<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/NCT03031288</url>
  </required_header>
  <id_info>
    <org_study_id>feeding-01</org_study_id>
    <nct_id>NCT03031288</nct_id>
  </id_info>
  <brief_title>Effects of Vented Base Feeding Bottle in Preterm Infants With GERD Symptoms.</brief_title>
  <acronym>FeedGERD</acronym>
  <official_title>Vented Base Feeding Bottle in Preterm Infants With GERD Symptoms: Effects on Respiration-swallow Patterns and Reflux.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Turin, Italy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Turin, Italy</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aim of the study is to evaluate the effects of vented base bottles on respiration-swallow&#xD;
      patterns and on gastroesophageal refluxes in preterm infants with clinical suspect of&#xD;
      gastroesophageal reflux disease (GERD).&#xD;
&#xD;
      In this crossover-randomized study, we compared the effects of standard feeding bottles (A)&#xD;
      versus vented base feeding bottles (B) on a group of patients with at least 2 clinical GERD&#xD;
      symptoms. 24 hours of synchronized cardiorespiratory (CR) and Esophageal Multichannel&#xD;
      intraluminal impedance (MII/pH) monitoring were evaluated for each patient. During this&#xD;
      period, patients were fed alternatively with feeding bottle A and B.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In preterm infants a deficit of both coordination and gastro-intestinal motility is often the&#xD;
      underpinning cause of oxygen desaturations and gastro-esophageal reflux. Breastfeeding&#xD;
      enhances the maturation of the respiration-swallow mechanism. For this reason, a feeding&#xD;
      bottle that best recreates the physiological sucking from the maternal breast is highly&#xD;
      desirable in non-breastfed newborns.&#xD;
&#xD;
      Population: newborns referred to esophageal Multichannel Intraluminal Impedance and pH-metry&#xD;
      (MII/pH) combined with cardiorespiratory (CR) monitoring for GERD or cardio-respiratory&#xD;
      symptoms&#xD;
&#xD;
      Materials and methods: we compare the effects of traditional feeding bottles (A) versus&#xD;
      vented base feeding bottles (B) on cardiorespiratory and reflux events in newborns undergoing&#xD;
      24 hours synchronized CR and MII/pH monitoring. During the exam, newborns are fed,&#xD;
      alternatively, by feeding bottle A and B with human milk or formula. Some training meals are&#xD;
      offered the day before monitoring to get newborns enrolled into the study used to vented base&#xD;
      feeding bottles.&#xD;
&#xD;
      Cardiorespiratory monitoring is performed through VitaGuard VG3100® (Getemed Medizin- und&#xD;
      Informationstechnik AG, Teltow, Germany) based on Masimo Signal Extraction Technology (SET)®&#xD;
      (Masimo Corp., Irvine, CA, USA). It operates with a blood oxygen saturation (SpO2) detector,&#xD;
      placed on the right wrist, and 3 thoracic electrodes. This instrument is able to record ECG,&#xD;
      heart rate, SpO2 and thoracic plethysmographic curve. The signals are analyzed with VitaWin&#xD;
      3® software (Getemed Medizin - und Informationstechnik AG, Teltow, Germany), by filtering&#xD;
      artifacts.&#xD;
&#xD;
      The MII/pH monitoring is performed through a neonatal catheter (Infant Comfort TEC®) with 7&#xD;
      impedence electrodes (creating 6 impedance channels) and one pH detector able to cover the&#xD;
      whole distance from the pharynx to the lower esophageal sphincter (LES) (channel 1). The pH&#xD;
      detector is placed within channel 1, 1.5 cm above the LES. The correct positioning of the&#xD;
      catheter is measured through fluoroscopy and eventually corrected. Data obtained from&#xD;
      impedance channels that result proximal to the superior esophageal sphincter are excluded&#xD;
      from the analysis. The acquisition and recording of MII/pH data are performed through Sleuth&#xD;
      System, Sandhill Scientific Inc., Highlands Ranch, Colorado, USA. The analysis of MII/pH&#xD;
      tracings is made visually by a single operator using BioView 5.3.4 software (Sleuth System,&#xD;
      Sandhill Scientific Inc., Highlands Ranch, Colorado, USA).&#xD;
&#xD;
      The variables analyzed are listed as follows:&#xD;
&#xD;
      Clinical variables:&#xD;
&#xD;
        -  feeding time (min)&#xD;
&#xD;
        -  feeding total volume (mL)&#xD;
&#xD;
        -  n. GER during feeding&#xD;
&#xD;
        -  n. GER in the post-prandial period (150 min after feeding)&#xD;
&#xD;
      Cardiorespiratory variables:&#xD;
&#xD;
        -  frequency of apnea, desaturation and bradycardia during feeding&#xD;
&#xD;
        -  frequency of apnea, desaturation and bradycardia during post-prandial period&#xD;
&#xD;
        -  mean duration of apnea during feeding and post-prandial period&#xD;
&#xD;
        -  mean and minimum desaturation level during feeding and post-prandial period&#xD;
&#xD;
        -  mean and minimum heart rate during feeding and post-prandial period&#xD;
&#xD;
      MII/pH variables:&#xD;
&#xD;
        -  Swallow frequency during feeding and post-prandial period (events/h)&#xD;
&#xD;
        -  Bolus Presence Time (BPT): seconds between bolus entry and bolus exit in the distal&#xD;
           channel&#xD;
&#xD;
        -  Bolus Head Advancing Time (BHAT): seconds between bolus entry in proximal channel and&#xD;
           entry in distal channel&#xD;
&#xD;
        -  Bolus Head Advancing Time Corrected for Esophageal Length (BHATc): BHAT corrected for&#xD;
           esophageal length (BHATc = BHAT / esophageal length)&#xD;
&#xD;
        -  Reflux pH: minimum pH value registered during each GER event. It classifies refluxes&#xD;
           into 3 different types: acid (pH &lt; 4), weakly acid (pH 4-7) and weakly alkaline (pH &gt; 7)&#xD;
&#xD;
        -  GER frequency, (events/h)&#xD;
&#xD;
        -  Bolus Clearance Time (BCT): reflux duration, recorded at distal channel (s)&#xD;
&#xD;
        -  Bolus Reflux Extent (BRE), (n. channels)&#xD;
