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/NCT05969990</url>
    </required_header>
    <id_info>
      <org_study_id>QLCR20210182</org_study_id>
      <nct_id>NCT05969990</nct_id>
    </id_info>
    <brief_title>Tryptophan Metabolites in Pediatric Migraine</brief_title>
    <official_title>Exploration of the Role of Tryptophan Metabolites in Pediatric Migraine</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Qilu Hospital of Shandong University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Qilu Hospital of Shandong 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>
        Background:&#xD;
  &#xD;
        Migraine is a common neurological disorder that also has a significant prevalence in&#xD;
        children. Although the exact etiology of migraine is unknown, recent studies suggest an&#xD;
        association between intestinal flora and migraine, and tryptophan metabolism is an important&#xD;
        link between intestinal flora and the nervous system. However, the role of tryptophan&#xD;
        metabolites in childhood migraine is not fully understood. Therefore, the aim of this study&#xD;
        was to investigate the specific role of tryptophan metabolites in childhood migraine.&#xD;
  &#xD;
        Study objectives:&#xD;
  &#xD;
        The main objectives of this study were to assess the changes in tryptophan metabolites in&#xD;
        childhood migraine and to explore their relationship with migraine attacks. Specific&#xD;
        objectives include:&#xD;
  &#xD;
          1. to determine the differences in tryptophan metabolites between children with migraine&#xD;
             and healthy children;&#xD;
  &#xD;
          2. to explore the correlation between tryptophan metabolites and migraine attacks&#xD;
  &#xD;
          3. to assess the potential mechanisms of the role of tryptophan metabolites in childhood&#xD;
             migraine.&#xD;
  &#xD;
        Study methods:&#xD;
  &#xD;
          1. participant recruitment: a certain number of pediatric migraine patients and healthy&#xD;
             children were recruited as controls.&#xD;
  &#xD;
          2. data collection: clinical information, medical history, and blood samples were collected&#xD;
             from participants.&#xD;
  &#xD;
          3. Tryptophan metabolite analysis: using appropriate experimental techniques, ELISA&#xD;
  &#xD;
        Statistical analysis:&#xD;
  &#xD;
        The main analyses included the following:&#xD;
  &#xD;
          1. comparison of differences in tryptophan metabolites between migraine and control groups,&#xD;
             using t-test or Wilcoxon rank sum test.&#xD;
  &#xD;
          2. To assess the value of tryptophan metabolites in the diagnosis of migraine, ROC curve&#xD;
             analysis was used to calculate the sensitivity, specificity, and AUC.&#xD;
  &#xD;
          3. To explore the factors associated with tryptophan metabolites and migraine, multiple&#xD;
             logistic regression analysis was used to assess the risk and protective effects of each&#xD;
             factor on migraine.&#xD;
  &#xD;
        Experimental hypothesis:&#xD;
  &#xD;
        Our experimental hypothesis was that tryptophan metabolites may play a key role in the&#xD;
        pathogenesis of childhood migraine, particularly kynurenine (KYN), quinolinic acid (QUINA),&#xD;
        and kynurenic acid (KYNA). We hypothesized that in pediatric migraine patients, the&#xD;
        concentrations of tryptophan metabolites would change significantly compared to healthy&#xD;
        children. We further hypothesized that the concentrations of certain tryptophan metabolites&#xD;
        correlate with the frequency and severity of migraine attacks. Based on these hypotheses, our&#xD;
        study will examine tryptophan metabolite concentrations in blood samples and perform a&#xD;
        comparative analysis between pediatric migraineurs and healthy children. We will also explore&#xD;
        the correlation between tryptophan metabolites and migraine attacks and determine their risk&#xD;
        and protective role in childhood migraine through multiple logistic regression analysis.&#xD;
  &#xD;
        Outlook:&#xD;
  &#xD;
        The results of this study are expected to reveal the important role of tryptophan metabolites&#xD;
        in the pathogenesis of migraine in children and provide a new basis for the diagnosis and&#xD;
        treatment of migraine in children. In addition, the study may also provide theoretical&#xD;
        support for the development of relevant therapeutic strategies and interventions, and provide&#xD;
        new ideas for the prevention and management of migraine in children.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Method for determination of tryptophan metabolite content:&#xD;
