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/NCT05983588</url>
    </required_header>
    <id_info>
      <org_study_id>PROFIL-2088-SIM-0032-I</org_study_id>
      <nct_id>NCT05983588</nct_id>
    </id_info>
    <brief_title>PROFIL Study to Investigate the Effect of GPB on NfL Levels in Patients With Corticobasal Syndrome (CBS)</brief_title>
    <acronym>PROFIL</acronym>
    <official_title>Double-blind, Randomised, Prospective, Placebo Controlled Parallel Group Phase II Study to Investigate the Effect of Glycerol Phenylbutyrate (GPB) on Neurofilament Light Chain (NfL) Levels in Patients With Corticobasal Syndrome (CBS)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Technical University of Munich</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Technical University of Munich</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>
        Corticobasal syndrome (CBS) is a rapidly progressive neurodegenerative disorder with an&#xD;
        average survival time of about 6-8 years after the first clinical manifestation. No potent&#xD;
        symptomatic treatment is currently available. A disease-modifying therapy does not exist&#xD;
        either. Neuroinflammation is key to the pathogenesis in neurodegenerative diseases with Tau-&#xD;
        and/or AD-pathology. There is strong evidence that phenylbutyrate can modulate microglial&#xD;
        function by enhancing their phagocytic activity, most likely by epigenetic mechanisms. So the&#xD;
        main goal of this clinical trial is to study a potential disease-modifying effect of&#xD;
        treatment with glycerol phenylbutyrate (GPB), which is a prodrug of phenylbutyric acid, for&#xD;
        26 weeks assessed by the levels of the biomarker neurofilament light chain (NfL) indicating&#xD;
        disease progression in CBS. Given the aggressive nature of CBS, it is feasible to study&#xD;
        effects of GPB on plasma NfL levels.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">March 2025</completion_date>
    <primary_completion_date type="Anticipated">August 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, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To assess the efficacy of glycerol phenylbutyrate vs. placebo in reducing the levels of neurofilament light chain (NfL) during 26 weeks of exposure to glycerol phenylbutyrate as well as safety and tolerability of glycerol phenylbutyrate in patients with</measure>
      <time_frame>26 weeks (between V1 and V3)</time_frame>
      <description>To assess the efficacy of glycerol phenylbutyrate vs. placebo in reducing the levels of neurofilament light chain (NfL) during 26 weeks of exposure to glyc-erol phenylbutyrate as well as safety and tolerability of glycerol phenylbutyrate in patients with CBS.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>To assess longitudinal changes in clinical scales</measure>
      <time_frame>26 weeks (between V1 and V3)</time_frame>
      <description>To assess longitudinal changes in clinical scale: Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III), min value 0- max value 132 (worse outcome)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess longitudinal changes in clinical scales</measure>
      <time_frame>26 weeks (between V1 and V3)</time_frame>
      <description>To assess longitudinal changes in clinical scale: Progressive Supranuclear Palsy Rating Scale (PSP-RS), min value 0- max value 100 (worse outcome)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess longitudinal changes in clinical scales</measure>
      <time_frame>26 weeks (between V1 and V3)</time_frame>
      <description>To assess longitudinal changes in clinical scale:Progressive Supranuclear Palsy Clinical Deficits Scale (PSP-CDS), min value 0- max value 21 (worse outcome)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess longitudinal changes in clinical scales</measure>
      <time_frame>26 weeks (between V1 and V3)</time_frame>
      <description>To assess longitudinal changes in clinical scale: Cortical Basal ganglia Functional Scale (CBFS), min value 0- max value 124 (worse outcome)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess longitudinal changes in clinical scales</measure>
      <time_frame>26 weeks (between V1 and V3)</time_frame>
