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/NCT05992493</url>
    </required_header>
    <id_info>
      <org_study_id>A-BR-109-005</org_study_id>
      <nct_id>NCT05992493</nct_id>
    </id_info>
    <brief_title>The Role of Human Milk Oligosaccharides and Microbiomes on Infantile Colic and Atopic Dermatitis in Term Infants</brief_title>
    <official_title>To Explore and Develop the Effective Human Milk Oligosaccharides and Microbiomes on Maternal and Infant Health and Neurodevelopment in Early Infancy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Cheng-Kung University Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Cheng-Kung University Hospital</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: Human milk oligosaccharides (HMO) and microbiota are both key factors for infants&#xD;
        to shape the gut flora and develop the immune system. Breastfed infant is beneficial to&#xD;
        prevent the occurrence of infantile colic (IC) and atopic dermatitis (AD), which may through&#xD;
        shaping a healthy microbiota. However, the gut microbiota biomarkers representing IC and AD&#xD;
        have not yet been discovered. In addition, the effectiveness of supplement of HMO in infant&#xD;
        formula reduce the incidence of IC and AD in infants is still debate.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Purpose: To investigate the preventive role of HMO-supplement formula on IC and AD in term&#xD;
        infants in a clinical trial.&#xD;
  &#xD;
        Method: The investigators will enroll three cohorts (exclusive breastfeeding, formula&#xD;
        feeding, and HMO-supplement formula feeding infants) for research. The investigators&#xD;
        collected samples of serial baby feces from subjects at 0, 1, 2, 4, 6, 12 months in this&#xD;
        study. The fecal microbiota composition will be analyzed by detecting 16S-rRNA using next&#xD;
        generation sequencing method. The demographic data and incidence of IC (0-5 months) and AD&#xD;
        (0-12 months) was followed and recorded.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 7, 2023</start_date>
    <completion_date type="Anticipated">August 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 30, 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of IC and AD will be compared between three groups</measure>
      <time_frame>The 1 months after birth follow-up</time_frame>
      <description>According to the feeding method, singleton full-term infants will divide into three groups (n=300) including recorded demographic data. The diagnosis of IC and AD is based on Rome IV criteria and the Taiwan Academy of Pediatric Allergy, Asthma, and Immunology (TAPAAI) criteria, respectively. The incidence of IC and AD will be compared between the three groups.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of IC and AD will be compared between three groups</measure>
      <time_frame>The 2 months after birth follow-up</time_frame>
      <description>According to the feeding method, singleton full-term infants will divide into three groups (n=300) including recorded demographic data. The diagnosis of IC and AD is based on Rome IV criteria and the Taiwan Academy of Pediatric Allergy, Asthma, and Immunology (TAPAAI) criteria, respectively. The incidence of IC and AD will be compared between the three groups.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of IC and AD will be compared between three groups</measure>
      <time_frame>The 4 months after birth follow-up</time_frame>
      <description>According to the feeding method, singleton full-term infants will divide into three groups (n=300) including recorded demographic data. The diagnosis of IC and AD is based on Rome IV criteria and the Taiwan Academy of Pediatric Allergy, Asthma, and Immunology (TAPAAI) criteria, respectively. The incidence of IC and AD will be compared between the three groups.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of IC and AD will be compared between three groups</measure>
      <time_frame>The 6 months after birth follow-up</time_frame>
      <description>According to the feeding method, singleton full-term infants will divide into three groups (n=300) including recorded demographic data. The diagnosis of IC and AD is based on Rome IV criteria and the Taiwan Academy of Pediatric Allergy, Asthma, and Immunology (TAPAAI) criteria, respectively. The incidence of IC and AD will be compared between the three groups.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of IC and AD will be compared between three groups</measure>
      <time_frame>The 12 months after birth follow-up</time_frame>
      <description>According to the feeding method, singleton full-term infants will divide into three groups (n=300) including recorded demographic data. The diagnosis of IC and AD is based on Rome IV criteria and the Taiwan Academy of Pediatric Allergy, Asthma, and Immunology (TAPAAI) criteria, respectively. The incidence of IC and AD will be compared between the three groups.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Next-generation sequencing analysis-based differences on gut microbiota in infants between three groups</measure>
      <time_frame>Infant stool samples will be collected at various time points from 0 to 1 year of age.</time_frame>
      <description>Singleton full-term infants will divide into three groups (n=300) according to feeding method. The collected fecal samples will be analyze the composition of microbiota using NGS method. The differences of microbiota pattern will be identified.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Infantile weight growth between different feeding pattern</measure>
