<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/NCT03010865</url>
  </required_header>
  <id_info>
    <org_study_id>2016-12</org_study_id>
    <nct_id>NCT03010865</nct_id>
  </id_info>
  <brief_title>Sodium Butyrate For Improving Cognitive Function In Schizophrenia</brief_title>
  <official_title>Sodium Butyrate As A Treatment For Improving Cognitive Function In Schizophrenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Mental Health Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Stanley Medical Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai Mental Health Center</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>
      The purpose of this grant is to evaluate the efficacy of sodium butyrate as a novel treatment&#xD;
      for cognitive deficits in schizophrenia (SZ). The aims will be to evaluate its effects on&#xD;
      improving symptoms and functioning in SZ, and the relationship of the drug's clinical effects&#xD;
      to epigenetic and inflammation related biochemical changes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The persistent cognitive deficits which can be appreciated across the course of SZ, from&#xD;
      prodromal to chronic SZ, may be the most important underlying dysfunction in preventing&#xD;
      functional, occupational, and social recovery in SZ compared to other symptom domains. Sodium&#xD;
      butyrate is a short chain fatty acid and binds to the zinc site of histone deacetylases&#xD;
      (HDAC). The inhibition of HDAC results in histone hyperacetylation. This study aims to&#xD;
      evaluate its effects on improving symptoms and functioning in SZ, and the relationship of the&#xD;
      drug's clinical effects to epigenetic and inflammation related biochemical changes.&#xD;
&#xD;
      The proposed study will be a double blind study of the effects of sodium butyrate on&#xD;
      cognitive function and symptoms in chronic SZ patients showing continued cognitive&#xD;
      deficits.The primary specific aims of the proposal will be to test the the MATRICS (MCCB)&#xD;
      battery,delayed recall performance, and performance on real world functional tasks as&#xD;
      assessed by the USCD Performance- Based Skills Assessment Battery (UPSA). In addition, we&#xD;
      will also investigate whether sodium butyrate may improve other aspects of cognition.&#xD;
&#xD;
      We will also explore whether improvement in cognition is related to change in HDAC activity&#xD;
      in peripheral blood cells and changes in inflammatory makers in the blood, and assess whether&#xD;
      there is any improvement in psychopathology as measured by PANSS scale.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    sponsor withdrew the funds because the smell of sodium butyrate made blinding impossible&#xD;
  </why_stopped>
  <start_date type="Actual">June 1, 2017</start_date>
  <completion_date type="Anticipated">February 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2019</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in MATRICS Battery Score</measure>
    <time_frame>Basline, week 6, up to 12 weeks</time_frame>
    <description>MATRICS Cognitive Battery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Logical Memory Test score</measure>
    <time_frame>Basline, up to 12 weeks</time_frame>
    <description>Logical Memory Test for longer term memory</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Positive and Negative Syndrome Scale (PANSS) total score</measure>
    <time_frame>Basline, week 6, up to 12 weeks</time_frame>
    <description>Positive and Negative Syndrome Scale (PANSS) symptom rating scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Paced Auditory Serial Addition Test (PASAT) score</measure>
    <time_frame>Basline, week 6, up to 12 weeks</time_frame>
    <description>Alternate working memory test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in UCSD Performance-Based Skills Assessment (UPSA) total score</measure>
    <time_frame>Baseline, up to 12 weeks</time_frame>
    <description>University of California, San Diego (UCSD) Performance-Based Skills Assessment Battery</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change from baseline in Side-Effect Scale Score</measure>
    <time_frame>Basline, week 2, week 6, up to 12 weeks</time_frame>
    <description>Patient self-report of side-effects of active or placebo medication</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Schizophrenic Disorder</condition>
  <condition>Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>Sodium Butyrate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dietary Supplement: Sodium Butyrate 4.38 gms of sodium butyrate per day for 12 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Oral Capsule</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Oral Capsule placebo capsules containing approximately 9 mg of sodium butyrate per day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Butyrate</intervention_name>
    <description>Sodium butyrate is being supplied by T.E. Neesby (Brain White, T.E. Neesby, Inc.) in 730 mg capsules. The company asserts that their material is 98% pure and food grade. We will have identical placebo capsules. Subjects will receive 3 capsules twice daily (morning and late afternoon or evening) for a total of 4380 mg/day.</description>
    <arm_group_label>Sodium Butyrate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Capsule</intervention_name>
    <description>Placebo Oral Capsule is also being supplied by T.E. Neesby (Brain White, T.E. Neesby, Inc.) and there is no difference from appearance, smell and taste. It contains 1.5 mg sodium butyrate per capsule. Subjects will receive 3 capsules twice daily (morning and late afternoon or evening) for a total of 9 mg/day.</description>
    <arm_group_label>Placebo Oral Capsule</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects who have cognitive deficits as indicated by a score of &lt; 85 on RBANS,&#xD;
&#xD;
          2. meet criteria for DSM-5 diagnosis of chronic SZ, schizoaffective disorder (SA),&#xD;
&#xD;
          3. Subjects who are stably treated with antipsychotic medications and are not in acute&#xD;
             exacerbation of illness symptoms.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of mental retardation or pervasive developmental disorder,&#xD;
&#xD;
          2. Subjects with a current serious neurological/CNS disorder (such as seizure disorder,&#xD;
             stroke or multiple sclerosis) or brain trauma,&#xD;
&#xD;
          3. Current treatment with valproic acid, butyrate drugs, sulforaphane, or other drugs or&#xD;
             chemicals known to have high HDAC inhibitory activity,&#xD;
&#xD;
          4. Pregnancy,&#xD;
&#xD;
          5. Severe unstable medical condition,&#xD;
&#xD;
          6. Current suicidal or homicidal thoughts,&#xD;
&#xD;
          7. Current alcohol or substance abuse (other than nicotine or occasional marijuana) in&#xD;
             the last month.&#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>Chunbo Li, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Mental Health Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Shanghai Mental Health Center</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>January 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>January 15, 2019</last_update_submitted>
  <last_update_submitted_qc>January 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HDAC inhibitors</keyword>
  <keyword>Inflammation</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>Butyric Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Stanley foundation requests: Based on the terms of your award, Stanley Medical Research Institute (SMRI) now requires submission of the individual patient data from all SMRI funded studies. In order to make the process as efficient as possible and provide a secure location for study data, National Institute of Mental Health (NIMH) is graciously allowing SMRI access to their National Database for Clinical Trials (NDCT) to collect and house data.</ipd_description>
  </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/NCT03010865
org study id: 2016-12
nct id: NCT03010865
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this grant is to evaluate the efficacy of sodium butyrate as a novel treatment
      for cognitive deficits in schizophrenia (SZ). The aims will be to evaluate its effects on
      improving symptoms and functioning in SZ, and the relationship of the drug's clinical effects
      to epigenetic and inflammation related biochemical changes.
