<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/NCT04443075</url>
  </required_header>
  <id_info>
    <org_study_id>XJTU1AF2020LSK-022</org_study_id>
    <nct_id>NCT04443075</nct_id>
  </id_info>
  <brief_title>Alterations of Gut Microbiome in the Frontline Medical Staff Under the Stress</brief_title>
  <acronym>AGMFMSS</acronym>
  <official_title>Alterations of Gut Microbiome in the Frontline Medical Staff Under the Stress of Fighting Against 2019-nCoV</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First Affiliated Hospital Xi'an Jiaotong University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>First Affiliated Hospital Xi'an Jiaotong 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      With the outbreak of 2019 novel coronavirus (2019-nCoV), the frontline medical workers faced&#xD;
      enormous stress, including a high risk of infection and inadequate protection from&#xD;
      contamination, isolation, patients with negative emotions, a lack of contact with their&#xD;
      families, and exhaustion, which may cause mental health problems. The investigators plan to&#xD;
      collect the faecal samples and clinical assessments from a part of frontline medical workers&#xD;
      in three time points to analyse the changing profile of gut microbiome according to outcomes&#xD;
      of 16s rRNA sequencing. The samples from the matched health controls will also be sequenced&#xD;
      to compare with the exposed group in gut microbiome community.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In December, 2019, a novel coronavirus outbreak of pneumonia emerged in Wuhan, Hubei&#xD;
      province, China, and has subsequently spread to more than 30 provinces in China and almost&#xD;
      100 countries in the world. In the fight against the 2019 novel coronavirus (2019-nCoV),&#xD;
      medical workers in Wuhan have been facing enormous stress, including a high risk of infection&#xD;
      and inadequate protection from contamination, isolation, patients with negative emotions, a&#xD;
      lack of contact with their families, and exhaustion. The severe situation is causing mental&#xD;
      health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger, and&#xD;
      fear. These mental health problems could also cause posttraumatic stress (PTS) symptoms in a&#xD;
      lasting time. A research examining the psychological impact of the 2003 outbreak of severe&#xD;
      acute respiratory syndrome on hospital empoyees found that about 10% of the respondents had&#xD;
      experienced high leves of PTS symptoms since the SARS outbreak.&#xD;
&#xD;
      Microbiome-gut-brain (MGB) axis has been validated in expanding studies, which means there&#xD;
      are bidirectional communication between commensal organisms within the gut and the brain. Gut&#xD;
      microbiota may influence brain function through neural, endocrine, and immune pathways. For&#xD;
      example, substances produced by the gut microbiota may be absorbed reaching the brain by the&#xD;
      blood stream. The brain, in turn, may influence the gut microbiota trough neuronal and&#xD;
      endocrine pathways. In recent years, many reseaches support the relevance of microbiota and&#xD;
      mental health status. Bercik et al. transplanted microbiota from adult germ-free (GF) BALB/c&#xD;
      mice (a high-anxiety mouse strain) into adult GF NIH Swiss mice (a low-anxiety mouse strain),&#xD;
      then found the behavioral profile of the donor was evident in the recipient animal, showing&#xD;
      that the microbiota can directly affect behavior. Moreover, preclinical studies have shown&#xD;
      that stress and emotions, including maternal separation and restraint, heat, and acoustic&#xD;
      stress, alters the composition of the gut microbiota, maybe through the release of stress&#xD;
      hormones or sympathetic neurotransmitters that influence gut physiology and alter the habitat&#xD;
      of the microbiota. In addition, researchers found that stress has the ability to increase&#xD;
      intestinal permeability, probably through the involvement of corticotrophin releasing factor&#xD;
      and its receptors (CRFR1 and CRFR2), which play a key role in stress-induced gut permeability&#xD;
      dysfunction. Increased intestinal permeability provides bacteria an opportunity to&#xD;
      translocate across the intestinal mucosa and directly access both the immune and neuronal&#xD;
      cells of the enteric nervous system (ENS). Stress also activates the autonomic nervous&#xD;
      system, which affects gastric acid, bile, and mucus secretion, as well as gut motility. Gut&#xD;
      motility is of particular importance since it is strongly associated with gut microbiota&#xD;
      composition and richness. Based on these researches, the gut microbiome increasingly deserve&#xD;
      attention to understand psychiatric disorders.&#xD;
&#xD;
      Therefore, the present study aim to collect the faecal samples and clinical assessments from&#xD;
      a part of frontline medical workers in three time points to analyse the changing profile of&#xD;
      gut microbiome according to outcomes of 16s rRNA sequencing. The samples from the matched&#xD;
