<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/NCT04446234</url>
  </required_header>
  <id_info>
    <org_study_id>YG2019QNB07</org_study_id>
    <nct_id>NCT04446234</nct_id>
  </id_info>
  <brief_title>Atypical Antipsychotics Influence on the Safety of the Heart and Monitoring Indicators Model Building</brief_title>
  <official_title>Atypical Antipsychotics Influence on the Safety of the Heart and Monitoring Indicators Model Building</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Mental Health Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai Jiao Tong University School of Medicine</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 study was to investigate the effect of atypical antipsychotics on cardiac&#xD;
      safety. The secondary purpose was to understand the rate of QTc prolongation in&#xD;
      electrocardiogram induced by atypical antipsychotics. And try to construct the model of&#xD;
      cardiac monitoring index. We conducted a randomized trial in which patients with&#xD;
      schizophrenia who were first on or off medication for more than two weeks took a single&#xD;
      atypical antipsychotic (Risperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine) for&#xD;
      12 weeks and monitored changes in biochemical, electrocardiogram and other indicators. And&#xD;
      then 50 patients with adverse cardiac reactions (ADRs) taking antipsychotics were selected to&#xD;
      review the data, analyze and construct a monitoring model.&#xD;
&#xD;
      We hypothesized that atypical antipsychotics with different mechanisms of action have&#xD;
      different effects on cardiac safety in patients with schizophrenia, and that they are&#xD;
      applicable to different populations. The monitoring index model can reduce the occurrence of&#xD;
      cardiotoxicity and improve the prognosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Atypical antipsychotics, also known as new antipsychotics, are a group of drugs that act on&#xD;
      the central nervous system to treat schizophrenia, psychotic disorder or bipolar disorder.&#xD;
      Compared with typical antipsychotics, atypical antipsychotics have the advantages of good&#xD;
      efficacy and fewer side effects. Therefore, currently, atypical antipsychotics are widely&#xD;
      used in clinical practice. In recent years, the effects of atypical antipsychotics on&#xD;
      metabolism and cardiovascular system have attracted more and more clinical attention. Studies&#xD;
      have found that long-term use of atypical antipsychotics can lead to arrhythmias,&#xD;
      drug-induced myocarditis, and even cardiac arrest. Since antipsychotics can cause cardiac&#xD;
      adverse events in patients with schizophrenia, accompanied by medical complications,&#xD;
      resulting in a generally shorter life span of 15-25 years compared with the general&#xD;
      population, cardiac safety assessment of drugs for patients with schizophrenia is becoming&#xD;
      increasingly important. But the domestic study of antipsychotics in the cardiovascular field,&#xD;
      especially about the safety of heart systemic evaluation are few and far between, so this&#xD;
      research has focused on patients with schizophrenia in China people use different mechanisms&#xD;
      of atypical antipsychotics (Risperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine)&#xD;
      on heart safety.&#xD;
&#xD;
      In the first stage, a total of 350 schizophrenia patients were enrolled who were either not&#xD;
      on medication for the first time or stopped for more than 2 weeks. They were treated with&#xD;
      atypical antipsychotics respectively, follow-up of 12 weeks, evaluating the effects of&#xD;
      antipsychotics on cardiac function and structure in patients with schizophrenia from general&#xD;
      data, biochemistry, electrocardiogram, etc. In the second stage, 50 patients of adverse&#xD;
      cardiac reactions caused by taking antipsychotics were selected from enrolled subjects, and a&#xD;
      retrospective analysis(day1, week4, week12, and week24) was conducted to try to build a&#xD;
      cardiac safety detection indicator model, so as to understand the impact of antipsychotics on&#xD;
      cardiac safety. More rational use of antipsychotics in the context of ensuring clinical&#xD;
      efficacy and minimum side effects, and the use of monitoring indicator models to reduce the&#xD;
      occurrence of cardiac toxicity, improve the safety of antipsychotics in use.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">May 2021</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cardiac QTc(corrected QT interval) interphase changes after drug administration.</measure>
    <time_frame>baseline, week2,4, 8, 12，24</time_frame>
    <description>Cardiac QTc interphase changes during the study duration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biochemical index： BNP(Brain Natriuretic Peptide)</measure>
    <time_frame>baseline, week2,4, 8, 12，24</time_frame>
    <description>Changes of biochemical indexes during the study duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical index：troponin</measure>
    <time_frame>baseline, week2,4, 8, 12，24</time_frame>
    <description>Changes of biochemical indexes during the study duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical index： myoglobin</measure>
    <time_frame>baseline, week2,4, 8, 12，24</time_frame>
    <description>Changes of biochemical indexes during the study duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Electrocardiogram：Heart rate</measure>
    <time_frame>baseline, week2,4, 8, 12，24</time_frame>
    <description>Changes of ECG indicators during the study duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Echocardiographic: EF(Ejection Fraction) value</measure>
    <time_frame>baseline, week2,4, 8, 12，24</time_frame>