  &#xD;
          1. Timing of blood collection In the case group, blood was collected at any time during the&#xD;
             first 2-4 hours of the migraine attack; in the inter-migraine attack group, blood was&#xD;
             collected at least 24 hours before and after the headache-free period. In the healthy&#xD;
             control group, blood was collected in a quiet state.&#xD;
  &#xD;
          2. Storage and testing methods 5 ml of elbow venous blood was collected from patients and&#xD;
             healthy children in purple tubes, and the samples were immediately transferred to&#xD;
             ice-cold glass tubes containing a mixture of anticoagulant and protease inhibitor, and&#xD;
             centrifuged at 3000 rpm for 5 minutes at 4°C. The supernatant was stored at -80°C, and&#xD;
             tryptophan metabolite levels were measured by ELISA, and the case and control groups&#xD;
             were compared and analyzed.&#xD;
  &#xD;
        Feasibility analysis&#xD;
  &#xD;
          1. The Elisa kit technology and medical statistics technology used in this project have&#xD;
             been widely and maturely applied in other biomedical research fields, and the project&#xD;
             has all the core technology reserves that can ensure the successful completion of the&#xD;
             project.&#xD;
  &#xD;
          2. The PICU of Qilu Hospital of Shandong University, which has rich experience in&#xD;
             scientific research and clinical medicine, as well as rich clinical cases, is sufficient&#xD;
             to meet the needs of scientific research; we have sufficient strength in terms of&#xD;
             scientific research strength, talent demand and economic support to ensure the&#xD;
             successful completion of our experiment.&#xD;
  &#xD;
          3. The pediatric outpatient clinic of Qilu Hospital of Shandong University receives a large&#xD;
             number of children with migraine every day, and the severity of the disease is complex&#xD;
             and varied, so the number and diversity of children with migraine are sufficient to meet&#xD;
             the needs of our experiment.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">January 1, 2022</start_date>
    <completion_date type="Anticipated">December 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Cross-Sectional</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Tryptophan</measure>
      <time_frame>In ictal period, during the first 2-4 hours of the attack. In interictal period, blood was collected at least 24 hours before and after the headache-free period. In the healthy group, blood was collected in the morning after fasting for eight hours.</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Kynurenine</measure>
      <time_frame>In ictal period, during the first 2-4 hours of the attack. In interictal period, blood was collected at least 24 hours before and after the headache-free period. In the healthy group, blood was collected in the morning after fasting for eight hours.</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Kynurenic acid</measure>
      <time_frame>In ictal period, during the first 2-4 hours of the attack. In interictal period, blood was collected at least 24 hours before and after the headache-free period. In the healthy group, blood was collected in the morning after fasting for eight hours.</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Quinolinic acid</measure>
      <time_frame>In ictal period, during the first 2-4 hours of the attack. In interictal period, blood was collected at least 24 hours before and after the headache-free period. In the healthy group, blood was collected in the morning after fasting for eight hours.</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Serotonin</measure>
      <time_frame>In ictal period, during the first 2-4 hours of the attack. In interictal period, blood was collected at least 24 hours before and after the headache-free period. In the healthy group, blood was collected in the morning after fasting for eight hours.</time_frame>
    </primary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">200</enrollment>
    <condition>Migraine in Children</condition>
    <arm_group>
      <arm_group_label>case group</arm_group_label>
      <description>100 children with migraine are included into case group and we will collect the blood of them to investigate tryptophan metabolites plasma concentration</description>
    </arm_group>
    <arm_group>
      <arm_group_label>control group</arm_group_label>
