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/NCT06020703</url>
    </required_header>
    <id_info>
      <org_study_id>23-005057</org_study_id>
      <nct_id>NCT06020703</nct_id>
    </id_info>
    <brief_title>A Study of Healthy Microbiome, Healthy Mind</brief_title>
    <official_title>Healthy Microbiome, Healthy Mind: Using Gut-brain Axis for Improving Psychocognitive Health Outcomes of Critical Illness Survivors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Mayo Clinic</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Mayo Clinic</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>
        Researchers are doing this study to find out if a high fermented food diet is tolerable, and&#xD;
        if it will help improve quality of life after surviving a critical illness, including severe&#xD;
        COVID-19, by promoting gut health recovery and decreasing gut inflammation.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Critical illness, including severe COVID, often lead to long term cognitive and mental health&#xD;
        complications. Current non-pharmacological interventions, including ABCDEF bundle, are of&#xD;
        limited efficacy. The largest psychological intervention trial to date also demonstrated no&#xD;
        beneficial effect. These impairments may persist for years and are associated with chronic&#xD;
        pain, impaired physical functioning, decreased quality of life, increased use of psychotropic&#xD;
        medications, opioid abuse, self-harm, and increased acute care service utilization. Half of&#xD;
        previously employed critical illness survivors, including those with long COVID, are not able&#xD;
        to return to work a year later resulting in loss of insurance and difficulty in seeking&#xD;
        professional help.&#xD;
  &#xD;
        Increasing recognition that the nervous system and the gastrointestinal tract are&#xD;
        communicating through a bidirectional network of signaling pathways, collectively known as&#xD;
        the gut-brain-axis, resulted in emergence of a novel discipline of &quot;nutritional psychiatry&quot;&#xD;
        advocating that diet and nutrition may be central determinants of both physical and mental&#xD;
        health. In the outpatient setting, fiber rich Mediterranean style diet has been linked to&#xD;
        improvements in cognitive and mood symptoms possibly via its known anti-inflammatory effect&#xD;
        whereby diets high in sugars and refined grains with high inflammatory potential have been&#xD;
        linked to the development of depression.&#xD;
  &#xD;
        Critical illness and associated interventions lead to the loss of normal gut bacteria,&#xD;
        allowing overgrowth of disease-promoting pathogenic bacteria resulting in severe dysbiosis.&#xD;
        During dysbiosis, gut-brain pathways are dysregulated resulting in neuroinflammation, anxiety&#xD;
        and depressive-like behaviors as well as cognitive impairment. Dysbiosis can persist months&#xD;
        after the resolution of critical illness. Restoration of healthy microbiome may thus be key&#xD;
        to facilitating psychiatric and cognitive recovery after critical illness.&#xD;
  &#xD;
        Can the Mediterranean diet be used to restore microbiome diversity in this population?&#xD;
        Perhaps not right away, as critical illness survivors have significant decrease in fiber&#xD;
        degrading bacterial organisms. Others demonstrated that high-fiber diet alone does not result&#xD;
        in increased microbial community diversity. What about probiotics? In patients with&#xD;
        antibiotics-associated dysbiosis, probiotics induced a persistently incomplete indigenous&#xD;
        stool microbiome recovery. How can microbiome diversity be restored? Fermented foods may be&#xD;
        the most promising approach. Consumption of fermented milk facilitated restoration of gut&#xD;
        homeostasis in patients with irritable bowel syndrome and increased their &quot;feeling good&quot;&#xD;
        scores. Other human intervention studies using fermented tea, sauerkraut, fermented plant&#xD;
        extract, kimchi, and fermented soybean milk reported increased presence of bacteria in the&#xD;
        gut known for their health promoting properties. Consumption of fermented foods was&#xD;
        associated with positive modulation in brain activity and fewer symptoms of social anxiety. A&#xD;
        10-week high fermented food diet intervention demonstrated increased microbiota diversity and&#xD;
        decreased inflammatory markers among healthy volunteers. Can it be applied to survivors of&#xD;
        critical illness including COVID to help them recover from dysbiosis and inflammation, and&#xD;
        improve their mental health and other outcomes?&#xD;
  &#xD;
        Specific Aim #1: to evaluate feasibility of high fermented food diet among critical illness&#xD;
        survivors and its effect on microbiome diversity Hypothesis 1a: critical illness survivors&#xD;
        will tolerate high fermented food diet Hypothesis 1b: high fermented food diet will increase&#xD;
        microbiome diversity in critical illness survivors.&#xD;
  &#xD;
        Specific Aim #2: to evaluate the effect of high fermented food diet on immune system&#xD;
        performance and recovery, mental health, cognition, and quality of life of critical illness&#xD;
        survivors.&#xD;
  &#xD;
        Hypothesis 2a: high fermented food diet will improve immune system performance among critical&#xD;
        illness survivors.&#xD;
  &#xD;
        Hypothesis 2b: critical illness survivors treated with fermented food diet for 3 months will&#xD;
        have a reduction in symptoms of anxiety, depression and acute stress/PTSD Hypothesis 2c:&#xD;
        critical illness survivors treated with fermented food diet for 3 months will have&#xD;
        improvement in cognition.&#xD;
  &#xD;
        Hypothesis 2c: critical illness survivors treated with fermented food diet for 3 months will&#xD;
        have improvement in quality of life.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Other</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Feasibility of high fermented food diet among critical illness survivors</measure>
      <time_frame>12 weeks</time_frame>
      <description>20 critical illness survivors assigned to the intervention arm will tolerate high fermented food diet on 75% of the study days or more</description>
    </primary_outcome>
    <primary_outcome>
      <measure>gut microbiome diversity</measure>
