xml: <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/NCT05967910</url>
    </required_header>
    <id_info>
      <org_study_id>XYEYY2023052602</org_study_id>
      <nct_id>NCT05967910</nct_id>
    </id_info>
    <brief_title>The Effect of Chronic Stress on Efficacy of ICIs in Esophageal Cancer Patients (STRESS-ESCA Study)</brief_title>
    <acronym>STRESS-ESCA</acronym>
    <official_title>The Effect of Chronic Stress on Efficacy of Immune Checkpoint Inhibitors in Patients With Newly Diagnosed Esophageal Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Second Xiangya Hospital of Central South University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Changsha Central Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Second Xiangya Hospital of Central South University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Chronic stress refers to a special emotional state caused by unexpected stress for a long&#xD;
        time, with an increasing incidence in the population. It can cause the body to release&#xD;
        hormones such as cortisol and adrenaline. Tumor patients often experience changes such as&#xD;
        psychological and emotional abnormalities, decreased quality of life, and impaired social&#xD;
        relationships. Under stimulation, patients often experience negative reactions such as&#xD;
        anxiety or depression. Epidemiological studies have shown that stress can affect the&#xD;
        prognosis of malignant tumors, but the effect of stress on the efficacy and prognosis of&#xD;
        esophageal cancer is still unclear.&#xD;
  &#xD;
        In animal models, chronic stress leads to an increase in tissue catecholamine levels,&#xD;
        increased tumor burden, and increased invasiveness of ovarian cancer cells in mouse models.&#xD;
        At the same time, stress can promote tumor neovascularization in mice. However, the mechanism&#xD;
        by which chronic stress affects the occurrence and development of esophageal cancer is&#xD;
        currently unclear. In addition to neurohumoral factors, chronic stress can cause changes in&#xD;
        the gut microbiota, which in turn affects the body's digestion, metabolism, and immune&#xD;
        function. It is a key gatekeeper of the immune response to tumors. Therefore, gut microbiota&#xD;
        as an intermediate factor may also affect the occurrence and prognosis of various types of&#xD;
        esophageal cancer.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">May 1, 2026</primary_completion_date>
    <study_type>Observational [Patient Registry]</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>
    <target_duration>5 Years</target_duration>
    <primary_outcome>
      <measure>Objective Response Rate (ORR)</measure>
      <time_frame>3 years</time_frame>
      <description>The proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>3 years</time_frame>
      <description>Time from the beginning of first-line immunotherapy to the first progression(PD) in patients with advanced esophageal cancer</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Effect of Chronic stress on efficacy of immune checkpoint inhibitors</measure>
      <time_frame>3 years</time_frame>
      <description>The chronic stress status including depression and anxiety symptoms.We will use two types of questionnaires, Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), as a whole to conduct a comprehensive psychological assessment of patients. And then evaluate the impact of chronic stress status on the efficacy of immune checkpoint inhibitors, including ORR, PFS, and OS.&#xD;
  PHQ-9 has 9 items, each on a scale of 0 to 3. The sum score (range 0 to 27) indicates the degree of depression, with scores of 5, 10, 15, and 20 represent mild, moderate, moderate to severe and severe levels of depression.&#xD;
  GAD-7 has 7 items, each on a scale of 0 to 3. Higher total scores (ranging from 0 to 21) indicate higher anxious symptoms with 5 to 9 classified as mild, 10 to 14 classified as moderate, and 15 to 21 classified as moderate-severe.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>5 years</time_frame>
      <description>Overall survival (OS) is defined as the duration from the beginning of first-line immunotherapy until death due to any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of chronic stress on quality of life</measure>
      <time_frame>5 years</time_frame>
      <description>Chronic stress status including depression and anxiety symptoms.We will use Short Form Health Survey 36 (SF-36) and EORTC QLQ-C30 (version. 3) questionnaires as a whole to evaluate the quality of life of patients.&#xD;
  SF-36 includes 36 items and assesses the functional status and well-being on eight multi-item subscales. The total score on each SF-36 subscale ranges between 0 and 100. A greater score indicates better QoL.&#xD;
  The EORTC QLQ-C30 is composed of 9 multi-item scales: 5 functioning scales (physical, role, cognitive, emotional, and social), a global QOL scale, and 3 symptom scales (fatigue, pain, and nausea/vomiting). All scales and single items are linearly transformed to an 0-100 scale. A higher score represents a better level of functioning.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>The correlation between gut microbiota and chronic stress and the efficacy of ICIs</measure>
      <time_frame>5 years</time_frame>
      <description>The baseline fetal is collected and assessed by 16S rRNA sequencing. We will measure the abundance of gut microbiota such as Bacteroides, Lactobacillus, and Ackermann's bacteria through 16s RNA sequencing. And expose the association between gut microbiota and chronic stress (PHQ-9 and GAD-7) and the efficacy of ICIs (ORR, PFS, and OS) during the enrolled observation process through correlation analysis.</description>
    </other_outcome>
    <other_outcome>
      <measure>The correlation between tumor microenvironment signature and chronic stress and the efficacy of ICIs</measure>
      <time_frame>5 years</time_frame>
