<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/NCT04474860</url>
  </required_header>
  <id_info>
    <org_study_id>2018HXFH006</org_study_id>
    <nct_id>NCT04474860</nct_id>
  </id_info>
  <brief_title>Gene Mutation Spectrum of Malignant Hyperthermia in China</brief_title>
  <official_title>Study on Gene Mutation Spectrum of Malignant Hyperthermia in China Based on the Establishment of Bioinformatics Database</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>West China Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>West China Hospital</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>
      In this study, case information and specimens of patients with malignant hyperthermia(MH)&#xD;
      will be collected from all over China, and gene fragment analysis, sanger sequencing method&#xD;
      and/or high-throughput whole-genome sequencing will be performed. The MH bioinformatics&#xD;
      database will be established to find the pathogenic gene and mutation site of MH in Chinese.&#xD;
      Based on the bioinformatics database, the genetic law of MH family will be studied. According&#xD;
      to the results of the study, the guideline for the diagnosis and treatment of MH that is in&#xD;
      line with Chinese population biology characteristics will be formulated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      When MH cases or suspected cases occur in China, anesthesiologists can seek help through&#xD;
      malignant hyperthermia emergency rescue WeChat group in which experts from all over the&#xD;
      country will give therapy instructions. Afterwards, the responsible anesthesiologist will&#xD;
      complete the case report form (CRF) and collect family history of MH. The quality of CRF is&#xD;
      reviewed by the investigator and all the queries are solved within 1~2 weeks.&#xD;
&#xD;
      Upon obtaining the informed consent, all biological specimens of MH confirmed or suspected&#xD;
      patients and their blood relations will be collected in the local hospitals and transported&#xD;
      to West China Hospital, Sichuan University in dry ice packaging. All specimens will be&#xD;
      checked by the trained investigator, registered and labeled in a standardized manner, and&#xD;
      then stored in the biological sample bank of West China Hospital, Sichuan University.&#xD;
&#xD;
      Firstly, investigators will use the method of gene fragment analysis to detect the samples at&#xD;
      the diagnostic mutation sites included in the current European malignant hyperthermia group.&#xD;
      Secondly, investigators will use sanger sequencing method to verify the mutation variants. If&#xD;
      the screening results are negative, then high-throughput whole-genome sequencing will be&#xD;
      performed.&#xD;
&#xD;
      The MH bioinformatics database will be established to find the pathogenic gene and mutation&#xD;
      site of MH in Chinese. Based on the bioinformatics database, the genetic law of MH family&#xD;
      will be studied. According to the results of the study, the guideline for the diagnosis and&#xD;
      treatment of MH that is in line with Chinese population biology characteristics will be&#xD;
      formulated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Anticipated">January 2024</completion_date>
  <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Pathogenic gene and mutation site of MH in Chinese</measure>
    <time_frame>Within data collection period (5 years total)</time_frame>
    <description>Samples from patients with MH and their blood relations in China will be detected by gene fragment analysis and then verified by Sanger sequencing method and/or detected by high-throughput whole-genome sequencing to find the pathogenic gene and mutation site of MH in Chinese.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical profiles and outcomes of patients with MH in China</measure>
    <time_frame>Within data collection period (5 years total)</time_frame>
    <description>This study will summarize the Clinical profiles of patients with MH in China by collecting and analyzing case information of patients with MH from all over China.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The genetic law of MH family</measure>
    <time_frame>Within data collection period (5 years total)</time_frame>
    <description>Collecting samples from the MH patients and their blood relations and undertaking gene fragment analysis, Sanger sequencing method and/or high-throughput whole-genome sequencing, family genitive tree for MH will be then drawn.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Malignant Hyperthermia</condition>
  <arm_group>
    <arm_group_label>Malignant Hyperthermia</arm_group_label>
    <description>Samples from Chinese whose malignant hyperthermia susceptibility had been confirmed after a positive clinical manifestation of malignant hyperthermia and samples from their blood relations will receive genetic testing.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>gene sequencing</intervention_name>
    <description>Gene fragment analysis, Sanger sequencing method and/or high-throughput whole-genome sequencing will be performed to find the pathogenic gene and mutation site of MH in Chinese population.</description>
    <arm_group_label>Malignant Hyperthermia</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Clinically diagnosed MH patients in China and their blood relations&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chinese whose malignant hyperthermia susceptibility had been confirmed after a&#xD;
             positive clinical manifestation of malignant hyperthermia which defined as their&#xD;
             scores of clinical grading scale for malignant hyperthermia are more than 35 and their&#xD;
             blood relations.&#xD;
&#xD;
          -  Sign informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have no adverse anaesthetic event, such as those patients referred with a&#xD;
             history of exertional heat illness, exertional or recurrent rhabdomyolysis, or a&#xD;
             congenital myopathy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bin Liu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>West China Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yunxia Zuo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>West China Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Bin Liu, MD</last_name>
    <phone>+86 18980601540</phone>
    <email>liubinhx@foxmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jun Ma, MD</last_name>
    <phone>+86 15882167753</phone>
    <email>2711416695@qq.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>West China Hospital, Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>November 9, 2021</last_update_submitted>
  <last_update_submitted_qc>November 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>West China Hospital</investigator_affiliation>
    <investigator_full_name>Bin Liu</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Malignant Hyperthermia</keyword>
  <keyword>Gene mutation spectrum</keyword>
  <keyword>Bioinformatics database</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperthermia</mesh_term>
    <mesh_term>Fever</mesh_term>
    <mesh_term>Malignant Hyperthermia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04474860
org study id: 2018HXFH006
nct id: NCT04474860
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this study, case information and specimens of patients with malignant hyperthermia(MH)
      will be collected from all over China, and gene fragment analysis, sanger sequencing method
      and/or high-throughput whole-genome sequencing will be performed. The MH bioinformatics
      database will be established to find the pathogenic gene and mutation site of MH in Chinese.
      Based on the bioinformatics database, the genetic law of MH family will be studied. According
      to the results of the study, the guideline for the diagnosis and treatment of MH that is in
      line with Chinese population biology characteristics will be formulated.
When MH cases or suspected cases occur in China, anesthesiologists can seek help through
      malignant hyperthermia emergency rescue WeChat group in which experts from all over the
      country will give therapy instructions. Afterwards, the responsible anesthesiologist will
      complete the case report form (CRF) and collect family history of MH. The quality of CRF is
      reviewed by the investigator and all the queries are solved within 1~2 weeks.