      <time_frame>The 1 months after birth follow-up</time_frame>
      <description>Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body weight growth (gm) will be recorded and compared between the three groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Infantile weight growth between different feeding pattern</measure>
      <time_frame>The 2 months after birth follow-up</time_frame>
      <description>Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body weight growth (gm) will be recorded and compared between the three groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Infantile weight growth between different feeding pattern</measure>
      <time_frame>The 4 months after birth follow-up</time_frame>
      <description>Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body weight growth (gm) will be recorded and compared between the three groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Infantile weight growth between different feeding pattern</measure>
      <time_frame>The 6 months after birth follow-up</time_frame>
      <description>Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body weight growth (gm) will be recorded and compared between the three groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Infantile weight growth between different feeding pattern</measure>
      <time_frame>The 12 months after birth follow-up</time_frame>
      <description>Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body weight growth (gm) will be recorded and compared between three groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Infantile height growth between different feeding pattern</measure>
      <time_frame>The 1 months after birth follow-up</time_frame>
      <description>Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body height growth (cm) will be recorded and compared between the three groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Infantile height growth between different feeding pattern</measure>
      <time_frame>The 2 months after birth follow-up</time_frame>
      <description>Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body height growth (cm) will be recorded and compared between the three groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Infantile height growth between different feeding pattern</measure>
      <time_frame>The 4 months after birth follow-up</time_frame>
      <description>Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body height growth (cm) will be recorded and compared between the three groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Infantile height growth between different feeding pattern</measure>
      <time_frame>The 6 months after birth follow-up</time_frame>
      <description>Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body height growth (cm) will be recorded and compared between the three groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Infantile height growth between different feeding pattern</measure>
      <time_frame>The 12 months after birth follow-up</time_frame>
      <description>Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body height growth (cm) will be recorded and compared between the three groups.</description>
    </secondary_outcome>
    <number_of_groups>3</number_of_groups>
    <enrollment type="Anticipated">300</enrollment>
    <condition>Infantile Colic</condition>
    <condition>Breast Feeding</condition>
    <condition>Atopic Dermatitis</condition>
    <condition>Infant Formula</condition>
    <arm_group>
      <arm_group_label>Breast-milk feeding</arm_group_label>
      <description>Exclusive breastfeeding for 4 months or more</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control Formula milk feeding</arm_group_label>
      <description>Exclusive formula milk for 4 months or more</description>
    </arm_group>
    <arm_group>
      <arm_group_label>HMO-Formula-milk feeding</arm_group_label>
      <description>Exclusive HMO-formula milk for 4 months or more</description>
    </arm_group>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        infant fecal sample and mother breast-milk sample&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          The investigators collected exclusive, formula-fed and HMO-supplement formula-fed infants.&#xD;
          Inclusion criteria were infants with a gestational age &gt;= 37 weeks and a birth weight&#xD;
          greater than 2500 gm. Exclusion criteria were infants born with perinatal injury, use of&#xD;
          antibiotics prior to stool collection, growth-related congenital anomalies, and major&#xD;
          illnesses requiring hospitalization.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. New born&#xD;
  &#xD;
            2. Gestational age of &gt;= 37 weeks&#xD;
  &#xD;
            3. birth weight greater than 2500 gm&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Born with Perinatal insults&#xD;
  &#xD;
            2. Mother with antimicrobial agents 1 month before delivery&#xD;
  &#xD;
            3. Congenital abnormalities related to growth&#xD;
  &#xD;
            4. Major disease admitted to Level II or NICU&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Day</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Yao-jong Yang, PhD</last_name>
      <phone>+886 928 720 689</phone>
