<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/NCT04504227</url>
  </required_header>
  <id_info>
    <org_study_id>ThickeningHRIM</org_study_id>
    <secondary_id>K23DK127251</secondary_id>
    <nct_id>NCT04504227</nct_id>
  </id_info>
  <brief_title>Effect of Thickened Feeds on Swallow Physiology in Children With Dysphagia</brief_title>
  <official_title>Effect of Thickened Feeds on Swallow Physiology in Children With Dysphagia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Boston Children's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This study will examine the effects of varying liquid viscosity on swallow physiology in&#xD;
      infants with oropharyngeal dysphagia and brief resolved unexplained event (BRUE) and other&#xD;
      children with dysphagia that would be at risk for symptoms of swallow dysfunction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Infants with oropharyngeal dysphagia and in particular brief resolved unexplained events&#xD;
      (BRUE) are a significant driver of pediatric health care expenditure since the mechanism for&#xD;
      their swallow dysfunction is incompletely understood and therefore frequently goes&#xD;
      unrecognized and untreated. We hypothesize that infants with oropharyngeal dysphagia and BRUE&#xD;
      have measurable differences in swallowing physiology to explain their symptoms of cyanotic&#xD;
      choking spells, that these differences can be quantified using pharyngeal high resolution&#xD;
      impedance-manometry compared to videofluoroscopic swallow study results, and that this&#xD;
      swallowing dysfunction can be safely corrected with a change of formula viscosity. Through&#xD;
      this research project, we will systematically investigate the effects of thickened feedings&#xD;
      on swallow function in infants with dysphagia and BRUE and perform detailed physiology&#xD;
      studies on pharyngeal and esophageal motility as critical mediators of improved outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2021</start_date>
  <completion_date type="Anticipated">August 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2025</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>
    <intervention_model_description>4-test consistency, randomized, crossover, single-blinded swallow physiology study comparing effects of different liquid viscosities on swallow coordination in infants and children</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Swallow risk indices for thin vs mildly thick vs slightly thick liquids</measure>
    <time_frame>30 minutes</time_frame>
    <description>We will calculate swallow risk index (SRI) from impedance-manometry results to compare mean SRI with thin liquids and thickened liquids for subjects with aspiration compared to mean SRI for thin liquids and thickened liquids in subjects without aspiration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Impedance-Manometry Swallow Physiology Metrics</measure>
    <time_frame>30 minutes</time_frame>
    <description>We will measure swallow physiology metrics from impedance-manometry results, including post-swallow impedance ratio, to compare these parameters with thin liquids between subjects with and without aspiration and with varied liquid consistencies within subjects.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Dysphagia</condition>
  <condition>Aspiration</condition>
  <condition>Brief Resolved Unexplained Event (BRUE)</condition>
  <condition>Apparent Life Threatening Event (ALTE)</condition>
  <arm_group>
    <arm_group_label>Thin liquid swallows</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Thin liquid swallows of formula or breastmilk or other liquid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Slightly thick liquid swallows</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Slightly thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mildly thick liquid swallows</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mildly thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderately thick liquid swallows</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Moderately thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Thin liquid swallows</intervention_name>
    <description>Thin liquid swallows of formula or breastmilk or other liquid</description>
    <arm_group_label>Thin liquid swallows</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Slightly thickened liquid swallows</intervention_name>
    <description>Slightly thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix</description>
    <arm_group_label>Slightly thick liquid swallows</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Mildly thickened liquid swallows</intervention_name>
    <description>Mildly thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix</description>
    <arm_group_label>Mildly thick liquid swallows</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Moderately thickened liquid swallows</intervention_name>
    <description>Moderately thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix</description>
    <arm_group_label>Moderately thick liquid swallows</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 0 to 21 years&#xD;
&#xD;
          -  Admitted to Boston Children's Hospital after experiencing first lifetime BRUE, or with&#xD;
             dysphagia symptoms such that they would be at risk for BRUE or other symptoms of&#xD;
             swallowing difficulty&#xD;
&#xD;
          -  Have had videofluoroscopic swallow study performed or might have future&#xD;
             videofluoroscopic swallow study performed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any pre-existing medical diagnoses that exclude brief resolved unexplained event&#xD;
             diagnosis including seizure disorders and cyanotic congenital heart disease&#xD;
&#xD;
          -  Any nasal/pharyngeal/esophageal anomalies that might affect safe placement of the&#xD;
             pharyngeal motility catheter&#xD;
&#xD;
          -  Children fed exclusively by enteral tube&#xD;
