<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/NCT04500236</url>
  </required_header>
  <id_info>
    <org_study_id>2020/14MAI/273</org_study_id>
    <nct_id>NCT04500236</nct_id>
  </id_info>
  <brief_title>Serum Neurofilament Light (NFL) in Surgery Under General Anaesthesia (GA) Compared to Surgery With Hypno-analgesia (Hyp)</brief_title>
  <official_title>Release of Serum Neurofilament Light (NFL), Biomarker of Neuronal Injury, in Surgery Under General Anaesthesia (GA) Compared to Surgery With Hypno-analgesia (Hyp): A Prospective, Non-inferiority Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cliniques universitaires Saint-Luc- Université Catholique de Louvain</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cliniques universitaires Saint-Luc- Université Catholique de Louvain</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Experimental studies have shown that inhalational anesthetics may be neurotoxic by for&#xD;
      example causing amyloid beta deposition. Otherwise a pre-clinical study reported an increase&#xD;
      in tau phosphorylation with the use of propofol.&#xD;
&#xD;
      Whether anesthesia and surgery contribute to the development of long-term cognitive decline&#xD;
      remains however controversial. A meta-analysis concluded that general anesthesia could&#xD;
      increase the risk of postoperative cognitive decline (POCD) compared with regional or&#xD;
      combined anesthesia but this was not shown for Postoperative delirium (POD). This conclusion&#xD;
      should be interpreted with caution as these studies showed many shortcomings.&#xD;
&#xD;
      Currently no study has compared the release of Neurofilament Light, a biomarker of neuronal&#xD;
      injury, in patients undergoing surgery under general anesthesia compared to surgery with&#xD;
      Hypno-analgesia and thus without anesthetic drugs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      POD and POCD are manifestations of cognitive dysfunction occurring in the perioperative&#xD;
      period. Whether surgery and specifically anesthesia contribute to the development of&#xD;
      perioperative cognitive dysfunctions is not clear.&#xD;
&#xD;
      Cell culture and animal studies have suggested detrimental effects of anesthetic&#xD;
      exposure.1,2,3 Otherwise, it has been shown in animals that surgery plus anesthesia produced&#xD;
      worse POCD than anesthesia alone.4 Proinflammatory cytokine levels increase during surgery.&#xD;
      These elevated levels of inflammatory markers associated with the activation of microglial&#xD;
      cells may induce neuroinflammation enhancing ongoing neurodegeneration.5 However, anesthetics&#xD;
      may be capable of modulating inflammation and may alter the neuroinflammatory response.&#xD;
&#xD;
      Clinical studies associating the effects of general anesthesia with POCD and POD are&#xD;
      conflicting.6 These varying results could be due to heterogeneity of patients' baseline&#xD;
      status (e.g. cognitive status, education, associated diseases), type of surgery, as well as&#xD;
      methods used to determine POCD and POD.&#xD;
&#xD;
      The use of serum neurobiomarkers, sensitive and specific for neuronal cell injury will&#xD;
      address the hypothesis of general anesthesia neurotoxicity. Serum Neurofilament Light (NFL)&#xD;
      is such a neurobiomarker.Currently no study has compared the release of Neurofilament Light,&#xD;
      a biomarker of neuronal injury, in patients undergoing surgery under general anesthesia&#xD;
      compared to surgery with Hypno-analgesia and thus without anesthetic drugs. Our hypothesis is&#xD;
      that surgery under GA compared to hypnosis does not statistically increase the risk of&#xD;
      neuronal injury as measured by serum NFL.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2020</start_date>
  <completion_date type="Anticipated">February 28, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Serum Neurofilament Light at first postoperative day (18 - 24 hours) postoperatively) between both groups</measure>
    <time_frame>18 hours to 24 hours postoperatively</time_frame>
