<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/NCT03297801</url>
  </required_header>
  <id_info>
    <org_study_id>H13-02523</org_study_id>
    <nct_id>NCT03297801</nct_id>
  </id_info>
  <brief_title>The Effects of Omega-3 PUFAs on the Infant Microbiome and Immunity</brief_title>
  <official_title>The Effects of Omega-3 Polyunsaturated Fatty Acids on the Infant Microbiome and Immunity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of British Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of British Columbia</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>
      Prenatal supplementation with fish oil, rich in omega-3 polyunsaturated fatty acids, is&#xD;
      widely recommended in Canada. The aim of this observational, prospective cohort study is to&#xD;
      determine the effects of maternal fish oil supplements on the development of their infants'&#xD;
      gut microbiota and immunity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      During infancy, the gastrointestinal tract is colonized with microbiota, a community of&#xD;
      microorganisms, which play a significant role in the development, regulation, and maintenance&#xD;
      of immune functions. Fish oil, rich in n-3 polyunsaturated fatty acids (PUFA), are thought to&#xD;
      be anti-inflammatory and consequently may increase susceptibility to infection by hindering&#xD;
      their body's ability to produce an adequate inflammatory response in defense against&#xD;
      infectious disease. Currently, women in Canada are supplementing their diets with n-3 PUFA&#xD;
      during gestation and lactation despite their being conflicting clinical evidence regarding&#xD;
      the beneficial effects on infant development. It is currently unknown how maternal fish oil&#xD;
      supplementation impacts the offspring's gut microbiota and immune functions. Considering that&#xD;
      diet influences microbiota and maternal microbiota is passed from mother to infant, the&#xD;
      investigators hypothesize that maternal fish oil supplementation will affect the&#xD;
      participants' infant gut microbiota and immunity.&#xD;
&#xD;
      This study will evaluate the effects of postnatal n-3 PUFA supplementation in breast milk on&#xD;
      the fecal microbiome in infants over a six-month period. The investigators will analyze the&#xD;
      fecal microbiome of infants born to mothers in the fish oil and non-fish oil groups via next&#xD;
      generation sequencing. As short-chain fatty acids (SCFA) are produced by gut bacteria and&#xD;
      affect immunity, the investigators will analyze SCFA in stool through gas chromatography.&#xD;
      Markers of inflammation like fecal calprotectin and sIgA in stool samples will also be&#xD;
      identified.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 22, 2014</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</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>Changes in infant fecal microbiota of the two groups.</measure>
    <time_frame>6 months</time_frame>
    <description>Fecal microbiota will be measured by examining microbial taxa from infant stool every month from birth until 6-months of age or until solids are introduced.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in infant short-chain fatty acid production of the two groups.</measure>
    <time_frame>6 months</time_frame>
    <description>Changes in short-chain fatty acid production will be analyzed in infant stool through gas chromatography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in infant IgA in shed intestinal epithelial cells of the two groups.</measure>
    <time_frame>6 months</time_frame>
    <description>We will examine the effects of fish oil on immunity by measuring fecal IgA concentrations using ELISA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in infant cytokines in shed intestinal epithelial cells of the two groups.</measure>
    <time_frame>6 months</time_frame>
    <description>We will examine the effects of fish oil on immunity by measuring fecal cytokines (TNF-a, IFN-y, IL-17) using real time PCR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare occurrences of sickness and incidences of disease between the two groups.</measure>
    <time_frame>2 years</time_frame>
    <description>Any incidences of disease in the infants will be closely monitored for the first 2 years of their lives.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in breast milk IgA composition of the two groups.</measure>
    <time_frame>6 months</time_frame>
    <description>Immune markers such as sIgA will be measured in breast milk using an addressable laser bead immunoassay (ALBIA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in breast milk cytokine composition of the two groups.</measure>
    <time_frame>6 months</time_frame>
    <description>Immune markers such cytokines will be measured in breast milk using an addressable laser bead immunoassay (ALBIA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in breast milk lipid composition of the two groups.</measure>
    <time_frame>6 months</time_frame>
    <description>Breast milk lipid concentrations will be analyzed using short-chain fatty acids</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">109</enrollment>
  <condition>Microbial Colonization</condition>
  <condition>Infant Development</condition>
  <arm_group>
    <arm_group_label>Fish oil group</arm_group_label>
    <description>Women who chose to supplement with fish oil, rich in omega-3 polyunsaturated fatty acids, during gestation or lactation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No fish oil group</arm_group_label>
    <description>Women who chose not to supplement with fish oil during gestation or lactation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Fish oil supplements</intervention_name>
    <description>Women who chose to supplement with fish oil during gestation or lactation.</description>
    <arm_group_label>Fish oil group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Healthy women in the Okanagan Valley who predominantly breastfeed their healthy, full-term&#xD;
        infants while self-administering fish oil supplements or not.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All mothers of infants in the Okanagan Valley are invited to participate in the study&#xD;
             between the first day of delivery to until solid food is introduced into the infant's&#xD;
             diet.&#xD;
&#xD;
          -  Healthy, full-term infants, who are predominantly breastfed by mothers who are or are&#xD;
             not supplementing with fish oil. Mothers must also be healthy, i.e., asymptomatic and&#xD;
             with no clinical indication of disease.&#xD;
&#xD;
          -  To remain within the inclusion criteria for this study, participants will be expected&#xD;
             to be consistent (i.e. maintain the same type and amount of omega-3 PUFA intake or no&#xD;
             intake) with whichever supplementation group they have decided to join for the&#xD;
             entirety of the breast milk and infant stool donation period. In other words, the&#xD;
             investigators will be asking the participants not to switch from one group to another&#xD;
             which would happen by changing their omega-3 PUFA supplementation patterns.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any infants who are ingesting juice or solid foods as part of their regular diet will&#xD;
             be excluded from the study.&#xD;
&#xD;
          -  Any infants who are clinically ill (fever, contagious diseases, or active diarrhea)&#xD;
             will be excluded from the study.&#xD;
&#xD;
          -  Any participants who decide to drastically change their omega-3 PUFA supplementation&#xD;
             intake patterns (i.e. causing them to switch between study groups) will result in all&#xD;
             subsequent samples to be excluded from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Deanna L Gibson, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of British Columbia</affiliation>
  </overall_official>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 25, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>May 1, 2018</last_update_submitted>
  <last_update_submitted_qc>May 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of British Columbia</investigator_affiliation>
    <investigator_full_name>Deanna Gibson</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Infections</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Infant stool microbial data will be made open access upon publishing.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03297801
org study id: H13-02523
nct id: NCT03297801
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Prenatal supplementation with fish oil, rich in omega-3 polyunsaturated fatty acids, is
      widely recommended in Canada. The aim of this observational, prospective cohort study is to
      determine the effects of maternal fish oil supplements on the development of their infants'
      gut microbiota and immunity.