&#xD;
        -  Proximal GER frequency (events/h)&#xD;
&#xD;
        -  Bolus Exposure Index (BEI): percentage of time in which GER involves esophagus during&#xD;
           MII/pH monitoring&#xD;
&#xD;
        -  Reflux Index (RI): percentage of time during which pH falls below 4 during MII/pH&#xD;
           monitoring&#xD;
&#xD;
      Randomization: the alternate use of feeding bottles A and B is set by a binary random&#xD;
      sequencing generated by Microsoft Office Excel software that indicates the first feeding&#xD;
      bottle to be used. This is a single-blind study since the sequence is unknown to the&#xD;
      specialist in charge of reporting MII/pH and CR monitoring.&#xD;
&#xD;
      Statistical analysis:&#xD;
&#xD;
      The analysis is made with Statistical Software Package For Windows® (StatSoft, Inc., Tulsa,&#xD;
      Oklahoma, USA). Kolmogorov-Smirnov test and exploratory data analysis are used to define&#xD;
      normality range. Data will be expressed as mean and standard deviation (SD), or as median and&#xD;
      interquartile range if more appropriate. Differences among cardiorespiratory and MII/pH&#xD;
      variables will be evaluated with Student paired T test or Wilcoxon test if more appropriate.&#xD;
      Significance will be considered as p&lt;0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Actual">December 1, 2018</completion_date>
  <primary_completion_date type="Actual">December 1, 2018</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of cardiorespiratory events (feeding+postprandial time)</measure>
    <time_frame>calculated throughout 24 hour</time_frame>
    <description>Cardiorespiratory events / hour&#xD;
apnea (no breathing movement for at least 20 s, or less if associated with desaturation/bradycardia)&#xD;
desaturation (SpO2 &lt;80%)&#xD;
bradycardia (heart rate &lt; 80 bpm for at least 1 s)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Swallow event characteristics (feeding time)</measure>
    <time_frame>calculated throughout 30 minute interval after the beginning of the milk meal</time_frame>
    <description>Swallow event is identified as a rapid increase in impedance preceded by a drop in impedance to 50% of baseline beginning in the proximal channel and proceeding in an anterograde direction to the most distal channel, followed by the recovery of baseline values at each channel</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of reflux events (postprandial time)</measure>
    <time_frame>calculated throughout 150 minute interval after the end of the milk meal</time_frame>
    <description>Reflux event is defined as: a drop of impedance to 50% of the basal value for at least 5 s, starting in the most distal channel and proceeding to one or more proximal channels and followed by a recovery of the impedance baseline values</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>GERD</condition>
  <condition>Apnea Neonatal</condition>
  <arm_group>
    <arm_group_label>Start feeding with Device A, &quot;standard&quot;</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Alternatively feeding with standard feeding bottle (Device A) and vented base feeding bottle (Device B)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Start feeding with Device B, &quot;vented&quot;</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Alternatively feeding with vented base feeding bottle (Device B) and standard feeding bottle (Device A)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>A</intervention_name>
    <description>standard bottle</description>
    <arm_group_label>Start feeding with Device A, &quot;standard&quot;</arm_group_label>
    <arm_group_label>Start feeding with Device B, &quot;vented&quot;</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>B</intervention_name>
    <description>vented base bottle</description>
    <arm_group_label>Start feeding with Device A, &quot;standard&quot;</arm_group_label>
    <arm_group_label>Start feeding with Device B, &quot;vented&quot;</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  weight ≥ 1500 g at the time of examination&#xD;
&#xD;
          -  at least 2 GERD symptoms&#xD;
&#xD;
          -  exclusive enteral feeding&#xD;
&#xD;
          -  parents' informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  congenital abnormalities&#xD;
&#xD;
          -  perinatal asphyxia&#xD;
&#xD;
          -  respiratory, genetic, metabolic, infectious and/or neurologic disease&#xD;
&#xD;
          -  pharmacological therapies, in the last 7 days, able to affect esophageal motility&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Week</minimum_age>
    <maximum_age>3 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francesco Cresi, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Turin, Italy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ospedale S.Anna di Torino</name>
      <address>
        <city>Torino</city>
        <state>(to)</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>March 27, 2020</last_update_submitted>
  <last_update_submitted_qc>March 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Turin, Italy</investigator_affiliation>
    <investigator_full_name>Francesco Cresi, MD, PhD</investigator_full_name>
    <investigator_title>MD PhD</investigator_title>
  </responsible_party>
  <keyword>gastroesophageal reflux</keyword>
  <keyword>swallow</keyword>
  <keyword>feeding bottle</keyword>
  <keyword>cardiorespiratory</keyword>
  <keyword>apnoea</keyword>
  <keyword>preterm</keyword>
  <keyword>impedance-pH-metry</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastroesophageal Reflux</mesh_term>
    <mesh_term>Premature Birth</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/NCT03031288
org study id: feeding-01
nct id: NCT03031288
lead sponsor: 
has dmc: Yes
Aim of the study is to evaluate the effects of vented base bottles on respiration-swallow
      patterns and on gastroesophageal refluxes in preterm infants with clinical suspect of
      gastroesophageal reflux disease (GERD).