      health controls will also be sequenced to compare with the exposed group in gut microbiome&#xD;
      community.&#xD;
&#xD;
      Methods Study design and sample collection The frontline workers in First Affiliated Hospital&#xD;
      of Xi'an Jiaotong University will be included if they conformed with (1) taking part in the&#xD;
      medical team to support Wuhan, (2) of 18 to 50 years old, (3) did not take antibiotics within&#xD;
      3 months before sample collection, (4) 17.5&lt;body mass index (BMI)&lt;30. The healthy controls&#xD;
      will be selected from the staffs in First Affiliated Hospital who didn't join in the medical&#xD;
      team but fulfill the last three conditions above to match with the frontline staffs for age,&#xD;
      gender, BMI, and diet. Any participant will be excluded if he/she fulfill the following&#xD;
      criteria: (1) have serious cardiovascular disease, blood disease, and endocrine disease, (2)&#xD;
      have a history of cancer or its complications, (3) have active gastrointestinal diseases or&#xD;
      complications and serious systemic diseases, (4) have history of brain organic diseases or&#xD;
      complications and mental retardation, (5) have mental disorders such as mood disorder and&#xD;
      anxiety disorders, (6) pregnant or lactating, (7) drink in the past week (liquor&gt;250ml or&#xD;
      beer&gt;1bottle) or the previous day (liquor&gt;50ml or beer&gt;50ml). All included persons should&#xD;
      provide signed informed consent before sample collection, and the protocol was approved by&#xD;
      the Ethics Committee of First Affiliated Hospital of Xi'an Jiaotong University&#xD;
      (KYLLSL-2020-043). Faecal samples from each staff should be freshly collected at the hospital&#xD;
      and frozen at -80℃ using specified faecal collector.&#xD;
&#xD;
      Clinical assessmant PHQ-15, PHQ-9, GAD-7, PSQI, SCL-90, and IES-R will be used for the&#xD;
      assessment of clinical symptoms related to psychiatric disorder for exposed group in three&#xD;
      time point and non-exposed group.&#xD;
&#xD;
      DNA extraction and 16S rRNA sequencing The investigators will perform 16S rRNA sequencing for&#xD;
      all the collected faecal samples. Briefly, bacterial genomic DNA will be extracted, and the&#xD;
      16S rRNA whole region will be amplified by PCR, and then sequenced.&#xD;
&#xD;
      Statistical analysis The 16S rRNA sequencing data will be analysed using Quantitative&#xD;
      Insights Into Microbial Ecology (QIIME). The investigators then use usearch to cluster&#xD;
      sequences into taxonomic units (OTUs) at 97% identity and construct the OTU table. Microbial&#xD;
      community structure, alpha diversity, and beta diversity will be analysed. LEfSe analysis,&#xD;
      and random forest analysis will be used to find the biomarker between different group.&#xD;
      Spearman's rank correlation will be used to identify the corrolation between clinical&#xD;
      assessments and stress-associated microbiome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 24, 2020</start_date>
  <completion_date type="Actual">December 24, 2020</completion_date>
  <primary_completion_date type="Actual">December 4, 2020</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>Gut microbiome composition of exposed group</measure>
    <time_frame>immediately after the frontline workers come back to Xi'an</time_frame>
    <description>Gut microbiome composition will be anaylysed using 16S rRNA sequencing.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gut microbiome composition of exposed group</measure>
    <time_frame>immediately after the frontline workers isolated for two weeks</time_frame>
    <description>Gut microbiome composition will be anaylysed using 16S rRNA sequencing.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gut microbiome composition of exposed group</measure>
    <time_frame>immediately after the frontline workers going back to normal work for one month</time_frame>
    <description>Gut microbiome composition will be anaylysed using 16S rRNA sequencing.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gut microbiome composition of non-exposed group</measure>
    <time_frame>During the procedure of collecting faecal samples from exposed group</time_frame>
    <description>Gut microbiome composition will be anaylysed using 16S rRNA sequencing.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Impact of Event Scale-Revised (IES-R) of exposed group</measure>
    <time_frame>immediately after the frontline workers come back to Xi'an</time_frame>
    <description>It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Impact of Event Scale-Revised (IES-R) of exposed group</measure>
    <time_frame>immediately after the frontline workers isolated for two weeks</time_frame>
    <description>It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Impact of Event Scale-Revised (IES-R) of exposed group</measure>
    <time_frame>immediately after the frontline workers going back to normal work for one month</time_frame>
    <description>It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Impact of Event Scale-Revised (IES-R) of non-exposed group</measure>