      <description>To assess longitudinal changes in clinical scale: Dementia Apraxia Test (DATE), min value 0 (worse outcome) - max value 60</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess longitudinal changes in clinical scales</measure>
      <time_frame>26 weeks (between V1 and V3)</time_frame>
      <description>To assess longitudinal changes in clinical scale: MONTREAL COGNITIVE ASSESSMENT (MoCA), min value 0 (worse outcome) - max value 30</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess longitudinal changes in clinical scales</measure>
      <time_frame>26 weeks (between V1 and V3)</time_frame>
      <description>To assess longitudinal changes in clinical scale: SCHWAB AND ENGLAND ACTIVITIES OF DAILY LIVING SCALE (SEADL), min value 0 (worse outcome) - max value 100%</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess longitudinal changes in clinical scales</measure>
      <time_frame>26 weeks (between V1 and V3)</time_frame>
      <description>To assess longitudinal changes in clinical scale: Clinical Global Impression (CGI-s), min value 1- max value 7 (worse outcome)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess longitudinal changes in clinical scales</measure>
      <time_frame>26 weeks (between V1 and V3)</time_frame>
      <description>To assess longitudinal changes in clinical scale: PSP RATING SCALE (PSP-QoL), min value 0- max value 180 (worse outcome)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">32</enrollment>
    <condition>Corticobasal Syndrome (CBS)</condition>
    <arm_group>
      <arm_group_label>Verum</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>RAVICTI 1.1 g/ml oral liquid (glycerol phenylbutyrate (GPB)) Duration of Treatment: 26 weeks, twice daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Matching Placebo, oral liquid Duration of Treatment: 26 weeks, twice daily</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>RAVICTI 1.1 g/ml</intervention_name>
      <description>Duration of Treatment: 26 weeks, twice daily&#xD;
  Dosage:&#xD;
  weeks 0 - 3: 3 ml/day (1,5ml - 0 - 1,5ml) (≙ 3,3 g glycerol phenylbutyrate/placebo)&#xD;
  weeks 4 - 26: 6 ml/day (3 ml - 0 - 3 ml) (≙ 6,6 g glycerol phenylbutyrate/placebo)</description>
      <arm_group_label>Verum</arm_group_label>
      <other_name>Glycerol phenylbutyrate</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Duration of Treatment: 26 weeks, twice daily&#xD;
  Dosage:&#xD;
  weeks 0 - 3: 3 ml/day (1,5ml - 0 - 1,5ml) (≙ 3,3 g glycerol phenylbutyrate/placebo)&#xD;
  weeks 4 - 26: 6 ml/day (3 ml - 0 - 3 ml) (≙ 6,6 g glycerol phenylbutyrate/placebo)</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age: ≥ 18 years&#xD;
  &#xD;
            2. &quot;clinical possible&quot; or &quot;clinical probable&quot; CBS (Armstrong et al., Neurol-ogy, 2013&#xD;
               80;496-503) and patients with Progressive Supranuclear Palsy-CBS according to&#xD;
               Höglinger et al. (Mov Disord. 2017 Jun;32(6):853-864)&#xD;
  &#xD;
            3. No regular consumption of glycerol phenylbutyrate within the last 6 months prior to V1&#xD;
  &#xD;
            4. Capable of thoroughly understanding all information given and giving full informed&#xD;
               consent according to GCP&#xD;
  &#xD;
            5. Capability and willingness to comply with the procedures of the clinical trial&#xD;
  &#xD;
            6. Women of childbearing age must be non-lactating and surgically sterile or using a&#xD;
               highly effective method of birth control and have a nega-tive pregnancy test. In case&#xD;
               of using a hormonal contraception, the method must be supplemented with a barrier&#xD;
               method (preferably male condom). Acceptable methods of birth control with a low&#xD;
               failure rate i.e. less than 1% per year when used consistently and correct are such as&#xD;
               implants, injectables, combined oral contraceptives, hormonal intrauterine devices&#xD;
               (IUDs), sexual abstinence (defined as refraining from heterosexual intercourse during&#xD;
               the clinical trial) or vasectomized partner. Unacceptable birth control methods are:&#xD;
               periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal&#xD;
               (coitus interruptus), spermicides only and lactational amenorrhoea method (LAM).&#xD;
