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/NCT05995132</url>
    </required_header>
    <id_info>
      <org_study_id>PI22/00216</org_study_id>
      <nct_id>NCT05995132</nct_id>
    </id_info>
    <brief_title>Compromised Sleep and Circadian Health After Critical Illness: From Diagnosis to Prediction (CHRONOCRIT)</brief_title>
    <acronym>CHRONOCRIT</acronym>
    <official_title>Compromised Sleep and Circadian Health After Critical Illness: From Diagnosis to Prediction (CHRONOCRIT)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Institut de Recerca Biomèdica de Lleida</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Instituto de Salud Carlos III</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Institut de Recerca Biomèdica de Lleida</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>
        The intensive care unit (ICU) is recognizably detrimental to sleep and circadian health, and&#xD;
        critical survivors frequently report the presence of alterations in this regard after&#xD;
        hospital discharge. However, an appropriate evaluation of sleep and circadian rhythms is&#xD;
        often neglected given the high associated cost and/or the need of collaboration of the&#xD;
        patients. In this project, the investigators propose alternatives to ultimately improve the&#xD;
        management of sleep and circadian health after critical illness. The researchers will&#xD;
        evaluate the role of microRNA (miRNAs) expression profile in identifying the compromised&#xD;
        sleep and circadian health of critical patients during the ICU stay, in the short (3 months&#xD;
        after hospital discharge), and in the long-term (12 months after hospital discharge). Also,&#xD;
        models based on machine learning techniques will be developed to predict adverse outcomes in&#xD;
        this regard after hospital discharge.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The intensive care unit environment is recognizably detrimental for sleep and circadian&#xD;
        rhythms due to a plethora of factors such as the mistimed and excessive use of artificial&#xD;
        light, unusual feeding schedules, night-time noise and interruptions, events associated with&#xD;
        acute illness, among others. The reported sleep and circadian alterations often persist after&#xD;
        hospital discharge, but there is a lack of quantitative data obtained through appropriate&#xD;
        tools for the intensive care unit context, with a proper sample size, and comprising the&#xD;
        different profiles of critical patients. The investigators will address this, by evaluating&#xD;
        the prevalence of sleep and circadian alterations during the intensive care unit stay and&#xD;
        after hospital discharge in the short (3-month follow-up) and long term (12-month follow-up).&#xD;
        This will indicate the magnitude of the problem to the healthcare professionals. In the&#xD;
        sequence, the investigators will evaluate whether the expected alterations in the sleep and&#xD;
        circadian rhythms of critical survivors are associated with important factors for their&#xD;
        recovery such as quality of life, mental health, respiratory, and immune function. This is&#xD;
        especially relevant given that it will indicate possible clinical markers for compromised&#xD;
        sleep and circadian health and thereby increase the probability of patients' referral to a&#xD;
        sleep unit whenever a marker is observed.&#xD;
  &#xD;
        Despite the frequent complaints of sleep and circadian alterations among critical survivors,&#xD;
        the evaluation of sleep and circadian health within this context is often neglected due to a&#xD;
        high associated cost and/or the need of collaboration of the patients, which is not always&#xD;
        possible. This proposal aims to counteract this matter, by identifying sleep and circadian&#xD;
        alterations with the use of a non-invasive, feasible, and reliable approach. Accordingly, the&#xD;
        investigators propose to identify such alterations by evaluating the levels of miRNAs, small&#xD;
        molecules that are easily obtained through blood collection. This has the potential to&#xD;
        increase the overlooked evaluations of sleep and circadian rhythms within this context.&#xD;
        Furthermore, with a prompt identification of sleep and circadian alterations, appropriate&#xD;
        strategies can be implemented, improving the quality of life and recovery of the patients,&#xD;
        also preventing the outcomes associated with compromised sleep and circadian health in the&#xD;
        long-term. Finally, the investigators propose to predict sleep and circadian alterations by&#xD;
        integrating the information available during the intensive care unit stay with the use of&#xD;
        informatic techniques. By doing so, the pertinent management will be implemented according to&#xD;
        the needs of each patient. A proper follow-up contributes to the prompt identification of&#xD;
        problems in this regard and consequent implementation of therapeutic strategies on time,&#xD;
        potentiating the benefits of appropriate sleep and circadian health for the recovery and&#xD;
        quality of life. It is important to note that such approach has the potential to aid in&#xD;
        decreasing the time and cost-associated burden to which the healthcare system is exposed.&#xD;
  &#xD;
        For doing all this, critical patients (n = 271) will be recruited during the ICU stay. Sleep&#xD;
        and circadian rhythms will be assessed through actigraphy, and blood samples will be&#xD;
        collected for miRNAs expression profile determination. Three months after hospital discharge,&#xD;
        a clinical evaluation will be performed, followed by the assessment of the quality of life,&#xD;
        mental health, and respiratory function. Sleep and circadian rhythms will be investigated&#xD;
        through validated questionnaires and 7 consecutive days of actigraphy. Furthermore, blood&#xD;
        will be collected for miRNAs expression profile determination and immune function evaluation.&#xD;
        The same procedures will be performed 12 months after hospital discharge&#xD;
  &#xD;
        The general objective of the study is to improve the management of sleep and circadian health&#xD;
        after critical illness.&#xD;
  &#xD;
        The specific objectives are:&#xD;
  &#xD;
          1. To evaluate the sleep and circadian health of critical patients in three time-points:&#xD;
             during the intensive care unit stay, in the short-term (3 months after hospital&#xD;
             discharge), and in the long-term (12 months after hospital discharge).&#xD;
  &#xD;
          2. To evaluate possible associations between sleep and circadian health and important&#xD;
             factors for the recovery of critical survivors such as quality of life, mental health,&#xD;
             respiratory, and immune function in the short and long-term.&#xD;
  &#xD;
          3. To evaluate the role of miRNAs expression profile in identifying the compromised sleep&#xD;
             and circadian health of critical patients during the intensive care unit stay, in the&#xD;