      <time_frame>Baseline, 12 weeks</time_frame>
      <description>assessed using Shannon index</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in inflammatory cytokines</measure>
      <time_frame>Baseline, 12 weeks</time_frame>
      <description>Targeted analyses will be performed to compare the values of inflammatory markers such as tumor necrosis factor-alpha, interleukin-2, interleukin-2 soluble receptor, interleukin-4, interleukin-5, interleukin-6, interleukin-8, interleukin-10, interleukin-12 interleukin-13, interleukin-17, interferon-gamma and interferon-1beta. All marker levels are measured in pg/ml.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Symptoms of anxiety and depression</measure>
      <time_frame>Baseline, 12 weeks</time_frame>
      <description>Measured using the self-reported Hospital Anxiety and Depression Scale (HADS). Total questions: 14. Anxiety 7, Depression 7. Each item is rated on a 4-point scale from 0 &quot;absence&quot; to 3 &quot;extreme presence&quot;. Total score is 21 per subscale: 0 - 7: Normal levels of anxiety/depression; 8-10: Borderline abnormal; &gt; 11: Abnormal</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cognitive Assessment</measure>
      <time_frame>Baseline, 12 weeks</time_frame>
      <description>Measured using the Montreal Cognitive Assessment (MoCA-BLIND). Total questions:13. Memory 3 Attention 4 Language 3 Abstraction 2 Orientation 1. Subscores for each of the 5 sections are calculated. The total score is summed from the subscores, with a maximum score of 22. A score equal &gt; 18 is considered normal cognition</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Self-Reported quality of life</measure>
      <time_frame>Baseline, 12 weeks</time_frame>
      <description>Measured using the self-reported EuroQol-5D-3L questionnaire. Total questions: 6. Mobility: 1, Self-Care: 1, Usual Activities: 1, Pain/discomfort: 1, Anxiety/depression: 1, Health State - Visual Analog Scale: 1. 3L - 3 levels of severity: no problems, some problems, extreme problems. The visual analog scale ranges from 0 to 100 with higher scores reflecting better perceived current health-related quality of life state.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>symptoms of acute stress/PTSD</measure>
      <time_frame>Baseline, 12 weeks</time_frame>
      <description>Measured using Impact of Events-revised (IES-r). Total questions: 22. Intrusion 7, Avoidance 8, Hyperarousal 7. Items are rated on a 5-point scale ranging from 0 (&quot;not at all&quot;) to 4 (&quot;extremely&quot;). Total scores are summed with higher scores indicating greater distress with regards to a specific event.&#xD;
  Orientation 1</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Critical Illness</condition>
    <condition>COVID-19</condition>
    <condition>PICS</condition>
    <condition>Cognitive Impairment</condition>
    <condition>Mental Health Impairment</condition>
    <condition>Weakness, Muscle</condition>
    <condition>Dysbiosis</condition>
    <arm_group>
      <arm_group_label>Fermented Foods Diet</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects will incorporate fermented food into their diet.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Normal Diet</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Subjects will continue their regular diet.</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Fermented Food Diet</intervention_name>
      <description>Subjects will incorporate 1 serving of fermented food a day and increase to 6 more each day as tolerated for 4 weeks. After the initial 4 weeks, subjects will eat 6 or more servings of fermented foods each day for 8 weeks.</description>
      <arm_group_label>Fermented Foods Diet</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          - Patients who survived critical illness and are at risk for mental health morbidity/long&#xD;
          COVID (spent &gt; 48 hours in the ICU or had COVID requiring ICU stay) who have a smartphone.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          - History of dementia, mental retardation, psychotic disorders such as schizophrenia,&#xD;
          patients not expected to survive the hospital stay or non-English speaking, participants&#xD;
          not able to tolerate foods by mouth or those with potential contraindications to such diet&#xD;
          (chronically immunosuppressed including organ transplant recipients; those with neutropenia&#xD;
          or currently undergoing chemotherapy, those taking Monoamine oxidase inhibitors).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Lioudmila Karnatovskaia, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Mayo Clinic</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Mayo Clinic Minnesota</name>
        <address>
          <city>Rochester</city>
          <state>Minnesota</state>
          <zip>55905</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://www.mayo.edu/research/clinical-trials</url>
      <description>Mayo Clinic Clinical Trials</description>
    </link>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Mayo Clinic</investigator_affiliation>
      <investigator_full_name>Lioudmila Karnatovskaia</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Muscle Weakness</mesh_term>
      <mesh_term>Critical Illness</mesh_term>
      <mesh_term>Dysbiosis</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/NCT06020703
  org study id: 23-005057
  nct id: NCT06020703
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Researchers are doing this study to find out if a high fermented food diet is tolerable, and
        if it will help improve quality of life after surviving a critical illness, including severe
        COVID-19, by promoting gut health recovery and decreasing gut inflammation.
  Critical illness, including severe COVID, often lead to long term cognitive and mental health
        complications. Current non-pharmacological interventions, including ABCDEF bundle, are of
        limited efficacy. The largest psychological intervention trial to date also demonstrated no
        beneficial effect. These impairments may persist for years and are associated with chronic
        pain, impaired physical functioning, decreased quality of life, increased use of psychotropic
        medications, opioid abuse, self-harm, and increased acute care service utilization. Half of
        previously employed critical illness survivors, including those with long COVID, are not able
        to return to work a year later resulting in loss of insurance and difficulty in seeking
        professional help.
  