      <description>The baseline paraffin-embedded tissue is collected and assessed by multiplex immunohistochemistry, including T lymphocytes, B lymphocytes, NK lymphocytes, macrophagocyte, and DC cells. And explore the association between tumor microenvironment signature and chronic stress (PHQ-9 and GAD-7) and the efficacy of ICIs (ORR, PFS, and OS) during the enrolled observation process through correlation analysis.</description>
    </other_outcome>
    <other_outcome>
      <measure>The correlation between peripheral immune cells signature and chronic stress and the efficacy of ICIs</measure>
      <time_frame>5 years</time_frame>
      <description>The baseline peripheral venous blood is collected and assessed by flow cytometry, including T lymphocytes, B lymphocytes, NK lymphocytes, macrophagocyte, and DC cells. And explore the association between peripheral immune cells signature signature and chronic stress (PHQ-9 and GAD-7) and the efficacy of ICIs (ORR, PFS, and OS) during the enrolled observation process through correlation analysis.</description>
    </other_outcome>
    <number_of_groups>4</number_of_groups>
    <enrollment type="Anticipated">200</enrollment>
    <condition>Small Cell Lung Cancer</condition>
    <condition>Immunotherapy</condition>
    <arm_group>
      <arm_group_label>Early esophageal cancer patients with chronic psychological stress</arm_group_label>
    </arm_group>
    <arm_group>
      <arm_group_label>Early esophageal cancer patients without chronic psychological stress</arm_group_label>
    </arm_group>
    <arm_group>
      <arm_group_label>Advanced esophageal cancer patients with chronic psychological stress</arm_group_label>
    </arm_group>
    <arm_group>
      <arm_group_label>Advanced esophageal cancer patients without chronic psychological stress</arm_group_label>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>chronic psychological stress</intervention_name>
      <description>Chronic psychological stress includes symptoms of anxiety and depression.</description>
      <arm_group_label>Advanced esophageal cancer patients with chronic psychological stress</arm_group_label>
      <arm_group_label>Early esophageal cancer patients with chronic psychological stress</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          200 cases of esophageal cancer patient are required and is divided into two groups: the&#xD;
          experimental group (stress group) and the control group (non stress group) within each&#xD;
          early and late stage group.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥18 years and ≤ 75 years old&#xD;
  &#xD;
            2. Pathologically diagnosed as esophageal cancer&#xD;
  &#xD;
            3. Patient tumor tissue samples can be obtained&#xD;
  &#xD;
            4. At least one measurable lesion can be evaluated according to the RECIST 1.1 standard&#xD;
  &#xD;
            5. As a newly treated patient, they have not received systematic anti-tumor treatment for&#xD;
               locally advanced or metastatic chest tumors&#xD;
  &#xD;
            6. There is no obvious abnormality in the electrocardiogram and no obvious cardiac&#xD;
               dysfunction&#xD;
  &#xD;
            7. Hematology and liver and kidney function indicators meet the requirements&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Merge with other malignant tumors&#xD;
  &#xD;
            2. Long term use of hormones or immunosuppressants&#xD;
  &#xD;
            3. Concomitant acute or chronic mental illness&#xD;
  &#xD;
            4. Patients who have been taking drugs that can alter the activity of the sympathetic&#xD;
               nervous system for a long time or are currently taking them&#xD;
  &#xD;
            5. Other malignant diseases that require systematic treatment&#xD;
  &#xD;
            6. Patients who have undergone other clinical drug experiments before&#xD;
  &#xD;
            7. Patients with symptomatic brain metastases&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Fang Wu, MD.PhD</last_name>
      <phone>+86 135744858332</phone>
      <email>wufang4461@csu.edu.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Department of Oncology, The Second Xiangya Hospital, 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>Fang Wu, MD, PhD</last_name>
        <phone>+86 13574858332</phone>
        <email>wufang4461@csu.edu.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>May 24, 2023</study_first_submitted>
    <study_first_submitted_qc>July 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 22, 2023</last_update_submitted>
    <last_update_submitted_qc>July 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Second Xiangya Hospital of Central South University</investigator_affiliation>
      <investigator_full_name>Fang Wu</investigator_full_name>
      <investigator_title>chief physician</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Esophageal Neoplasms</mesh_term>
      <mesh_term>Small Cell Lung Carcinoma</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05967910
  org study id: XYEYY2023052602
  nct id: NCT05967910
  lead sponsor: 
  collaborator: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  Chronic stress refers to a special emotional state caused by unexpected stress for a long
        time, with an increasing incidence in the population. It can cause the body to release
        hormones such as cortisol and adrenaline. Tumor patients often experience changes such as
        psychological and emotional abnormalities, decreased quality of life, and impaired social
        relationships. Under stimulation, patients often experience negative reactions such as
        anxiety or depression. Epidemiological studies have shown that stress can affect the
        prognosis of malignant tumors, but the effect of stress on the efficacy and prognosis of
        esophageal cancer is still unclear.
  
        In animal models, chronic stress leads to an increase in tissue catecholamine levels,
        increased tumor burden, and increased invasiveness of ovarian cancer cells in mouse models.
