<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/NCT03805685</url>
  </required_header>
  <id_info>
    <org_study_id>Lifestyle-Delirium</org_study_id>
    <nct_id>NCT03805685</nct_id>
  </id_info>
  <brief_title>Preoperative Risk Factors and Perioperative Neurocognitive Disorders</brief_title>
  <official_title>The Influence of Preoperative Risk Factors on Perioperative Neurocognitive Disorders in Patients Scheduled for Non-cardiac Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Université Libre de Bruxelles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>CHU de Charleroi</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Université Libre de Bruxelles</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>
      Perioperative neurocognitive disorders (PND's) remain an important complication after&#xD;
      surgery. After many years of speculating about the etiology of this complication, currently&#xD;
      studies are pointing to an inflammatory cascade being set in motion.&#xD;
&#xD;
      This prospective study is designed to examine preoperative lifestyle factors (such as&#xD;
      sedentary behavior) associated with postoperative cognitive impairment in a group of patients&#xD;
      undergoing non-cardiac surgery.&#xD;
&#xD;
      The objectives in our study are to:&#xD;
&#xD;
      identify perioperative risk factors for the development of PND's measure the incidence and&#xD;
      duration of perioperative neurocognitive disorders in a known high-risk group of elective&#xD;
      surgical patients measure a peripheral inflammatory marker (interleukin 6: IL-6) in the same&#xD;
      group of surgical patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Perioperative neurocognitive disorders remain an important complication after surgery. After&#xD;
      many years of speculating about the etiology of this complication, currently studies are&#xD;
      pointing to an inflammatory cascade being set in motion. Following the combination of&#xD;
      surgery/ anesthesia, high molecular group box protein 1 (HMGB1) is released. This&#xD;
      damage-associated molecular pattern (DAMP) binds to pattern recognition receptors (PRR) on&#xD;
      circulating bone marrow-derived monocytes (BM-DMs). Through an intracellular signaling&#xD;
      pathway, the transcription factor NF-kappaB passes into the nucleus, is activated and&#xD;
      increases expression and release of pro-inflammatory cytokines. These in turn disrupt the&#xD;
      blood brain barrier. Within the brain parenchyma the chemokine MCP-1 (also referred to as&#xD;
      CCL2) is upregulated and attracts the BM-DMs through binding to its receptor, CCR2. In turn,&#xD;
      this activates the resident quiescent microglia. Together, the BM-DMs and activated microglia&#xD;
      release HMGB1 and pro-inflammatory cytokines that disrupt long-term potentiation (LTP)&#xD;
      thereby blocking synaptic plasticity changes that are required for the cognitive functions of&#xD;
      learning and memory.&#xD;
&#xD;
      Unfortunately, treatment currently is lacking, however optimising lifestyle seems to be a&#xD;
      promising pathway in a murine population.&#xD;
&#xD;
      This prospective study is designed to examine preoperative lifestyle factors (such as&#xD;
      sedentary behavior) associated with postoperative cognitive impairment in a group of patients&#xD;
      undergoing non-cardiac surgery.&#xD;
&#xD;
      Prior to surgery, patients will have a baseline MMSE (mini mental state examination)&#xD;
      assessment. At the same time, a standardized history form will be completed to document&#xD;
      pertinent patient information, with special emphasis on patterns of smoking and ethanol&#xD;
      consumption. French IPAQ data will be collected as well as the Geriatric Depression Scale.&#xD;
&#xD;
      Right before the surgery, a peripheral blood sample will be drawn (to analyse IL-6 levels).&#xD;
&#xD;
      Induction and Maintenance of General Anesthesia: All patients will receive general anesthesia&#xD;
      using an endotracheal tube to facilitate ventilatory support.&#xD;
&#xD;
      Induction of anesthesia will be performed using the following:&#xD;
&#xD;
      I.V. (intravenous) Sufentanil 0.1- 0.2 mcg/kg I.V. Lidocaine 1.5 mg/kg I.V. Propofol 2-3&#xD;
      mg/kg I.V. Rocuronium 0.6 -1.2 mg/kg General anesthesia will be maintained using 0.5-2.5%&#xD;
      sevoflurane in an O2:air mixture, the latter titrated to maintain an oxygen saturation (SpO2)&#xD;
      value of 96% or greater via pulse oximetry.&#xD;
&#xD;
      Additional analgesia will be provided with I.V. Acetaminophen 15 mg/kg and I.V. Diclofenac 1&#xD;
      mg/kg and, if necessary, I.V. sufentanil 5 mcg.&#xD;
&#xD;
      Non-invasive blood pressure will be measured on the upper arm, and a phenylephrine infusion&#xD;
      of 0-100 mcg/min will be administered to maintain mean arterial blood pressure within 20% of&#xD;
      the preoperative value.&#xD;
&#xD;
      If muscle relaxation is required by the surgeon, I.V. rocuronium may be administered in 10-20&#xD;
      mg boluses. I.V. Sugammadex 4 mg/kg will be administered if needed to reverse neuromuscular&#xD;
      blockade.&#xD;
&#xD;
      At the end of the surgery, just prior to emergence from general anesthesia, each patient will&#xD;
