<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/NCT04456985</url>
  </required_header>
  <id_info>
    <org_study_id>SH9H-2020-T57-2</org_study_id>
    <nct_id>NCT04456985</nct_id>
  </id_info>
  <brief_title>Effect of Preoperative Intervention With Folic Acid and Vitamin B12 on Postoperative Neurobehavioral Changes in Children</brief_title>
  <official_title>Effect of Preoperative Intervention With Folic Acid and Vitamin B12 on Postoperative Neurobehavioral Changes in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong 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>
      Comparison of preoperative folic acid and VitB12 intervention on postoperative delirium and&#xD;
      long-term neurobehavioral changes in children under general anesthesia&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Folic acid, as a one-carbon unit transferase coenzyme, participates in the synthesis of&#xD;
      purine and thymine, and is an important element of the nervous system. Vitamin B12&#xD;
      participates in methyl conversion and folate metabolism in the body, promoting the conversion&#xD;
      of 5-methyltetrahydrofolate to tetrahydrofolate. It has been reported that the lack of serum&#xD;
      folic acid and B12 is associated with an increased risk of cognitive impairment. The&#xD;
      explanation mechanism of the relationship between folic acid deficiency and cognitive&#xD;
      dysfunction may be that folic acid deficiency leads to impaired central nervous system&#xD;
      methylation, resulting in insufficient methyl synthesis of myelin sheaths, neurotransmitters,&#xD;
      membrane phospholipids and deoxyribonucleic acid. Our previous studies showed that&#xD;
      preoperative folic acid supplementation can alleviate myelin damage and cognitive impairment&#xD;
      in young rats caused by sevoflurane anesthesia. Therefore, this study further explored the&#xD;
      preoperative folic acid and coenzyme B12 supplementation for children's delirium and&#xD;
      long-term neurobehavioral changes after general anesthesia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PAED scale</measure>
    <time_frame>10 minutes after surgery</time_frame>
    <description>Observe whether the index will cause delirium during the recovery period.The evaluation range of the PAED scale is 0-20 points, If the score exceeds 10 points, Then it is considered delirium.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gesell scale</measure>
    <time_frame>2 day after surgery</time_frame>
    <description>Through the gesell scale, 5 tests are carried out on children: gross motor ability, fine movement, physical ability, verbal ability, and human ability.The evaluation range of the Gesell scale is 0-100 points. If the score is higher, it means good. If the score is low, it means that the result is not good. If the result is not good, it may be caused by anesthesia, so we conducted this evaluation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heart Rate</measure>
    <time_frame>During the induction period of anesthesia, intubation, and the operation period；immediately after entering the resuscitation room (T1), 5 minutes before extubation (T2), immediately after extubation (T3), and 2 minutes after extubation (T4);</time_frame>
    <description>Observe heart rate through a monitor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Blood Pressure</measure>
    <time_frame>During the induction period of anesthesia, intubation, and the operation period；immediately after entering the resuscitation room (T1), 5 minutes before extubation (T2), immediately after extubation (T3), and 2 minutes after extubation (T4);</time_frame>
    <description>Observe and calculated mean blood pressure through a monitor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extubation time</measure>
    <time_frame>immediately after surgery</time_frame>
    <description>Extubation time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ramsay sedation score</measure>
    <time_frame>10 minutes after extubation</time_frame>
    <description>Ramsay sedation score after recovery, extubation and every 10min within 30min after extubation，Ramsay sedation score is 1-6 points. If the score is 2-4 points，That result is satisfactory, 5-6 points are excessive sedation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative pain CHEOPs scores</measure>
    <time_frame>20 minutes after extubation</time_frame>
    <description>The postoperative pain CHEOPs scores were taken at the time of extubation and every 10 minutes within 30 minutes after extubation (the total score was less than 6 points, there was no pain, and ≥10 points for corresponding analgesia treatment).&#xD;
The total score is 46 points, if the total score is less than 6 points, it is judged as no pain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Narcotic drugs</measure>
    <time_frame>During the surgery</time_frame>
    <description>The use of narcotic drugs (eg pentazocine, propofol)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Other adverse events during the recovery period</measure>
    <time_frame>Immediately after the surgery</time_frame>
    <description>Other adverse events during the recovery period (eg nausea and vomiting, bronchospasm, respiratory depression, etc.)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>recovery time</measure>
    <time_frame>immediately after recovery</time_frame>
    <description>recovery time</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">360</enrollment>
