<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/NCT04422925</url>
  </required_header>
  <id_info>
    <org_study_id>s100β, NSE n GFAP in LDH</org_study_id>
    <nct_id>NCT04422925</nct_id>
  </id_info>
  <brief_title>s100β, NSE n GFAP in Living Donor Hepatectomy and Delirium</brief_title>
  <official_title>In Living Donor Hepatectomy Cases, the Preoperative and Postoperative Relationship Between s100β, NSE and GFAP Levels and Postoperative Delirium</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Akdeniz University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Akdeniz University</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>
      The post-operative delirium picture is a serious and common complication seen after any major&#xD;
      surgery, including hepatic resection. Patients who will be planned to undergo donor&#xD;
      hepatectomy for liver transplantation will be included in the study. Basic clinical and&#xD;
      demographic information of patients undergoes donor hepatectomy will be recorded before&#xD;
      surgery. The anatomical parameters such as liver volume, medications performed during the&#xD;
      surgery, complications, bleeding amounts, fluids given, blood and blood products, vital signs&#xD;
      during surgery, fluid balance, duration of surgery, recovery length at post-operative period,&#xD;
      complications after surgery, approaches to complications, analgesics and other medications&#xD;
      used, hemogram and other biochemical parameters (electrolytes, albumin, liver frontier tests,&#xD;
      etc.), weight status, vital signs, duration of intensive care, post-operative VAS scores,&#xD;
      drainage and information such as length of stay, length of hospital stay, the healing time of&#xD;
      the wound will also be recorded.&#xD;
&#xD;
      During the hospitalization, the delirium status of the patients will be evaluated with a&#xD;
      delirium evaluation scale by consultant doctor. Blood will be taken for the measurement of&#xD;
      S100β, NSE, and GFAP levels one day before donor hepatectomy and following day of&#xD;
      hepatectomy, 3rd day, and 7th day in the post-operative period. The plasma of the blood taken&#xD;
      will be separated and stored at -80 0C until working. Laboratory values are taken from the&#xD;
      patients before the operation will be recorded over the system. The relationship between the&#xD;
      results obtained and the delirium evaluation scores performed on the days followed will be&#xD;
      evaluated.&#xD;
&#xD;
      This study aims to analyze the delirium incidence and post-operative early S100β, NSE, and&#xD;
      GFAP levels within the first week following the hepatectomy performed in live donors for&#xD;
      liver transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The postoperative delirium picture is a serious and common complication seen after any major&#xD;
      surgery, including hepatic resection. Delirium is an acute state of confusion characterized&#xD;
      by impaired consciousness, reduced ability to focus on attention, changes in cognitive&#xD;
      functions, a perceptual disturbance development, and an uncomfortable sleep-wake cycle.&#xD;
      Postoperative delirium has an acute onset and has a fluctuating course. This complication&#xD;
      results in a long recovery period, a longer stay in the intensive care unit, higher&#xD;
      complication rates, extra nursing care, and higher costs. Therefore, appropriate methods are&#xD;
      needed to prevent and treat postoperative delirium.&#xD;
&#xD;
      The pathophysiology of delirium is thought to be due to many reasons. Examined in titles:&#xD;
      Changes in the electrolyte and fluid balance, nutritional imbalance (low serum&#xD;
      protein/albumin level, hypovitaminosis, especially cobalamin deficiencies (B12), folate (B9),&#xD;
      niacin (B3, pellagra), thiamine, age (&gt; 65) and gender (m&gt; f), hyperthermia and hypothermia,&#xD;
      major surgical procedures, endocrine disorders, drug use, anemia, anoxia, hypoxia and low&#xD;
      perfusion/oxygenation states, postoperative pain and painkiller medication, end-organ&#xD;
      failure, social isolation, decreased intellectual stimulation (long-term intensive care&#xD;
      therapy), sleep disorders and changes in the circadian rhythm, metabolic disorders (acidosis,&#xD;
      alkalosis, hyperammonemia, hypersensitivity reactions, glucose, and acid-base disorders,&#xD;
      limitations, and inactivity. Cases are exposed to these predisposing causes.&#xD;
&#xD;
      Postoperative delirium is a type of delirium that is exposed to surgical procedure and&#xD;
      anesthesia, usually seen between the 1st and 3rd days after surgery. Postoperative delirium&#xD;
      can be seen at rates ranging from 9 to 87% depending on the age of the patient and the type&#xD;
      of surgery. Although its etiology is not yet understood, it is probably thought to be&#xD;
      multifactorial.&#xD;
&#xD;
      S100β is secreted by astrocytes in brain damage. S100β rises while brain damage starts, so it&#xD;
      can be used in the diagnosis of early brain damage. Neuron-specific enolase (NSE) acts as an&#xD;