    <description>Changes of cardiac ultrasound indicators during the study duration</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">350</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Risperidone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Risperidone tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aripiprazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aripiprazole tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ziprasidone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ziprasidone tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Amisulpride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Amisulpride tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Quetiapine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Quetiapine tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Risperidone</intervention_name>
    <description>Use medicine according to patients condition</description>
    <arm_group_label>Risperidone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aripiprazole</intervention_name>
    <description>Use medicine according to patients condition</description>
    <arm_group_label>Aripiprazole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ziprasidone</intervention_name>
    <description>Use medicine according to patients condition</description>
    <arm_group_label>Ziprasidone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amisulpride</intervention_name>
    <description>Use medicine according to patients condition</description>
    <arm_group_label>Amisulpride</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Quetiapine</intervention_name>
    <description>Use medicine according to patients condition</description>
    <arm_group_label>Quetiapine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Phase one:Effects of different types of atypical antipsychotics on cardiac safety.&#xD;
&#xD;
               1. Meet the diagnostic of &quot;schizophrenia&quot; according to DSM-IV and fail to take&#xD;
                  medication in the first episode or stop taking medication for more than 2 weeks&#xD;
&#xD;
               2. Han ethnic, 18-45 years old;&#xD;
&#xD;
               3. Exclude persons with mental disorders caused by organic diseases, drugs or&#xD;
                  alcohol, and other mental disorders, and serious suicide attempts.&#xD;
&#xD;
               4. Willing to participate in the trial and receive treatment;&#xD;
&#xD;
               5. Course of disease within 2 years;&#xD;
&#xD;
               6. Able to communicate effectively with the researcher and complete the written&#xD;
                  informed consent signed by hand.&#xD;
&#xD;
        Phase two:Construction of cardiac safety monitoring model&#xD;
&#xD;
          1. Meet the diagnostic of &quot;schizophrenia&quot; according to DSM-IV and fail to take medication&#xD;
             in the first episode or stop taking medication for more than 2 weeks&#xD;
&#xD;
          2. Han ethnic, 18-45 years old;&#xD;
&#xD;
          3. Exclude persons with mental disorders caused by organic diseases, drugs or alcohol,&#xD;
             and other mental disorders, and serious suicide attempts.&#xD;
&#xD;
          4. Willing to participate in the trial and receive treatment;&#xD;
&#xD;
          5. Serious arrhythmia, myocarditis, cardiomyopathy and cardiac insufficiency during&#xD;
             taking medicine;&#xD;
&#xD;
          6. Able to communicate effectively with the researcher and complete the written informed&#xD;
             consent signed by hand.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  (1) Participating in other clinical studies; (2) Combination of DSM-IV diagnoses other&#xD;
             than schizophrenia; (3) History of heart disease; (4) History of drug abuse in the&#xD;
             previous 6 months; (5) Pregnant or in the first three months of lactation; (6)&#xD;
             Combination of antipsychotics, mood stabilizers and antidepressants was used in the&#xD;
             study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>LV QINYU</last_name>
    <role>Principal Investigator</role>
    <affiliation>SHANGHAI MENTAL HEALTH CENTRE</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>LV QINYU</last_name>
    <phone>18017311158</phone>
    <email>18616550357@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>YI ZHENGHUI</last_name>
    <phone>18017311007</phone>
    <email>yizhenghui1971@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CHINA</name>
      <address>
        <city>Shanghai</city>
        <state>Minhang</state>
        <zip>201108</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>August 25, 2020</last_update_submitted>
  <last_update_submitted_qc>August 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Atypical antipsychotics</keyword>
  <keyword>Cardiac safety</keyword>
  <keyword>Model building</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>Risperidone</mesh_term>
    <mesh_term>Aripiprazole</mesh_term>
    <mesh_term>Quetiapine Fumarate</mesh_term>
    <mesh_term>Ziprasidone</mesh_term>
    <mesh_term>Amisulpride</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/NCT04446234
org study id: YG2019QNB07
nct id: NCT04446234
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study was to investigate the effect of atypical antipsychotics on cardiac
      safety. The secondary purpose was to understand the rate of QTc prolongation in
      electrocardiogram induced by atypical antipsychotics. And try to construct the model of
      cardiac monitoring index. We conducted a randomized trial in which patients with
      schizophrenia who were first on or off medication for more than two weeks took a single
      atypical antipsychotic (Risperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine) for
      12 weeks and monitored changes in biochemical, electrocardiogram and other indicators. And
      then 50 patients with adverse cardiac reactions (ADRs) taking antipsychotics were selected to
      review the data, analyze and construct a monitoring model.