    <time_frame>During the procedure of collecting faecal samples from non-exposed group</time_frame>
    <description>It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The 15-item Patient Health Questionnaire (PHQ-15) of exposed group</measure>
    <time_frame>immediately after the frontline workers come back to Xi'an</time_frame>
    <description>It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 15-item Patient Health Questionnaire (PHQ-15) of exposed group</measure>
    <time_frame>immediately after the frontline workers isolated for two weeks</time_frame>
    <description>It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 15-item Patient Health Questionnaire (PHQ-15) of exposed group</measure>
    <time_frame>immediately after the frontline workers going back to normal work for one month</time_frame>
    <description>It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 15-item Patient Health Questionnaire-15 (PHQ-15) of non-exposed group</measure>
    <time_frame>During the procedure of collecting faecal samples from non-exposed group</time_frame>
    <description>It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 9-item Patient Health Questionnaire (PHQ-9) of exposed group</measure>
    <time_frame>immediately after the frontline workers come back to Xi'an</time_frame>
    <description>It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 9-item Patient Health Questionnaire (PHQ-9) of exposed group</measure>
    <time_frame>immediately after the frontline workers isolated for two weeks</time_frame>
    <description>It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 9-item Patient Health Questionnaire (PHQ-9) of exposed group</measure>
    <time_frame>immediately after the frontline workers going back to normal work for one month</time_frame>
    <description>It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 9-item Patient Health Questionnaire (PHQ-9) of non-exposed group</measure>
    <time_frame>During the procedure of collecting faecal samples from non-exposed group</time_frame>
    <description>It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 7-item Generalized Anxiety Disorder Scale (GAD-7) of exposed group</measure>
    <time_frame>immediately after the frontline workers come back to Xi'an</time_frame>
    <description>It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 7-item Generalized Anxiety Disorder Scale (GAD-7) of exposed group</measure>
    <time_frame>immediately after the frontline workers isolated for two weeks</time_frame>
    <description>It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 7-item Generalized Anxiety Disorder Scale (GAD-7) of exposed group</measure>
    <time_frame>immediately after the frontline workers going back to normal work for one month</time_frame>
    <description>It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 7-item Generalized Anxiety Disorder Scale (GAD-7) of non-exposed group</measure>
    <time_frame>During the procedure of collecting faecal samples from non-exposed group</time_frame>
    <description>It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Pittsburgh Sleep Quality Index (PSQI) of exposed group</measure>
    <time_frame>immediately after the frontline workers come back to Xi'an</time_frame>
    <description>It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Pittsburgh Sleep Quality Index (PSQI) of exposed group</measure>
    <time_frame>immediately after the frontline workers isolated for two weeks</time_frame>
    <description>It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Pittsburgh Sleep Quality Index (PSQI) of exposed group</measure>
    <time_frame>immediately after the frontline workers going back to normal work for one month</time_frame>
    <description>It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Pittsburgh Sleep Quality Index (PSQI) of non-exposed group</measure>
    <time_frame>During the procedure of collecting faecal samples from non-exposed group</time_frame>
    <description>It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Symptom Check List 90 (SCL-90) of exposed group</measure>
    <time_frame>immediately after the frontline workers come back to Xi'an</time_frame>
    <description>It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Symptom Check List 90 (SCL-90) of exposed group</measure>
    <time_frame>immediately after the frontline workers isolated for two weeks</time_frame>
    <description>It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Symptom Check List 90 (SCL-90) of exposed group</measure>
    <time_frame>immediately after the frontline workers going back to normal work for one month</time_frame>
    <description>It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Symptom Check List 90 (SCL-90) of non-exposed group</measure>
    <time_frame>During the procedure of collecting faecal samples from non-exposed group</time_frame>
    <description>It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">180</enrollment>
  <condition>Stress Disorders, Post-Traumatic</condition>
  <arm_group>
    <arm_group_label>exposed group</arm_group_label>