The persistent cognitive deficits which can be appreciated across the course of SZ, from
      prodromal to chronic SZ, may be the most important underlying dysfunction in preventing
      functional, occupational, and social recovery in SZ compared to other symptom domains. Sodium
      butyrate is a short chain fatty acid and binds to the zinc site of histone deacetylases
      (HDAC). The inhibition of HDAC results in histone hyperacetylation. This study aims to
      evaluate its effects on improving symptoms and functioning in SZ, and the relationship of the
      drug's clinical effects to epigenetic and inflammation related biochemical changes.

      The proposed study will be a double blind study of the effects of sodium butyrate on
      cognitive function and symptoms in chronic SZ patients showing continued cognitive
      deficits.The primary specific aims of the proposal will be to test the the MATRICS (MCCB)
      battery,delayed recall performance, and performance on real world functional tasks as
      assessed by the USCD Performance- Based Skills Assessment Battery (UPSA). In addition, we
      will also investigate whether sodium butyrate may improve other aspects of cognition.

      We will also explore whether improvement in cognition is related to change in HDAC activity
      in peripheral blood cells and changes in inflammatory makers in the blood, and assess whether
      there is any improvement in psychopathology as measured by PANSS scale.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from baseline in MATRICS Battery Score
time frame: Basline, week 6, up to 12 weeks
description: MATRICS Cognitive Battery
measure: Change from baseline in Logical Memory Test score
time frame: Basline, up to 12 weeks
description: Logical Memory Test for longer term memory
measure: Change from baseline in Positive and Negative Syndrome Scale (PANSS) total score
time frame: Basline, week 6, up to 12 weeks
description: Positive and Negative Syndrome Scale (PANSS) symptom rating scale
measure: Change from baseline in Paced Auditory Serial Addition Test (PASAT) score
time frame: Basline, week 6, up to 12 weeks
description: Alternate working memory test
measure: Change from baseline in UCSD Performance-Based Skills Assessment (UPSA) total score
time frame: Baseline, up to 12 weeks
description: University of California, San Diego (UCSD) Performance-Based Skills Assessment Battery
measure: Change from baseline in Side-Effect Scale Score
time frame: Basline, week 2, week 6, up to 12 weeks
description: Patient self-report of side-effects of active or placebo medication
arm group label: Sodium Butyrate
arm group type: Experimental
description: Dietary Supplement: Sodium Butyrate 4.38 gms of sodium butyrate per day for 12 weeks
arm group label: Placebo Oral Capsule
arm group type: Placebo Comparator
description: Placebo Oral Capsule placebo capsules containing approximately 9 mg of sodium butyrate per day
intervention type: Drug
intervention name: Sodium Butyrate
description: Sodium butyrate is being supplied by T.E. Neesby (Brain White, T.E. Neesby, Inc.) in 730 mg capsules. The company asserts that their material is 98% pure and food grade. We will have identical placebo capsules. Subjects will receive 3 capsules twice daily (morning and late afternoon or evening) for a total of 4380 mg/day.
arm group label: Sodium Butyrate
intervention type: Drug
intervention name: Placebo Oral Capsule
description: Placebo Oral Capsule is also being supplied by T.E. Neesby (Brain White, T.E. Neesby, Inc.) and there is no difference from appearance, smell and taste. It contains 1.5 mg sodium butyrate per capsule. Subjects will receive 3 capsules twice daily (morning and late afternoon or evening) for a total of 9 mg/day.
arm group label: Placebo Oral Capsule
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Chunbo Li, M.D.
role: Principal Investigator
affiliation: Shanghai Mental Health Center
facility: 
country: China
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Butyric Acid
sharing ipd: Undecided
ipd description: Stanley foundation requests: Based on the terms of your award, Stanley Medical Research Institute (SMRI) now requires submission of the individual patient data from all SMRI funded studies. In order to make the process as efficient as possible and provide a secure location for study data, National Institute of Mental Health (NIMH) is graciously allowing SMRI access to their National Database for Clinical Trials (NDCT) to collect and house data.