      <email>yaojong@mail.ncku.edu.tw</email>
    </overall_contact>
    <location>
      <facility>
        <name>National Cheng Kung University &amp; Hospital</name>
        <address>
          <city>Tainan</city>
          <zip>704</zip>
          <country>Taiwan</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Yao-jong Yang, PhD</last_name>
        <phone>+886 928 720 689</phone>
        <email>yaojong@mail.ncku.edu.tw</email>
      </contact>
    </location>
    <location_countries>
      <country>Taiwan</country>
    </location_countries>
    <reference>
      <citation>Zivkovic AM, German JB, Lebrilla CB, Mills DA. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1(Suppl 1):4653-8. doi: 10.1073/pnas.1000083107. Epub 2010 Aug 2.</citation>
      <PMID>20679197</PMID>
    </reference>
    <reference>
      <citation>Le Doare K, Holder B, Bassett A, Pannaraj PS. Mother's Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity. Front Immunol. 2018 Feb 28;9:361. doi: 10.3389/fimmu.2018.00361. eCollection 2018.</citation>
      <PMID>29599768</PMID>
    </reference>
    <reference>
      <citation>Ward RE, Ninonuevo M, Mills DA, Lebrilla CB, German JB. In vitro fermentation of breast milk oligosaccharides by Bifidobacterium infantis and Lactobacillus gasseri. Appl Environ Microbiol. 2006 Jun;72(6):4497-9. doi: 10.1128/AEM.02515-05.</citation>
      <PMID>16751577</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>September 30, 2022</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>National Cheng-Kung University Hospital</investigator_affiliation>
      <investigator_full_name>Yao-Jong Yang</investigator_full_name>
      <investigator_title>professor</investigator_title>
    </responsible_party>
    <keyword>Breast milk</keyword>
    <keyword>microbiota</keyword>
    <keyword>infant health</keyword>
    <keyword>Human milk oligosaccharides</keyword>
    <keyword>prebiotics</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dermatitis, Atopic</mesh_term>
      <mesh_term>Colic</mesh_term>
      <mesh_term>Dermatitis</mesh_term>
      <mesh_term>Eczema</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05992493
  org study id: A-BR-109-005
  nct id: NCT05992493
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Background: Human milk oligosaccharides (HMO) and microbiota are both key factors for infants
        to shape the gut flora and develop the immune system. Breastfed infant is beneficial to
        prevent the occurrence of infantile colic (IC) and atopic dermatitis (AD), which may through
        shaping a healthy microbiota. However, the gut microbiota biomarkers representing IC and AD
        have not yet been discovered. In addition, the effectiveness of supplement of HMO in infant
        formula reduce the incidence of IC and AD in infants is still debate.
  Purpose: To investigate the preventive role of HMO-supplement formula on IC and AD in term
        infants in a clinical trial.
  
        Method: The investigators will enroll three cohorts (exclusive breastfeeding, formula
        feeding, and HMO-supplement formula feeding infants) for research. The investigators
        collected samples of serial baby feces from subjects at 0, 1, 2, 4, 6, 12 months in this
        study. The fecal microbiota composition will be analyzed by detecting 16S-rRNA using next
        generation sequencing method. The demographic data and incidence of IC (0-5 months) and AD
        (0-12 months) was followed and recorded.
  observational model: Cohort
  time perspective: Prospective
  measure: Incidence of IC and AD will be compared between three groups
  time frame: The 1 months after birth follow-up
  description: According to the feeding method, singleton full-term infants will divide into three groups (n=300) including recorded demographic data. The diagnosis of IC and AD is based on Rome IV criteria and the Taiwan Academy of Pediatric Allergy, Asthma, and Immunology (TAPAAI) criteria, respectively. The incidence of IC and AD will be compared between the three groups.
  measure: Incidence of IC and AD will be compared between three groups
  time frame: The 2 months after birth follow-up
  description: According to the feeding method, singleton full-term infants will divide into three groups (n=300) including recorded demographic data. The diagnosis of IC and AD is based on Rome IV criteria and the Taiwan Academy of Pediatric Allergy, Asthma, and Immunology (TAPAAI) criteria, respectively. The incidence of IC and AD will be compared between the three groups.
  measure: Incidence of IC and AD will be compared between three groups
  time frame: The 4 months after birth follow-up
  description: According to the feeding method, singleton full-term infants will divide into three groups (n=300) including recorded demographic data. The diagnosis of IC and AD is based on Rome IV criteria and the Taiwan Academy of Pediatric Allergy, Asthma, and Immunology (TAPAAI) criteria, respectively. The incidence of IC and AD will be compared between the three groups.
  measure: Incidence of IC and AD will be compared between three groups
  time frame: The 6 months after birth follow-up
  description: According to the feeding method, singleton full-term infants will divide into three groups (n=300) including recorded demographic data. The diagnosis of IC and AD is based on Rome IV criteria and the Taiwan Academy of Pediatric Allergy, Asthma, and Immunology (TAPAAI) criteria, respectively. The incidence of IC and AD will be compared between the three groups.