      intracytoplasmic enzyme, and serum levels are increased in neuron damage. The glial fibrillar&#xD;
      acidic protein (GFAP) is the intermediate filament cytoskeleton protein in astrocytes. It&#xD;
      originates from the same root structure as S100β. After hepatectomy, the donor candidates are&#xD;
      exposed to physiological changes that include the central nervous system due to surgical&#xD;
      stress as well as the functional change of the remaining liver tissue. Determining the&#xD;
      increase in serum level of biomarkers specific to the central nervous system mentioned before&#xD;
      the development of cognitive disorders such as delirium may prevent the complications that&#xD;
      may arise during the postoperative period. It also helps to provide treatment in the&#xD;
      postoperative period as well as evaluation.&#xD;
&#xD;
      The aim of this study is to analyze the delirium incidence and postoperative early S100β,&#xD;
      NSE, and GFAP levels within the first week following the hepatectomy performed in living&#xD;
      donors for liver transplantation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2019</start_date>
  <completion_date type="Actual">December 1, 2021</completion_date>
  <primary_completion_date type="Actual">November 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of serum s100β</measure>
    <time_frame>2 years</time_frame>
    <description>Approximately 25 patients planned to have living donor hepatectomy will be included in the study. The blood samples are taken in the preoperative period before the induction of anesthesia in the operating room and postoperative (the first day, the third day and the seventh day) period to analyze S100β serum concentrations and neurologic damage of living donor hepatectomy patients besides evaluating its effect on prognosis. These samples shall be kept at -80 0C until the plasma separation process.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of serum NSE</measure>
    <time_frame>2 years</time_frame>
    <description>Approximately 25 patients planned to have living donor hepatectomy will be included in the study. The blood samples are taken in the preoperative period before the induction of anesthesia in the operating room and postoperative (the first day, the third day and the seventh day) period to analyze NSE serum concentrations and neurologic damage of living donor hepatectomy patients besides evaluating its effect on prognosis. These samples shall be kept at -80 0C until the plasma separation process.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of serum GFAP</measure>
    <time_frame>2 years</time_frame>
    <description>Approximately 25 patients planned to have living donor hepatectomy will be included in the study. The blood samples are taken in the preoperative period before the induction of anesthesia in the operating room and postoperative (the first day, the third day and the seventh day) period to analyze GFAP serum concentrations and neurologic damage of living donor hepatectomy patients besides evaluating its effect on prognosis. These samples shall be kept at -80 0C until the plasma separation process.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of serum cognitive functions and delirium status</measure>
    <time_frame>2 years</time_frame>
    <description>During the hospitalization, the delirium status of the patients will be evaluated with the delirium evaluation scale (Delirium Rating Scale-Revised - 98 Turkish version). Functional and cognitive information and other results will be collected at each follow-up point.</description>
  </primary_outcome>
  <enrollment type="Actual">56</enrollment>
  <condition>Donor Site Complication</condition>
  <condition>Delirium</condition>
  <condition>Uremic Encephalopathy</condition>
  <condition>Neurologic Manifestations</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Living Donor Hepatectomy</intervention_name>
    <description>On living donor hepatectomy (preoperative), the first following day of surgery, 3rd day, and 7th day, blood will be taken for the measurement of S100β, NSE, and GFAP levels in the postoperative period. The plasma of the blood taken will be separated and stored at -800C. Values will be measured by the ELISA method. During the hospitalization, the delirium status of the patients will be evaluated with the delirium evaluation scale (Delirium Rating Scale-Revised - 98 Turkish version). Functional and cognitive information and other results will be collected at each follow-up point.</description>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      s100β, neuron specific enolase and glial fibrillary acidic&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients' demographic data (age, gender, weight, height), accompanying diseases, ASA&#xD;
        classification, main etiology, preoperative serums taken in the preoperative period; serum&#xD;
        sodium, potassium, ammonium, total bilirubin, ALT, AST, albumin, alkaline phosphatase, INR,&#xD;
        creatinine, and BUN shall be recorded accordingly. In addition, routinely taken&#xD;
        anesthetics, duration of the operation, duration of anesthesia, duration before the&#xD;