      <description>100 healthy children are included into control group and we will collect the blood of them to investigate tryptophan metabolites plasma concentration</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>tryptophan metabolites in plasma</intervention_name>
      <description>we will investigate the tryptophan metabolites in plasma of children with migraine</description>
      <arm_group_label>case group</arm_group_label>
      <arm_group_label>control group</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          100 children with migraine and 100 healthy children&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age 4-18 years, male or female.&#xD;
  &#xD;
            -  Meet the ICHD-3 diagnostic criteria for migraine with aura, without aura, and chronic&#xD;
               migraine.&#xD;
  &#xD;
            -  Migraine is diagnosed by two or more specialized neurologists.&#xD;
  &#xD;
            -  PedMIDAS score was more than 11.&#xD;
  &#xD;
            -  Migraine was never treated.&#xD;
  &#xD;
            -  Patients and family members gave informed consent to the study's purpose,&#xD;
               significance, risks, benefits, and information of the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Presence of drug overdose.&#xD;
  &#xD;
            -  Autoimmune diseases.&#xD;
  &#xD;
            -  Neurological disorders other than migraine, intracranial masses.&#xD;
  &#xD;
            -  Congenital or genetic disorders.&#xD;
  &#xD;
            -  Diabetes, bronchial asthma, cardiovascular disease, pulmonary disease.&#xD;
  &#xD;
            -  Other types of primary and secondary headaches.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>4 Years</minimum_age>
      <maximum_age>18 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Xinjie Liu</last_name>
      <role>Study Director</role>
      <affiliation>Qilu Hospital of Shandong University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Junhui Liu</last_name>
      <phone>15064039296</phone>
      <email>15064039296@163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Xinjie Liu</last_name>
      <phone>18560086300</phone>
      <email>liuxinjie-ert@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Junhui Liu</name>
        <address>
          <city>Jinan</city>
          <zip>250012</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Junhui Liu</last_name>
        <phone>15064039296</phone>
        <email>15064039296@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <link>
      <url>https://pubmed.ncbi.nlm.nih.gov/36497053/</url>
      <description>Exploring the Tryptophan Metabolic Pathways in Migraine-Related Mechanisms</description>
    </link>
    <link>
      <url>https://pubmed.ncbi.nlm.nih.gov/27000870/</url>
      <description>Altered serum levels of kynurenine metabolites in patients affected by cluster headache.</description>
    </link>
    <reference>
      <citation>Kortesi T, Spekker E, Vecsei L. Exploring the Tryptophan Metabolic Pathways in Migraine-Related Mechanisms. Cells. 2022 Nov 27;11(23):3795. doi: 10.3390/cells11233795.</citation>
      <PMID>36497053</PMID>
    </reference>
    <reference>
      <citation>Curto M, Lionetto L, Negro A, Capi M, Perugino F, Fazio F, Giamberardino MA, Simmaco M, Nicoletti F, Martelletti P. Altered serum levels of kynurenine metabolites in patients affected by cluster headache. J Headache Pain. 2015;17(1):27. doi: 10.1186/s10194-016-0620-2. Epub 2016 Mar 22.</citation>
      <PMID>27000870</PMID>
    </reference>
    <verification_date>January 2023</verification_date>
    <study_first_submitted>May 15, 2023</study_first_submitted>
    <study_first_submitted_qc>July 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 23, 2023</last_update_submitted>
    <last_update_submitted_qc>July 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Migraine in Children, tryptophan metabolites</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Migraine Disorders</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tryptophan</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <provided_document_section>
      <provided_document>
        <document_type>Statistical Analysis Plan</document_type>
        <document_has_protocol>No</document_has_protocol>
        <document_has_icf>No</document_has_icf>
        <document_has_sap>Yes</document_has_sap>
        <document_date>May 1, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT05969990/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 1, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT05969990/ICF_001.pdf</document_url>
      </provided_document>
    </provided_document_section>
    <!-- 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/NCT05969990
  org study id: QLCR20210182
  nct id: NCT05969990
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Background:
  