      In this crossover-randomized study, we compared the effects of standard feeding bottles (A)
      versus vented base feeding bottles (B) on a group of patients with at least 2 clinical GERD
      symptoms. 24 hours of synchronized cardiorespiratory (CR) and Esophageal Multichannel
      intraluminal impedance (MII/pH) monitoring were evaluated for each patient. During this
      period, patients were fed alternatively with feeding bottle A and B.
In preterm infants a deficit of both coordination and gastro-intestinal motility is often the
      underpinning cause of oxygen desaturations and gastro-esophageal reflux. Breastfeeding
      enhances the maturation of the respiration-swallow mechanism. For this reason, a feeding
      bottle that best recreates the physiological sucking from the maternal breast is highly
      desirable in non-breastfed newborns.

      Population: newborns referred to esophageal Multichannel Intraluminal Impedance and pH-metry
      (MII/pH) combined with cardiorespiratory (CR) monitoring for GERD or cardio-respiratory
      symptoms

      Materials and methods: we compare the effects of traditional feeding bottles (A) versus
      vented base feeding bottles (B) on cardiorespiratory and reflux events in newborns undergoing
      24 hours synchronized CR and MII/pH monitoring. During the exam, newborns are fed,
      alternatively, by feeding bottle A and B with human milk or formula. Some training meals are
      offered the day before monitoring to get newborns enrolled into the study used to vented base
      feeding bottles.

      Cardiorespiratory monitoring is performed through VitaGuard VG3100® (Getemed Medizin- und
      Informationstechnik AG, Teltow, Germany) based on Masimo Signal Extraction Technology (SET)®
      (Masimo Corp., Irvine, CA, USA). It operates with a blood oxygen saturation (SpO2) detector,
      placed on the right wrist, and 3 thoracic electrodes. This instrument is able to record ECG,
      heart rate, SpO2 and thoracic plethysmographic curve. The signals are analyzed with VitaWin
      3® software (Getemed Medizin - und Informationstechnik AG, Teltow, Germany), by filtering
      artifacts.

      The MII/pH monitoring is performed through a neonatal catheter (Infant Comfort TEC®) with 7
      impedence electrodes (creating 6 impedance channels) and one pH detector able to cover the
      whole distance from the pharynx to the lower esophageal sphincter (LES) (channel 1). The pH
      detector is placed within channel 1, 1.5 cm above the LES. The correct positioning of the
      catheter is measured through fluoroscopy and eventually corrected. Data obtained from
      impedance channels that result proximal to the superior esophageal sphincter are excluded
      from the analysis. The acquisition and recording of MII/pH data are performed through Sleuth
      System, Sandhill Scientific Inc., Highlands Ranch, Colorado, USA. The analysis of MII/pH
      tracings is made visually by a single operator using BioView 5.3.4 software (Sleuth System,
      Sandhill Scientific Inc., Highlands Ranch, Colorado, USA).

