<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/NCT03263533</url>
  </required_header>
  <id_info>
    <org_study_id>HM20007977</org_study_id>
    <nct_id>NCT03263533</nct_id>
  </id_info>
  <brief_title>HDAC Inhibitor Augmentation to Clozapine</brief_title>
  <official_title>HDAC Inhibitor Augmentation to Clozapine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Virginia Commonwealth 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main goal of this pilot study is to test the extent to which adjunctive treatment with&#xD;
      the histone deacetylase (HDAC) inhibitor vorinostat improves brain plasticity and cognition&#xD;
      in a pilot placebo-controlled trial in patients with schizophrenia who are on clozapine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The goal of this study is to perform a pilot clinical study with a small sample of subjects&#xD;
      to evaluate the safety and tolerability of vorinostat when combined with clozapine treatment&#xD;
      in patients with schizophrenia. The investigators will also evaluate the potential&#xD;
      translation of our preclinical data into a clinical use of vorinostat for cognitive&#xD;
      impairment in clozapine-treated schizophrenic patients.&#xD;
&#xD;
      Potential participants will be receiving stables doses of clozapine for a minimum period of 6&#xD;
      months before entry into the study. Clozapine was selected because i) the majority of our&#xD;
      studies in mouse models were performed after chronic treatment with this atypical&#xD;
      antipsychotic, and ii) the investigators' data in postmortem human brain samples of subjects&#xD;
      with antemortem diagnosis of schizophrenia suggest up-regulation of HDAC2 in frontal cortex&#xD;
      of schizophrenic subjects treated with atypical, but not typical, antipsychotic drugs.&#xD;
&#xD;
      The HDAC inhibitor vorinostat was selected because preliminary data suggest that chronic&#xD;
      treatment with vorinostat improves HDAC2-dependent cognitive function in rodent models.&#xD;
      Additionally, vorinostat is the first HDAC inhibitor approved by the U.S. Food and Drug&#xD;
      Administration (FDA) for the treatment of cutaneous T-cell lymphoma. Dose(s) of vorinostat&#xD;
      have been selected based on previous clinical studies in such patients with brain metastasis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    PIs were unable to recruit any participants&#xD;
  </why_stopped>
  <start_date type="Anticipated">April 2017</start_date>
  <completion_date type="Anticipated">February 2019</completion_date>
  <primary_completion_date type="Anticipated">February 2019</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)</measure>
    <time_frame>10 weeks</time_frame>
    <description>Safety of vorinostat measured by number of adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in clinical cognitive symptoms during adjunctive vorinostat therapy in schizophrenia patients treated with clozapine</measure>
    <time_frame>Baseline, Visit 4 (end of first intervention group/week 4), Visit 7 (end of study/10 weeks)</time_frame>
    <description>Participants will be given a cognitive test to assess executive function and speed.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Vorinostat Group 1 (P-V-P-P)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group will receive this sequence after the 1 initial week washout:&#xD;
vorinstat (4 weeks) placebo (1 week) placebo (4 weeks)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vorinostat Group 2 (P-P-P-V)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group will receive this sequence after the 1 initial week washout:&#xD;
placebo (4 weeks) placebo (1 week) vorinostat (4 weeks)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vorinostat Oral Capsule Group 1</intervention_name>
    <description>Following the initial washout and first 4-week period of the trial, all patients will enter a second 1-week washout. After the washout, all patients will then enter a second 4 week alternate treatment (vorinostat or placebo). During the vorinostat sequence, doses will be increased over the first 2 weeks in each phase of the crossover study, starting by 100 mg per day, and increasing to 200 mg by week 2 and 300 mg per day at the start of week 3 until the end of week 4.</description>
    <arm_group_label>Vorinostat Group 1 (P-V-P-P)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vorinostat Oral Capsule Group 2</intervention_name>
    <description>Following the initial washout and first 4-week period of the trial, all patients will enter a second 1-week washout. After the washout, all patients will then enter a second 4 week alternate treatment (vorinostat or placebo). During the vorinostat sequence, doses will be increased over the first 2 weeks in each phase of the crossover study, starting by 100 mg per day, and increasing to 200 mg by week 2 and 300 mg per day at the start of week 3 until the end of week 4.</description>
    <arm_group_label>Vorinostat Group 2 (P-P-P-V)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with DSM-5 Schizophrenia&#xD;
&#xD;
          -  Receiving stable dose pf clozapine (≥ 300 mg per day) for at least 6 months before&#xD;
             entering the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Taking specific psychotropic medications (lamotrigine and valproic acid)&#xD;
&#xD;
          -  Current or recent (12-months) substance use or induced disorder&#xD;
&#xD;
          -  History of significant neurological or medical disorders&#xD;
&#xD;
          -  Intellectual disability&#xD;
&#xD;
          -  Known contraindications to the administration of vorinostat per product labeling&#xD;
&#xD;
          -  Women currently pregnant, planning to become pregnant, or receiving hormone therapy&#xD;
             and refusing any form of birth control&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Javier Gonzalez-Maeso, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Virginia Commonwealth University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>February 20, 2019</last_update_submitted>
  <last_update_submitted_qc>February 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>schizophrenia</keyword>
  <keyword>clozapine</keyword>
  <keyword>vorinostat</keyword>
  <keyword>HDAC</keyword>
  <keyword>histone deacetylase inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vorinostat</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03263533
org study id: HM20007977
nct id: NCT03263533
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The main goal of this pilot study is to test the extent to which adjunctive treatment with
      the histone deacetylase (HDAC) inhibitor vorinostat improves brain plasticity and cognition
      in a pilot placebo-controlled trial in patients with schizophrenia who are on clozapine.
