<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/NCT03271866</url>
  </required_header>
  <id_info>
    <org_study_id>WU201708MET</org_study_id>
    <nct_id>NCT03271866</nct_id>
  </id_info>
  <brief_title>Metformin Treatment on Cognitive Impairment of Schizophrenia Co-morbid Metabolic Syndrome</brief_title>
  <official_title>The Effect of Metformin Treatment on Cognitive Impairment in Patients With Schizophrenia Co-morbid Metabolic Syndrome: a Prospective Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Central South University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Central South University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, the investigators will investigate the impact and the related mechanism of&#xD;
      metformin treatment on cognitive impairment of schizophrenia with a high risk of metabolic&#xD;
      syndrome. Patients will be randomized to the metformin group or non-metformin control group&#xD;
      (40 patients per arm) for 24 weeks. Clinical assessment will be done at screen/baseline, 4&#xD;
      weeks, 12 weeks, and 24 weeks. The specific aims are to compare the metformin group versus&#xD;
      controls on 1) clinical core symptoms; 2) cognition. Biological samples also will be&#xD;
      collected, and stored to research related mechanisms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, the investigators will investigate the impact and the related mechanism of&#xD;
      metformin treatment on cognitive impairment of schizophrenia with a high risk of metabolic&#xD;
      syndrome. Patients will be randomized to the metformin group or non-metformin control group&#xD;
      (40 patients per arm) . Clinical assessment will be done at screen/baseline, 4 week, 12 week&#xD;
      and 24 week. The specific aims are to compare the metformin group versus controls on: 1)&#xD;
      clinical core symptoms; 2) cognition. Biological samples also will be collected, and stored&#xD;
      to research related mechanisms. Clinical symptoms will be measured by the Positive and&#xD;
      Negative Syndrome Scale and Calgary Depression Scale for Schizophrenia (Chinese version).&#xD;
      Cognitive function will be assessed by the MATRICS Consensus Cognitive Battery.&#xD;
&#xD;
      The investigators hypothesize that 1) metformin may improve the cognitive impairment of&#xD;
      schizophrenia patients; 2) metformin may alter oxidative stress indexes or inflammatory&#xD;
      biomarkers thus influencing the oxidative and inflammatory mechanism, and the structure and&#xD;
      function of the hippocampus that may be significantly associated with cognitive function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 28, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Two groups were observed longitudinally for 24 weeks.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cognitive improvement will be assessed using the MATRICS Consensus Cognitive Battery (MCCB) composite score</measure>
    <time_frame>12 weeks</time_frame>
    <description>The investigators will use the MATRICS Consensus Cognitive Battery (MCCB) Composite score as primary cognitive outcome measure before and after treatment at different follow up point.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of clinical symptoms by PANSS</measure>
    <time_frame>12 weeks</time_frame>
    <description>The change of Positive And Negative Syndrome Scale (PANSS) total, positive and negative symptoms before and after treatment at different follow up point.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Depression by CDSS-C</measure>
    <time_frame>12 weeks</time_frame>
    <description>The investigators will assess depression by Calgary Depression Scale for Schizophrenia （Chinese version, CDSS-C）</description>
  </other_outcome>
  <other_outcome>
    <measure>Biological markers will be measured by ELISA</measure>
    <time_frame>12 weeks</time_frame>
    <description>The oxidative stress indexes and inflammatory biomarkers will measured by Enzyme-linked Immuno Sorbent Assay (ELISA).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>metformin treatment</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>non-metformin treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>metformin</intervention_name>
    <description>metformin 1500mg per day</description>
    <arm_group_label>metformin treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Meet the Diagnostic and Statistical Manual (DSM-5) diagnostic criteria for&#xD;
             schizophrenia;&#xD;
&#xD;
          2. Duration of illness less than 5 years with current symptoms exacerbation;&#xD;
