<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/NCT03297008</url>
  </required_header>
  <id_info>
    <org_study_id>BIO-MK-001</org_study_id>
    <nct_id>NCT03297008</nct_id>
  </id_info>
  <brief_title>Biomarkers in Saliva and Stool</brief_title>
  <official_title>Understanding Innate and Adaptive Immunological Response in Stool and Saliva Samples in Healthy Donors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Danone Asia Pacific Holdings Pte, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Danone Asia Pacific Holdings Pte, Ltd.</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>
      To collect saliva and stool samples using the salimetrics swab and self-stool collection kit,&#xD;
      process and store samples in a standardized manner. Following this, perform immunological&#xD;
      assays such as enzyme-linked immunosorbent assay, multiplex bead assay and Immunocap to&#xD;
      correlate the salivary and fecal levels of biomarkers in healthy donors. As this method is&#xD;
      non-invasive, we believe that more people will be willing to donate samples.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Many soluble factors found in blood can be detected in saliva and stool. Often levels of&#xD;
      these factors are found to correlate between body fluids, though the exact relationship&#xD;
      between systemic (blood) and local (saliva and stool) immunity is not well established yet.&#xD;
      Saliva- and stool-associated factors are produced in the oral cavity and in the gut, which&#xD;
      represent mucosal sites that potentially come in direct contact with pathogens. Thus, the&#xD;
      levels of mucosal-associated soluble factors can better represent the local immune response&#xD;
      at these sites.&#xD;
&#xD;
      It is becoming clear now that saliva and stool can be used to analyze inflammatory responses&#xD;
      as well. In a recent study, 20 possible salivary biomarkers related to obesity were surveyed&#xD;
      and the authors found four biomarkers that exhibit significant change with increasing body&#xD;
      weight in a pediatric population. Salivary C-reactive protein (CRP), salivary insulin, leptin&#xD;
      and adiponectin were found to be different in obese children compared to healthy normal&#xD;
      weight children. This data suggests that saliva could be a useful blood surrogate for the&#xD;
      study of metabolic complications of obesity in children, where repeated blood sampling can be&#xD;
      both traumatic and difficult. The results of this study also provide insight into the early&#xD;
      development of metabolic disease in children. (Goodson, Kantarci et al. 2014). In another&#xD;
      study, cytokines-chemokines-growth factors (CCGFs) were measured using multiplex bead assays&#xD;
      and compared between plasma, saliva and urine collected from 20 male and female healthy&#xD;
      volunteers. By analyzing more than one sample types from the same subject would increase the&#xD;
      possibility of identifying biomarker(s) for any inflammatory disease. In this study,&#xD;
      gender-specific CCGFs were also observed and concentrations of some CCGFs varied between&#xD;
      genders. This information is also valuable for biomarker discovery that by combining male and&#xD;
      female subjects in a clinical trial would eliminate false discovery of biomarkers (Khan&#xD;
      2012).&#xD;
&#xD;
      The mucosal immune system can be also understood by analyzing stool samples. In a recent&#xD;
      study, it is shown that a particular bacterial predominance, such as Bifidobacterium sp., may&#xD;
      enhance thymic development and immune responses to both oral and parenteral vaccines early in&#xD;
      infancy, whereas a deviation from this pattern, resulting in greater bacterial diversity, may&#xD;
      cause systemic inflammation (neutrophilia) and lower vaccine responses. Thus, vaccine&#xD;
      responsiveness may be improved by promoting intestinal Bifidobacteria sp. and minimizing&#xD;
      dysbiosis early in infancy (Huda, Lewis et al. 2014). Of note, the hallmark of adequate&#xD;
      mucosal immune responses is the production of secretory immunoglobulin A (SIgA), which can&#xD;
      prevent infection and remove antigen crossing the mucosal barrier.SIgAis also imperative to&#xD;
      establish mutualism between host and the intestinal microbiota (Maynard, Elson et al. 2012).&#xD;
      Hence measurement of SIgA can help to assess the mucosal immunity.&#xD;
&#xD;
      Despite saliva and stool samples are increasingly studied in order to assess mucosal immune&#xD;
      response and/or clinical outcomes, there is still a lack of established methodology to be&#xD;
      routinely used in diagnostic laboratories and clinical trials. Therefore our aim is to&#xD;
      collect saliva and stool samples using the salimetrics swab and self-stool collection kit&#xD;
      from a cohort of 60 volunteers, process and store samples in a standardized manner. Following&#xD;
      this, we intend to perform immunological assays such as enzyme-linked immunosorbent assay,&#xD;
      multiplex bead assay and Immunocap to correlate the salivary and fecal levels of biomarkers&#xD;
