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/NCT05970575</url>
    </required_header>
    <id_info>
      <org_study_id>NE3107-TBI-TRP</org_study_id>
      <nct_id>NCT05970575</nct_id>
    </id_info>
    <brief_title>Insulin-sensitizing NE3107 in Improving Sleep and Fatigue in Subjects With Traumatic Brain Injury</brief_title>
    <official_title>Open Label Phase IIa Study Evaluating the Safety and Efficacy of NE3107 in Improving Sleep and Fatigue in Subjects With Traumatic Brain Injury</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Neurological Associates of West Los Angeles</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>BioVie Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Neurological Associates of West Los Angeles</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study seeks to measure changes in cognition through verbal and visual test procedures&#xD;
        and changes in biomarkers of Traumatic Brain Injury and inflammatory and metabolic&#xD;
        parameters.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        A growing body of literature recognizes neuroinflammation as a pivotal contributor to the&#xD;
        pathogenesis of TBI. A surge of inflammatory cytokines and chemokines, including tumor&#xD;
        necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and nuclear factor&#xD;
        kappa-light-chain-enhancer of activated B cells (NF-kB), often follows TBI, leading to a&#xD;
        complex cascade of secondary events that ultimately result in neuronal damage and long-term&#xD;
        consequences.&#xD;
  &#xD;
        It has been shown that patients with mild TBI have higher plasma inflammatory cytokine levels&#xD;
        than those without TBI at both 24 hours and 6 months following initial injury.The activation&#xD;
        of these inflammatory mediators has been demonstrated in both cerebrospinal fluid (CSF) and&#xD;
        serum of TBI patients. Elevated levels of TNF-α in CSF and serum have been associated with&#xD;
        injury severity and unfavorable outcomes in TBI.&#xD;
  &#xD;
        IL-1, IL-6, and TNF-α induce the extracellular signal-regulated kinase (ERK) pathway,&#xD;
        promoting neuroinflammation. Furthermore, NF-kB, a crucial transcription factor in the&#xD;
        inflammatory response, plays a significant role in amplifying neuroinflammation post-TBI,&#xD;
        mediating the expression of several inflammatory cytokines and contributing to neuronal&#xD;
        apoptosis and cognitive impairment.&#xD;
  &#xD;
        Neuroinflammation's contribution to sleep disturbances, fatigue, and cognitive impairment has&#xD;
        been increasingly recognized. These inflammatory cytokines may influence the&#xD;
        hypothalamic-pituitary-adrenal (HPA) axis and disrupt sleep architecture, leading to sleep&#xD;
        disturbances and fatigue. Further, they are known to induce synaptic alterations and neuronal&#xD;
        apoptosis, contributing to cognitive impairment.&#xD;
  &#xD;
        Chronic, low-grade inflammation often ensues post-TBI, contributing to the persistent and&#xD;
        potentially insidious process leading to long-term impairment and diminished quality of life.&#xD;
  &#xD;
        Apart from neuroinflammation, intracranial insulin resistance, another secondary consequence&#xD;
        of TBI, plays a significant role in the pathogenesis of TBI. Insulin resistance has been&#xD;
        observed in TBI patients, and it's linked to worse outcomes. In mouse models, induced TBI has&#xD;
        been shown to demonstrate reduced glucose uptake in mice brains on positron emission&#xD;
        tomography (PET) scans, consistent with the insulin resistance that has been seen in TBI&#xD;
        patients. Insulin resistance may exacerbate neuroinflammation, disrupt synaptic plasticity,&#xD;
        and contribute to cognitive deficits, further compounding the injury's impact.&#xD;
  &#xD;
        If these symptoms remain untreated, they can significantly impair quality of life, limiting&#xD;
        independent living and reducing the ability to perform daily activities. They can also&#xD;