&#xD;
          3. Male and female aged 18 to 65 years;&#xD;
&#xD;
          4. PANSS total score &lt; 60 and CDSS-C total score &lt; 6;&#xD;
&#xD;
          5. Signed the study consent for participation;&#xD;
&#xD;
          6. Patients with higher risk factors for MetS, or patients who gained weight &gt; 10% of&#xD;
             their pre-drug weight within the first year after antipsychotic medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Having a history of substance dependence or abuse or whose symptoms are caused by&#xD;
             other diagnosable mental disorders;&#xD;
&#xD;
          2. Having a history of traumatic brain injury, seizures, or other known neurological or&#xD;
             organic diseases of the central nervous system;&#xD;
&#xD;
          3. Taking antidepressants, stimulants, mood stabilizers or accepting electricity shock&#xD;
             treatment;&#xD;
&#xD;
          4. Having current suicidal or homicidal thoughts or any safety concern by research staff&#xD;
             that cannot be managed in an inpatient setting;&#xD;
&#xD;
          5. The routine blood tests showing abnormal renal, and liver function;&#xD;
&#xD;
          6. Pregnant or lactating women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tiannan Shao, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Central South University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dongyu Kang, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Central South University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Renrong Wu, M.D., Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Central South University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tiannan Shao, M.D., Ph.D.</last_name>
    <phone>+86 13341318057</phone>
    <email>shaostndoc@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>The Second Xiangya Hospital of Central South University</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410011</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tiannan Shao, M.D., Ph.D.</last_name>
      <phone>+86 13341318057</phone>
      <email>shaostndoc@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Renrong Wu, M.D., Ph.D.</last_name>
      <email>wurenrong2013@163.com</email>
    </contact_backup>
    <investigator>
      <last_name>Dongyu Kang, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Lindenmayer JP, Khan A, Kaushik S, Thanju A, Praveen R, Hoffman L, Cherath L, Valdez G, Wance D. Relationship between metabolic syndrome and cognition in patients with schizophrenia. Schizophr Res. 2012 Dec;142(1-3):171-6. doi: 10.1016/j.schres.2012.09.019. Epub 2012 Oct 26.</citation>
    <PMID>23106932</PMID>
  </reference>
  <reference>
    <citation>Bora E, Akdede BB, Alptekin K. The relationship between cognitive impairment in schizophrenia and metabolic syndrome: a systematic review and meta-analysis. Psychol Med. 2017 Apr;47(6):1030-1040. doi: 10.1017/S0033291716003366. Epub 2016 Dec 29. Erratum In: Psychol Med. 2018 May;48(7):1224.</citation>
    <PMID>28032535</PMID>
  </reference>
  <reference>
    <citation>Ying MA, Maruschak N, Mansur R, Carvalho AF, Cha DS, McIntyre RS. Metformin: repurposing opportunities for cognitive and mood dysfunction. CNS Neurol Disord Drug Targets. 2014;13(10):1836-45. doi: 10.2174/1871527313666141130205514.</citation>
    <PMID>25470390</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>April 8, 2023</last_update_submitted>
  <last_update_submitted_qc>April 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Central South University</investigator_affiliation>
    <investigator_full_name>Renrong Wu</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Schizophrenia</keyword>
  <keyword>Metabolic syndrome</keyword>
  <keyword>Metformin</keyword>
  <keyword>Cognitive impairment</keyword>
  <keyword>Clinical trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03271866
org study id: WU201708MET
nct id: NCT03271866
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
In this study, the investigators will investigate the impact and the related mechanism of
      metformin treatment on cognitive impairment of schizophrenia with a high risk of metabolic
      syndrome. Patients will be randomized to the metformin group or non-metformin control group
      (40 patients per arm) for 24 weeks. Clinical assessment will be done at screen/baseline, 4
      weeks, 12 weeks, and 24 weeks. The specific aims are to compare the metformin group versus
      controls on 1) clinical core symptoms; 2) cognition. Biological samples also will be
      collected, and stored to research related mechanisms.