        Migraine is a common neurological disorder that also has a significant prevalence in
        children. Although the exact etiology of migraine is unknown, recent studies suggest an
        association between intestinal flora and migraine, and tryptophan metabolism is an important
        link between intestinal flora and the nervous system. However, the role of tryptophan
        metabolites in childhood migraine is not fully understood. Therefore, the aim of this study
        was to investigate the specific role of tryptophan metabolites in childhood migraine.
  
        Study objectives:
  
        The main objectives of this study were to assess the changes in tryptophan metabolites in
        childhood migraine and to explore their relationship with migraine attacks. Specific
        objectives include:
  
          1. to determine the differences in tryptophan metabolites between children with migraine
             and healthy children;
  
          2. to explore the correlation between tryptophan metabolites and migraine attacks
  
          3. to assess the potential mechanisms of the role of tryptophan metabolites in childhood
             migraine.
  
        Study methods:
  
          1. participant recruitment: a certain number of pediatric migraine patients and healthy
             children were recruited as controls.
  
          2. data collection: clinical information, medical history, and blood samples were collected
             from participants.
  
          3. Tryptophan metabolite analysis: using appropriate experimental techniques, ELISA
  
        Statistical analysis:
  
        The main analyses included the following:
  
          1. comparison of differences in tryptophan metabolites between migraine and control groups,
             using t-test or Wilcoxon rank sum test.
  
          2. To assess the value of tryptophan metabolites in the diagnosis of migraine, ROC curve
             analysis was used to calculate the sensitivity, specificity, and AUC.
  
          3. To explore the factors associated with tryptophan metabolites and migraine, multiple
             logistic regression analysis was used to assess the risk and protective effects of each
             factor on migraine.
  
        Experimental hypothesis:
  
        Our experimental hypothesis was that tryptophan metabolites may play a key role in the
        pathogenesis of childhood migraine, particularly kynurenine (KYN), quinolinic acid (QUINA),
        and kynurenic acid (KYNA). We hypothesized that in pediatric migraine patients, the
        concentrations of tryptophan metabolites would change significantly compared to healthy
        children. We further hypothesized that the concentrations of certain tryptophan metabolites
        correlate with the frequency and severity of migraine attacks. Based on these hypotheses, our
        study will examine tryptophan metabolite concentrations in blood samples and perform a
        comparative analysis between pediatric migraineurs and healthy children. We will also explore
        the correlation between tryptophan metabolites and migraine attacks and determine their risk
        and protective role in childhood migraine through multiple logistic regression analysis.
  
        Outlook:
  
        The results of this study are expected to reveal the important role of tryptophan metabolites
        in the pathogenesis of migraine in children and provide a new basis for the diagnosis and
        treatment of migraine in children. In addition, the study may also provide theoretical
        support for the development of relevant therapeutic strategies and interventions, and provide
        new ideas for the prevention and management of migraine in children.
  Method for determination of tryptophan metabolite content:
  
          1. Timing of blood collection In the case group, blood was collected at any time during the
             first 2-4 hours of the migraine attack; in the inter-migraine attack group, blood was
             collected at least 24 hours before and after the headache-free period. In the healthy
             control group, blood was collected in a quiet state.
  
          2. Storage and testing methods 5 ml of elbow venous blood was collected from patients and
             healthy children in purple tubes, and the samples were immediately transferred to
             ice-cold glass tubes containing a mixture of anticoagulant and protease inhibitor, and
             centrifuged at 3000 rpm for 5 minutes at 4°C. The supernatant was stored at -80°C, and
             tryptophan metabolite levels were measured by ELISA, and the case and control groups
             were compared and analyzed.
  