  measure: Incidence of IC and AD will be compared between three groups
  time frame: The 12 months after birth follow-up
  description: According to the feeding method, singleton full-term infants will divide into three groups (n=300) including recorded demographic data. The diagnosis of IC and AD is based on Rome IV criteria and the Taiwan Academy of Pediatric Allergy, Asthma, and Immunology (TAPAAI) criteria, respectively. The incidence of IC and AD will be compared between the three groups.
  measure: Next-generation sequencing analysis-based differences on gut microbiota in infants between three groups
  time frame: Infant stool samples will be collected at various time points from 0 to 1 year of age.
  description: Singleton full-term infants will divide into three groups (n=300) according to feeding method. The collected fecal samples will be analyze the composition of microbiota using NGS method. The differences of microbiota pattern will be identified.
  measure: Infantile weight growth between different feeding pattern
  time frame: The 1 months after birth follow-up
  description: Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body weight growth (gm) will be recorded and compared between the three groups.
  measure: Infantile weight growth between different feeding pattern
  time frame: The 2 months after birth follow-up
  description: Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body weight growth (gm) will be recorded and compared between the three groups.
  measure: Infantile weight growth between different feeding pattern
  time frame: The 4 months after birth follow-up
  description: Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body weight growth (gm) will be recorded and compared between the three groups.
  measure: Infantile weight growth between different feeding pattern
  time frame: The 6 months after birth follow-up
  description: Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body weight growth (gm) will be recorded and compared between the three groups.
  measure: Infantile weight growth between different feeding pattern
  time frame: The 12 months after birth follow-up
  description: Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body weight growth (gm) will be recorded and compared between three groups.
  measure: Infantile height growth between different feeding pattern
  time frame: The 1 months after birth follow-up
  description: Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body height growth (cm) will be recorded and compared between the three groups.
  measure: Infantile height growth between different feeding pattern
  time frame: The 2 months after birth follow-up
  description: Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body height growth (cm) will be recorded and compared between the three groups.
  measure: Infantile height growth between different feeding pattern
  time frame: The 4 months after birth follow-up
  description: Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body height growth (cm) will be recorded and compared between the three groups.
  measure: Infantile height growth between different feeding pattern
  time frame: The 6 months after birth follow-up
  description: Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body height growth (cm) will be recorded and compared between the three groups.
  measure: Infantile height growth between different feeding pattern
  time frame: The 12 months after birth follow-up
  description: Singleton full-term infants will divide into three groups (n=300) according to feeding method. The body height growth (cm) will be recorded and compared between the three groups.
  arm group label: Breast-milk feeding
  description: Exclusive breastfeeding for 4 months or more
  arm group label: Control Formula milk feeding
  description: Exclusive formula milk for 4 months or more
  arm group label: HMO-Formula-milk feeding
  description: Exclusive HMO-formula milk for 4 months or more
  infant fecal sample and mother breast-milk sample
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 1 Day
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Yao-jong Yang, PhD
  phone: +886 928 720 689
  email: yaojong@mail.ncku.edu.tw
  facility: 
  status: Recruiting
  contact: 
  country: Taiwan
  citation: Zivkovic AM, German JB, Lebrilla CB, Mills DA. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1(Suppl 1):4653-8. doi: 10.1073/pnas.1000083107. Epub 2010 Aug 2.
  PMID: 20679197
  citation: Le Doare K, Holder B, Bassett A, Pannaraj PS. Mother's Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity. Front Immunol. 2018 Feb 28;9:361. doi: 10.3389/fimmu.2018.00361. eCollection 2018.
  PMID: 29599768
  citation: Ward RE, Ninonuevo M, Mills DA, Lebrilla CB, German JB. In vitro fermentation of breast milk oligosaccharides by Bifidobacterium infantis and Lactobacillus gasseri. Appl Environ Microbiol. 2006 Jun;72(6):4497-9. doi: 10.1128/AEM.02515-05.
  PMID: 16751577
  responsible party type: Principal Investigator
  investigator affiliation: National Cheng-Kung University Hospital
  investigator full name: Yao-Jong Yang
  investigator title: professor
  mesh term: Dermatitis, Atopic
  mesh term: Colic
  mesh term: Dermatitis
  mesh term: Eczema
  sharing ipd: Undecided