    <description>The exposed group consists of the frontline medical workers who take part in the medical team to support Wuhan.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-exposed group</arm_group_label>
    <description>This group includs medical workers who didn't join in the medical team to support Wuhan.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>faecal sample collector</intervention_name>
    <description>The frontline medical workers mainly exposed under the stress of fighting against 2019-nCoV</description>
    <arm_group_label>exposed group</arm_group_label>
    <arm_group_label>non-exposed group</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Gut microbiome DNA in faecal samples from included subjects will be extracted and sequnced&#xD;
      for the statistical analysis.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        They are all medical staff in First Affiliated Hospital of Xi'an Jiaotong University&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  taking part in the medical team to support Wuhan&#xD;
&#xD;
          -  of 18 to 50 years old&#xD;
&#xD;
          -  did not take antibiotics within 3 months before sample collection&#xD;
&#xD;
          -  17.5&lt;body mass index (BMI)&lt;30&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  have serious cardiovascular disease, blood disease, and endocrine disease&#xD;
&#xD;
          -  have a history of cancer or its complications&#xD;
&#xD;
          -  have active gastrointestinal diseases or complications and serious systemic diseases&#xD;
&#xD;
          -  have history of brain organic diseases or complications and mental retardation&#xD;
&#xD;
          -  have mental disorders such as mood disorder and anxiety disorders&#xD;
&#xD;
          -  pregnant or lactating&#xD;
&#xD;
          -  drink in the past week (liquor&gt;250ml or beer&gt;1bottle) or the previous day (liquor&gt;50ml&#xD;
             or beer&gt;50ml)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiancang Ma, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>First Affiliated Hospital Xi'an Jiaotong University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>First Affiliated Hospital of Xian Jiaotong University</name>
      <address>
        <city>Xi'an</city>
        <state>Shaanxi</state>
        <zip>710061</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020 Feb 15;395(10223):470-473. doi: 10.1016/S0140-6736(20)30185-9. Epub 2020 Jan 24. No abstract available. Erratum In: Lancet. 2020 Jan 29;:</citation>
    <PMID>31986257</PMID>
  </reference>
  <reference>
    <citation>Kang L, Li Y, Hu S, Chen M, Yang C, Yang BX, Wang Y, Hu J, Lai J, Ma X, Chen J, Guan L, Wang G, Ma H, Liu Z. The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus. Lancet Psychiatry. 2020 Mar;7(3):e14. doi: 10.1016/S2215-0366(20)30047-X. Epub 2020 Feb 5. No abstract available.</citation>
    <PMID>32035030</PMID>
  </reference>
  <reference>
    <citation>Malan-Muller S, Valles-Colomer M, Raes J, Lowry CA, Seedat S, Hemmings SMJ. The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders. OMICS. 2018 Feb;22(2):90-107. doi: 10.1089/omi.2017.0077. Epub 2017 Aug 2.</citation>
    <PMID>28767318</PMID>
  </reference>
  <reference>
    <citation>Foster JA, McVey Neufeld KA. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013 May;36(5):305-12. doi: 10.1016/j.tins.2013.01.005. Epub 2013 Feb 4.</citation>
    <PMID>23384445</PMID>
  </reference>
  <reference>
    <citation>Wu P, Fang Y, Guan Z, Fan B, Kong J, Yao Z, Liu X, Fuller CJ, Susser E, Lu J, Hoven CW. The psychological impact of the SARS epidemic on hospital employees in China: exposure, risk perception, and altruistic acceptance of risk. Can J Psychiatry. 2009 May;54(5):302-11. doi: 10.1177/070674370905400504.</citation>
    <PMID>19497162</PMID>
  </reference>
  <reference>
    <citation>Rieder R, Wisniewski PJ, Alderman BL, Campbell SC. Microbes and mental health: A review. Brain Behav Immun. 2017 Nov;66:9-17. doi: 10.1016/j.bbi.2017.01.016. Epub 2017 Jan 25.</citation>
    <PMID>28131791</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>March 2, 2021</last_update_submitted>
  <last_update_submitted_qc>March 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stress Disorders, Post-Traumatic</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/NCT04443075
org study id: XJTU1AF2020LSK-022
nct id: NCT04443075
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
With the outbreak of 2019 novel coronavirus (2019-nCoV), the frontline medical workers faced
      enormous stress, including a high risk of infection and inadequate protection from
      contamination, isolation, patients with negative emotions, a lack of contact with their
      families, and exhaustion, which may cause mental health problems. The investigators plan to
      collect the faecal samples and clinical assessments from a part of frontline medical workers
      in three time points to analyse the changing profile of gut microbiome according to outcomes
      of 16s rRNA sequencing. The samples from the matched health controls will also be sequenced
      to compare with the exposed group in gut microbiome community.
