sodium valproate: pregnancy; liver&#xD;
               disease or severe hepatic insufficiency (ALT, AST 3 times higher than the upper normal&#xD;
               limit); hemorrhagic tendency (such as platelet count &lt;100x109/L, APTT≥35s); allergy to&#xD;
               sodium valproate, sodium divalproate, or valproamide; hepatic porphyria; combined use&#xD;
               of mefloquine; patients known to have mitochondrial diseases related to POLG&#xD;
               mutations; patients known to have disorders of the urea cycle;&#xD;
  &#xD;
            9. Patients have used other medications containing active ingredients that can be&#xD;
               converted to valproic acid, including sodium divalproate, valproamide;&#xD;
  &#xD;
           10. Patients who have MRI contraindications or cannot tolerate MRI;&#xD;
  &#xD;
           11. Patients undergoing other clinical trials;&#xD;
  &#xD;
           12. Any other conditions for which the investigator considers the patient ineligible to&#xD;
               participate in this trial, such as mental illness, cognitive impairment, or inability&#xD;
               to follow trial procedures.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Peiying Li, Doctor</last_name>
      <role>Principal Investigator</role>
      <affiliation>RenJi Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Jieqing Wan, Doctor</last_name>
      <role>Principal Investigator</role>
      <affiliation>RenJi Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Peiying Li, Doctor</last_name>
      <phone>+8615800616866</phone>
      <email>peiyingli.md@gmail.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Renji Hospital, Shanghai Jiao Tong University School of Medicine</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200127</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Peiying Li, Doctor</last_name>
        <phone>+8615800616866</phone>
        <email>peiyingli.md@gmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 26, 2023</last_update_submitted>
    <last_update_submitted_qc>August 26, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>RenJi Hospital</investigator_affiliation>
      <investigator_full_name>Peiying Li</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Sodium valproate</keyword>
    <keyword>Acute ischemic stroke</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Stroke</mesh_term>
      <mesh_term>Ischemic Stroke</mesh_term>
      <mesh_term>Cerebral Infarction</mesh_term>
      <mesh_term>Ischemia</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Valproic Acid</mesh_term>
    </intervention_browse>
    <!-- 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/NCT06020898
  org study id: LY2023-138-A
  nct id: NCT06020898
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This prospective pilot study is intended to clarify whether the use of sodium valproate in
        patients with acute ischemic stroke can improve clinical outcomes, and to explore the
        mechanism: whether valproate could increase peripheral anti-inflammatory CD177+ neutrophils
        levels.
  
        Patients with acute ischemic stroke included in the study will be randomly assigned to
        low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides
        receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium
        valproate or normal saline were given intravenously for 3 consecutive days, respectively. The
        investigators evaluate whether sodium valproate can improve clinical outcomes and increase
        peripheral CD177+ neutrophil levels.
  Ischemic stroke is one of the leading causes of disability and mortality worldwide, which
        imposes a huge burden on families and society. Currently, the effective treatment strategies
        of ischemic stroke are limited. It is of great clinical value and significance to explore
        effective neuroprotective medications besides reperfusion therapy.
  
        Sodium valproate is widely used in clinical practice, and its safety and tolerability has
        been confirmed. It is mainly used in the treatment of epilepsy, bipolar disorder, neuropathic
        pain and other diseases. In recent years, a number of preclinical studies have found that
        valproic acid has a potential neuroprotective effect in acute ischemic brain injury, which
        can decrease infarct volume, reduce blood-brain barrier damage, and improve neurological
        function. However, the neuroprotective mechanism of sodium valproate has not been fully
        revealed, and there is still a lack of clinical studies to clarify the neuroprotective effect
        of sodium valproate in patients with ischemic stroke.
  
        The goal of this study is to test whether sodium valproate could become a new therapeutic
        approach to improve the functional outcome after ischemic stroke. This prospective pilot
        study is intended to clarify whether the use of sodium valproate in patients with acute
        ischemic stroke can improve clinical outcomes, and to explore the mechanism: whether
        valproate could increase peripheral anti-inflammatory CD177+ neutrophils levels to reduce
        neuroinflammation caused by the infiltrated peripheral immune cells.
  