               Female condom and male condom should not be used together.&#xD;
  &#xD;
            7. A stable regimen for at least 1 month prior to V1 and no foreseeable need to change&#xD;
               the regimen throughout the 26 week treatment period for&#xD;
  &#xD;
                 1. drugs acting against Parkinsonism (e.g. Levodopa, Dopamine-Agonists, Amantadine&#xD;
                    and MAO-B-Inhibitors)&#xD;
  &#xD;
                 2. other CNS-active substances including e.g. antidepressants and antidementia drugs&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Neurodegenerative diseases other than CBS&#xD;
  &#xD;
            2. Underlying Alzheimer's pathology as defined by positive β-amyloid-PET or reduced Aβ&#xD;
               1-42 in CSF&#xD;
  &#xD;
            3. Participation in another clinical trial involving administration of an investigational&#xD;
               medicinal product within 1 month or 5 half-lives of the investigational medicinal&#xD;
               product, whichever is longer, prior to V1&#xD;
  &#xD;
            4. Known hypersensitivity to glycerol phenylbutyrate or its further components, or to&#xD;
               drugs with a similar chemical structure or to any of the components of the placebo&#xD;
  &#xD;
            5. Treatment with valproic acid, haloperidol or probenecid&#xD;
  &#xD;
            6. A physical or psychiatric condition (e.g. frontal lobe syndrome, psychotic disorder or&#xD;
               major depression), which at the investigator's discretion may put the subject at risk,&#xD;
               may confound the trial results or may interfere with the subject's participation in&#xD;
               this clinical trial&#xD;
  &#xD;
            7. Persistent abuse of medication, drugs or alcohol&#xD;
  &#xD;
            8. Current or planned pregnancy or breast-feeding in females&#xD;
  &#xD;
            9. Other severe medical conditions upon the discretion of the investigator&#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_contact>
      <last_name>Johannes Prof. Dr. Levin</last_name>
      <phone>089/440046455</phone>
      <email>johannes.levin@med.uni-muenchen.de</email>
    </overall_contact>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 13, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 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>Corticobasal Degeneration</mesh_term>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Glycerol</mesh_term>
    </intervention_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/NCT05983588
  org study id: PROFIL-2088-SIM-0032-I
  nct id: NCT05983588
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Corticobasal syndrome (CBS) is a rapidly progressive neurodegenerative disorder with an
        average survival time of about 6-8 years after the first clinical manifestation. No potent
        symptomatic treatment is currently available. A disease-modifying therapy does not exist
        either. Neuroinflammation is key to the pathogenesis in neurodegenerative diseases with Tau-
        and/or AD-pathology. There is strong evidence that phenylbutyrate can modulate microglial
        function by enhancing their phagocytic activity, most likely by epigenetic mechanisms. So the
        main goal of this clinical trial is to study a potential disease-modifying effect of
        treatment with glycerol phenylbutyrate (GPB), which is a prodrug of phenylbutyric acid, for
        26 weeks assessed by the levels of the biomarker neurofilament light chain (NfL) indicating
        disease progression in CBS. Given the aggressive nature of CBS, it is feasible to study
        effects of GPB on plasma NfL levels.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: To assess the efficacy of glycerol phenylbutyrate vs. placebo in reducing the levels of neurofilament light chain (NfL) during 26 weeks of exposure to glycerol phenylbutyrate as well as safety and tolerability of glycerol phenylbutyrate in patients with
  time frame: 26 weeks (between V1 and V3)
  description: To assess the efficacy of glycerol phenylbutyrate vs. placebo in reducing the levels of neurofilament light chain (NfL) during 26 weeks of exposure to glyc-erol phenylbutyrate as well as safety and tolerability of glycerol phenylbutyrate in patients with CBS.