             short, and in the long-term.&#xD;
  &#xD;
          4. To identify possible biological events underlying the compromised sleep and circadian&#xD;
             health of critical patients during the intensive care unit stay, in the short, and in&#xD;
             the long-term.&#xD;
  &#xD;
          5. To develop models to predict the compromised sleep and circadian health of critical&#xD;
             survivors in the short and long-term.&#xD;
  &#xD;
          6. To establish a cohort of critical survivors with available information related to sleep&#xD;
             and circadian health to further explore this unravelled research field.&#xD;
  &#xD;
          7. To validate the findings in an independent cohort outside Europe.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">December 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>Sleep efficiency</measure>
      <time_frame>12-month follow-up</time_frame>
      <description>The sleep health of critical patients will be evaluated using this parameter, which will be obtained through 7 days of actigraphy at the 3- and 12-month follow-up. Sleep efficiency is defined as the ratio between total sleep time and the time spent in bed. The following cut-offs are used: i) sleep efficiency ≥ 85% (represents good sleep quality), ii) sleep efficiency &lt;85% (represents inappropriate sleep quality).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Circadian function index (CFI)</measure>
      <time_frame>12-month follow-up</time_frame>
      <description>The circadian health of critical patients will be evaluated using this parameter, which will be obtained through 7 days of actigraphy at the 3- and 12-month follow-up. The circadian function index is defined as the average of intradaily variability, interdaily stability, and relative amplitude of the rhythm. There are no specific cut-offs for this parameter. The circadian function index values range from 0-1, in which 1 represents an appropriate circadian function.</description>
    </primary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">271</enrollment>
    <condition>Circadian Dysregulation</condition>
    <condition>Sleep Fragmentation</condition>
    <arm_group>
      <arm_group_label>Intensive care unit</arm_group_label>
      <description>This group will be composed of patients admitted to the intensive care unit who did not receive invasive mechanical ventilation.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Intensive care unit and invasive mechanical ventilation</arm_group_label>
      <description>This group will be composed of patients admitted to the intensive care unit who did receive invasive mechanical ventilation.</description>
    </arm_group>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        -  2 Tubes EDTA (6ml)&#xD;
  &#xD;
          -  1 tempus RNS tube (2,5 ml)&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Critical patients admited to the intensive care unit of the Hospital Arnau de Vilanova de&#xD;
          Lleida who meet the eligibility criteria.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Being older than 18 years old.&#xD;
  &#xD;
            -  Intensive care unit admission.&#xD;
  &#xD;
            -  Intensive care unit stay ≥7 days.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Transference to another hospital during hospitalization or follow-up.&#xD;
  &#xD;
            -  Mental or physical disability that could prevent the proposed evaluations.&#xD;
  &#xD;
            -  Palliative care&#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>Adriano Targa Dias Santos, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Institut de Recerca Biomèdica de Lleida</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Adriano Targa Dias Santos, PhD</last_name>
      <phone>+34 973702491</phone>
      <email>adrianotargads@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>David de Gonzalo Calvo, PhD</last_name>
      <phone>+34 973702491</phone>
      <email>dgonzalo@irblleida.cat</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Institut de Recerca Biomèdica de Lleida</investigator_affiliation>
      <investigator_full_name>Adriano Targa</investigator_full_name>
      <investigator_title>PhD</investigator_title>
    </responsible_party>
    <keyword>microRNA</keyword>
    <keyword>circadian rhythms</keyword>
    <keyword>intensive care unit</keyword>
    <keyword>sleep</keyword>
    <keyword>critical survivors</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Sleep Deprivation</mesh_term>
      <mesh_term>Chronobiology Disorders</mesh_term>
      <mesh_term>Critical Illness</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/NCT05995132
  org study id: PI22/00216
  nct id: NCT05995132
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  The intensive care unit (ICU) is recognizably detrimental to sleep and circadian health, and
        critical survivors frequently report the presence of alterations in this regard after
        hospital discharge. However, an appropriate evaluation of sleep and circadian rhythms is
        often neglected given the high associated cost and/or the need of collaboration of the
        patients. In this project, the investigators propose alternatives to ultimately improve the
        management of sleep and circadian health after critical illness. The researchers will
        evaluate the role of microRNA (miRNAs) expression profile in identifying the compromised
        sleep and circadian health of critical patients during the ICU stay, in the short (3 months
        after hospital discharge), and in the long-term (12 months after hospital discharge). Also,
        models based on machine learning techniques will be developed to predict adverse outcomes in
        this regard after hospital discharge.
  The intensive care unit environment is recognizably detrimental for sleep and circadian
        rhythms due to a plethora of factors such as the mistimed and excessive use of artificial
        light, unusual feeding schedules, night-time noise and interruptions, events associated with
        acute illness, among others. The reported sleep and circadian alterations often persist after
        hospital discharge, but there is a lack of quantitative data obtained through appropriate
        tools for the intensive care unit context, with a proper sample size, and comprising the
        different profiles of critical patients. The investigators will address this, by evaluating
        the prevalence of sleep and circadian alterations during the intensive care unit stay and
        after hospital discharge in the short (3-month follow-up) and long term (12-month follow-up).
        This will indicate the magnitude of the problem to the healthcare professionals. In the
        sequence, the investigators will evaluate whether the expected alterations in the sleep and
        circadian rhythms of critical survivors are associated with important factors for their
        recovery such as quality of life, mental health, respiratory, and immune function. This is
        especially relevant given that it will indicate possible clinical markers for compromised
        sleep and circadian health and thereby increase the probability of patients' referral to a
        sleep unit whenever a marker is observed.
  