      receive I.V. ondansetron 4 mg for anti-emetic purposes.&#xD;
&#xD;
      Upon emergence from anesthesia, all patients will be transferred to the post-operative&#xD;
      recovery unit.&#xD;
&#xD;
      Depth of anesthesia monitoring will be done via BIS monitor. The BIS monitor value will be&#xD;
      maintained in the range of 40-60 to ensure uniform sedation levels in all subjects.&#xD;
&#xD;
      Monitoring of Other Physiological Parameters During General Anesthesia: Heart rate, oxygen&#xD;
      saturation (SpO2), respiratory rate, non-invasive blood pressure, end-tidal CO2 levels,&#xD;
      inspired/end-tidal O2 levels, inspired/end-tidal sevoflurane concentrations, temperature, and&#xD;
      BIS values will be continuously monitored and recorded throughout the surgical procedure, to&#xD;
      ensure that the measured physiological parameters are within the normal range. Similarly, the&#xD;
      cumulative doses of all sedative and analgesic medications will also be recorded.&#xD;
&#xD;
      Six hours post-operatively, a peripheral blood sample will be drawn again (to analyse IL-6&#xD;
      levels) as well as 24 hours post-operatively.&#xD;
&#xD;
      Once discharged from the hospital, patients will come for a follow-up visit at six weeks&#xD;
      post-operatively as well as three months. During this follow-up visit, patients will repeat&#xD;
      MMSE testing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 3, 2019</start_date>
  <completion_date type="Actual">October 30, 2019</completion_date>
  <primary_completion_date type="Actual">September 25, 2019</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>Pre-operative MMSE</measure>
    <time_frame>12 hours</time_frame>
    <description>Mini mental state examination will be evaluated prior to the surgery</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MMSE 6 weeks post-operative</measure>
    <time_frame>6 weeks</time_frame>
    <description>Mini mental state examination will be evaluated 6 weeks after surgery</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MMSE 3 months post-operative</measure>
    <time_frame>3 months</time_frame>
    <description>Mini mental state examination will be evaluated 3 months after surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentration of patient's baseline pre-operative peripheral IL-6</measure>
    <time_frame>12 hours</time_frame>
    <description>Blood samples to measure IL-6 will be drawn prior to the surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of patient's post-operative peripheral IL-6; 6 hours post-operative</measure>
    <time_frame>24 hours</time_frame>
    <description>Blood samples to measure IL-6 will be drawn 6 hours after the surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of patient's post-operative peripheral IL-6 ; 24 hours post-operative</measure>
    <time_frame>24 hours</time_frame>
    <description>Blood samples to measure IL-6 will be drawn 24 hours after the surgery</description>
  </secondary_outcome>
  <enrollment type="Actual">38</enrollment>
  <condition>Cognitive Change</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Non-Cardiac Surgery</intervention_name>
    <description>Non-cardiac surgery</description>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood sample (as usual)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        All patients participating in the study will have to provide written informed consent.&#xD;
        Patients of both genders aged 55 or more scheduled for non-cardiac surgery between 8 and 10&#xD;
        AM (with a duration of 1 to 4 hours) will be eligible for enrolment in the study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed written consent&#xD;
&#xD;
          -  Patients scheduled for non-cardiac surgery (with a duration of 1 to 4 hours)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lack of comprehension of the French, English or Dutch language&#xD;
&#xD;
          -  Visual or auditory impairment&#xD;
&#xD;
          -  Any other reason that makes patients unable to perform cognitive testing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Jean Boogaerts, MD; PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Université Libre de Bruxelles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU-Charleroi Hopital Civil Marie Curie</name>
      <address>
        <city>Charleroi</city>
        <state>Hainaut</state>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>January 5, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>December 21, 2019</last_update_submitted>
  <last_update_submitted_qc>December 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 24, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Université Libre de Bruxelles</investigator_affiliation>
    <investigator_full_name>Sarah Saxena</investigator_full_name>
    <investigator_title>Anesthesiologist; Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neurocognitive Disorders</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/NCT03805685
org study id: Lifestyle-Delirium
nct id: NCT03805685
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Perioperative neurocognitive disorders (PND's) remain an important complication after
      surgery. After many years of speculating about the etiology of this complication, currently
      studies are pointing to an inflammatory cascade being set in motion.