During infancy, the gastrointestinal tract is colonized with microbiota, a community of
      microorganisms, which play a significant role in the development, regulation, and maintenance
      of immune functions. Fish oil, rich in n-3 polyunsaturated fatty acids (PUFA), are thought to
      be anti-inflammatory and consequently may increase susceptibility to infection by hindering
      their body's ability to produce an adequate inflammatory response in defense against
      infectious disease. Currently, women in Canada are supplementing their diets with n-3 PUFA
      during gestation and lactation despite their being conflicting clinical evidence regarding
      the beneficial effects on infant development. It is currently unknown how maternal fish oil
      supplementation impacts the offspring's gut microbiota and immune functions. Considering that
      diet influences microbiota and maternal microbiota is passed from mother to infant, the
      investigators hypothesize that maternal fish oil supplementation will affect the
      participants' infant gut microbiota and immunity.

      This study will evaluate the effects of postnatal n-3 PUFA supplementation in breast milk on
      the fecal microbiome in infants over a six-month period. The investigators will analyze the
      fecal microbiome of infants born to mothers in the fish oil and non-fish oil groups via next
      generation sequencing. As short-chain fatty acids (SCFA) are produced by gut bacteria and
      affect immunity, the investigators will analyze SCFA in stool through gas chromatography.
      Markers of inflammation like fecal calprotectin and sIgA in stool samples will also be
      identified.
observational model: Cohort
time perspective: Prospective
measure: Changes in infant fecal microbiota of the two groups.
time frame: 6 months
description: Fecal microbiota will be measured by examining microbial taxa from infant stool every month from birth until 6-months of age or until solids are introduced.
measure: Changes in infant short-chain fatty acid production of the two groups.
time frame: 6 months
description: Changes in short-chain fatty acid production will be analyzed in infant stool through gas chromatography.
measure: Changes in infant IgA in shed intestinal epithelial cells of the two groups.
time frame: 6 months
description: We will examine the effects of fish oil on immunity by measuring fecal IgA concentrations using ELISA
measure: Changes in infant cytokines in shed intestinal epithelial cells of the two groups.
time frame: 6 months
description: We will examine the effects of fish oil on immunity by measuring fecal cytokines (TNF-a, IFN-y, IL-17) using real time PCR.
measure: Compare occurrences of sickness and incidences of disease between the two groups.
time frame: 2 years
description: Any incidences of disease in the infants will be closely monitored for the first 2 years of their lives.
measure: Changes in breast milk IgA composition of the two groups.
time frame: 6 months
description: Immune markers such as sIgA will be measured in breast milk using an addressable laser bead immunoassay (ALBIA)
measure: Changes in breast milk cytokine composition of the two groups.
time frame: 6 months
description: Immune markers such cytokines will be measured in breast milk using an addressable laser bead immunoassay (ALBIA)
measure: Changes in breast milk lipid composition of the two groups.
time frame: 6 months
description: Breast milk lipid concentrations will be analyzed using short-chain fatty acids
arm group label: Fish oil group
description: Women who chose to supplement with fish oil, rich in omega-3 polyunsaturated fatty acids, during gestation or lactation.
arm group label: No fish oil group
description: Women who chose not to supplement with fish oil during gestation or lactation.
intervention type: Dietary Supplement
intervention name: Fish oil supplements
description: Women who chose to supplement with fish oil during gestation or lactation.
arm group label: Fish oil group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
last name: Deanna L Gibson, Ph.D.
role: Principal Investigator
affiliation: University of British Columbia
responsible party type: Principal Investigator
investigator affiliation: University of British Columbia
investigator full name: Deanna Gibson
investigator title: Associate Professor
mesh term: Communicable Diseases
mesh term: Infections
sharing ipd: No
ipd description: Infant stool microbial data will be made open access upon publishing.