      We hypothesized that atypical antipsychotics with different mechanisms of action have
      different effects on cardiac safety in patients with schizophrenia, and that they are
      applicable to different populations. The monitoring index model can reduce the occurrence of
      cardiotoxicity and improve the prognosis.
Atypical antipsychotics, also known as new antipsychotics, are a group of drugs that act on
      the central nervous system to treat schizophrenia, psychotic disorder or bipolar disorder.
      Compared with typical antipsychotics, atypical antipsychotics have the advantages of good
      efficacy and fewer side effects. Therefore, currently, atypical antipsychotics are widely
      used in clinical practice. In recent years, the effects of atypical antipsychotics on
      metabolism and cardiovascular system have attracted more and more clinical attention. Studies
      have found that long-term use of atypical antipsychotics can lead to arrhythmias,
      drug-induced myocarditis, and even cardiac arrest. Since antipsychotics can cause cardiac
      adverse events in patients with schizophrenia, accompanied by medical complications,
      resulting in a generally shorter life span of 15-25 years compared with the general
      population, cardiac safety assessment of drugs for patients with schizophrenia is becoming
      increasingly important. But the domestic study of antipsychotics in the cardiovascular field,
      especially about the safety of heart systemic evaluation are few and far between, so this
      research has focused on patients with schizophrenia in China people use different mechanisms
      of atypical antipsychotics (Risperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine)
      on heart safety.

      In the first stage, a total of 350 schizophrenia patients were enrolled who were either not
      on medication for the first time or stopped for more than 2 weeks. They were treated with
      atypical antipsychotics respectively, follow-up of 12 weeks, evaluating the effects of
      antipsychotics on cardiac function and structure in patients with schizophrenia from general
      data, biochemistry, electrocardiogram, etc. In the second stage, 50 patients of adverse
      cardiac reactions caused by taking antipsychotics were selected from enrolled subjects, and a
      retrospective analysis(day1, week4, week12, and week24) was conducted to try to build a
      cardiac safety detection indicator model, so as to understand the impact of antipsychotics on
      cardiac safety. More rational use of antipsychotics in the context of ensuring clinical
      efficacy and minimum side effects, and the use of monitoring indicator models to reduce the
      occurrence of cardiac toxicity, improve the safety of antipsychotics in use.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cardiac QTc(corrected QT interval) interphase changes after drug administration.
time frame: baseline, week2,4, 8, 12，24
description: Cardiac QTc interphase changes during the study duration
measure: Biochemical index： BNP(Brain Natriuretic Peptide)
time frame: baseline, week2,4, 8, 12，24
description: Changes of biochemical indexes during the study duration
measure: Biochemical index：troponin
time frame: baseline, week2,4, 8, 12，24
description: Changes of biochemical indexes during the study duration
measure: Biochemical index： myoglobin
time frame: baseline, week2,4, 8, 12，24
description: Changes of biochemical indexes during the study duration
measure: Electrocardiogram：Heart rate
time frame: baseline, week2,4, 8, 12，24
description: Changes of ECG indicators during the study duration
measure: Echocardiographic: EF(Ejection Fraction) value
time frame: baseline, week2,4, 8, 12，24
description: Changes of cardiac ultrasound indicators during the study duration
arm group label: Risperidone
arm group type: Experimental
description: Risperidone tablet
arm group label: Aripiprazole
arm group type: Experimental
description: Aripiprazole tablet
arm group label: Ziprasidone
arm group type: Experimental
description: Ziprasidone tablet
arm group label: Amisulpride
arm group type: Experimental
description: Amisulpride tablet
arm group label: Quetiapine
arm group type: Experimental
description: Quetiapine tablet
intervention type: Drug
intervention name: Risperidone
description: Use medicine according to patients condition
arm group label: Risperidone
intervention type: Drug
intervention name: Aripiprazole
description: Use medicine according to patients condition
arm group label: Aripiprazole
intervention type: Drug
intervention name: Ziprasidone
description: Use medicine according to patients condition
arm group label: Ziprasidone
intervention type: Drug
intervention name: Amisulpride
description: Use medicine according to patients condition
arm group label: Amisulpride
intervention type: Drug
intervention name: Quetiapine
description: Use medicine according to patients condition
arm group label: Quetiapine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: LV QINYU
role: Principal Investigator
affiliation: SHANGHAI MENTAL HEALTH CENTRE
last name: LV QINYU
phone: 18017311158
email: 18616550357@163.com
last name: YI ZHENGHUI
phone: 18017311007
email: yizhenghui1971@163.com
facility: 
country: China
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Risperidone
mesh term: Aripiprazole
mesh term: Quetiapine Fumarate
mesh term: Ziprasidone
mesh term: Amisulpride