  <condition>Delirium</condition>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Before the operation, the patient took 20ml of brown sugar aqueous solution containing folic acid and VitB12 for 3 days (folic acid concentration is 0.4mg / d for 2 year old children + 1.2μg / d of VitB12, dissolved in 20ml brown sugar water once a day). Postoperatively, PAED scores were performed at the time of awakening, extubation and every 10min within 30min after extubation. 10 points is defined as delirium during the recovery period). Long-term neurobehavioral changes were evaluated using the Gesell scale, followed up every six months until the age of three</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The patients in the placebo group took 20 ml of brown sugar aqueous solution with the same concentration as the intervention group 3 days before the operation. Postoperatively, PAED scores were performed at the time of recovery, extubation, and every 10 minutes within 30 minutes after extubation. The PAED scores of all children were measured by the same person. (The total score is 0-20, and the score ≥10 is defined as delirium during the recovery period). Long-term neurobehavioral changes were evaluated using the Gesell scale, followed up every six months until the age of three</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Folic acid and vitamin B12</intervention_name>
    <description>Take folic acid and VitB12 for 3 consecutive days before surgery</description>
    <arm_group_label>Intervention group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>brown sugar aqueous</intervention_name>
    <description>take 20 ml of brown sugar aqueous solution with the same concentration as the intervention group 3 days before the operation</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ASA grade is Ⅰ ~ Ⅱ;&#xD;
&#xD;
          2. Children aged 6 months to 2 years old;&#xD;
&#xD;
          3. It is planned to undergo head, neck and maxillofacial surgery under general anesthesia&#xD;
             with anesthesia for less than 6 hours&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Children with a history of respiratory tract infection within 1 week;&#xD;
&#xD;
          2. Children with congenital malformations such as congenital heart disease;&#xD;
&#xD;
          3. Children with central nervous system diseases or mental disorders or mental disorders;&#xD;
&#xD;
          4. Children with long-term use of sedative or analgesic drugs;&#xD;
&#xD;
          5. Children with severe liver and kidney dysfunction;&#xD;
&#xD;
          6. Received folic acid and VitB12 supplement treatment or taken related derivatives;&#xD;
&#xD;
          7. Have taken drugs that affect absorption within the past month, such as sulfonamides,&#xD;
             aspirin, etc .;&#xD;
&#xD;
          8. Those who have participated in other relevant clinical research in the past 3 months;&#xD;
&#xD;
          9. Children with stunting&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>24 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>hong jiang, Doctor</last_name>
    <role>Study Director</role>
    <affiliation>Director of Anesthesiology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>lei zhang, Doctor</last_name>
    <phone>0086-18717822662</phone>
    <email>weiymzhl@126.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>hong jiang, Doctor</last_name>
    <phone>0086-021-23271699</phone>
    <email>jianghongjiuyuan@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>China</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200001</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>lei zhang, doctor</last_name>
      <phone>+86-18717822662</phone>
      <email>weiymzhl@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 14, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>June 29, 2020</last_update_submitted>
  <last_update_submitted_qc>June 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University</investigator_affiliation>
    <investigator_full_name>Zhang Lei</investigator_full_name>
    <investigator_title>Deputy Chief Physician and Associate Researcher</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Folic Acid</mesh_term>
    <mesh_term>Vitamin B 12</mesh_term>
    <mesh_term>Hydroxocobalamin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 7, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT04456985/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 7, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT04456985/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04456985
org study id: SH9H-2020-T57-2
nct id: NCT04456985
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Comparison of preoperative folic acid and VitB12 intervention on postoperative delirium and
      long-term neurobehavioral changes in children under general anesthesia
Folic acid, as a one-carbon unit transferase coenzyme, participates in the synthesis of
      purine and thymine, and is an important element of the nervous system. Vitamin B12
      participates in methyl conversion and folate metabolism in the body, promoting the conversion
      of 5-methyltetrahydrofolate to tetrahydrofolate. It has been reported that the lack of serum
      folic acid and B12 is associated with an increased risk of cognitive impairment. The
      explanation mechanism of the relationship between folic acid deficiency and cognitive
      dysfunction may be that folic acid deficiency leads to impaired central nervous system
      methylation, resulting in insufficient methyl synthesis of myelin sheaths, neurotransmitters,
      membrane phospholipids and deoxyribonucleic acid. Our previous studies showed that
      preoperative folic acid supplementation can alleviate myelin damage and cognitive impairment
      in young rats caused by sevoflurane anesthesia. Therefore, this study further explored the
      preoperative folic acid and coenzyme B12 supplementation for children's delirium and
      long-term neurobehavioral changes after general anesthesia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: PAED scale
time frame: 10 minutes after surgery
description: Observe whether the index will cause delirium during the recovery period.The evaluation range of the PAED scale is 0-20 points, If the score exceeds 10 points, Then it is considered delirium.