&#xD;
          -  Allergy to rice cereal or Gelmix thickener, which will be used to adjust liquid&#xD;
             viscosity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Months</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel R Duncan, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Boston Children's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rachel Rosen, MD, MPH</last_name>
    <role>Study Director</role>
    <affiliation>Boston Children's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sudarshan Jadcherla, MD</last_name>
    <role>Study Director</role>
    <affiliation>Nationwide Children's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Taher Omari, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Flinders University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Samuel Nurko, MD, MPH</last_name>
    <role>Study Director</role>
    <affiliation>Boston Children's Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Daniel R Duncan, MD, MPH</last_name>
    <phone>617-355-0897</phone>
    <email>daniel.duncan@childrens.harvard.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniel R Duncan, MD, MPH</last_name>
      <phone>617-355-0897</phone>
      <email>daniel.duncan@childrens.harvard.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Duncan DR, Amirault J, Mitchell PD, Larson K, Rosen RL. Oropharyngeal Dysphagia Is Strongly Correlated With Apparent Life-Threatening Events. J Pediatr Gastroenterol Nutr. 2017 Aug;65(2):168-172. doi: 10.1097/MPG.0000000000001439.</citation>
    <PMID>27741062</PMID>
  </reference>
  <reference>
    <citation>Duncan DR, Larson K, Rosen RL. Clinical Aspects of Thickeners for Pediatric Gastroesophageal Reflux and Oropharyngeal Dysphagia. Curr Gastroenterol Rep. 2019 May 16;21(7):30. doi: 10.1007/s11894-019-0697-2.</citation>
    <PMID>31098722</PMID>
  </reference>
  <reference>
    <citation>Duncan DR, Growdon AS, Liu E, Larson K, Gonzalez M, Norris K, Rosen RL. The Impact of the American Academy of Pediatrics Brief Resolved Unexplained Event Guidelines on Gastrointestinal Testing and Prescribing Practices. J Pediatr. 2019 Aug;211:112-119.e4. doi: 10.1016/j.jpeds.2019.04.007. Epub 2019 May 15.</citation>
    <PMID>31103259</PMID>
  </reference>
  <reference>
    <citation>Rommel N, Selleslagh M, Hoffman I, Smet MH, Davidson G, Tack J, Omari TI. Objective assessment of swallow function in children with suspected aspiration using pharyngeal automated impedance manometry. J Pediatr Gastroenterol Nutr. 2014 Jun;58(6):789-94. doi: 10.1097/MPG.0000000000000337.</citation>
    <PMID>24552674</PMID>
  </reference>
  <reference>
    <citation>Omari TI, Dejaeger E, Van Beckevoort D, Goeleven A, De Cock P, Hoffman I, Smet MH, Davidson GP, Tack J, Rommel N. A novel method for the nonradiological assessment of ineffective swallowing. Am J Gastroenterol. 2011 Oct;106(10):1796-802. doi: 10.1038/ajg.2011.143. Epub 2011 May 10.</citation>
    <PMID>21556039</PMID>
  </reference>
  <reference>
    <citation>Duncan DR, Liu E, Growdon AS, Larson K, Rosen RL. A Prospective Study of Brief Resolved Unexplained Events: Risk Factors for Persistent Symptoms. Hosp Pediatr. 2022 Dec 1;12(12):1030-1043. doi: 10.1542/hpeds.2022-006550.</citation>
    <PMID>36336644</PMID>
  </reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>August 5, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>June 20, 2023</last_update_submitted>
  <last_update_submitted_qc>June 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Boston Children's Hospital</investigator_affiliation>
    <investigator_full_name>Daniel Duncan</investigator_full_name>
    <investigator_title>Assistant Professor of Pediatrics</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Deglutition Disorders</mesh_term>
    <mesh_term>Brief, Resolved, Unexplained Event</mesh_term>
  </condition_browse>
  <!-- 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/NCT04504227
org study id: ThickeningHRIM
secondary id: K23DK127251
nct id: NCT04504227
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study will examine the effects of varying liquid viscosity on swallow physiology in
      infants with oropharyngeal dysphagia and brief resolved unexplained event (BRUE) and other
      children with dysphagia that would be at risk for symptoms of swallow dysfunction.
Infants with oropharyngeal dysphagia and in particular brief resolved unexplained events
      (BRUE) are a significant driver of pediatric health care expenditure since the mechanism for
      their swallow dysfunction is incompletely understood and therefore frequently goes
      unrecognized and untreated. We hypothesize that infants with oropharyngeal dysphagia and BRUE
      have measurable differences in swallowing physiology to explain their symptoms of cyanotic
      choking spells, that these differences can be quantified using pharyngeal high resolution
      impedance-manometry compared to videofluoroscopic swallow study results, and that this
      swallowing dysfunction can be safely corrected with a change of formula viscosity. Through
      this research project, we will systematically investigate the effects of thickened feedings
      on swallow function in infants with dysphagia and BRUE and perform detailed physiology
      studies on pharyngeal and esophageal motility as critical mediators of improved outcomes.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: 4-test consistency, randomized, crossover, single-blinded swallow physiology study comparing effects of different liquid viscosities on swallow coordination in infants and children
primary purpose: Diagnostic
masking: Single (Investigator)
measure: Swallow risk indices for thin vs mildly thick vs slightly thick liquids
time frame: 30 minutes
description: We will calculate swallow risk index (SRI) from impedance-manometry results to compare mean SRI with thin liquids and thickened liquids for subjects with aspiration compared to mean SRI for thin liquids and thickened liquids in subjects without aspiration.