        predispose individuals to mental health disorders such as depression and anxiety and lead to&#xD;
        a higher risk of chronic diseases and premature death.&#xD;
  &#xD;
        Currently, there is no therapeutic option to halt or fully reverse the sequelae from&#xD;
        traumatic brain injuries or the attendant neurophysiological deterioration. Other conditions&#xD;
        with similarly limited-to-no available and effective treatment strategies, including&#xD;
        Alzheimer's disease, share an overlapping deteriorative quality relating to neuroinflammation&#xD;
        and even reduced insulin functioning. A promising area of research among traumatic brain&#xD;
        injury and Alzheimer's treatment is investigating the use of insulin synthesizers; this study&#xD;
        group has also initiated a project involving NE3107 among patients with Alzheimer's disease&#xD;
        (IND 159271). In addition to IND 159271, several Phase 3 studies had been previously&#xD;
        initiated and/or completed with compounds such as Semaglutide, a hormone that stimulates&#xD;
        insulin signaling, Metformin, an insulin synthesizer , and NE3107, an anti-inflammatory&#xD;
        insulin-sensitizing agent.&#xD;
  &#xD;
        In this study, the drug under investigation is NE3107 (17a-ethynyl0androst-5-ene-3b, 7b,&#xD;
        17b-triol). NE3107 is a small, blood-brain permeable molecule with anti-inflammatory and&#xD;
        insulin-sensitizing properties. The mechanism of action for NE3107 involves selective&#xD;
        inhibition of inflammatory mediators.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 21, 2023</start_date>
    <completion_date type="Anticipated">July 21, 2024</completion_date>
    <primary_completion_date type="Anticipated">June 21, 2024</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Safety as Assessed by Quantification of Adverse Events</measure>
      <time_frame>up to 6 months</time_frame>
      <description>Primary outcome will be collection of AEs and SAEs</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Pittsburgh Sleep Quality Index (PSQI)</measure>
      <time_frame>Baseline, 3 months, 6 months</time_frame>
      <description>a tool used to measure the quality and patterns of sleep</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Multidimensional Fatigue Inventory (MFI)</measure>
      <time_frame>Baseline, 3 Months, 6 Months</time_frame>
      <description>to measure overall fatigue</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Montreal Objective Cognitive Assessment change</measure>
      <time_frame>Baseline, 3 Months, 6 Months</time_frame>
      <description>The MoCA evaluates frontal-executive functions (e.g., verbal abstraction and mental calculation), language (e.g., confrontation naming, phonemic fluency), orientation (e.g., person, place, date, day of the week, and time), visuospatial construction (e.g., simple figure copy), divided visual attention, and immediate and delayed memory of unstructured information. MoCA scores range from 0-30 possible points; 26 or greater is considered to reflect normal cognitive status.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">5</enrollment>
    <condition>Traumatic Brain Injury</condition>
    <arm_group>
      <arm_group_label>Experimental Arm: NE3107</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>All participants will take 200mg BID (12 hours apart) of NE3107 for 6 months.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NE3107</intervention_name>
      <description>Participants will take 20mg twice daily (BID) approximately 12 hours apart. The dose will be stable the duration of the study intervention (6 months)</description>
      <arm_group_label>Experimental Arm: NE3107</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Diagnosis of traumatic brain injury, confirmed by neurologist or other medical&#xD;
               professional&#xD;
  &#xD;
          Age within range of 18-75 years old&#xD;
  &#xD;
          Multidimensional Fatigue Inventory (MFI) score of 27 or greater&#xD;
  &#xD;
          Epworth Sleepiness Scale (ESS) score of 10 or greater AND/OR a Pittsburgh Sleep Index (PSI)&#xD;