measure: Gesell scale
time frame: 2 day after surgery
description: Through the gesell scale, 5 tests are carried out on children: gross motor ability, fine movement, physical ability, verbal ability, and human ability.The evaluation range of the Gesell scale is 0-100 points. If the score is higher, it means good. If the score is low, it means that the result is not good. If the result is not good, it may be caused by anesthesia, so we conducted this evaluation.
measure: Heart Rate
time frame: During the induction period of anesthesia, intubation, and the operation period；immediately after entering the resuscitation room (T1), 5 minutes before extubation (T2), immediately after extubation (T3), and 2 minutes after extubation (T4);
description: Observe heart rate through a monitor
measure: Mean Blood Pressure
time frame: During the induction period of anesthesia, intubation, and the operation period；immediately after entering the resuscitation room (T1), 5 minutes before extubation (T2), immediately after extubation (T3), and 2 minutes after extubation (T4);
description: Observe and calculated mean blood pressure through a monitor
measure: Extubation time
time frame: immediately after surgery
description: Extubation time
measure: Ramsay sedation score
time frame: 10 minutes after extubation
description: Ramsay sedation score after recovery, extubation and every 10min within 30min after extubation，Ramsay sedation score is 1-6 points. If the score is 2-4 points，That result is satisfactory, 5-6 points are excessive sedation.
measure: Postoperative pain CHEOPs scores
time frame: 20 minutes after extubation
description: The postoperative pain CHEOPs scores were taken at the time of extubation and every 10 minutes within 30 minutes after extubation (the total score was less than 6 points, there was no pain, and ≥10 points for corresponding analgesia treatment).
The total score is 46 points, if the total score is less than 6 points, it is judged as no pain
measure: Narcotic drugs
time frame: During the surgery
description: The use of narcotic drugs (eg pentazocine, propofol)
measure: Other adverse events during the recovery period
time frame: Immediately after the surgery
description: Other adverse events during the recovery period (eg nausea and vomiting, bronchospasm, respiratory depression, etc.)
measure: recovery time
time frame: immediately after recovery
description: recovery time
arm group label: Intervention group
arm group type: Active Comparator
description: Before the operation, the patient took 20ml of brown sugar aqueous solution containing folic acid and VitB12 for 3 days (folic acid concentration is 0.4mg / d for 2 year old children + 1.2μg / d of VitB12, dissolved in 20ml brown sugar water once a day). Postoperatively, PAED scores were performed at the time of awakening, extubation and every 10min within 30min after extubation. 10 points is defined as delirium during the recovery period). Long-term neurobehavioral changes were evaluated using the Gesell scale, followed up every six months until the age of three
arm group label: Placebo group
arm group type: Placebo Comparator
description: The patients in the placebo group took 20 ml of brown sugar aqueous solution with the same concentration as the intervention group 3 days before the operation. Postoperatively, PAED scores were performed at the time of recovery, extubation, and every 10 minutes within 30 minutes after extubation. The PAED scores of all children were measured by the same person. (The total score is 0-20, and the score ≥10 is defined as delirium during the recovery period). Long-term neurobehavioral changes were evaluated using the Gesell scale, followed up every six months until the age of three
intervention type: Dietary Supplement
intervention name: Folic acid and vitamin B12
description: Take folic acid and VitB12 for 3 consecutive days before surgery
arm group label: Intervention group
intervention type: Dietary Supplement
intervention name: brown sugar aqueous
description: take 20 ml of brown sugar aqueous solution with the same concentration as the intervention group 3 days before the operation
arm group label: Placebo group
criteria: 
gender: All
minimum age: 6 Months
maximum age: 24 Months
healthy volunteers: No
last name: hong jiang, Doctor
role: Study Director
affiliation: Director of Anesthesiology
last name: lei zhang, Doctor
phone: 0086-18717822662
email: weiymzhl@126.com
last name: hong jiang, Doctor
phone: 0086-021-23271699
email: jianghongjiuyuan@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
investigator full name: Zhang Lei
investigator title: Deputy Chief Physician and Associate Researcher
mesh term: Delirium
mesh term: Folic Acid
mesh term: Vitamin B 12
mesh term: Hydroxocobalamin
sharing ipd: No
provided document: 
provided document: 