      The variables analyzed are listed as follows:

      Clinical variables:

        -  feeding time (min)

        -  feeding total volume (mL)

        -  n. GER during feeding

        -  n. GER in the post-prandial period (150 min after feeding)

      Cardiorespiratory variables:

        -  frequency of apnea, desaturation and bradycardia during feeding

        -  frequency of apnea, desaturation and bradycardia during post-prandial period

        -  mean duration of apnea during feeding and post-prandial period

        -  mean and minimum desaturation level during feeding and post-prandial period

        -  mean and minimum heart rate during feeding and post-prandial period

      MII/pH variables:

        -  Swallow frequency during feeding and post-prandial period (events/h)

        -  Bolus Presence Time (BPT): seconds between bolus entry and bolus exit in the distal
           channel

        -  Bolus Head Advancing Time (BHAT): seconds between bolus entry in proximal channel and
           entry in distal channel

        -  Bolus Head Advancing Time Corrected for Esophageal Length (BHATc): BHAT corrected for
           esophageal length (BHATc = BHAT / esophageal length)

        -  Reflux pH: minimum pH value registered during each GER event. It classifies refluxes
           into 3 different types: acid (pH < 4), weakly acid (pH 4-7) and weakly alkaline (pH > 7)

        -  GER frequency, (events/h)

        -  Bolus Clearance Time (BCT): reflux duration, recorded at distal channel (s)

        -  Bolus Reflux Extent (BRE), (n. channels)

        -  Proximal GER frequency (events/h)

        -  Bolus Exposure Index (BEI): percentage of time in which GER involves esophagus during
           MII/pH monitoring

        -  Reflux Index (RI): percentage of time during which pH falls below 4 during MII/pH
           monitoring

      Randomization: the alternate use of feeding bottles A and B is set by a binary random
      sequencing generated by Microsoft Office Excel software that indicates the first feeding
      bottle to be used. This is a single-blind study since the sequence is unknown to the
      specialist in charge of reporting MII/pH and CR monitoring.

      Statistical analysis:

      The analysis is made with Statistical Software Package For Windows® (StatSoft, Inc., Tulsa,
      Oklahoma, USA). Kolmogorov-Smirnov test and exploratory data analysis are used to define
      normality range. Data will be expressed as mean and standard deviation (SD), or as median and
      interquartile range if more appropriate. Differences among cardiorespiratory and MII/pH
      variables will be evaluated with Student paired T test or Wilcoxon test if more appropriate.
      Significance will be considered as p<0.05.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Frequency of cardiorespiratory events (feeding+postprandial time)
time frame: calculated throughout 24 hour
description: Cardiorespiratory events / hour
apnea (no breathing movement for at least 20 s, or less if associated with desaturation/bradycardia)
desaturation (SpO2 <80%)
bradycardia (heart rate < 80 bpm for at least 1 s)
measure: Swallow event characteristics (feeding time)
time frame: calculated throughout 30 minute interval after the beginning of the milk meal
description: Swallow event is identified as a rapid increase in impedance preceded by a drop in impedance to 50% of baseline beginning in the proximal channel and proceeding in an anterograde direction to the most distal channel, followed by the recovery of baseline values at each channel
measure: Frequency of reflux events (postprandial time)
time frame: calculated throughout 150 minute interval after the end of the milk meal
description: Reflux event is defined as: a drop of impedance to 50% of the basal value for at least 5 s, starting in the most distal channel and proceeding to one or more proximal channels and followed by a recovery of the impedance baseline values
arm group label: Start feeding with Device A, "standard"
arm group type: Experimental
description: Alternatively feeding with standard feeding bottle (Device A) and vented base feeding bottle (Device B)
arm group label: Start feeding with Device B, "vented"
arm group type: Experimental
description: Alternatively feeding with vented base feeding bottle (Device B) and standard feeding bottle (Device A)
intervention type: Device
intervention name: A
description: standard bottle
arm group label: Start feeding with Device A, "standard"
arm group label: Start feeding with Device B, "vented"
intervention type: Device
intervention name: B
description: vented base bottle
arm group label: Start feeding with Device A, "standard"
arm group label: Start feeding with Device B, "vented"
criteria: 
gender: All
minimum age: 1 Week
maximum age: 3 Months
healthy volunteers: No
last name: Francesco Cresi, MD PhD
role: Principal Investigator
affiliation: University of Turin, Italy
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Turin, Italy
investigator full name: Francesco Cresi, MD, PhD
investigator title: MD PhD
mesh term: Gastroesophageal Reflux
mesh term: Premature Birth
sharing ipd: No