        reperfusion, duration of postperfusion, first measured central venous pressure, volume&#xD;
        replacement therapy, blood component transfusion, the total fluid amount given during the&#xD;
        operation, corticosteroids and immunosuppressive drugs given during the operation shall be&#xD;
        recorded. Besides, the cognitive functions of the patients and blood samples for mentioned&#xD;
        values will be evaluated in the preoperative and postoperative periods.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who are admitted as a donor who will undergo living donor hepatectomy&#xD;
             operation by Akdeniz University Faculty of Medicine Organ Transplant Center and&#xD;
             planned to have a donor right hepatectomy operation&#xD;
&#xD;
          -  Patients who have read and accepted the detailed informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Failure to supply routine blood sampling during follow-up&#xD;
&#xD;
          -  Having major complications after surgery (pulmonary embolization, sepsis, etc.)&#xD;
&#xD;
          -  Individuals with mental health disorders detected by the organ transplantation&#xD;
             committee in the preoperative period.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>77 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bora Di̇nc, MD, Assist. Prof.</last_name>
    <role>Study Director</role>
    <affiliation>Akdeniz University Medical Faculty</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Akdeniz University Medical Faculty Department of Anesthesiology and Reanimation</name>
      <address>
        <city>Antalya</city>
        <zip>07059</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>June 5, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>January 7, 2022</last_update_submitted>
  <last_update_submitted_qc>January 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Akdeniz University</investigator_affiliation>
    <investigator_full_name>Bora Dinc</investigator_full_name>
    <investigator_title>MD. Assist. Prof.</investigator_title>
  </responsible_party>
  <keyword>donor living hepatectomy</keyword>
  <keyword>s100β</keyword>
  <keyword>neuron specific enolase</keyword>
  <keyword>glial fibrillary acidic protein</keyword>
  <keyword>delirium</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Neurologic Manifestations</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/NCT04422925
org study id: s100β, NSE n GFAP in LDH
nct id: NCT04422925
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The post-operative delirium picture is a serious and common complication seen after any major
      surgery, including hepatic resection. Patients who will be planned to undergo donor
      hepatectomy for liver transplantation will be included in the study. Basic clinical and
      demographic information of patients undergoes donor hepatectomy will be recorded before
      surgery. The anatomical parameters such as liver volume, medications performed during the
      surgery, complications, bleeding amounts, fluids given, blood and blood products, vital signs
      during surgery, fluid balance, duration of surgery, recovery length at post-operative period,
      complications after surgery, approaches to complications, analgesics and other medications
      used, hemogram and other biochemical parameters (electrolytes, albumin, liver frontier tests,
      etc.), weight status, vital signs, duration of intensive care, post-operative VAS scores,
      drainage and information such as length of stay, length of hospital stay, the healing time of
      the wound will also be recorded.

      During the hospitalization, the delirium status of the patients will be evaluated with a
      delirium evaluation scale by consultant doctor. Blood will be taken for the measurement of
      S100β, NSE, and GFAP levels one day before donor hepatectomy and following day of
      hepatectomy, 3rd day, and 7th day in the post-operative period. The plasma of the blood taken
      will be separated and stored at -80 0C until working. Laboratory values are taken from the
      patients before the operation will be recorded over the system. The relationship between the
      results obtained and the delirium evaluation scores performed on the days followed will be
      evaluated.

      This study aims to analyze the delirium incidence and post-operative early S100β, NSE, and
      GFAP levels within the first week following the hepatectomy performed in live donors for
      liver transplantation.
The postoperative delirium picture is a serious and common complication seen after any major
      surgery, including hepatic resection. Delirium is an acute state of confusion characterized
      by impaired consciousness, reduced ability to focus on attention, changes in cognitive
      functions, a perceptual disturbance development, and an uncomfortable sleep-wake cycle.
      Postoperative delirium has an acute onset and has a fluctuating course. This complication
      results in a long recovery period, a longer stay in the intensive care unit, higher
      complication rates, extra nursing care, and higher costs. Therefore, appropriate methods are
      needed to prevent and treat postoperative delirium.