          score of 5 or greater&#xD;
  &#xD;
          Ability to Consent: Participants need to be capable of giving informed consent or have a&#xD;
          legally authorized representative who can do so.&#xD;
  &#xD;
          Ability to participate for the duration of the study&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  In order for a subject to be considered for this study, he/she may NOT have any of the&#xD;
               following:&#xD;
  &#xD;
          Diagnosis of other chronic Neurological Conditions: Examples are participants with other&#xD;
          pre-existing neurological conditions, such as Alzheimer's or Parkinson's Disease or&#xD;
          untreated epilepsy.&#xD;
  &#xD;
          Severe Psychiatric Illness: Conditions such as schizophrenia, bipolar disorder, or severe&#xD;
          depression.&#xD;
  &#xD;
          Current diagnosis of Substance Abuse Disorder, including opioid use disorder.&#xD;
  &#xD;
          Dysphagia or Significant GI dysmotility or conditions that would significantly impair&#xD;
          absorption&#xD;
  &#xD;
          Significant language impairment with expressive or receptive aphasia&#xD;
  &#xD;
          Hematological or Metabolic derangement or diagnosis of other medical condition that could&#xD;
          be negatively affected by participating in this clinical trial.&#xD;
  &#xD;
          Pregnant or plans for pregnancy or breastfeeding during the course of the study&#xD;
  &#xD;
          Diagnosis of genetic or developmental disorder with cognitive impairment&#xD;
  &#xD;
          Use of more than 2 sleep aids including melatonin&#xD;
  &#xD;
          Advanced stages of any terminal illness or any active cancer that requires chemotherapy&#xD;
  &#xD;
          History of breast cancer&#xD;
  &#xD;
          Women with child-bearing potential who are not willing to use a double-barrier birth&#xD;
          control method&#xD;
  &#xD;
          Males not willing to use a double-barrier birth control method with female sex partners&#xD;
          with child-bearing potential&#xD;
  &#xD;
          Individuals with hepatic impairment as defined by:&#xD;
  &#xD;
          Alanine aminotransferase (ALT) lab values &gt;3x the upper normal limit (UNL)&#xD;
  &#xD;
          Aspartate aminotransferase (AST) lab values &gt;3x UNL&#xD;
  &#xD;
          OR&#xD;
  &#xD;
          History of clinically significant liver disease in the Principal Investigator's medical&#xD;
          judgment&#xD;
  &#xD;
          Individuals with renal impairment as defined by Creatinine clearance (Cockcroft-Gault&#xD;
          formula) of &lt;45 mL/min.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>74 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Kennedy Mahdavi</last_name>
      <phone>3108295968</phone>
      <email>kmahdavi@theneuroassociates.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jonathan Haroon</last_name>
      <phone>3108295968</phone>
      <email>jharoon@theneuroassociates.com</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Brain Injuries</mesh_term>
      <mesh_term>Brain Injuries, Traumatic</mesh_term>
      <mesh_term>Wounds and Injuries</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</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/NCT05970575
  org study id: NE3107-TBI-TRP
  nct id: NCT05970575
  lead sponsor: 
  collaborator: 
  is fda regulated drug: Yes
  is fda regulated device: No
  This study seeks to measure changes in cognition through verbal and visual test procedures
        and changes in biomarkers of Traumatic Brain Injury and inflammatory and metabolic
        parameters.
  A growing body of literature recognizes neuroinflammation as a pivotal contributor to the
        pathogenesis of TBI. A surge of inflammatory cytokines and chemokines, including tumor
        necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and nuclear factor
        kappa-light-chain-enhancer of activated B cells (NF-kB), often follows TBI, leading to a
        complex cascade of secondary events that ultimately result in neuronal damage and long-term
        consequences.
  
