<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/NCT03230032</url>
  </required_header>
  <id_info>
    <org_study_id>IRB16-00862</org_study_id>
    <nct_id>NCT03230032</nct_id>
  </id_info>
  <brief_title>Pacifier Activated Device and Mother's Voice in Infants at High-risk for Cerebral Palsy</brief_title>
  <official_title>RCT of Feeding Intervention With Pacifier Activated Device and Mother's Voice in Infants at High-risk for Cerebral Palsy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nationwide Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cerebral Palsy Alliance</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nationwide Children's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study seeks to determine the efficacy of non-nutritive suck (NNS) training using a&#xD;
      pacifier-activated device (PAM) with mothers' voice to condition suck-strength and&#xD;
      rhythmicity, in improving the feeding and developmental outcomes of infants at high-risk for&#xD;
      CP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Poor neuromotor and sensory function of the aerodigestive system in children with CP often&#xD;
      originates in the neonatal period, when they are still classified as &quot;high-risk for CP&quot;.&#xD;
      Characteristic neuroimaging abnormalities including severe intraventricular (IVH)&#xD;
      hydrocephalus and periventricular leukomalacia (PVL), stroke or ischemia with lesions affect&#xD;
      the posterior limb of the internal capsule are strong Indicators of high-risk for CP,&#xD;
      especially when combined with abnormal General Movements Assessment (Guidelines for Early&#xD;
      Detection of CP; Stockholm, 2016). Early intervention, when plasticity is greatest has the&#xD;
      largest impact on functional recovery in CP. While intervening in infancy involves treating&#xD;
      some infants who will not develop CP, the goal is to establish new neuronal connections and&#xD;
      functional patterns before less efficient adaptations can occur. However, no current&#xD;
      interventions target the oral-motor dysfunction of infants at high-risk for CP, before their&#xD;
      discharge from the NICU.&#xD;
&#xD;
      Evidence for behavioral interventions in feeding disorders for children with CP ranges from&#xD;
      insufficient to moderate, with a clear need for rigorous studies. In healthy preterm and&#xD;
      late-preterm infants, oromotor practice opportunities such as non-nutritive suck (NNS) are&#xD;
      safe and promote effective suck-swallow-breathe patterns, with decreased time to achieving&#xD;
      oral feeds. While NNS opportunities are frequent in most NICUs, they must be adapted for&#xD;
      effectiveness in infants at high-risk for CP. Motor learning in these infants must&#xD;
      incorporate repetitive, self-initiated and task-directed activities. Learning is optimized&#xD;
      when contingent on feedback, such as positive reinforcement.&#xD;
&#xD;
      NNS training (rather than simple exposure) has been implemented successfully using rhythmic&#xD;
      sound of mother's voice singing contingent upon suck strength and pattern, as detected by a&#xD;
      pacifier-sensor device (Pacifier-activated music; PAM) in an cohort of predominantly healthy&#xD;
      preterm infants. An RCT demonstrated that NNS-trained infants had feeding tubes removed one&#xD;
      week earlier than controls, with fewer aspiration events and feeding difficulties in infancy.&#xD;
      The intervention was promising in the dozen infants with significant neural injury. Following&#xD;
      this preliminary data, this study seeks to further determining the efficacy of non-nutritive&#xD;
      suck (NNS) training using a pacifier-activated device (PAM) with mothers' voice to condition&#xD;
      suck-strength and rhythmicity, in improving the feeding and developmental outcomes of infants&#xD;
      at high-risk for CP.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 9, 2017</start_date>
  <completion_date type="Actual">July 31, 2021</completion_date>
  <primary_completion_date type="Actual">July 31, 2021</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>
    <intervention_model_description>There participants will be randomized to two groups: PAL (pacifier and mother's voice provided contingently on sucking behavior) or Sounds of Love (listening to mother's voice not contingent upon sucking behavior on the pacifier, but pacifier available, per standard of care). To allow for high repetitiveness of the treatment, participants in both groups will receive 2 daily 15-min sessions of the intervention or control treatments for a total of 20 sessions. Sessions occur 15-30 min prior to feeding.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Oral Feeding Efficiency</measure>
    <time_frame>Twelve months</time_frame>
    <description>Continuous measure of suck strength and suck rate during non-nutritive suck via PAM sensor, as well as suck burst pattern and average oral feeding volumes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HINE</measure>
    <time_frame>3-4 month and 12 month assessments</time_frame>
    <description>Hammersmith Infant Neurologic Exam (HINE): standardized and scored neurological examination for infants 2-24 months; sequential use allows identification of early signs of CP and other neuromotor disorders. It includes 26 items assessing cranial nerve function, posture, quality and quantity of movements, muscle tone, and reflexes and reactions. Each item is scored individually (0, 1, 2 or 3), with a sum score of all individual items (range: 0-78). The maximum score for any one item is a score of 3 and the minimum is a score of 0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bayley-III</measure>