        Despite the frequent complaints of sleep and circadian alterations among critical survivors,
        the evaluation of sleep and circadian health within this context is often neglected due to a
        high associated cost and/or the need of collaboration of the patients, which is not always
        possible. This proposal aims to counteract this matter, by identifying sleep and circadian
        alterations with the use of a non-invasive, feasible, and reliable approach. Accordingly, the
        investigators propose to identify such alterations by evaluating the levels of miRNAs, small
        molecules that are easily obtained through blood collection. This has the potential to
        increase the overlooked evaluations of sleep and circadian rhythms within this context.
        Furthermore, with a prompt identification of sleep and circadian alterations, appropriate
        strategies can be implemented, improving the quality of life and recovery of the patients,
        also preventing the outcomes associated with compromised sleep and circadian health in the
        long-term. Finally, the investigators propose to predict sleep and circadian alterations by
        integrating the information available during the intensive care unit stay with the use of
        informatic techniques. By doing so, the pertinent management will be implemented according to
        the needs of each patient. A proper follow-up contributes to the prompt identification of
        problems in this regard and consequent implementation of therapeutic strategies on time,
        potentiating the benefits of appropriate sleep and circadian health for the recovery and
        quality of life. It is important to note that such approach has the potential to aid in
        decreasing the time and cost-associated burden to which the healthcare system is exposed.
  