In December, 2019, a novel coronavirus outbreak of pneumonia emerged in Wuhan, Hubei
      province, China, and has subsequently spread to more than 30 provinces in China and almost
      100 countries in the world. In the fight against the 2019 novel coronavirus (2019-nCoV),
      medical workers in Wuhan have been facing enormous stress, including a high risk of infection
      and inadequate protection from contamination, isolation, patients with negative emotions, a
      lack of contact with their families, and exhaustion. The severe situation is causing mental
      health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger, and
      fear. These mental health problems could also cause posttraumatic stress (PTS) symptoms in a
      lasting time. A research examining the psychological impact of the 2003 outbreak of severe
      acute respiratory syndrome on hospital empoyees found that about 10% of the respondents had
      experienced high leves of PTS symptoms since the SARS outbreak.

      Microbiome-gut-brain (MGB) axis has been validated in expanding studies, which means there
      are bidirectional communication between commensal organisms within the gut and the brain. Gut
      microbiota may influence brain function through neural, endocrine, and immune pathways. For
      example, substances produced by the gut microbiota may be absorbed reaching the brain by the
      blood stream. The brain, in turn, may influence the gut microbiota trough neuronal and
      endocrine pathways. In recent years, many reseaches support the relevance of microbiota and
      mental health status. Bercik et al. transplanted microbiota from adult germ-free (GF) BALB/c
      mice (a high-anxiety mouse strain) into adult GF NIH Swiss mice (a low-anxiety mouse strain),
      then found the behavioral profile of the donor was evident in the recipient animal, showing
      that the microbiota can directly affect behavior. Moreover, preclinical studies have shown
      that stress and emotions, including maternal separation and restraint, heat, and acoustic
      stress, alters the composition of the gut microbiota, maybe through the release of stress
      hormones or sympathetic neurotransmitters that influence gut physiology and alter the habitat
      of the microbiota. In addition, researchers found that stress has the ability to increase
      intestinal permeability, probably through the involvement of corticotrophin releasing factor
      and its receptors (CRFR1 and CRFR2), which play a key role in stress-induced gut permeability
      dysfunction. Increased intestinal permeability provides bacteria an opportunity to
      translocate across the intestinal mucosa and directly access both the immune and neuronal
      cells of the enteric nervous system (ENS). Stress also activates the autonomic nervous
      system, which affects gastric acid, bile, and mucus secretion, as well as gut motility. Gut
      motility is of particular importance since it is strongly associated with gut microbiota
      composition and richness. Based on these researches, the gut microbiome increasingly deserve
      attention to understand psychiatric disorders.

      Therefore, the present study aim to collect the faecal samples and clinical assessments from
      a part of frontline medical workers in three time points to analyse the changing profile of
      gut microbiome according to outcomes of 16s rRNA sequencing. The samples from the matched
      health controls will also be sequenced to compare with the exposed group in gut microbiome
      community.

      Methods Study design and sample collection The frontline workers in First Affiliated Hospital
      of Xi'an Jiaotong University will be included if they conformed with (1) taking part in the
      medical team to support Wuhan, (2) of 18 to 50 years old, (3) did not take antibiotics within
      3 months before sample collection, (4) 17.5<body mass index (BMI)<30. The healthy controls
      will be selected from the staffs in First Affiliated Hospital who didn't join in the medical
      team but fulfill the last three conditions above to match with the frontline staffs for age,
      gender, BMI, and diet. Any participant will be excluded if he/she fulfill the following
      criteria: (1) have serious cardiovascular disease, blood disease, and endocrine disease, (2)
      have a history of cancer or its complications, (3) have active gastrointestinal diseases or
      complications and serious systemic diseases, (4) have history of brain organic diseases or
      complications and mental retardation, (5) have mental disorders such as mood disorder and
      anxiety disorders, (6) pregnant or lactating, (7) drink in the past week (liquor>250ml or
      beer>1bottle) or the previous day (liquor>50ml or beer>50ml). All included persons should
      provide signed informed consent before sample collection, and the protocol was approved by
      the Ethics Committee of First Affiliated Hospital of Xi'an Jiaotong University
      (KYLLSL-2020-043). Faecal samples from each staff should be freshly collected at the hospital
      and frozen at -80℃ using specified faecal collector.