  measure: To assess longitudinal changes in clinical scales
  time frame: 26 weeks (between V1 and V3)
  description: To assess longitudinal changes in clinical scale: Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III), min value 0- max value 132 (worse outcome)
  measure: To assess longitudinal changes in clinical scales
  time frame: 26 weeks (between V1 and V3)
  description: To assess longitudinal changes in clinical scale: Progressive Supranuclear Palsy Rating Scale (PSP-RS), min value 0- max value 100 (worse outcome)
  measure: To assess longitudinal changes in clinical scales
  time frame: 26 weeks (between V1 and V3)
  description: To assess longitudinal changes in clinical scale:Progressive Supranuclear Palsy Clinical Deficits Scale (PSP-CDS), min value 0- max value 21 (worse outcome)
  measure: To assess longitudinal changes in clinical scales
  time frame: 26 weeks (between V1 and V3)
  description: To assess longitudinal changes in clinical scale: Cortical Basal ganglia Functional Scale (CBFS), min value 0- max value 124 (worse outcome)
  measure: To assess longitudinal changes in clinical scales
  time frame: 26 weeks (between V1 and V3)
  description: To assess longitudinal changes in clinical scale: Dementia Apraxia Test (DATE), min value 0 (worse outcome) - max value 60
  measure: To assess longitudinal changes in clinical scales
  time frame: 26 weeks (between V1 and V3)
  description: To assess longitudinal changes in clinical scale: MONTREAL COGNITIVE ASSESSMENT (MoCA), min value 0 (worse outcome) - max value 30
  measure: To assess longitudinal changes in clinical scales
  time frame: 26 weeks (between V1 and V3)
  description: To assess longitudinal changes in clinical scale: SCHWAB AND ENGLAND ACTIVITIES OF DAILY LIVING SCALE (SEADL), min value 0 (worse outcome) - max value 100%
  measure: To assess longitudinal changes in clinical scales
  time frame: 26 weeks (between V1 and V3)
  description: To assess longitudinal changes in clinical scale: Clinical Global Impression (CGI-s), min value 1- max value 7 (worse outcome)
  measure: To assess longitudinal changes in clinical scales
  time frame: 26 weeks (between V1 and V3)
  description: To assess longitudinal changes in clinical scale: PSP RATING SCALE (PSP-QoL), min value 0- max value 180 (worse outcome)
  arm group label: Verum
  arm group type: Experimental
  description: RAVICTI 1.1 g/ml oral liquid (glycerol phenylbutyrate (GPB)) Duration of Treatment: 26 weeks, twice daily
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Matching Placebo, oral liquid Duration of Treatment: 26 weeks, twice daily
  intervention type: Drug
  intervention name: RAVICTI 1.1 g/ml
  description: Duration of Treatment: 26 weeks, twice daily
  Dosage:
  weeks 0 - 3: 3 ml/day (1,5ml - 0 - 1,5ml) (≙ 3,3 g glycerol phenylbutyrate/placebo)
  weeks 4 - 26: 6 ml/day (3 ml - 0 - 3 ml) (≙ 6,6 g glycerol phenylbutyrate/placebo)
  arm group label: Verum
  other name: Glycerol phenylbutyrate
  intervention type: Drug
  intervention name: Placebo
  description: Duration of Treatment: 26 weeks, twice daily
  Dosage:
  weeks 0 - 3: 3 ml/day (1,5ml - 0 - 1,5ml) (≙ 3,3 g glycerol phenylbutyrate/placebo)
  weeks 4 - 26: 6 ml/day (3 ml - 0 - 3 ml) (≙ 6,6 g glycerol phenylbutyrate/placebo)
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Johannes Prof. Dr. Levin
  phone: 089/440046455
  email: johannes.levin@med.uni-muenchen.de
  responsible party type: Sponsor
  mesh term: Corticobasal Degeneration
  mesh term: Syndrome
  mesh term: Glycerol
  sharing ipd: No