      in healthy donors. As this method is non-invasive, we believe that more people will be&#xD;
      willing to donate samples. It is also easy to self-collect and it is cost efficient.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">March 11, 2015</start_date>
  <completion_date type="Actual">December 31, 2017</completion_date>
  <primary_completion_date type="Actual">December 31, 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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Establish methods to detect immune markers in non-invasive samples: Saliva and stool in healthy volunteers</measure>
    <time_frame>1 year after completion of recruitment</time_frame>
    <description>ELISA RSV specific Immunoglobulin in saliva</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Establish methods to detect immune markers in non-invasive samples: Saliva and stool in healthy volunteers</measure>
    <time_frame>1 year after completion of recruitment</time_frame>
    <description>ELISA Rotavirus specific Immunoglobulin in stool</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference in RSV-specific Immunoglobulins between age groups.</measure>
    <time_frame>1 year after completion of primary outcome</time_frame>
    <description>Correlation between age and RSV-specific Immunoglobulins in saliva</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in RSV-specific Immunoglobulins between age groups.</measure>
    <time_frame>1 year after completion of primary outcome</time_frame>
    <description>Correlation between age and rotavirus-specific Immunoglobulins in stool</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Establish methods to detect immune markers in non-invasive samples: Saliva and stool in healthy volunteers</measure>
    <time_frame>1 year after completion of primary outcome</time_frame>
    <description>ELISA RSV specific Immunoglobulin in stool</description>
  </other_outcome>
  <other_outcome>
    <measure>Establish methods to detect immune markers in non-invasive samples: Saliva and stool in healthy volunteers</measure>
    <time_frame>1 year after completion of primary outcome</time_frame>
    <description>ELISA Rotavirus specific Immunoglobulin in saliva</description>
  </other_outcome>
  <enrollment type="Actual">86</enrollment>
  <condition>Healthy</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No internvetion</intervention_name>
    <description>No intervention, this is an observational study</description>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Saliva, Stool samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Healthy Volunteers in Singapore between 0 and 60 years of age&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        • Healthy volunteers of age 0-60 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Volunteers with any known infectious diseases, such as HIV and Hepatitis B&#xD;
&#xD;
          -  Volunteers with any acute or chronic illness, such as chronic inflammatory bowel&#xD;
             disease (e.g. Crohn's disease or ulcerative colitis)&#xD;
&#xD;
          -  Volunteers with oral diseases/ulcers&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elena Sandalova, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nutricia Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Danone Nutricia Research</name>
      <address>
        <city>Singapore</city>
        <zip>138671</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>March 9, 2018</last_update_submitted>
  <last_update_submitted_qc>March 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 12, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>healthy</keyword>
  <keyword>saliva</keyword>
  <keyword>stool</keyword>
  <keyword>biomarkers</keyword>
  <keyword>Respiratory Syncytial Virus</keyword>
  <keyword>Rotavirus</keyword>
  <keyword>Immunoglobulin</keyword>
  <keyword>Antibody</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>IDP is not going to be shared.</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/NCT03297008
org study id: BIO-MK-001
nct id: NCT03297008
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To collect saliva and stool samples using the salimetrics swab and self-stool collection kit,
      process and store samples in a standardized manner. Following this, perform immunological
      assays such as enzyme-linked immunosorbent assay, multiplex bead assay and Immunocap to
      correlate the salivary and fecal levels of biomarkers in healthy donors. As this method is
      non-invasive, we believe that more people will be willing to donate samples.
Many soluble factors found in blood can be detected in saliva and stool. Often levels of
      these factors are found to correlate between body fluids, though the exact relationship
      between systemic (blood) and local (saliva and stool) immunity is not well established yet.
      Saliva- and stool-associated factors are produced in the oral cavity and in the gut, which
      represent mucosal sites that potentially come in direct contact with pathogens. Thus, the
      levels of mucosal-associated soluble factors can better represent the local immune response
      at these sites.