      Clinical assessmant PHQ-15, PHQ-9, GAD-7, PSQI, SCL-90, and IES-R will be used for the
      assessment of clinical symptoms related to psychiatric disorder for exposed group in three
      time point and non-exposed group.

      DNA extraction and 16S rRNA sequencing The investigators will perform 16S rRNA sequencing for
      all the collected faecal samples. Briefly, bacterial genomic DNA will be extracted, and the
      16S rRNA whole region will be amplified by PCR, and then sequenced.

      Statistical analysis The 16S rRNA sequencing data will be analysed using Quantitative
      Insights Into Microbial Ecology (QIIME). The investigators then use usearch to cluster
      sequences into taxonomic units (OTUs) at 97% identity and construct the OTU table. Microbial
      community structure, alpha diversity, and beta diversity will be analysed. LEfSe analysis,
      and random forest analysis will be used to find the biomarker between different group.
      Spearman's rank correlation will be used to identify the corrolation between clinical
      assessments and stress-associated microbiome.
observational model: Cohort
time perspective: Prospective
measure: Gut microbiome composition of exposed group
time frame: immediately after the frontline workers come back to Xi'an
description: Gut microbiome composition will be anaylysed using 16S rRNA sequencing.
measure: Gut microbiome composition of exposed group
time frame: immediately after the frontline workers isolated for two weeks
description: Gut microbiome composition will be anaylysed using 16S rRNA sequencing.
measure: Gut microbiome composition of exposed group
time frame: immediately after the frontline workers going back to normal work for one month
description: Gut microbiome composition will be anaylysed using 16S rRNA sequencing.
measure: Gut microbiome composition of non-exposed group
time frame: During the procedure of collecting faecal samples from exposed group
description: Gut microbiome composition will be anaylysed using 16S rRNA sequencing.
measure: The Impact of Event Scale-Revised (IES-R) of exposed group
time frame: immediately after the frontline workers come back to Xi'an
description: It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome
measure: The Impact of Event Scale-Revised (IES-R) of exposed group
time frame: immediately after the frontline workers isolated for two weeks
description: It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome
measure: The Impact of Event Scale-Revised (IES-R) of exposed group
time frame: immediately after the frontline workers going back to normal work for one month
description: It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome
measure: The Impact of Event Scale-Revised (IES-R) of non-exposed group
time frame: During the procedure of collecting faecal samples from non-exposed group
description: It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome
measure: The 15-item Patient Health Questionnaire (PHQ-15) of exposed group
time frame: immediately after the frontline workers come back to Xi'an
description: It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.
measure: The 15-item Patient Health Questionnaire (PHQ-15) of exposed group
time frame: immediately after the frontline workers isolated for two weeks
description: It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.
measure: The 15-item Patient Health Questionnaire (PHQ-15) of exposed group
time frame: immediately after the frontline workers going back to normal work for one month
description: It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.
measure: The 15-item Patient Health Questionnaire-15 (PHQ-15) of non-exposed group
time frame: During the procedure of collecting faecal samples from non-exposed group
description: It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.
measure: The 9-item Patient Health Questionnaire (PHQ-9) of exposed group
time frame: immediately after the frontline workers come back to Xi'an
description: It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.
measure: The 9-item Patient Health Questionnaire (PHQ-9) of exposed group
time frame: immediately after the frontline workers isolated for two weeks
description: It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.
measure: The 9-item Patient Health Questionnaire (PHQ-9) of exposed group
time frame: immediately after the frontline workers going back to normal work for one month
description: It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.
measure: The 9-item Patient Health Questionnaire (PHQ-9) of non-exposed group
time frame: During the procedure of collecting faecal samples from non-exposed group
description: It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.