    <description>Comparison of postoperative serum Neurofilament Light between both groups</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total postoperative analgesic consumption between both groups</measure>
    <time_frame>24 hours postoperatively</time_frame>
    <description>Comparison of total consumed analgesics in the postoperative period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative C-reactive protein between both groups</measure>
    <time_frame>24 hours postoperatively</time_frame>
    <description>Comparison of postoperative highest C-reactive protein between both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative serum Neurofilament Light in function of type of surgery</measure>
    <time_frame>24 hours postoperatively</time_frame>
    <description>Analysis of postoperative serum Neurofilament Light in function of type of surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of postoperative Montreal Cognitive Assessment on a scale of 30 (higher scores are better) between both groups</measure>
    <time_frame>Day 8 to day 10</time_frame>
    <description>Postoperative Montreal Cognitive Assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative serum Neurofilament Light at postoperative day 8 - 10</measure>
    <time_frame>Day 8 to day 10</time_frame>
    <description>Analysis of postoperative serum Neurofilament Light between both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Recovery F15 questionnaire with 15 questions on a scale of 10 (higher scores are better) between both groups</measure>
    <time_frame>Day 8 to day 10</time_frame>
    <description>Comparison of quality of recovery between both groups based on a validated questionnaire with 15 items</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Frontal EEG analysis of patients under hypnosis</measure>
    <time_frame>Intraoperatively</time_frame>
    <description>Analysis of raw frontal EEG power (in slow, delta, theta, alpha, beta and gamma band) from the depth-of-anesthesia monitor as a sub-analysis of this study</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>General Surgery</condition>
  <arm_group>
    <arm_group_label>General Anesthesia (GA)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients undergoing thyroid or breast cancer surgery under general anesthesia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hypno-analgesia (Hyp)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients undergoing thyroid or breast cancer surgery under Hypno-analgesia; i.e.hypnosis combined with the use of analgesics.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>General anesthesia</intervention_name>
    <description>Surgery under general anesthesia with the use of propofol</description>
    <arm_group_label>General Anesthesia (GA)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Hypno-analgesia</intervention_name>
    <description>Surgery under Hypnosis session and analgesics</description>
    <arm_group_label>Hypno-analgesia (Hyp)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients undergoing thyroid or breast cancer surgery and necessitating one night&#xD;
             of hospital stay&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Renal insufficiency with a GFR &lt; 30 mL/min&#xD;
&#xD;
          -  Mammectomy&#xD;
&#xD;
          -  Preoperative psychiatric problems&#xD;
&#xD;
          -  Patients not speaking fluently French&#xD;
&#xD;
          -  Patients at risk of postoperative hyperalgesia (Kalkman score &gt; 4/15)&#xD;
&#xD;
          -  Allergy to local anesthetics, NSAID and to Rocuronium&#xD;
&#xD;
          -  Patients undergoing one day surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mona Momeni, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cliniques universitaires Saint-Luc</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mona Momeni, MD, PhD</last_name>
    <phone>003227647029</phone>
    <email>mona.momeni@uclouvain.be</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint Luc</name>
      <address>
        <city>Brussels</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>MONA MOMENI, M.D.; PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <reference>