        For doing all this, critical patients (n = 271) will be recruited during the ICU stay. Sleep
        and circadian rhythms will be assessed through actigraphy, and blood samples will be
        collected for miRNAs expression profile determination. Three months after hospital discharge,
        a clinical evaluation will be performed, followed by the assessment of the quality of life,
        mental health, and respiratory function. Sleep and circadian rhythms will be investigated
        through validated questionnaires and 7 consecutive days of actigraphy. Furthermore, blood
        will be collected for miRNAs expression profile determination and immune function evaluation.
        The same procedures will be performed 12 months after hospital discharge
  
        The general objective of the study is to improve the management of sleep and circadian health
        after critical illness.
  
        The specific objectives are:
  
          1. To evaluate the sleep and circadian health of critical patients in three time-points:
             during the intensive care unit stay, in the short-term (3 months after hospital
             discharge), and in the long-term (12 months after hospital discharge).
  
          2. To evaluate possible associations between sleep and circadian health and important
             factors for the recovery of critical survivors such as quality of life, mental health,
             respiratory, and immune function in the short and long-term.
  
          3. To evaluate the role of miRNAs expression profile in identifying the compromised sleep
             and circadian health of critical patients during the intensive care unit stay, in the
             short, and in the long-term.
  
          4. To identify possible biological events underlying the compromised sleep and circadian
             health of critical patients during the intensive care unit stay, in the short, and in
             the long-term.
  
          5. To develop models to predict the compromised sleep and circadian health of critical
             survivors in the short and long-term.
  
          6. To establish a cohort of critical survivors with available information related to sleep
             and circadian health to further explore this unravelled research field.
  
          7. To validate the findings in an independent cohort outside Europe.
  observational model: Cohort
  time perspective: Prospective
  measure: Sleep efficiency
  time frame: 12-month follow-up
  description: The sleep health of critical patients will be evaluated using this parameter, which will be obtained through 7 days of actigraphy at the 3- and 12-month follow-up. Sleep efficiency is defined as the ratio between total sleep time and the time spent in bed. The following cut-offs are used: i) sleep efficiency ≥ 85% (represents good sleep quality), ii) sleep efficiency <85% (represents inappropriate sleep quality).
  measure: Circadian function index (CFI)
  time frame: 12-month follow-up
  description: The circadian health of critical patients will be evaluated using this parameter, which will be obtained through 7 days of actigraphy at the 3- and 12-month follow-up. The circadian function index is defined as the average of intradaily variability, interdaily stability, and relative amplitude of the rhythm. There are no specific cut-offs for this parameter. The circadian function index values range from 0-1, in which 1 represents an appropriate circadian function.
  arm group label: Intensive care unit
  description: This group will be composed of patients admitted to the intensive care unit who did not receive invasive mechanical ventilation.
  arm group label: Intensive care unit and invasive mechanical ventilation
  description: This group will be composed of patients admitted to the intensive care unit who did receive invasive mechanical ventilation.
  -  2 Tubes EDTA (6ml)
  
          -  1 tempus RNS tube (2,5 ml)
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Adriano Targa Dias Santos, PhD
  role: Principal Investigator
  affiliation: Institut de Recerca Biomèdica de Lleida
  last name: Adriano Targa Dias Santos, PhD
  phone: +34 973702491
  email: adrianotargads@gmail.com
  last name: David de Gonzalo Calvo, PhD
  phone: +34 973702491
  email: dgonzalo@irblleida.cat
  responsible party type: Principal Investigator
  investigator affiliation: Institut de Recerca Biomèdica de Lleida
  investigator full name: Adriano Targa
  investigator title: PhD
  mesh term: Sleep Deprivation
  mesh term: Chronobiology Disorders
  mesh term: Critical Illness
  sharing ipd: No