        At the same time, stress can promote tumor neovascularization in mice. However, the mechanism
        by which chronic stress affects the occurrence and development of esophageal cancer is
        currently unclear. In addition to neurohumoral factors, chronic stress can cause changes in
        the gut microbiota, which in turn affects the body's digestion, metabolism, and immune
        function. It is a key gatekeeper of the immune response to tumors. Therefore, gut microbiota
        as an intermediate factor may also affect the occurrence and prognosis of various types of
        esophageal cancer.
  observational model: Cohort
  time perspective: Prospective
  measure: Objective Response Rate (ORR)
  time frame: 3 years
  description: The proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
  measure: Progression-free survival (PFS)
  time frame: 3 years
  description: Time from the beginning of first-line immunotherapy to the first progression(PD) in patients with advanced esophageal cancer
  measure: Effect of Chronic stress on efficacy of immune checkpoint inhibitors
  time frame: 3 years
  description: The chronic stress status including depression and anxiety symptoms.We will use two types of questionnaires, Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), as a whole to conduct a comprehensive psychological assessment of patients. And then evaluate the impact of chronic stress status on the efficacy of immune checkpoint inhibitors, including ORR, PFS, and OS.
  PHQ-9 has 9 items, each on a scale of 0 to 3. The sum score (range 0 to 27) indicates the degree of depression, with scores of 5, 10, 15, and 20 represent mild, moderate, moderate to severe and severe levels of depression.
  GAD-7 has 7 items, each on a scale of 0 to 3. Higher total scores (ranging from 0 to 21) indicate higher anxious symptoms with 5 to 9 classified as mild, 10 to 14 classified as moderate, and 15 to 21 classified as moderate-severe.
  measure: Overall survival (OS)
  time frame: 5 years
  description: Overall survival (OS) is defined as the duration from the beginning of first-line immunotherapy until death due to any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status.
  measure: Effect of chronic stress on quality of life
  time frame: 5 years
  description: Chronic stress status including depression and anxiety symptoms.We will use Short Form Health Survey 36 (SF-36) and EORTC QLQ-C30 (version. 3) questionnaires as a whole to evaluate the quality of life of patients.
  SF-36 includes 36 items and assesses the functional status and well-being on eight multi-item subscales. The total score on each SF-36 subscale ranges between 0 and 100. A greater score indicates better QoL.
  The EORTC QLQ-C30 is composed of 9 multi-item scales: 5 functioning scales (physical, role, cognitive, emotional, and social), a global QOL scale, and 3 symptom scales (fatigue, pain, and nausea/vomiting). All scales and single items are linearly transformed to an 0-100 scale. A higher score represents a better level of functioning.
  measure: The correlation between gut microbiota and chronic stress and the efficacy of ICIs
  time frame: 5 years
  description: The baseline fetal is collected and assessed by 16S rRNA sequencing. We will measure the abundance of gut microbiota such as Bacteroides, Lactobacillus, and Ackermann's bacteria through 16s RNA sequencing. And expose the association between gut microbiota and chronic stress (PHQ-9 and GAD-7) and the efficacy of ICIs (ORR, PFS, and OS) during the enrolled observation process through correlation analysis.
  measure: The correlation between tumor microenvironment signature and chronic stress and the efficacy of ICIs
  time frame: 5 years
  description: The baseline paraffin-embedded tissue is collected and assessed by multiplex immunohistochemistry, including T lymphocytes, B lymphocytes, NK lymphocytes, macrophagocyte, and DC cells. And explore the association between tumor microenvironment signature and chronic stress (PHQ-9 and GAD-7) and the efficacy of ICIs (ORR, PFS, and OS) during the enrolled observation process through correlation analysis.
  measure: The correlation between peripheral immune cells signature and chronic stress and the efficacy of ICIs
  time frame: 5 years
  description: The baseline peripheral venous blood is collected and assessed by flow cytometry, including T lymphocytes, B lymphocytes, NK lymphocytes, macrophagocyte, and DC cells. And explore the association between peripheral immune cells signature signature and chronic stress (PHQ-9 and GAD-7) and the efficacy of ICIs (ORR, PFS, and OS) during the enrolled observation process through correlation analysis.
  arm group label: Early esophageal cancer patients with chronic psychological stress
  arm group label: Early esophageal cancer patients without chronic psychological stress
  arm group label: Advanced esophageal cancer patients with chronic psychological stress
  arm group label: Advanced esophageal cancer patients without chronic psychological stress
  intervention type: Other
  intervention name: chronic psychological stress
  description: Chronic psychological stress includes symptoms of anxiety and depression.
  arm group label: Advanced esophageal cancer patients with chronic psychological stress
  arm group label: Early esophageal cancer patients with chronic psychological stress
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Fang Wu, MD.PhD
  phone: +86 135744858332
  email: wufang4461@csu.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Second Xiangya Hospital of Central South University
  investigator full name: Fang Wu
  investigator title: chief physician
  mesh term: Esophageal Neoplasms
  mesh term: Small Cell Lung Carcinoma
  sharing ipd: No