    <citation>Whittington RA, Virag L, Marcouiller F, Papon MA, El Khoury NB, Julien C, Morin F, Emala CW, Planel E. Propofol directly increases tau phosphorylation. PLoS One. 2011 Jan 31;6(1):e16648. doi: 10.1371/journal.pone.0016648.</citation>
    <PMID>21304998</PMID>
  </reference>
  <reference>
    <citation>Eckenhoff RG, Johansson JS, Wei H, Carnini A, Kang B, Wei W, Pidikiti R, Keller JM, Eckenhoff MF. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology. 2004 Sep;101(3):703-9. doi: 10.1097/00000542-200409000-00019.</citation>
    <PMID>15329595</PMID>
  </reference>
  <reference>
    <citation>Wei H, Xie Z. Anesthesia, calcium homeostasis and Alzheimer's disease. Curr Alzheimer Res. 2009 Feb;6(1):30-5. doi: 10.2174/156720509787313934.</citation>
    <PMID>19199872</PMID>
  </reference>
  <reference>
    <citation>Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M. Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology. 2007 Mar;106(3):436-43. doi: 10.1097/00000542-200703000-00007.</citation>
    <PMID>17325501</PMID>
  </reference>
  <reference>
    <citation>Riedel B, Browne K, Silbert B. Cerebral protection: inflammation, endothelial dysfunction, and postoperative cognitive dysfunction. Curr Opin Anaesthesiol. 2014 Feb;27(1):89-97. doi: 10.1097/ACO.0000000000000032.</citation>
    <PMID>24300462</PMID>
  </reference>
  <reference>
    <citation>Mason SE, Noel-Storr A, Ritchie CW. The impact of general and regional anesthesia on the incidence of post-operative cognitive dysfunction and post-operative delirium: a systematic review with meta-analysis. J Alzheimers Dis. 2010;22 Suppl 3:67-79. doi: 10.3233/JAD-2010-101086.</citation>
    <PMID>20858956</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>April 21, 2022</last_update_submitted>
  <last_update_submitted_qc>April 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>All data will be available at the moment of publication of results</ipd_description>
  </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/NCT04500236
org study id: 2020/14MAI/273
nct id: NCT04500236
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Experimental studies have shown that inhalational anesthetics may be neurotoxic by for
      example causing amyloid beta deposition. Otherwise a pre-clinical study reported an increase
      in tau phosphorylation with the use of propofol.

      Whether anesthesia and surgery contribute to the development of long-term cognitive decline
      remains however controversial. A meta-analysis concluded that general anesthesia could
      increase the risk of postoperative cognitive decline (POCD) compared with regional or
      combined anesthesia but this was not shown for Postoperative delirium (POD). This conclusion
      should be interpreted with caution as these studies showed many shortcomings.

      Currently no study has compared the release of Neurofilament Light, a biomarker of neuronal
      injury, in patients undergoing surgery under general anesthesia compared to surgery with
      Hypno-analgesia and thus without anesthetic drugs.
POD and POCD are manifestations of cognitive dysfunction occurring in the perioperative
      period. Whether surgery and specifically anesthesia contribute to the development of
      perioperative cognitive dysfunctions is not clear.

      Cell culture and animal studies have suggested detrimental effects of anesthetic
      exposure.1,2,3 Otherwise, it has been shown in animals that surgery plus anesthesia produced
      worse POCD than anesthesia alone.4 Proinflammatory cytokine levels increase during surgery.
      These elevated levels of inflammatory markers associated with the activation of microglial
      cells may induce neuroinflammation enhancing ongoing neurodegeneration.5 However, anesthetics
      may be capable of modulating inflammation and may alter the neuroinflammatory response.

      Clinical studies associating the effects of general anesthesia with POCD and POD are
      conflicting.6 These varying results could be due to heterogeneity of patients' baseline
      status (e.g. cognitive status, education, associated diseases), type of surgery, as well as
      methods used to determine POCD and POD.