In this study, the investigators will investigate the impact and the related mechanism of
      metformin treatment on cognitive impairment of schizophrenia with a high risk of metabolic
      syndrome. Patients will be randomized to the metformin group or non-metformin control group
      (40 patients per arm) . Clinical assessment will be done at screen/baseline, 4 week, 12 week
      and 24 week. The specific aims are to compare the metformin group versus controls on: 1)
      clinical core symptoms; 2) cognition. Biological samples also will be collected, and stored
      to research related mechanisms. Clinical symptoms will be measured by the Positive and
      Negative Syndrome Scale and Calgary Depression Scale for Schizophrenia (Chinese version).
      Cognitive function will be assessed by the MATRICS Consensus Cognitive Battery.

      The investigators hypothesize that 1) metformin may improve the cognitive impairment of
      schizophrenia patients; 2) metformin may alter oxidative stress indexes or inflammatory
      biomarkers thus influencing the oxidative and inflammatory mechanism, and the structure and
      function of the hippocampus that may be significantly associated with cognitive function.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Two groups were observed longitudinally for 24 weeks.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Cognitive improvement will be assessed using the MATRICS Consensus Cognitive Battery (MCCB) composite score
time frame: 12 weeks
description: The investigators will use the MATRICS Consensus Cognitive Battery (MCCB) Composite score as primary cognitive outcome measure before and after treatment at different follow up point.
measure: Change of clinical symptoms by PANSS
time frame: 12 weeks
description: The change of Positive And Negative Syndrome Scale (PANSS) total, positive and negative symptoms before and after treatment at different follow up point.
measure: Depression by CDSS-C
time frame: 12 weeks
description: The investigators will assess depression by Calgary Depression Scale for Schizophrenia （Chinese version, CDSS-C）
measure: Biological markers will be measured by ELISA
time frame: 12 weeks
description: The oxidative stress indexes and inflammatory biomarkers will measured by Enzyme-linked Immuno Sorbent Assay (ELISA).
arm group label: metformin treatment
arm group type: Other
arm group label: non-metformin treatment
arm group type: No Intervention
intervention type: Drug
intervention name: metformin
description: metformin 1500mg per day
arm group label: metformin treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Tiannan Shao, M.D., Ph.D.
role: Principal Investigator
affiliation: Central South University
last name: Dongyu Kang, M.D.
role: Principal Investigator
affiliation: Central South University
last name: Renrong Wu, M.D., Ph.D.
role: Study Chair
affiliation: Central South University
last name: Tiannan Shao, M.D., Ph.D.
phone: +86 13341318057
email: shaostndoc@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
citation: Lindenmayer JP, Khan A, Kaushik S, Thanju A, Praveen R, Hoffman L, Cherath L, Valdez G, Wance D. Relationship between metabolic syndrome and cognition in patients with schizophrenia. Schizophr Res. 2012 Dec;142(1-3):171-6. doi: 10.1016/j.schres.2012.09.019. Epub 2012 Oct 26.
PMID: 23106932
citation: Bora E, Akdede BB, Alptekin K. The relationship between cognitive impairment in schizophrenia and metabolic syndrome: a systematic review and meta-analysis. Psychol Med. 2017 Apr;47(6):1030-1040. doi: 10.1017/S0033291716003366. Epub 2016 Dec 29. Erratum In: Psychol Med. 2018 May;48(7):1224.
PMID: 28032535
citation: Ying MA, Maruschak N, Mansur R, Carvalho AF, Cha DS, McIntyre RS. Metformin: repurposing opportunities for cognitive and mood dysfunction. CNS Neurol Disord Drug Targets. 2014;13(10):1836-45. doi: 10.2174/1871527313666141130205514.
PMID: 25470390
responsible party type: Principal Investigator
investigator affiliation: Central South University
investigator full name: Renrong Wu
investigator title: Professor
mesh term: Metabolic Syndrome
mesh term: Schizophrenia
mesh term: Cognitive Dysfunction
mesh term: Metformin