<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/NCT03016195</url>
  </required_header>
  <id_info>
    <org_study_id>16/NS/0105</org_study_id>
    <nct_id>NCT03016195</nct_id>
  </id_info>
  <brief_title>Evaluation of the Normal Range of Urinary Sodium Levels in Healthy Newborn Babies</brief_title>
  <acronym>USALTI</acronym>
  <official_title>Evaluation of the Normal Range of Urinary Sodium Levels in Healthy Newborn Babies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Glasgow</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Glasgow</source>
  <brief_summary>
    <textblock>
      Oral sodium supplementation is currently administered in cases of poor weight gain in infants&#xD;
      particularly in patients who have undergone gastrointestinal surgical procedures. The&#xD;
      decision to start oral supplementation is based on urinary sodium levels although the level&#xD;
      at which to start treatment is variable as the range in normal, healthy infants is unknown.&#xD;
      This study aims to ascertain the normal range of sodium in urine specimens collected from&#xD;
      healthy newborn babies.&#xD;
&#xD;
      It is believed that by increasing the level of salt in the intestine, glucose can be more&#xD;
      easily be absorbed and therefore weight gain improved. Babies with conditions where they are&#xD;
      at risk of salt depletion (i.e. those with a stoma) are currently administered oral sodium&#xD;
      supplementation if they are failing to gain weight and have an associated 'low' urinary&#xD;
      sodium level. Low levels of urinary sodium are considered to represent a state of low body&#xD;
      sodium levels, as the kidneys attempt to reabsorb most of the sodium in the urine before it&#xD;
      is excreted.&#xD;
&#xD;
      Current practice varies widely as to the level below which treatment should be instigated.&#xD;
      Some centres advise below 20 mmol/L (Birmingham Children's Hospital and Nottingham Children's&#xD;
      Hospital guidelines), others below 10 mmol/L (University Children's Hospital, Zurich). In&#xD;
      Glasgow, babies with poor weight gain are given sodium supplementation if urinary sodium&#xD;
      levels are below 40 mmol/L. There are no documented ranges for the levels of urinary sodium&#xD;
      in healthy, newborn babies.&#xD;
&#xD;
      By determining the reference range of urinary sodium levels in healthy, term babies who are&#xD;
      gaining weight appropriately, the investigators hope to be able to have a better&#xD;
      understanding about both the level below which supplementation should be considered and the&#xD;
      target range that should be aimed for.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design&#xD;
&#xD;
      The study has been designed as a cross sectional study where participants details are&#xD;
      recorded at birth, followed by a second time point at 6 weeks of age when a corresponding&#xD;
      sample of urine will be obtained. The population being studied is healthy term (37-41 week&#xD;
      gestation) babies with no significant ante- or post-natal history born within the study&#xD;
      period in a single maternity unit. Participants will be required to collect a sample of urine&#xD;
      at 6 weeks post-natal age (they will be provided with a standardized means to collect the&#xD;
      specimen) and return it to the investigators in a pre-paid, pre-addressed envelope (UN602&#xD;
      compliant packaging). This design has been chosen to obtain an unbiased sample group, with&#xD;
      minimal inconvenience or risk to participants. All confounding factors will be measured on a&#xD;
      data-sheet accompanying the specimen (sex, weight, method of feeding and medications). The&#xD;
      study should not be susceptible to bias as there is no perceived association between those&#xD;
      participants who either wish to take part in the study or subsequently choose to collect and&#xD;
      return the specimen, and their baby's urinary sodium level.&#xD;
&#xD;
      Prospective participants will be identified and approached by the neonatal/maternity staff at&#xD;
      the pre-discharge routine baby check (see Inclusion/Exclusion criteria) from the starting&#xD;
      date of the study for a period of 3 months (estimate based on average newborn deliveries per&#xD;
      week and expected return yield of urinary sodium samples i.e. participant drop-out rate).&#xD;
      There will be no coercion to participate. Mothers will be supplied with a patient information&#xD;
      statement and informed consent obtained. The consent will be filed in the mother's medical&#xD;
      notes and there will be no means of identification on the consent form that will link it with&#xD;