      Upon obtaining the informed consent, all biological specimens of MH confirmed or suspected
      patients and their blood relations will be collected in the local hospitals and transported
      to West China Hospital, Sichuan University in dry ice packaging. All specimens will be
      checked by the trained investigator, registered and labeled in a standardized manner, and
      then stored in the biological sample bank of West China Hospital, Sichuan University.

      Firstly, investigators will use the method of gene fragment analysis to detect the samples at
      the diagnostic mutation sites included in the current European malignant hyperthermia group.
      Secondly, investigators will use sanger sequencing method to verify the mutation variants. If
      the screening results are negative, then high-throughput whole-genome sequencing will be
      performed.

      The MH bioinformatics database will be established to find the pathogenic gene and mutation
      site of MH in Chinese. Based on the bioinformatics database, the genetic law of MH family
      will be studied. According to the results of the study, the guideline for the diagnosis and
      treatment of MH that is in line with Chinese population biology characteristics will be
      formulated.
observational model: Cohort
time perspective: Prospective
measure: Pathogenic gene and mutation site of MH in Chinese
time frame: Within data collection period (5 years total)
description: Samples from patients with MH and their blood relations in China will be detected by gene fragment analysis and then verified by Sanger sequencing method and/or detected by high-throughput whole-genome sequencing to find the pathogenic gene and mutation site of MH in Chinese.
measure: Clinical profiles and outcomes of patients with MH in China
time frame: Within data collection period (5 years total)
description: This study will summarize the Clinical profiles of patients with MH in China by collecting and analyzing case information of patients with MH from all over China.
measure: The genetic law of MH family
time frame: Within data collection period (5 years total)
description: Collecting samples from the MH patients and their blood relations and undertaking gene fragment analysis, Sanger sequencing method and/or high-throughput whole-genome sequencing, family genitive tree for MH will be then drawn.
arm group label: Malignant Hyperthermia
description: Samples from Chinese whose malignant hyperthermia susceptibility had been confirmed after a positive clinical manifestation of malignant hyperthermia and samples from their blood relations will receive genetic testing.
intervention type: Diagnostic Test
intervention name: gene sequencing
description: Gene fragment analysis, Sanger sequencing method and/or high-throughput whole-genome sequencing will be performed to find the pathogenic gene and mutation site of MH in Chinese population.
arm group label: Malignant Hyperthermia
whole blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Bin Liu, MD
role: Principal Investigator
affiliation: West China Hospital
last name: Yunxia Zuo, MD
role: Principal Investigator
affiliation: West China Hospital
last name: Bin Liu, MD
phone: +86 18980601540
email: liubinhx@foxmail.com
last name: Jun Ma, MD
phone: +86 15882167753
email: 2711416695@qq.com
facility: 
status: Recruiting
country: China
responsible party type: Principal Investigator
investigator affiliation: West China Hospital
investigator full name: Bin Liu
investigator title: Professor
mesh term: Hyperthermia
mesh term: Fever
mesh term: Malignant Hyperthermia
sharing ipd: Undecided