<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/NCT03000543</url>
  </required_header>
  <id_info>
    <org_study_id>PR-14126</org_study_id>
    <nct_id>NCT03000543</nct_id>
  </id_info>
  <brief_title>Novel Isotope Dilution Technique to Assess Vitamin A Status</brief_title>
  <official_title>Validation of a Novel Isotope Dilution Technique to Assess Vitamin A Status in Infants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>International Centre for Diarrhoeal Disease Research, Bangladesh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Newcastle University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>International Centre for Diarrhoeal Disease Research, Bangladesh</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      There is no reliable method for vitamin A (VA) assessment for infants and young children.&#xD;
      Serum VA concentration is not an authenticate indicator of VA status, while existing&#xD;
      deuterium- VA isotope dilution methods to determine the whole body VA status require 3 weeks&#xD;
      and not applicable for infants and children. The investigator's research group recently&#xD;
      developed a new simplified equation to measure VA pool size in 4-5 days, correlated with&#xD;
      compartmental model-predicted value and estimate VA pool size in adults with high precision.&#xD;
      In this study, we validate the method in healthy infants and infants with an inflammatory&#xD;
      condition.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      Whole-body VA status in infant and children can be estimated without accounting for the&#xD;
      fractional catabolic rate in the context of an inflammatory condition&#xD;
&#xD;
      Specific Objectives:&#xD;
&#xD;
      In this study, the investigators propose to determine the early time point equation for&#xD;
      assessing VA pool size in infants with or without inflammatory condition using model-based&#xD;
      compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma&#xD;
      over time.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      A total of 183 infants (9-18 mo of age) will participate in this study in the following two&#xD;
      phases of the &quot;Super Kid study&quot; that ensure no more than 2 venous blood samples from each&#xD;
      infant, even though multiple time points (at least 4 subjects / time-point) over a 28-day&#xD;
      study period will be available for mathematical modeling. In this study, investigators will&#xD;
      use two different stable isotopic vitamin A e.g., 13C10-retinyl acetate and 13C4-retinyl&#xD;
      acetate. 400 μg of these isotopes, dissolved in 0.5 mL of sunflower oil, will be provided&#xD;
      directly into the infant's mouth by using a direct replacement pipette. Mothers will be asked&#xD;
      to breastfeed their infant after oral dosing to enhance absorption of the labeled vitamin A.&#xD;
      Specific activity of 13C10- and 13C4- retinyl acetate in the blood samples will be measured&#xD;
      by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Dietary and morbidity&#xD;
      questionnaires will be used. Investigators will also use PENTA vaccines as a means to induce&#xD;
      controlled inflammation (closely mimic to natural infection). PENTA is a combination of five&#xD;
      different vaccine antigens (Hepatitis B (HBV)/ Haemophilus influenza type b (Hib) /&#xD;
      Tetanus-Diphtheria-whole cell Pertussis (TDwP)). This vaccination is beneficial to the&#xD;
      infants since the World Health Organization recommends a booster vaccination dose. At the end&#xD;
      of the study, PENTA vaccines will also be provided to the study infants in the &quot;no-vaccine&quot;&#xD;
      group.&#xD;
&#xD;
      (A) 115 infants will be enrolled randomly into 16 groups of them 40 infants will be in the&#xD;
      first group, while other infants will be assigned in the other 15 groups (n=5/group). On day&#xD;
      0 (at 0h), all infants (n=115) will receive an oral dose of 13C10-retinyl acetate. Blood&#xD;
      samples (5 mL) will be taken from 6h to 16th day of dosing at 9 different time-points. On day&#xD;
      16 (at 0h), randomly selected 50% infants (n=20) in the first group, as well as 30 infants in&#xD;
      the other 6 groups, will receive PENTA vaccines, while the other 50% infants (n=20) in the&#xD;
      first Group, as well as 45 infants in the other 9 groups, will receive no vaccines. 24 hours&#xD;
      after vaccination (On day 17) a finger-prick blood sample will be obtained from the infants&#xD;
      in the vaccinated group to measure CRP (QuikRead go, Orion, Finland). Infants who do not&#xD;
      develop inflammation (CRP&gt; 5mg/L) after PENTA vaccination will be excluded from the study. On&#xD;
      day 17 (at 0h), all infants (n=115) will receive another oral dose of 13C4-retinyl acetate.&#xD;
      Blood samples (5mL) will be collected from day 16 to day 28 at 11 different time-points for&#xD;
      each of the vaccinated and non-vaccinated infants. This study will also assess the absorption&#xD;