The goal of this study is to perform a pilot clinical study with a small sample of subjects
      to evaluate the safety and tolerability of vorinostat when combined with clozapine treatment
      in patients with schizophrenia. The investigators will also evaluate the potential
      translation of our preclinical data into a clinical use of vorinostat for cognitive
      impairment in clozapine-treated schizophrenic patients.

      Potential participants will be receiving stables doses of clozapine for a minimum period of 6
      months before entry into the study. Clozapine was selected because i) the majority of our
      studies in mouse models were performed after chronic treatment with this atypical
      antipsychotic, and ii) the investigators' data in postmortem human brain samples of subjects
      with antemortem diagnosis of schizophrenia suggest up-regulation of HDAC2 in frontal cortex
      of schizophrenic subjects treated with atypical, but not typical, antipsychotic drugs.

      The HDAC inhibitor vorinostat was selected because preliminary data suggest that chronic
      treatment with vorinostat improves HDAC2-dependent cognitive function in rodent models.
      Additionally, vorinostat is the first HDAC inhibitor approved by the U.S. Food and Drug
      Administration (FDA) for the treatment of cutaneous T-cell lymphoma. Dose(s) of vorinostat
      have been selected based on previous clinical studies in such patients with brain metastasis.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
time frame: 10 weeks
description: Safety of vorinostat measured by number of adverse events
measure: Change in clinical cognitive symptoms during adjunctive vorinostat therapy in schizophrenia patients treated with clozapine
time frame: Baseline, Visit 4 (end of first intervention group/week 4), Visit 7 (end of study/10 weeks)
description: Participants will be given a cognitive test to assess executive function and speed.
arm group label: Vorinostat Group 1 (P-V-P-P)
arm group type: Experimental
description: This group will receive this sequence after the 1 initial week washout:
vorinstat (4 weeks) placebo (1 week) placebo (4 weeks)
arm group label: Vorinostat Group 2 (P-P-P-V)
arm group type: Experimental
description: This group will receive this sequence after the 1 initial week washout:
placebo (4 weeks) placebo (1 week) vorinostat (4 weeks)
intervention type: Drug
intervention name: Vorinostat Oral Capsule Group 1
description: Following the initial washout and first 4-week period of the trial, all patients will enter a second 1-week washout. After the washout, all patients will then enter a second 4 week alternate treatment (vorinostat or placebo). During the vorinostat sequence, doses will be increased over the first 2 weeks in each phase of the crossover study, starting by 100 mg per day, and increasing to 200 mg by week 2 and 300 mg per day at the start of week 3 until the end of week 4.
arm group label: Vorinostat Group 1 (P-V-P-P)
intervention type: Drug
intervention name: Vorinostat Oral Capsule Group 2
description: Following the initial washout and first 4-week period of the trial, all patients will enter a second 1-week washout. After the washout, all patients will then enter a second 4 week alternate treatment (vorinostat or placebo). During the vorinostat sequence, doses will be increased over the first 2 weeks in each phase of the crossover study, starting by 100 mg per day, and increasing to 200 mg by week 2 and 300 mg per day at the start of week 3 until the end of week 4.
arm group label: Vorinostat Group 2 (P-P-P-V)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Javier Gonzalez-Maeso, PhD
role: Principal Investigator
affiliation: Virginia Commonwealth University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Vorinostat
sharing ipd: No