    <time_frame>3-4 months and 12 month assessments</time_frame>
    <description>Bayley Scales of Infant and Toddler Development (Bailey-III): Standardized comprehensive assessment tool for assessing child development in children one month to 42 months old. Subtests assess adaptive behavior, cognitive, language, motor, and social-emotional domains. The highest possible scaled score on each subtest is 19, and the lowest possible score is 1. Scores from 8 to 12 are considered average. Composite scores are derived for each domain from sums of subtest scaled scores. Composite scores range from 40-160.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral feeding development questionnaire</measure>
    <time_frame>3-4 months and 12 month assessments</time_frame>
    <description>Age-calibrated questionnaire (&lt; or &gt; 6 months) in the American Speech-Language-Hearing Association evidence maps for evaluation of feeding problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NOMAS</measure>
    <time_frame>33-41 weeks PMA and 35-43 weeks PMA</time_frame>
    <description>Neonatal Oral-Motor Assessment Scale (NOMAS): A tool for the evaluation of neonatal nutritive sucking patterns in pre-term and term infants. Sub-scores are made up of dichotomous assessments of jaw and tongue movements during a feed. An overall sucking pattern of &quot;normal,&quot; &quot;disorganized,&quot; or &quot;dysfunctional&quot; is determined based on the items checked in each category.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">130</enrollment>
  <condition>Infant Development</condition>
  <condition>Infant,Premature</condition>
  <condition>Hydrocephalus</condition>
  <condition>Neonatal Encephalopathy</condition>
  <condition>Infarction</condition>
  <condition>PVL</condition>
  <condition>Thrombosis</condition>
  <condition>Intraventricular Hemorrhage</condition>
  <arm_group>
    <arm_group_label>Intervention Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sessions will use a pacifier-activated device (PAL) system. The device sensor attaches to a routinely-used pacifier and measures timing and pressure of the sucks. If the infant reaches the preset suck pressure, he receives 10 seconds of mother's voice. The receiver/speaker box controls the volume to &lt; 65dB on scale C. PAM will be set to the lowest settings for the first session. Using sensor measurements, the therapist will increase the threshold for number of sucks and strength once the infant produces three consecutive sucks above current level and continue per protocol.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Infants will receive 2 daily 15-min listening sessions of mother's voice recording, contiguous but not simultaneous with PAM NNS sessions without suck-contingent reinforcement (no voice).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>pacifier-activated device</intervention_name>
    <description>The utilization of the pacifier-activated-music player combines the sound of the mother's voice with a pacifier routinely used with each patient during their inpatient NICU stay</description>
    <arm_group_label>Intervention Group</arm_group_label>
    <other_name>PAL</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  PMA at enrollment &gt;32 6/7 and &lt;42 AND&#xD;
&#xD;
          -  Diagnoses of Grade III/IV IVH, hydrocephalus or PVL, neonatal encephalopathy or&#xD;
             thrombosis/infarct with involvement of the posterior limb of the internal capsule OR&#xD;
&#xD;
          -  Abnormal GMA by certified study staff and masked gold-standard reading&#xD;
&#xD;
        Exclusion Criteria: Infants cannot be&#xD;
&#xD;
          -  on assisted ventilation&#xD;
&#xD;
          -  receiving more than 50% of their feeds orally averaged over the 72 hours prior to&#xD;
             study start&#xD;
&#xD;
          -  receiving less than 50% of their feeds enterally&#xD;
&#xD;
          -  receiving enteral feed for greater than 60 min.&#xD;
&#xD;
          -  considered medically unsafe to feed orally by the medical or feeding team as defined&#xD;
             by unit/clinical protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>32 Weeks</minimum_age>
    <maximum_age>12 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nathalie L Maitre, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nationwide Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 22, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>September 11, 2023</last_update_submitted>
  <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nationwide Children's Hospital</investigator_affiliation>
    <investigator_full_name>Kristen Benninger, MD</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Palsy</mesh_term>
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Hydrocephalus</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Infarction</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03230032
org study id: IRB16-00862
nct id: NCT03230032
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The study seeks to determine the efficacy of non-nutritive suck (NNS) training using a
      pacifier-activated device (PAM) with mothers' voice to condition suck-strength and
      rhythmicity, in improving the feeding and developmental outcomes of infants at high-risk for
      CP.
Poor neuromotor and sensory function of the aerodigestive system in children with CP often
      originates in the neonatal period, when they are still classified as "high-risk for CP".