        Increasing recognition that the nervous system and the gastrointestinal tract are
        communicating through a bidirectional network of signaling pathways, collectively known as
        the gut-brain-axis, resulted in emergence of a novel discipline of "nutritional psychiatry"
        advocating that diet and nutrition may be central determinants of both physical and mental
        health. In the outpatient setting, fiber rich Mediterranean style diet has been linked to
        improvements in cognitive and mood symptoms possibly via its known anti-inflammatory effect
        whereby diets high in sugars and refined grains with high inflammatory potential have been
        linked to the development of depression.
  
        Critical illness and associated interventions lead to the loss of normal gut bacteria,
        allowing overgrowth of disease-promoting pathogenic bacteria resulting in severe dysbiosis.
        During dysbiosis, gut-brain pathways are dysregulated resulting in neuroinflammation, anxiety
        and depressive-like behaviors as well as cognitive impairment. Dysbiosis can persist months
        after the resolution of critical illness. Restoration of healthy microbiome may thus be key
        to facilitating psychiatric and cognitive recovery after critical illness.
  
        Can the Mediterranean diet be used to restore microbiome diversity in this population?
        Perhaps not right away, as critical illness survivors have significant decrease in fiber
        degrading bacterial organisms. Others demonstrated that high-fiber diet alone does not result
        in increased microbial community diversity. What about probiotics? In patients with
        antibiotics-associated dysbiosis, probiotics induced a persistently incomplete indigenous
        stool microbiome recovery. How can microbiome diversity be restored? Fermented foods may be
        the most promising approach. Consumption of fermented milk facilitated restoration of gut
        homeostasis in patients with irritable bowel syndrome and increased their "feeling good"
        scores. Other human intervention studies using fermented tea, sauerkraut, fermented plant
        extract, kimchi, and fermented soybean milk reported increased presence of bacteria in the
        gut known for their health promoting properties. Consumption of fermented foods was
        associated with positive modulation in brain activity and fewer symptoms of social anxiety. A
        10-week high fermented food diet intervention demonstrated increased microbiota diversity and
        decreased inflammatory markers among healthy volunteers. Can it be applied to survivors of
        critical illness including COVID to help them recover from dysbiosis and inflammation, and
        improve their mental health and other outcomes?
  