        Patients with acute ischemic stroke included in the study will be randomly assigned to
        low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides
        receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium
        valproate or normal saline were given intravenously for 3 consecutive days, respectively. The
        investigators evaluate whether sodium valproate can improve clinical outcomes and increase
        peripheral CD177+ neutrophil levels.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Outcomes Assessor)
  measure: Favorable outcome at 90 days (the Modified Rankin Scale (mRS) score≤2)
  time frame: Day 90
  description: The proportion of patients with favorable outcome, which is defined as the Modified Rankin Scale (mRS) score 0-2.
  measure: The Modified Rankin Scale (mRS) score at 90 days
  time frame: Day 90
  description: The detailed distribution of Modified Rankin Scale (mRS) score will be recorded. The mRS score ranges from 0 to 5, where high scores mean a worse outcome.
  measure: Favorable outcome at 30 days (the Modified Rankin Scale (mRS) score≤2)
  time frame: Day 30
  description: The proportion of patients with favorable outcome, which is defined as the Modified Rankin Scale (mRS) score 0-2.
  measure: The Modified Rankin Scale (mRS) score at 30 days
  time frame: Day 30
  description: The detailed distribution of Modified Rankin Scale (mRS) score will be recorded. The mRS score ranges from 0 to 5, where high scores mean a worse outcome.
  measure: NIH Stroke Scale (NIHSS) score at 3 days
  time frame: Day 3
  description: The NIH Stroke Scale (NIHSS) score ranges from 0 to 42, where high scores mean a worse outcome.
  measure: NIH Stroke Scale (NIHSS) score at 7 days
  time frame: Day 7
  description: The NIH Stroke Scale (NIHSS) score ranges from 0 to 42, where high scores mean a worse outcome.
  measure: Changes of lesion volume from baseline to day 7
  time frame: Day 7
  description: The infarct lesion volume will be measures on magnetic resonance imaging DWI and FLAIR.
  measure: Length of hospital stay
  time frame: Up to 30 days
  description: Record the time when patients discharge from hospital.
  measure: The peripheral CD177+ neutrophil levels
  time frame: Day 3 and Day 7
  description: The CD177+ neutrophil levels in peripheral blood will be evaluated using flow cytometry.
  measure: The levels of inflammatory cytokines in peripheral blood
  time frame: Day 3 and Day 7
  description: IL-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12、IL-17A、IFN-α、IFN-γ、TNF-α
  arm group label: Low-dose sodium valproate group
  arm group type: Experimental
  description: Within 3 days after admission, 10mg/kg sodium valproate will be given daily. Specifically, sodium valproate will be intravenously infused at the dose of 5mg/kg within 15 minutes, followed by intravenous drip (1mg/kg/h) for 5 hours.
  arm group label: High-dose sodium valproate group
  arm group type: Experimental
  description: Within 3 days after admission, 20mg/kg sodium valproate will be given daily. Specifically, sodium valproate will be intravenously infused at the dose of 15mg/kg within 15 minutes, followed by intravenous drip (1mg/kg/h) for 5 hours.
  arm group label: Placebo group
  arm group type: Placebo Comparator
  description: Within 3 days after admission, normal saline will be given daily in the same way.
  intervention type: Drug
  intervention name: Sodium valproate
  description: Patients with acute ischemic stroke included in the study are randomly assigned to low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium valproate or normal saline were given intravenously for 3 consecutive days, respectively.
  arm group label: High-dose sodium valproate group
  arm group label: Low-dose sodium valproate group
  intervention type: Drug
  intervention name: Normal saline
  description: Patients with acute ischemic stroke included in the study are randomly assigned to low-dose sodium valproate group, high-dose sodium valproate group and placebo group. Besides receiving conventional treatment for stroke, 10mg/kg sodium valproate, 20mg/kg sodium valproate or normal saline were given intravenously for 3 consecutive days, respectively.
  arm group label: Placebo group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Peiying Li, Doctor
  role: Principal Investigator
  affiliation: RenJi Hospital
  last name: Jieqing Wan, Doctor
  role: Principal Investigator
  affiliation: RenJi Hospital
  last name: Peiying Li, Doctor
  phone: +8615800616866
  email: peiyingli.md@gmail.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: RenJi Hospital
  investigator full name: Peiying Li
  investigator title: Professor
  mesh term: Stroke
  mesh term: Ischemic Stroke
  mesh term: Cerebral Infarction
  mesh term: Ischemia
  mesh term: Valproic Acid