        It has been shown that patients with mild TBI have higher plasma inflammatory cytokine levels
        than those without TBI at both 24 hours and 6 months following initial injury.The activation
        of these inflammatory mediators has been demonstrated in both cerebrospinal fluid (CSF) and
        serum of TBI patients. Elevated levels of TNF-α in CSF and serum have been associated with
        injury severity and unfavorable outcomes in TBI.
  
        IL-1, IL-6, and TNF-α induce the extracellular signal-regulated kinase (ERK) pathway,
        promoting neuroinflammation. Furthermore, NF-kB, a crucial transcription factor in the
        inflammatory response, plays a significant role in amplifying neuroinflammation post-TBI,
        mediating the expression of several inflammatory cytokines and contributing to neuronal
        apoptosis and cognitive impairment.
  
        Neuroinflammation's contribution to sleep disturbances, fatigue, and cognitive impairment has
        been increasingly recognized. These inflammatory cytokines may influence the
        hypothalamic-pituitary-adrenal (HPA) axis and disrupt sleep architecture, leading to sleep
        disturbances and fatigue. Further, they are known to induce synaptic alterations and neuronal
        apoptosis, contributing to cognitive impairment.
  
        Chronic, low-grade inflammation often ensues post-TBI, contributing to the persistent and
        potentially insidious process leading to long-term impairment and diminished quality of life.
  
        Apart from neuroinflammation, intracranial insulin resistance, another secondary consequence
        of TBI, plays a significant role in the pathogenesis of TBI. Insulin resistance has been
        observed in TBI patients, and it's linked to worse outcomes. In mouse models, induced TBI has
        been shown to demonstrate reduced glucose uptake in mice brains on positron emission
        tomography (PET) scans, consistent with the insulin resistance that has been seen in TBI
        patients. Insulin resistance may exacerbate neuroinflammation, disrupt synaptic plasticity,
        and contribute to cognitive deficits, further compounding the injury's impact.
  
        If these symptoms remain untreated, they can significantly impair quality of life, limiting
        independent living and reducing the ability to perform daily activities. They can also
        predispose individuals to mental health disorders such as depression and anxiety and lead to
        a higher risk of chronic diseases and premature death.
  
        Currently, there is no therapeutic option to halt or fully reverse the sequelae from
        traumatic brain injuries or the attendant neurophysiological deterioration. Other conditions
        with similarly limited-to-no available and effective treatment strategies, including
        Alzheimer's disease, share an overlapping deteriorative quality relating to neuroinflammation
        and even reduced insulin functioning. A promising area of research among traumatic brain
        injury and Alzheimer's treatment is investigating the use of insulin synthesizers; this study
        group has also initiated a project involving NE3107 among patients with Alzheimer's disease
        (IND 159271). In addition to IND 159271, several Phase 3 studies had been previously
        initiated and/or completed with compounds such as Semaglutide, a hormone that stimulates
        insulin signaling, Metformin, an insulin synthesizer , and NE3107, an anti-inflammatory
        insulin-sensitizing agent.
  
        In this study, the drug under investigation is NE3107 (17a-ethynyl0androst-5-ene-3b, 7b,
        17b-triol). NE3107 is a small, blood-brain permeable molecule with anti-inflammatory and
        insulin-sensitizing properties. The mechanism of action for NE3107 involves selective
        inhibition of inflammatory mediators.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Safety as Assessed by Quantification of Adverse Events
  time frame: up to 6 months
  description: Primary outcome will be collection of AEs and SAEs
  measure: Pittsburgh Sleep Quality Index (PSQI)
  time frame: Baseline, 3 months, 6 months
  description: a tool used to measure the quality and patterns of sleep
  measure: Multidimensional Fatigue Inventory (MFI)
  time frame: Baseline, 3 Months, 6 Months
  description: to measure overall fatigue
  measure: Montreal Objective Cognitive Assessment change
  time frame: Baseline, 3 Months, 6 Months
  description: The MoCA evaluates frontal-executive functions (e.g., verbal abstraction and mental calculation), language (e.g., confrontation naming, phonemic fluency), orientation (e.g., person, place, date, day of the week, and time), visuospatial construction (e.g., simple figure copy), divided visual attention, and immediate and delayed memory of unstructured information. MoCA scores range from 0-30 possible points; 26 or greater is considered to reflect normal cognitive status.
  arm group label: Experimental Arm: NE3107
  arm group type: Experimental
  description: All participants will take 200mg BID (12 hours apart) of NE3107 for 6 months.
  intervention type: Drug
  intervention name: NE3107
  description: Participants will take 20mg twice daily (BID) approximately 12 hours apart. The dose will be stable the duration of the study intervention (6 months)
  arm group label: Experimental Arm: NE3107
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 74 Years
  healthy volunteers: No
  last name: Kennedy Mahdavi
  phone: 3108295968
  email: kmahdavi@theneuroassociates.com
  last name: Jonathan Haroon
  phone: 3108295968
  email: jharoon@theneuroassociates.com
  responsible party type: Sponsor
  mesh term: Brain Injuries
  mesh term: Brain Injuries, Traumatic
  mesh term: Wounds and Injuries
  sharing ipd: No