        Specific Aim #1: to evaluate feasibility of high fermented food diet among critical illness
        survivors and its effect on microbiome diversity Hypothesis 1a: critical illness survivors
        will tolerate high fermented food diet Hypothesis 1b: high fermented food diet will increase
        microbiome diversity in critical illness survivors.
  
        Specific Aim #2: to evaluate the effect of high fermented food diet on immune system
        performance and recovery, mental health, cognition, and quality of life of critical illness
        survivors.
  
        Hypothesis 2a: high fermented food diet will improve immune system performance among critical
        illness survivors.
  
        Hypothesis 2b: critical illness survivors treated with fermented food diet for 3 months will
        have a reduction in symptoms of anxiety, depression and acute stress/PTSD Hypothesis 2c:
        critical illness survivors treated with fermented food diet for 3 months will have
        improvement in cognition.
  
        Hypothesis 2c: critical illness survivors treated with fermented food diet for 3 months will
        have improvement in quality of life.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Other
  masking: None (Open Label)
  measure: Feasibility of high fermented food diet among critical illness survivors
  time frame: 12 weeks
  description: 20 critical illness survivors assigned to the intervention arm will tolerate high fermented food diet on 75% of the study days or more
  measure: gut microbiome diversity
  time frame: Baseline, 12 weeks
  description: assessed using Shannon index
  measure: Change in inflammatory cytokines
  time frame: Baseline, 12 weeks
  description: Targeted analyses will be performed to compare the values of inflammatory markers such as tumor necrosis factor-alpha, interleukin-2, interleukin-2 soluble receptor, interleukin-4, interleukin-5, interleukin-6, interleukin-8, interleukin-10, interleukin-12 interleukin-13, interleukin-17, interferon-gamma and interferon-1beta. All marker levels are measured in pg/ml.
  measure: Symptoms of anxiety and depression
  time frame: Baseline, 12 weeks
  description: Measured using the self-reported Hospital Anxiety and Depression Scale (HADS). Total questions: 14. Anxiety 7, Depression 7. Each item is rated on a 4-point scale from 0 "absence" to 3 "extreme presence". Total score is 21 per subscale: 0 - 7: Normal levels of anxiety/depression; 8-10: Borderline abnormal; > 11: Abnormal
  measure: Cognitive Assessment
  time frame: Baseline, 12 weeks
  description: Measured using the Montreal Cognitive Assessment (MoCA-BLIND). Total questions:13. Memory 3 Attention 4 Language 3 Abstraction 2 Orientation 1. Subscores for each of the 5 sections are calculated. The total score is summed from the subscores, with a maximum score of 22. A score equal > 18 is considered normal cognition
  measure: Self-Reported quality of life
  time frame: Baseline, 12 weeks
  description: Measured using the self-reported EuroQol-5D-3L questionnaire. Total questions: 6. Mobility: 1, Self-Care: 1, Usual Activities: 1, Pain/discomfort: 1, Anxiety/depression: 1, Health State - Visual Analog Scale: 1. 3L - 3 levels of severity: no problems, some problems, extreme problems. The visual analog scale ranges from 0 to 100 with higher scores reflecting better perceived current health-related quality of life state.
  measure: symptoms of acute stress/PTSD
  time frame: Baseline, 12 weeks
  description: Measured using Impact of Events-revised (IES-r). Total questions: 22. Intrusion 7, Avoidance 8, Hyperarousal 7. Items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). Total scores are summed with higher scores indicating greater distress with regards to a specific event.
  Orientation 1
  arm group label: Fermented Foods Diet
  arm group type: Experimental
  description: Subjects will incorporate fermented food into their diet.
  arm group label: Normal Diet
  arm group type: No Intervention
  description: Subjects will continue their regular diet.
  intervention type: Behavioral
  intervention name: Fermented Food Diet
  description: Subjects will incorporate 1 serving of fermented food a day and increase to 6 more each day as tolerated for 4 weeks. After the initial 4 weeks, subjects will eat 6 or more servings of fermented foods each day for 8 weeks.
  arm group label: Fermented Foods Diet
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Lioudmila Karnatovskaia, MD
  role: Principal Investigator
  affiliation: Mayo Clinic
  facility: 
  country: United States
  url: https://www.mayo.edu/research/clinical-trials
  description: Mayo Clinic Clinical Trials
  responsible party type: Principal Investigator
  investigator affiliation: Mayo Clinic
  investigator full name: Lioudmila Karnatovskaia
  investigator title: Principal Investigator
  mesh term: Muscle Weakness
  mesh term: Critical Illness
  mesh term: Dysbiosis
  sharing ipd: No