      any specimen obtained from the mother's baby. Instead, it will be a generic form indicating&#xD;
      intent to participate in the study. If mothers do wish to take part in the study, an initial&#xD;
      data-set will be obtained that will be identified by a unique study participation number.&#xD;
      This will include sex of the baby, birth weight, intended method of feeding/milk and any&#xD;
      medication. A study pack will be issued containing a set of instructions outlining the study,&#xD;
      a gender-specific urine collection bag, a specimen pot labeled with the participant's unique&#xD;
      identifying number (into which the urine sample should be transferred prior to returning it),&#xD;
      the data-set collection form and pre-paid, pre-addressed envelope (UN602 compliant packaging)&#xD;
      in which to return the specimen and completed form.&#xD;
&#xD;
      It will be made clear to all participants that they are free to withdraw from the study for&#xD;
      any reason at any stage and that this will not affect their future care. No attempts will be&#xD;
      made to contact the families if samples are not returned after the 6 week time period.&#xD;
&#xD;
      There is no planned interim analysis. The study will continue until sufficient samples have&#xD;
      been returned in order to complete meaningful statistical analysis. It is anticipated that&#xD;
      this study should last no longer than 3 months.&#xD;
&#xD;
      Safety analysis&#xD;
&#xD;
      Participation in the study is not deemed to involve any risk for patients, their families or&#xD;
      staff involved.&#xD;
&#xD;
      Sample size and estimation&#xD;
&#xD;
      135 participants recruited over 3 months. An independent statistician has been consulted. The&#xD;
      sample size or reference limits has been based upon the precision of the confidence intervals&#xD;
      around each limit. On computing a 95% reference interval based on a normal distribution (with&#xD;
      reference limits to be at most 15% of the reference interval size) gives a sample size of&#xD;
      135.&#xD;
&#xD;
      A dropout rate of at least 25% is expected, and therefore, in order to achieve an adequate&#xD;
      sample size, we intend to pause the study after 200 participants have enrolled. If less than&#xD;
      135 samples are returned within 6 weeks after the final participant is enrolled, then further&#xD;
      participants will be recruited to achieve the desired sample size.&#xD;
&#xD;
      Sample analysis&#xD;
&#xD;
      Urinary electrolytes will be measured in the Biochemistry laboratory in the Royal Hospital&#xD;
      for Sick Children. Urinary electrolytes (potassium, sodium and chloride) are measured by&#xD;
      in-direct (diluted) ion-selective electrodes (ISEs) which utilize membranes selective for&#xD;
      each ion species. A set volume of urine (15 ul) is diluted with diluent. A measuring&#xD;
      electrode is then submersed in this solution. An electrical potential (voltage) is developed&#xD;
      across the membranes between the reference and measuring electrodes in accordance with the&#xD;
      Nernst equation. The measured voltage is compared to previously determined calibrator&#xD;
      voltages and converted into ion concentrations (mmol/L).&#xD;
&#xD;
      Following analysis samples will be disposed in accordance with the Human Tissue Authority's&#xD;
      Code of Practice.&#xD;
&#xD;
      Statistical analysis&#xD;
&#xD;
      The variation of urinary sodium for the cohort will be presented as a normal range.&#xD;
&#xD;
      The urinary sodium of children who have not achieved a satisfactory weight gain will be&#xD;
      compared with those who have by a standard t test (as long as the urinary sodium values are&#xD;
      normally distributed).&#xD;
&#xD;
      Study closure&#xD;
&#xD;
      The study will end if any one of the following criteria is met:&#xD;
&#xD;
        -  The planned sample size has been achieved&#xD;
&#xD;
        -  There is insufficient funding to support further recruitment, and no reasonable prospect&#xD;
           of additional support being obtained&#xD;
&#xD;
      Ethical Consideration&#xD;
&#xD;
      The study will be carried out in accordance with the World Medical Association Declaration of&#xD;
      Helsinki (1964) and its revisions (Tokyo [1975], Venice [1983], Hong Kong [1989], South&#xD;
      Africa [1996] and Edinburgh[2000]). Favourable ethical opinion will be sought from an&#xD;
      appropriate Research and Ethics Committee (REC) before patients are entered into this study.&#xD;
      Patients will only be allowed to enter the study once either they have provided written&#xD;