      This prospective study is designed to examine preoperative lifestyle factors (such as
      sedentary behavior) associated with postoperative cognitive impairment in a group of patients
      undergoing non-cardiac surgery.

      The objectives in our study are to:

      identify perioperative risk factors for the development of PND's measure the incidence and
      duration of perioperative neurocognitive disorders in a known high-risk group of elective
      surgical patients measure a peripheral inflammatory marker (interleukin 6: IL-6) in the same
      group of surgical patients
Perioperative neurocognitive disorders remain an important complication after surgery. After
      many years of speculating about the etiology of this complication, currently studies are
      pointing to an inflammatory cascade being set in motion. Following the combination of
      surgery/ anesthesia, high molecular group box protein 1 (HMGB1) is released. This
      damage-associated molecular pattern (DAMP) binds to pattern recognition receptors (PRR) on
      circulating bone marrow-derived monocytes (BM-DMs). Through an intracellular signaling
      pathway, the transcription factor NF-kappaB passes into the nucleus, is activated and
      increases expression and release of pro-inflammatory cytokines. These in turn disrupt the
      blood brain barrier. Within the brain parenchyma the chemokine MCP-1 (also referred to as
      CCL2) is upregulated and attracts the BM-DMs through binding to its receptor, CCR2. In turn,
      this activates the resident quiescent microglia. Together, the BM-DMs and activated microglia
      release HMGB1 and pro-inflammatory cytokines that disrupt long-term potentiation (LTP)
      thereby blocking synaptic plasticity changes that are required for the cognitive functions of
      learning and memory.

      Unfortunately, treatment currently is lacking, however optimising lifestyle seems to be a
      promising pathway in a murine population.

      This prospective study is designed to examine preoperative lifestyle factors (such as
      sedentary behavior) associated with postoperative cognitive impairment in a group of patients
      undergoing non-cardiac surgery.

      Prior to surgery, patients will have a baseline MMSE (mini mental state examination)
      assessment. At the same time, a standardized history form will be completed to document
      pertinent patient information, with special emphasis on patterns of smoking and ethanol
      consumption. French IPAQ data will be collected as well as the Geriatric Depression Scale.

      Right before the surgery, a peripheral blood sample will be drawn (to analyse IL-6 levels).

      Induction and Maintenance of General Anesthesia: All patients will receive general anesthesia
      using an endotracheal tube to facilitate ventilatory support.