        Feasibility analysis
  
          1. The Elisa kit technology and medical statistics technology used in this project have
             been widely and maturely applied in other biomedical research fields, and the project
             has all the core technology reserves that can ensure the successful completion of the
             project.
  
          2. The PICU of Qilu Hospital of Shandong University, which has rich experience in
             scientific research and clinical medicine, as well as rich clinical cases, is sufficient
             to meet the needs of scientific research; we have sufficient strength in terms of
             scientific research strength, talent demand and economic support to ensure the
             successful completion of our experiment.
  
          3. The pediatric outpatient clinic of Qilu Hospital of Shandong University receives a large
             number of children with migraine every day, and the severity of the disease is complex
             and varied, so the number and diversity of children with migraine are sufficient to meet
             the needs of our experiment.
  observational model: Case-Control
  time perspective: Cross-Sectional
  measure: Tryptophan
  time frame: In ictal period, during the first 2-4 hours of the attack. In interictal period, blood was collected at least 24 hours before and after the headache-free period. In the healthy group, blood was collected in the morning after fasting for eight hours.
  measure: Kynurenine
  time frame: In ictal period, during the first 2-4 hours of the attack. In interictal period, blood was collected at least 24 hours before and after the headache-free period. In the healthy group, blood was collected in the morning after fasting for eight hours.
  measure: Kynurenic acid
  time frame: In ictal period, during the first 2-4 hours of the attack. In interictal period, blood was collected at least 24 hours before and after the headache-free period. In the healthy group, blood was collected in the morning after fasting for eight hours.
  measure: Quinolinic acid
  time frame: In ictal period, during the first 2-4 hours of the attack. In interictal period, blood was collected at least 24 hours before and after the headache-free period. In the healthy group, blood was collected in the morning after fasting for eight hours.
  measure: Serotonin
  time frame: In ictal period, during the first 2-4 hours of the attack. In interictal period, blood was collected at least 24 hours before and after the headache-free period. In the healthy group, blood was collected in the morning after fasting for eight hours.
  arm group label: case group
  description: 100 children with migraine are included into case group and we will collect the blood of them to investigate tryptophan metabolites plasma concentration
  arm group label: control group
  description: 100 healthy children are included into control group and we will collect the blood of them to investigate tryptophan metabolites plasma concentration
  intervention type: Other
  intervention name: tryptophan metabolites in plasma
  description: we will investigate the tryptophan metabolites in plasma of children with migraine
  arm group label: case group
  arm group label: control group
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 4 Years
  maximum age: 18 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Xinjie Liu
  role: Study Director
  affiliation: Qilu Hospital of Shandong University
  last name: Junhui Liu
  phone: 15064039296
  email: 15064039296@163.com
  last name: Xinjie Liu
  phone: 18560086300
  email: liuxinjie-ert@163.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  url: https://pubmed.ncbi.nlm.nih.gov/36497053/
  description: Exploring the Tryptophan Metabolic Pathways in Migraine-Related Mechanisms
  url: https://pubmed.ncbi.nlm.nih.gov/27000870/
  description: Altered serum levels of kynurenine metabolites in patients affected by cluster headache.
  citation: Kortesi T, Spekker E, Vecsei L. Exploring the Tryptophan Metabolic Pathways in Migraine-Related Mechanisms. Cells. 2022 Nov 27;11(23):3795. doi: 10.3390/cells11233795.
  PMID: 36497053
  citation: Curto M, Lionetto L, Negro A, Capi M, Perugino F, Fazio F, Giamberardino MA, Simmaco M, Nicoletti F, Martelletti P. Altered serum levels of kynurenine metabolites in patients affected by cluster headache. J Headache Pain. 2015;17(1):27. doi: 10.1186/s10194-016-0620-2. Epub 2016 Mar 22.
  PMID: 27000870
  responsible party type: Sponsor
  mesh term: Migraine Disorders
  mesh term: Tryptophan
  sharing ipd: No
  provided document: 
  provided document: 