      informed consent or their next of kin have provided written informed consent. The Chief&#xD;
      Investigator (CI) will be responsible for updating the Ethics committee of any new&#xD;
      information related to the study.&#xD;
&#xD;
      Finance and indemnity&#xD;
&#xD;
      This study is currently not sponsored. As the study is not deemed to confer risk to&#xD;
      participants, their families or staff, indemnity has not been sought.&#xD;
&#xD;
      Dissemination of results&#xD;
&#xD;
      It is not the intent of the researchers to inform the participants of the results of the&#xD;
      study. Firstly, all of the specimens collected and analyzed during the study are&#xD;
      unidentifiable there will be no way of contacting those who have taken part in the research&#xD;
      project. Secondly, the question that the study is designed to answer has no direct impact on&#xD;
      the care of any of the participants. Instead, the researchers aim to present their results at&#xD;
      a specialty-specific conference (e.g. British Association of Paediatric Surgeons annual&#xD;
      congress) and in an appropriate peer-reviewed journal, regardless of the outcome of the&#xD;
      results.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Poor return rate/high dropout rate requiring alteration to study methodology&#xD;
  </why_stopped>
  <start_date type="Actual">October 2016</start_date>
  <completion_date type="Actual">April 2017</completion_date>
  <primary_completion_date type="Actual">April 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>Random urinary sodium concentration (mmol/L)</measure>
    <time_frame>Approximately 6 weeks after birth - sample asked to be collected by parents at 6 weeks of age</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Weight velocity (by World Health Organization growth chart centiles)</measure>
    <time_frame>Birth weight to weight at 6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feeding practices - which milk type mothers use to feed their babies e.g. exclusive breastmilk, exclusive formula, mixed</measure>
    <time_frame>At birth and 6 weeks</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">200</enrollment>
  <condition>Electrolyte Depletion</condition>
  <condition>Stoma Ileostomy</condition>
  <condition>Stoma Colostomy</condition>
  <condition>Growth Failure</condition>
  <eligibility>
    <study_pop>
      <textblock>
        The population being studied is healthy term (37-41 week gestation) babies with no&#xD;
        significant ante- or post-natal history born within the study period in a single maternity&#xD;
        unit.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Term (37-41 week gestation) infant&#xD;
&#xD;
          -  Born at specified maternity unit within study period&#xD;
&#xD;
          -  Uncomplicated pregnancy with no antenatal diagnosis&#xD;
&#xD;
          -  Uncomplicated postnatal period: no admission to neonatal/special care unit&#xD;
&#xD;
          -  Full enteral milk feeds since birth&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  &lt; 37/40 gestation or &gt; 41/40 gestation infants&#xD;
&#xD;
          -  Antenatal diagnosis of congenital abnormality&#xD;
&#xD;
          -  Postnatal admission to the neonatal unit/special care baby unit&#xD;
&#xD;
          -  Period of total parenteral nutrition&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>7 Days</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Royal Hospital for Children Glasgow</name>
      <address>
        <city>Glasgow</city>
        <state>South Lanarkshire</state>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>January 6, 2017</study_first_submitted>
  <study_first_submitted_qc>January 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>May 3, 2017</last_update_submitted>
  <last_update_submitted_qc>May 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Glasgow</investigator_affiliation>
    <investigator_full_name>Paul Cullis</investigator_full_name>
    <investigator_title>Honorary clinical lecturer</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Failure to Thrive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03016195
org study id: 16/NS/0105
nct id: NCT03016195
lead sponsor: 
Oral sodium supplementation is currently administered in cases of poor weight gain in infants
      particularly in patients who have undergone gastrointestinal surgical procedures. The
      decision to start oral supplementation is based on urinary sodium levels although the level
      at which to start treatment is variable as the range in normal, healthy infants is unknown.
      This study aims to ascertain the normal range of sodium in urine specimens collected from
      healthy newborn babies.