      It is becoming clear now that saliva and stool can be used to analyze inflammatory responses
      as well. In a recent study, 20 possible salivary biomarkers related to obesity were surveyed
      and the authors found four biomarkers that exhibit significant change with increasing body
      weight in a pediatric population. Salivary C-reactive protein (CRP), salivary insulin, leptin
      and adiponectin were found to be different in obese children compared to healthy normal
      weight children. This data suggests that saliva could be a useful blood surrogate for the
      study of metabolic complications of obesity in children, where repeated blood sampling can be
      both traumatic and difficult. The results of this study also provide insight into the early
      development of metabolic disease in children. (Goodson, Kantarci et al. 2014). In another
      study, cytokines-chemokines-growth factors (CCGFs) were measured using multiplex bead assays
      and compared between plasma, saliva and urine collected from 20 male and female healthy
      volunteers. By analyzing more than one sample types from the same subject would increase the
      possibility of identifying biomarker(s) for any inflammatory disease. In this study,
      gender-specific CCGFs were also observed and concentrations of some CCGFs varied between
      genders. This information is also valuable for biomarker discovery that by combining male and
      female subjects in a clinical trial would eliminate false discovery of biomarkers (Khan
      2012).

      The mucosal immune system can be also understood by analyzing stool samples. In a recent
      study, it is shown that a particular bacterial predominance, such as Bifidobacterium sp., may
      enhance thymic development and immune responses to both oral and parenteral vaccines early in
      infancy, whereas a deviation from this pattern, resulting in greater bacterial diversity, may
      cause systemic inflammation (neutrophilia) and lower vaccine responses. Thus, vaccine
      responsiveness may be improved by promoting intestinal Bifidobacteria sp. and minimizing
      dysbiosis early in infancy (Huda, Lewis et al. 2014). Of note, the hallmark of adequate
      mucosal immune responses is the production of secretory immunoglobulin A (SIgA), which can
      prevent infection and remove antigen crossing the mucosal barrier.SIgAis also imperative to
      establish mutualism between host and the intestinal microbiota (Maynard, Elson et al. 2012).
      Hence measurement of SIgA can help to assess the mucosal immunity.

      Despite saliva and stool samples are increasingly studied in order to assess mucosal immune
      response and/or clinical outcomes, there is still a lack of established methodology to be
      routinely used in diagnostic laboratories and clinical trials. Therefore our aim is to
      collect saliva and stool samples using the salimetrics swab and self-stool collection kit
      from a cohort of 60 volunteers, process and store samples in a standardized manner. Following
      this, we intend to perform immunological assays such as enzyme-linked immunosorbent assay,
      multiplex bead assay and Immunocap to correlate the salivary and fecal levels of biomarkers
      in healthy donors. As this method is non-invasive, we believe that more people will be
      willing to donate samples. It is also easy to self-collect and it is cost efficient.
observational model: Cohort
time perspective: Cross-Sectional
measure: Establish methods to detect immune markers in non-invasive samples: Saliva and stool in healthy volunteers
time frame: 1 year after completion of recruitment
description: ELISA RSV specific Immunoglobulin in saliva
measure: Establish methods to detect immune markers in non-invasive samples: Saliva and stool in healthy volunteers
time frame: 1 year after completion of recruitment
description: ELISA Rotavirus specific Immunoglobulin in stool
measure: Difference in RSV-specific Immunoglobulins between age groups.
time frame: 1 year after completion of primary outcome
description: Correlation between age and RSV-specific Immunoglobulins in saliva
measure: Difference in RSV-specific Immunoglobulins between age groups.
time frame: 1 year after completion of primary outcome
description: Correlation between age and rotavirus-specific Immunoglobulins in stool
measure: Establish methods to detect immune markers in non-invasive samples: Saliva and stool in healthy volunteers
time frame: 1 year after completion of primary outcome
description: ELISA RSV specific Immunoglobulin in stool
measure: Establish methods to detect immune markers in non-invasive samples: Saliva and stool in healthy volunteers
time frame: 1 year after completion of primary outcome
description: ELISA Rotavirus specific Immunoglobulin in saliva
intervention type: Other
intervention name: No internvetion
description: No intervention, this is an observational study
Saliva, Stool samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Elena Sandalova, PhD
role: Principal Investigator
affiliation: Nutricia Research
facility: 
country: Singapore
responsible party type: Sponsor
sharing ipd: No
ipd description: IDP is not going to be shared.