      The pathophysiology of delirium is thought to be due to many reasons. Examined in titles:
      Changes in the electrolyte and fluid balance, nutritional imbalance (low serum
      protein/albumin level, hypovitaminosis, especially cobalamin deficiencies (B12), folate (B9),
      niacin (B3, pellagra), thiamine, age (> 65) and gender (m> f), hyperthermia and hypothermia,
      major surgical procedures, endocrine disorders, drug use, anemia, anoxia, hypoxia and low
      perfusion/oxygenation states, postoperative pain and painkiller medication, end-organ
      failure, social isolation, decreased intellectual stimulation (long-term intensive care
      therapy), sleep disorders and changes in the circadian rhythm, metabolic disorders (acidosis,
      alkalosis, hyperammonemia, hypersensitivity reactions, glucose, and acid-base disorders,
      limitations, and inactivity. Cases are exposed to these predisposing causes.

      Postoperative delirium is a type of delirium that is exposed to surgical procedure and
      anesthesia, usually seen between the 1st and 3rd days after surgery. Postoperative delirium
      can be seen at rates ranging from 9 to 87% depending on the age of the patient and the type
      of surgery. Although its etiology is not yet understood, it is probably thought to be
      multifactorial.

      S100β is secreted by astrocytes in brain damage. S100β rises while brain damage starts, so it
      can be used in the diagnosis of early brain damage. Neuron-specific enolase (NSE) acts as an
      intracytoplasmic enzyme, and serum levels are increased in neuron damage. The glial fibrillar
      acidic protein (GFAP) is the intermediate filament cytoskeleton protein in astrocytes. It
      originates from the same root structure as S100β. After hepatectomy, the donor candidates are
      exposed to physiological changes that include the central nervous system due to surgical
      stress as well as the functional change of the remaining liver tissue. Determining the
      increase in serum level of biomarkers specific to the central nervous system mentioned before
      the development of cognitive disorders such as delirium may prevent the complications that
      may arise during the postoperative period. It also helps to provide treatment in the
      postoperative period as well as evaluation.

      The aim of this study is to analyze the delirium incidence and postoperative early S100β,
      NSE, and GFAP levels within the first week following the hepatectomy performed in living
      donors for liver transplantation.
observational model: Case-Only
time perspective: Prospective
measure: Assessment of serum s100β
time frame: 2 years
description: Approximately 25 patients planned to have living donor hepatectomy will be included in the study. The blood samples are taken in the preoperative period before the induction of anesthesia in the operating room and postoperative (the first day, the third day and the seventh day) period to analyze S100β serum concentrations and neurologic damage of living donor hepatectomy patients besides evaluating its effect on prognosis. These samples shall be kept at -80 0C until the plasma separation process.
measure: Assessment of serum NSE
time frame: 2 years
description: Approximately 25 patients planned to have living donor hepatectomy will be included in the study. The blood samples are taken in the preoperative period before the induction of anesthesia in the operating room and postoperative (the first day, the third day and the seventh day) period to analyze NSE serum concentrations and neurologic damage of living donor hepatectomy patients besides evaluating its effect on prognosis. These samples shall be kept at -80 0C until the plasma separation process.
measure: Assessment of serum GFAP
time frame: 2 years
description: Approximately 25 patients planned to have living donor hepatectomy will be included in the study. The blood samples are taken in the preoperative period before the induction of anesthesia in the operating room and postoperative (the first day, the third day and the seventh day) period to analyze GFAP serum concentrations and neurologic damage of living donor hepatectomy patients besides evaluating its effect on prognosis. These samples shall be kept at -80 0C until the plasma separation process.
measure: Assessment of serum cognitive functions and delirium status
time frame: 2 years
description: During the hospitalization, the delirium status of the patients will be evaluated with the delirium evaluation scale (Delirium Rating Scale-Revised - 98 Turkish version). Functional and cognitive information and other results will be collected at each follow-up point.
intervention type: Procedure
intervention name: Living Donor Hepatectomy
description: On living donor hepatectomy (preoperative), the first following day of surgery, 3rd day, and 7th day, blood will be taken for the measurement of S100β, NSE, and GFAP levels in the postoperative period. The plasma of the blood taken will be separated and stored at -800C. Values will be measured by the ELISA method. During the hospitalization, the delirium status of the patients will be evaluated with the delirium evaluation scale (Delirium Rating Scale-Revised - 98 Turkish version). Functional and cognitive information and other results will be collected at each follow-up point.
s100β, neuron specific enolase and glial fibrillary acidic
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 77 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bora Di̇nc, MD, Assist. Prof.
role: Study Director
affiliation: Akdeniz University Medical Faculty
facility: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Akdeniz University
investigator full name: Bora Dinc
investigator title: MD. Assist. Prof.
mesh term: Delirium
mesh term: Brain Diseases
mesh term: Neurologic Manifestations
sharing ipd: Undecided