      It is believed that by increasing the level of salt in the intestine, glucose can be more
      easily be absorbed and therefore weight gain improved. Babies with conditions where they are
      at risk of salt depletion (i.e. those with a stoma) are currently administered oral sodium
      supplementation if they are failing to gain weight and have an associated 'low' urinary
      sodium level. Low levels of urinary sodium are considered to represent a state of low body
      sodium levels, as the kidneys attempt to reabsorb most of the sodium in the urine before it
      is excreted.

      Current practice varies widely as to the level below which treatment should be instigated.
      Some centres advise below 20 mmol/L (Birmingham Children's Hospital and Nottingham Children's
      Hospital guidelines), others below 10 mmol/L (University Children's Hospital, Zurich). In
      Glasgow, babies with poor weight gain are given sodium supplementation if urinary sodium
      levels are below 40 mmol/L. There are no documented ranges for the levels of urinary sodium
      in healthy, newborn babies.

      By determining the reference range of urinary sodium levels in healthy, term babies who are
      gaining weight appropriately, the investigators hope to be able to have a better
      understanding about both the level below which supplementation should be considered and the
      target range that should be aimed for.
Study design

      The study has been designed as a cross sectional study where participants details are
      recorded at birth, followed by a second time point at 6 weeks of age when a corresponding
      sample of urine will be obtained. The population being studied is healthy term (37-41 week
      gestation) babies with no significant ante- or post-natal history born within the study
      period in a single maternity unit. Participants will be required to collect a sample of urine
      at 6 weeks post-natal age (they will be provided with a standardized means to collect the
      specimen) and return it to the investigators in a pre-paid, pre-addressed envelope (UN602
      compliant packaging). This design has been chosen to obtain an unbiased sample group, with
      minimal inconvenience or risk to participants. All confounding factors will be measured on a
      data-sheet accompanying the specimen (sex, weight, method of feeding and medications). The
      study should not be susceptible to bias as there is no perceived association between those
      participants who either wish to take part in the study or subsequently choose to collect and
      return the specimen, and their baby's urinary sodium level.

      Prospective participants will be identified and approached by the neonatal/maternity staff at
      the pre-discharge routine baby check (see Inclusion/Exclusion criteria) from the starting
      date of the study for a period of 3 months (estimate based on average newborn deliveries per
      week and expected return yield of urinary sodium samples i.e. participant drop-out rate).
      There will be no coercion to participate. Mothers will be supplied with a patient information
      statement and informed consent obtained. The consent will be filed in the mother's medical
      notes and there will be no means of identification on the consent form that will link it with
      any specimen obtained from the mother's baby. Instead, it will be a generic form indicating
      intent to participate in the study. If mothers do wish to take part in the study, an initial
      data-set will be obtained that will be identified by a unique study participation number.
      This will include sex of the baby, birth weight, intended method of feeding/milk and any
      medication. A study pack will be issued containing a set of instructions outlining the study,
      a gender-specific urine collection bag, a specimen pot labeled with the participant's unique
      identifying number (into which the urine sample should be transferred prior to returning it),
      the data-set collection form and pre-paid, pre-addressed envelope (UN602 compliant packaging)
      in which to return the specimen and completed form.

      It will be made clear to all participants that they are free to withdraw from the study for
      any reason at any stage and that this will not affect their future care. No attempts will be
      made to contact the families if samples are not returned after the 6 week time period.