      The use of serum neurobiomarkers, sensitive and specific for neuronal cell injury will
      address the hypothesis of general anesthesia neurotoxicity. Serum Neurofilament Light (NFL)
      is such a neurobiomarker.Currently no study has compared the release of Neurofilament Light,
      a biomarker of neuronal injury, in patients undergoing surgery under general anesthesia
      compared to surgery with Hypno-analgesia and thus without anesthetic drugs. Our hypothesis is
      that surgery under GA compared to hypnosis does not statistically increase the risk of
      neuronal injury as measured by serum NFL.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Serum Neurofilament Light at first postoperative day (18 - 24 hours) postoperatively) between both groups
time frame: 18 hours to 24 hours postoperatively
description: Comparison of postoperative serum Neurofilament Light between both groups
measure: Total postoperative analgesic consumption between both groups
time frame: 24 hours postoperatively
description: Comparison of total consumed analgesics in the postoperative period
measure: Postoperative C-reactive protein between both groups
time frame: 24 hours postoperatively
description: Comparison of postoperative highest C-reactive protein between both groups
measure: Postoperative serum Neurofilament Light in function of type of surgery
time frame: 24 hours postoperatively
description: Analysis of postoperative serum Neurofilament Light in function of type of surgery
measure: Comparison of postoperative Montreal Cognitive Assessment on a scale of 30 (higher scores are better) between both groups
time frame: Day 8 to day 10
description: Postoperative Montreal Cognitive Assessment
measure: Postoperative serum Neurofilament Light at postoperative day 8 - 10
time frame: Day 8 to day 10
description: Analysis of postoperative serum Neurofilament Light between both groups
measure: Quality of Recovery F15 questionnaire with 15 questions on a scale of 10 (higher scores are better) between both groups
time frame: Day 8 to day 10
description: Comparison of quality of recovery between both groups based on a validated questionnaire with 15 items
measure: Frontal EEG analysis of patients under hypnosis
time frame: Intraoperatively
description: Analysis of raw frontal EEG power (in slow, delta, theta, alpha, beta and gamma band) from the depth-of-anesthesia monitor as a sub-analysis of this study
arm group label: General Anesthesia (GA)
arm group type: Active Comparator
description: Patients undergoing thyroid or breast cancer surgery under general anesthesia
arm group label: Hypno-analgesia (Hyp)
arm group type: Placebo Comparator
description: Patients undergoing thyroid or breast cancer surgery under Hypno-analgesia; i.e.hypnosis combined with the use of analgesics.
intervention type: Other
intervention name: General anesthesia
description: Surgery under general anesthesia with the use of propofol
arm group label: General Anesthesia (GA)
intervention type: Other
intervention name: Hypno-analgesia
description: Surgery under Hypnosis session and analgesics
arm group label: Hypno-analgesia (Hyp)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Mona Momeni, MD, PhD
role: Principal Investigator
affiliation: Cliniques universitaires Saint-Luc
last name: Mona Momeni, MD, PhD
phone: 003227647029
email: mona.momeni@uclouvain.be
facility: 
status: Recruiting
investigator: 
country: Belgium
citation: Whittington RA, Virag L, Marcouiller F, Papon MA, El Khoury NB, Julien C, Morin F, Emala CW, Planel E. Propofol directly increases tau phosphorylation. PLoS One. 2011 Jan 31;6(1):e16648. doi: 10.1371/journal.pone.0016648.
PMID: 21304998
citation: Eckenhoff RG, Johansson JS, Wei H, Carnini A, Kang B, Wei W, Pidikiti R, Keller JM, Eckenhoff MF. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology. 2004 Sep;101(3):703-9. doi: 10.1097/00000542-200409000-00019.
PMID: 15329595
citation: Wei H, Xie Z. Anesthesia, calcium homeostasis and Alzheimer's disease. Curr Alzheimer Res. 2009 Feb;6(1):30-5. doi: 10.2174/156720509787313934.
PMID: 19199872
citation: Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M. Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology. 2007 Mar;106(3):436-43. doi: 10.1097/00000542-200703000-00007.
PMID: 17325501
citation: Riedel B, Browne K, Silbert B. Cerebral protection: inflammation, endothelial dysfunction, and postoperative cognitive dysfunction. Curr Opin Anaesthesiol. 2014 Feb;27(1):89-97. doi: 10.1097/ACO.0000000000000032.
PMID: 24300462
citation: Mason SE, Noel-Storr A, Ritchie CW. The impact of general and regional anesthesia on the incidence of post-operative cognitive dysfunction and post-operative delirium: a systematic review with meta-analysis. J Alzheimers Dis. 2010;22 Suppl 3:67-79. doi: 10.3233/JAD-2010-101086.
PMID: 20858956
responsible party type: Sponsor
mesh term: Anesthetics
sharing ipd: No
ipd description: All data will be available at the moment of publication of results