      of isotopic retinol by determining in total excreted stool up to 72 h post isotope dosing in&#xD;
      a subsample of infants&#xD;
&#xD;
      (B) 68 infants will be enrolled in this phase. Of them, 28 infants will be assigned randomly&#xD;
      into 7 groups (n=4/group). They will receive PENTA vaccines on day -1, and the next day (day&#xD;
      0) they will receive an oral dose of 13C4-retinyl acetate. Blood samples (5mL) will be&#xD;
      collected from day 1 to day 28 at 8 different time points. In a separate design, 40 infants&#xD;
      will receive an oral dose of 13C10-retinyl acetate on day 0 and blood samples (5mL) will be&#xD;
      collected on day 4. On day 7 they all will receive another oral dose of 13C4-retinyl acetate&#xD;
      (400 μg, dissolved in 0.5 mL of sunflower oil). On day 10, infants will receive PENTA&#xD;
      vaccines (n=30) or no vaccine (n=10) and 1-day after vaccination, blood samples (5 mL) will&#xD;
      be obtained from infants who develop inflammation (CRP&gt; 5mg/L) in the vaccine group and also&#xD;
      from infants in the control group (day 11).&#xD;
&#xD;
      Outcome measures:&#xD;
&#xD;
      The early time point equation for assessing VA pool size in a group of infants with or&#xD;
      without inflammation&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2016</start_date>
  <completion_date type="Actual">June 30, 2019</completion_date>
  <primary_completion_date type="Actual">June 30, 2019</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Vitamin A pool size in infants with or without inflammation</measure>
    <time_frame>Kinetic study for 28 days for each of the 2 groups of infants</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">250</enrollment>
  <condition>Healthy Infants</condition>
  <condition>Infants With an Inflammatory Condition</condition>
  <arm_group>
    <arm_group_label>Vitamin A pool size in infants without inflammatory condition</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Assessing vitamin A (VA) pool size in infants without inflammatory condition using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma over time.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin A pool size in infants with inflammatory condition</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Assessing vitamin A (VA) pool size in infants without inflammatory condition using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma over time.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Vaccine</intervention_name>
    <description>Pentavalent vaccine. It is a combination of five different antigens (Hepatitis B (HBV)/ Haemophilus influenzae type b (HiB) / Tetanus-Diphtheria-whole cell Pertussis (TDwP)).</description>
    <arm_group_label>Vitamin A pool size in infants with inflammatory condition</arm_group_label>
    <other_name>PENTA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. 9 - 18 months of age&#xD;
&#xD;
          2. Infants with normal body temperature and normal CRP (&lt;5 mg/L)&#xD;
&#xD;
          3. Infants receive breast milk from the mother at least once per day&#xD;
&#xD;
          4. Mothers produce a breast milk containing 30-40 nmol vitamin A /g milk fat&#xD;
&#xD;
          5. Infants received a high-dose vitamin A capsules at the time of the most recent&#xD;
             national distribution campaign (within the last 2-4 months)&#xD;
&#xD;
          6. Mother is 18 - 45 years of age&#xD;
&#xD;
          7. Mother and her infant plan to stay in the study area for the duration of the study&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Mother or infant has chronic disease&#xD;
&#xD;
          2. Mother or infant has acute illness on the day of data collection&#xD;
&#xD;
          3. Infant is anemic (Hb &lt;90 g/L)&#xD;
&#xD;
          4. Infant has weight for length &lt;80% of the reference median&#xD;
&#xD;
          5. Infants do not develop inflammation (CRP ≥5 mg/L) after PENTA vaccination&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>9 Months</minimum_age>
    <maximum_age>18 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shaikh M Ahmad, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>International Centre for Diarrhoeal Disease Research, Bangladesh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Trail Unit (CTU), icddr,b.</name>
      <address>
        <city>Dhaka</city>
        <zip>1212</zip>
        <country>Bangladesh</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shaikh Meshbahuddin Ahmad</name>
      <address>
        <city>Dhaka</city>
        <zip>1212</zip>
        <country>Bangladesh</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bangladesh</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 22, 2016</study_first_posted>
  <last_update_submitted>August 19, 2019</last_update_submitted>
  <last_update_submitted_qc>August 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>vitamin A</keyword>
  <keyword>vitamin A isotope</keyword>
  <keyword>Inflammation</keyword>
  <!-- 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/NCT03000543
org study id: PR-14126
nct id: NCT03000543
lead sponsor: 
collaborator: 
Background:

      There is no reliable method for vitamin A (VA) assessment for infants and young children.
      Serum VA concentration is not an authenticate indicator of VA status, while existing
      deuterium- VA isotope dilution methods to determine the whole body VA status require 3 weeks
      and not applicable for infants and children. The investigator's research group recently
      developed a new simplified equation to measure VA pool size in 4-5 days, correlated with
      compartmental model-predicted value and estimate VA pool size in adults with high precision.
      In this study, we validate the method in healthy infants and infants with an inflammatory
      condition.

      Hypothesis:

      Whole-body VA status in infant and children can be estimated without accounting for the
      fractional catabolic rate in the context of an inflammatory condition

      Specific Objectives:

      In this study, the investigators propose to determine the early time point equation for
      assessing VA pool size in infants with or without inflammatory condition using model-based
      compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma
      over time.

      Methods:

      A total of 183 infants (9-18 mo of age) will participate in this study in the following two
      phases of the "Super Kid study" that ensure no more than 2 venous blood samples from each
      infant, even though multiple time points (at least 4 subjects / time-point) over a 28-day
      study period will be available for mathematical modeling. In this study, investigators will
      use two different stable isotopic vitamin A e.g., 13C10-retinyl acetate and 13C4-retinyl
      acetate. 400 μg of these isotopes, dissolved in 0.5 mL of sunflower oil, will be provided
      directly into the infant's mouth by using a direct replacement pipette. Mothers will be asked
      to breastfeed their infant after oral dosing to enhance absorption of the labeled vitamin A.
      Specific activity of 13C10- and 13C4- retinyl acetate in the blood samples will be measured
      by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Dietary and morbidity
      questionnaires will be used. Investigators will also use PENTA vaccines as a means to induce
      controlled inflammation (closely mimic to natural infection). PENTA is a combination of five
      different vaccine antigens (Hepatitis B (HBV)/ Haemophilus influenza type b (Hib) /
      Tetanus-Diphtheria-whole cell Pertussis (TDwP)). This vaccination is beneficial to the
      infants since the World Health Organization recommends a booster vaccination dose. At the end
      of the study, PENTA vaccines will also be provided to the study infants in the "no-vaccine"
      group.

      (A) 115 infants will be enrolled randomly into 16 groups of them 40 infants will be in the
      first group, while other infants will be assigned in the other 15 groups (n=5/group). On day
      0 (at 0h), all infants (n=115) will receive an oral dose of 13C10-retinyl acetate. Blood
      samples (5 mL) will be taken from 6h to 16th day of dosing at 9 different time-points. On day
      16 (at 0h), randomly selected 50% infants (n=20) in the first group, as well as 30 infants in
      the other 6 groups, will receive PENTA vaccines, while the other 50% infants (n=20) in the
      first Group, as well as 45 infants in the other 9 groups, will receive no vaccines. 24 hours
      after vaccination (On day 17) a finger-prick blood sample will be obtained from the infants
      in the vaccinated group to measure CRP (QuikRead go, Orion, Finland). Infants who do not
      develop inflammation (CRP> 5mg/L) after PENTA vaccination will be excluded from the study. On
      day 17 (at 0h), all infants (n=115) will receive another oral dose of 13C4-retinyl acetate.
      Blood samples (5mL) will be collected from day 16 to day 28 at 11 different time-points for
      each of the vaccinated and non-vaccinated infants. This study will also assess the absorption
      of isotopic retinol by determining in total excreted stool up to 72 h post isotope dosing in
      a subsample of infants

      (B) 68 infants will be enrolled in this phase. Of them, 28 infants will be assigned randomly
      into 7 groups (n=4/group). They will receive PENTA vaccines on day -1, and the next day (day
      0) they will receive an oral dose of 13C4-retinyl acetate. Blood samples (5mL) will be
      collected from day 1 to day 28 at 8 different time points. In a separate design, 40 infants
      will receive an oral dose of 13C10-retinyl acetate on day 0 and blood samples (5mL) will be
      collected on day 4. On day 7 they all will receive another oral dose of 13C4-retinyl acetate
      (400 μg, dissolved in 0.5 mL of sunflower oil). On day 10, infants will receive PENTA
      vaccines (n=30) or no vaccine (n=10) and 1-day after vaccination, blood samples (5 mL) will
      be obtained from infants who develop inflammation (CRP> 5mg/L) in the vaccine group and also
      from infants in the control group (day 11).

      Outcome measures:

      The early time point equation for assessing VA pool size in a group of infants with or
      without inflammation
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Vitamin A pool size in infants with or without inflammation
time frame: Kinetic study for 28 days for each of the 2 groups of infants
arm group label: Vitamin A pool size in infants without inflammatory condition
arm group type: No Intervention
description: Assessing vitamin A (VA) pool size in infants without inflammatory condition using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma over time.
arm group label: Vitamin A pool size in infants with inflammatory condition
arm group type: Experimental
description: Assessing vitamin A (VA) pool size in infants without inflammatory condition using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma over time.
intervention type: Biological
intervention name: Vaccine
description: Pentavalent vaccine. It is a combination of five different antigens (Hepatitis B (HBV)/ Haemophilus influenzae type b (HiB) / Tetanus-Diphtheria-whole cell Pertussis (TDwP)).
arm group label: Vitamin A pool size in infants with inflammatory condition
other name: PENTA
criteria: 
gender: All
minimum age: 9 Months
maximum age: 18 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Shaikh M Ahmad, Ph.D.
role: Principal Investigator
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
facility: 
facility: 
country: Bangladesh
responsible party type: Sponsor