      There is no planned interim analysis. The study will continue until sufficient samples have
      been returned in order to complete meaningful statistical analysis. It is anticipated that
      this study should last no longer than 3 months.

      Safety analysis

      Participation in the study is not deemed to involve any risk for patients, their families or
      staff involved.

      Sample size and estimation

      135 participants recruited over 3 months. An independent statistician has been consulted. The
      sample size or reference limits has been based upon the precision of the confidence intervals
      around each limit. On computing a 95% reference interval based on a normal distribution (with
      reference limits to be at most 15% of the reference interval size) gives a sample size of
      135.

      A dropout rate of at least 25% is expected, and therefore, in order to achieve an adequate
      sample size, we intend to pause the study after 200 participants have enrolled. If less than
      135 samples are returned within 6 weeks after the final participant is enrolled, then further
      participants will be recruited to achieve the desired sample size.

      Sample analysis

      Urinary electrolytes will be measured in the Biochemistry laboratory in the Royal Hospital
      for Sick Children. Urinary electrolytes (potassium, sodium and chloride) are measured by
      in-direct (diluted) ion-selective electrodes (ISEs) which utilize membranes selective for
      each ion species. A set volume of urine (15 ul) is diluted with diluent. A measuring
      electrode is then submersed in this solution. An electrical potential (voltage) is developed
      across the membranes between the reference and measuring electrodes in accordance with the
      Nernst equation. The measured voltage is compared to previously determined calibrator
      voltages and converted into ion concentrations (mmol/L).

      Following analysis samples will be disposed in accordance with the Human Tissue Authority's
      Code of Practice.

      Statistical analysis

      The variation of urinary sodium for the cohort will be presented as a normal range.

      The urinary sodium of children who have not achieved a satisfactory weight gain will be
      compared with those who have by a standard t test (as long as the urinary sodium values are
      normally distributed).

      Study closure

      The study will end if any one of the following criteria is met:

        -  The planned sample size has been achieved

        -  There is insufficient funding to support further recruitment, and no reasonable prospect
           of additional support being obtained

      Ethical Consideration

      The study will be carried out in accordance with the World Medical Association Declaration of
      Helsinki (1964) and its revisions (Tokyo [1975], Venice [1983], Hong Kong [1989], South
      Africa [1996] and Edinburgh[2000]). Favourable ethical opinion will be sought from an
      appropriate Research and Ethics Committee (REC) before patients are entered into this study.
      Patients will only be allowed to enter the study once either they have provided written
      informed consent or their next of kin have provided written informed consent. The Chief
      Investigator (CI) will be responsible for updating the Ethics committee of any new
      information related to the study.

      Finance and indemnity

      This study is currently not sponsored. As the study is not deemed to confer risk to
      participants, their families or staff, indemnity has not been sought.

      Dissemination of results

      It is not the intent of the researchers to inform the participants of the results of the
      study. Firstly, all of the specimens collected and analyzed during the study are
      unidentifiable there will be no way of contacting those who have taken part in the research
      project. Secondly, the question that the study is designed to answer has no direct impact on
      the care of any of the participants. Instead, the researchers aim to present their results at
      a specialty-specific conference (e.g. British Association of Paediatric Surgeons annual
      congress) and in an appropriate peer-reviewed journal, regardless of the outcome of the
      results.
observational model: Cohort
time perspective: Cross-Sectional
measure: Random urinary sodium concentration (mmol/L)
time frame: Approximately 6 weeks after birth - sample asked to be collected by parents at 6 weeks of age
measure: Weight velocity (by World Health Organization growth chart centiles)
time frame: Birth weight to weight at 6 weeks
measure: Feeding practices - which milk type mothers use to feed their babies e.g. exclusive breastmilk, exclusive formula, mixed
time frame: At birth and 6 weeks
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 7 Days
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University of Glasgow
investigator full name: Paul Cullis
investigator title: Honorary clinical lecturer
mesh term: Failure to Thrive
sharing ipd: No