      Induction of anesthesia will be performed using the following:

      I.V. (intravenous) Sufentanil 0.1- 0.2 mcg/kg I.V. Lidocaine 1.5 mg/kg I.V. Propofol 2-3
      mg/kg I.V. Rocuronium 0.6 -1.2 mg/kg General anesthesia will be maintained using 0.5-2.5%
      sevoflurane in an O2:air mixture, the latter titrated to maintain an oxygen saturation (SpO2)
      value of 96% or greater via pulse oximetry.

      Additional analgesia will be provided with I.V. Acetaminophen 15 mg/kg and I.V. Diclofenac 1
      mg/kg and, if necessary, I.V. sufentanil 5 mcg.

      Non-invasive blood pressure will be measured on the upper arm, and a phenylephrine infusion
      of 0-100 mcg/min will be administered to maintain mean arterial blood pressure within 20% of
      the preoperative value.

      If muscle relaxation is required by the surgeon, I.V. rocuronium may be administered in 10-20
      mg boluses. I.V. Sugammadex 4 mg/kg will be administered if needed to reverse neuromuscular
      blockade.

      At the end of the surgery, just prior to emergence from general anesthesia, each patient will
      receive I.V. ondansetron 4 mg for anti-emetic purposes.

      Upon emergence from anesthesia, all patients will be transferred to the post-operative
      recovery unit.

      Depth of anesthesia monitoring will be done via BIS monitor. The BIS monitor value will be
      maintained in the range of 40-60 to ensure uniform sedation levels in all subjects.

      Monitoring of Other Physiological Parameters During General Anesthesia: Heart rate, oxygen
      saturation (SpO2), respiratory rate, non-invasive blood pressure, end-tidal CO2 levels,
      inspired/end-tidal O2 levels, inspired/end-tidal sevoflurane concentrations, temperature, and
      BIS values will be continuously monitored and recorded throughout the surgical procedure, to
      ensure that the measured physiological parameters are within the normal range. Similarly, the
      cumulative doses of all sedative and analgesic medications will also be recorded.

      Six hours post-operatively, a peripheral blood sample will be drawn again (to analyse IL-6
      levels) as well as 24 hours post-operatively.

      Once discharged from the hospital, patients will come for a follow-up visit at six weeks
      post-operatively as well as three months. During this follow-up visit, patients will repeat
      MMSE testing.
observational model: Cohort
time perspective: Prospective
measure: Pre-operative MMSE
time frame: 12 hours
description: Mini mental state examination will be evaluated prior to the surgery
measure: MMSE 6 weeks post-operative
time frame: 6 weeks
description: Mini mental state examination will be evaluated 6 weeks after surgery
measure: MMSE 3 months post-operative
time frame: 3 months
description: Mini mental state examination will be evaluated 3 months after surgery
measure: Concentration of patient's baseline pre-operative peripheral IL-6
time frame: 12 hours
description: Blood samples to measure IL-6 will be drawn prior to the surgery
measure: Concentration of patient's post-operative peripheral IL-6; 6 hours post-operative
time frame: 24 hours
description: Blood samples to measure IL-6 will be drawn 6 hours after the surgery
measure: Concentration of patient's post-operative peripheral IL-6 ; 24 hours post-operative
time frame: 24 hours
description: Blood samples to measure IL-6 will be drawn 24 hours after the surgery
intervention type: Procedure
intervention name: Non-Cardiac Surgery
description: Non-cardiac surgery
Blood sample (as usual)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 55 Years
maximum age: 75 Years
last name: Jean Boogaerts, MD; PhD
role: Principal Investigator
affiliation: Université Libre de Bruxelles
facility: 
country: Belgium
responsible party type: Principal Investigator
investigator affiliation: Université Libre de Bruxelles
investigator full name: Sarah Saxena
investigator title: Anesthesiologist; Principal Investigator
mesh term: Neurocognitive Disorders
sharing ipd: Undecided