measure: The 7-item Generalized Anxiety Disorder Scale (GAD-7) of exposed group
time frame: immediately after the frontline workers come back to Xi'an
description: It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.
measure: The 7-item Generalized Anxiety Disorder Scale (GAD-7) of exposed group
time frame: immediately after the frontline workers isolated for two weeks
description: It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.
measure: The 7-item Generalized Anxiety Disorder Scale (GAD-7) of exposed group
time frame: immediately after the frontline workers going back to normal work for one month
description: It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.
measure: The 7-item Generalized Anxiety Disorder Scale (GAD-7) of non-exposed group
time frame: During the procedure of collecting faecal samples from non-exposed group
description: It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.
measure: The Pittsburgh Sleep Quality Index (PSQI) of exposed group
time frame: immediately after the frontline workers come back to Xi'an
description: It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome
measure: The Pittsburgh Sleep Quality Index (PSQI) of exposed group
time frame: immediately after the frontline workers isolated for two weeks
description: It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome
measure: The Pittsburgh Sleep Quality Index (PSQI) of exposed group
time frame: immediately after the frontline workers going back to normal work for one month
description: It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome
measure: The Pittsburgh Sleep Quality Index (PSQI) of non-exposed group
time frame: During the procedure of collecting faecal samples from non-exposed group
description: It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome
measure: The Symptom Check List 90 (SCL-90) of exposed group
time frame: immediately after the frontline workers come back to Xi'an
description: It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.
measure: The Symptom Check List 90 (SCL-90) of exposed group
time frame: immediately after the frontline workers isolated for two weeks
description: It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.
measure: The Symptom Check List 90 (SCL-90) of exposed group
time frame: immediately after the frontline workers going back to normal work for one month
description: It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.
measure: The Symptom Check List 90 (SCL-90) of non-exposed group
time frame: During the procedure of collecting faecal samples from non-exposed group
description: It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.
arm group label: exposed group
description: The exposed group consists of the frontline medical workers who take part in the medical team to support Wuhan.
arm group label: non-exposed group
description: This group includs medical workers who didn't join in the medical team to support Wuhan.
intervention type: Device
intervention name: faecal sample collector
description: The frontline medical workers mainly exposed under the stress of fighting against 2019-nCoV
arm group label: exposed group
arm group label: non-exposed group
Gut microbiome DNA in faecal samples from included subjects will be extracted and sequnced
      for the statistical analysis.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Xiancang Ma, M.D.
role: Principal Investigator
affiliation: First Affiliated Hospital Xi'an Jiaotong University
facility: 
country: China
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PMID: 31986257
citation: Kang L, Li Y, Hu S, Chen M, Yang C, Yang BX, Wang Y, Hu J, Lai J, Ma X, Chen J, Guan L, Wang G, Ma H, Liu Z. The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus. Lancet Psychiatry. 2020 Mar;7(3):e14. doi: 10.1016/S2215-0366(20)30047-X. Epub 2020 Feb 5. No abstract available.
PMID: 32035030
citation: Malan-Muller S, Valles-Colomer M, Raes J, Lowry CA, Seedat S, Hemmings SMJ. The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders. OMICS. 2018 Feb;22(2):90-107. doi: 10.1089/omi.2017.0077. Epub 2017 Aug 2.
PMID: 28767318
citation: Foster JA, McVey Neufeld KA. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013 May;36(5):305-12. doi: 10.1016/j.tins.2013.01.005. Epub 2013 Feb 4.
PMID: 23384445
citation: Wu P, Fang Y, Guan Z, Fan B, Kong J, Yao Z, Liu X, Fuller CJ, Susser E, Lu J, Hoven CW. The psychological impact of the SARS epidemic on hospital employees in China: exposure, risk perception, and altruistic acceptance of risk. Can J Psychiatry. 2009 May;54(5):302-11. doi: 10.1177/070674370905400504.
PMID: 19497162
citation: Rieder R, Wisniewski PJ, Alderman BL, Campbell SC. Microbes and mental health: A review. Brain Behav Immun. 2017 Nov;66:9-17. doi: 10.1016/j.bbi.2017.01.016. Epub 2017 Jan 25.
PMID: 28131791
responsible party type: Sponsor
mesh term: Stress Disorders, Post-Traumatic
sharing ipd: Undecided