measure: Impedance-Manometry Swallow Physiology Metrics
time frame: 30 minutes
description: We will measure swallow physiology metrics from impedance-manometry results, including post-swallow impedance ratio, to compare these parameters with thin liquids between subjects with and without aspiration and with varied liquid consistencies within subjects.
arm group label: Thin liquid swallows
arm group type: Placebo Comparator
description: Thin liquid swallows of formula or breastmilk or other liquid
arm group label: Slightly thick liquid swallows
arm group type: Experimental
description: Slightly thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix
arm group label: Mildly thick liquid swallows
arm group type: Experimental
description: Mildly thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix
arm group label: Moderately thick liquid swallows
arm group type: Experimental
description: Moderately thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix
intervention type: Dietary Supplement
intervention name: Thin liquid swallows
description: Thin liquid swallows of formula or breastmilk or other liquid
arm group label: Thin liquid swallows
intervention type: Dietary Supplement
intervention name: Slightly thickened liquid swallows
description: Slightly thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix
arm group label: Slightly thick liquid swallows
intervention type: Dietary Supplement
intervention name: Mildly thickened liquid swallows
description: Mildly thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix
arm group label: Mildly thick liquid swallows
intervention type: Dietary Supplement
intervention name: Moderately thickened liquid swallows
description: Moderately thick liquid swallows of formula thickened with rice cereal or breastmilk or other liquid thickened with Gelmix
arm group label: Moderately thick liquid swallows
criteria: 
gender: All
minimum age: 0 Months
maximum age: 21 Years
healthy volunteers: No
last name: Daniel R Duncan, MD, MPH
role: Principal Investigator
affiliation: Boston Children's Hospital
last name: Rachel Rosen, MD, MPH
role: Study Director
affiliation: Boston Children's Hospital
last name: Sudarshan Jadcherla, MD
role: Study Director
affiliation: Nationwide Children's Hospital
last name: Taher Omari, PhD
role: Study Director
affiliation: Flinders University
last name: Samuel Nurko, MD, MPH
role: Study Director
affiliation: Boston Children's Hospital
last name: Daniel R Duncan, MD, MPH
phone: 617-355-0897
email: daniel.duncan@childrens.harvard.edu
facility: 
status: Recruiting
contact: 
country: United States
citation: Duncan DR, Amirault J, Mitchell PD, Larson K, Rosen RL. Oropharyngeal Dysphagia Is Strongly Correlated With Apparent Life-Threatening Events. J Pediatr Gastroenterol Nutr. 2017 Aug;65(2):168-172. doi: 10.1097/MPG.0000000000001439.
PMID: 27741062
citation: Duncan DR, Larson K, Rosen RL. Clinical Aspects of Thickeners for Pediatric Gastroesophageal Reflux and Oropharyngeal Dysphagia. Curr Gastroenterol Rep. 2019 May 16;21(7):30. doi: 10.1007/s11894-019-0697-2.
PMID: 31098722
citation: Duncan DR, Growdon AS, Liu E, Larson K, Gonzalez M, Norris K, Rosen RL. The Impact of the American Academy of Pediatrics Brief Resolved Unexplained Event Guidelines on Gastrointestinal Testing and Prescribing Practices. J Pediatr. 2019 Aug;211:112-119.e4. doi: 10.1016/j.jpeds.2019.04.007. Epub 2019 May 15.
PMID: 31103259
citation: Rommel N, Selleslagh M, Hoffman I, Smet MH, Davidson G, Tack J, Omari TI. Objective assessment of swallow function in children with suspected aspiration using pharyngeal automated impedance manometry. J Pediatr Gastroenterol Nutr. 2014 Jun;58(6):789-94. doi: 10.1097/MPG.0000000000000337.
PMID: 24552674
citation: Omari TI, Dejaeger E, Van Beckevoort D, Goeleven A, De Cock P, Hoffman I, Smet MH, Davidson GP, Tack J, Rommel N. A novel method for the nonradiological assessment of ineffective swallowing. Am J Gastroenterol. 2011 Oct;106(10):1796-802. doi: 10.1038/ajg.2011.143. Epub 2011 May 10.
PMID: 21556039
citation: Duncan DR, Liu E, Growdon AS, Larson K, Rosen RL. A Prospective Study of Brief Resolved Unexplained Events: Risk Factors for Persistent Symptoms. Hosp Pediatr. 2022 Dec 1;12(12):1030-1043. doi: 10.1542/hpeds.2022-006550.
PMID: 36336644
responsible party type: Principal Investigator
investigator affiliation: Boston Children's Hospital
investigator full name: Daniel Duncan
investigator title: Assistant Professor of Pediatrics
mesh term: Deglutition Disorders
mesh term: Brief, Resolved, Unexplained Event