      Characteristic neuroimaging abnormalities including severe intraventricular (IVH)
      hydrocephalus and periventricular leukomalacia (PVL), stroke or ischemia with lesions affect
      the posterior limb of the internal capsule are strong Indicators of high-risk for CP,
      especially when combined with abnormal General Movements Assessment (Guidelines for Early
      Detection of CP; Stockholm, 2016). Early intervention, when plasticity is greatest has the
      largest impact on functional recovery in CP. While intervening in infancy involves treating
      some infants who will not develop CP, the goal is to establish new neuronal connections and
      functional patterns before less efficient adaptations can occur. However, no current
      interventions target the oral-motor dysfunction of infants at high-risk for CP, before their
      discharge from the NICU.

      Evidence for behavioral interventions in feeding disorders for children with CP ranges from
      insufficient to moderate, with a clear need for rigorous studies. In healthy preterm and
      late-preterm infants, oromotor practice opportunities such as non-nutritive suck (NNS) are
      safe and promote effective suck-swallow-breathe patterns, with decreased time to achieving
      oral feeds. While NNS opportunities are frequent in most NICUs, they must be adapted for
      effectiveness in infants at high-risk for CP. Motor learning in these infants must
      incorporate repetitive, self-initiated and task-directed activities. Learning is optimized
      when contingent on feedback, such as positive reinforcement.

      NNS training (rather than simple exposure) has been implemented successfully using rhythmic
      sound of mother's voice singing contingent upon suck strength and pattern, as detected by a
      pacifier-sensor device (Pacifier-activated music; PAM) in an cohort of predominantly healthy
      preterm infants. An RCT demonstrated that NNS-trained infants had feeding tubes removed one
      week earlier than controls, with fewer aspiration events and feeding difficulties in infancy.
      The intervention was promising in the dozen infants with significant neural injury. Following
      this preliminary data, this study seeks to further determining the efficacy of non-nutritive
      suck (NNS) training using a pacifier-activated device (PAM) with mothers' voice to condition
      suck-strength and rhythmicity, in improving the feeding and developmental outcomes of infants
      at high-risk for CP.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: There participants will be randomized to two groups: PAL (pacifier and mother's voice provided contingently on sucking behavior) or Sounds of Love (listening to mother's voice not contingent upon sucking behavior on the pacifier, but pacifier available, per standard of care). To allow for high repetitiveness of the treatment, participants in both groups will receive 2 daily 15-min sessions of the intervention or control treatments for a total of 20 sessions. Sessions occur 15-30 min prior to feeding.
primary purpose: Prevention
masking: Double (Care Provider, Outcomes Assessor)
measure: Oral Feeding Efficiency
time frame: Twelve months
description: Continuous measure of suck strength and suck rate during non-nutritive suck via PAM sensor, as well as suck burst pattern and average oral feeding volumes.
measure: HINE
time frame: 3-4 month and 12 month assessments
description: Hammersmith Infant Neurologic Exam (HINE): standardized and scored neurological examination for infants 2-24 months; sequential use allows identification of early signs of CP and other neuromotor disorders. It includes 26 items assessing cranial nerve function, posture, quality and quantity of movements, muscle tone, and reflexes and reactions. Each item is scored individually (0, 1, 2 or 3), with a sum score of all individual items (range: 0-78). The maximum score for any one item is a score of 3 and the minimum is a score of 0.
measure: Bayley-III
time frame: 3-4 months and 12 month assessments
description: Bayley Scales of Infant and Toddler Development (Bailey-III): Standardized comprehensive assessment tool for assessing child development in children one month to 42 months old. Subtests assess adaptive behavior, cognitive, language, motor, and social-emotional domains. The highest possible scaled score on each subtest is 19, and the lowest possible score is 1. Scores from 8 to 12 are considered average. Composite scores are derived for each domain from sums of subtest scaled scores. Composite scores range from 40-160.
measure: Oral feeding development questionnaire
time frame: 3-4 months and 12 month assessments
description: Age-calibrated questionnaire (< or > 6 months) in the American Speech-Language-Hearing Association evidence maps for evaluation of feeding problems.
measure: NOMAS
time frame: 33-41 weeks PMA and 35-43 weeks PMA
description: Neonatal Oral-Motor Assessment Scale (NOMAS): A tool for the evaluation of neonatal nutritive sucking patterns in pre-term and term infants. Sub-scores are made up of dichotomous assessments of jaw and tongue movements during a feed. An overall sucking pattern of "normal," "disorganized," or "dysfunctional" is determined based on the items checked in each category.
arm group label: Intervention Group
arm group type: Experimental
description: Sessions will use a pacifier-activated device (PAL) system. The device sensor attaches to a routinely-used pacifier and measures timing and pressure of the sucks. If the infant reaches the preset suck pressure, he receives 10 seconds of mother's voice. The receiver/speaker box controls the volume to < 65dB on scale C. PAM will be set to the lowest settings for the first session. Using sensor measurements, the therapist will increase the threshold for number of sucks and strength once the infant produces three consecutive sucks above current level and continue per protocol.
arm group label: Control Group
arm group type: No Intervention
description: Infants will receive 2 daily 15-min listening sessions of mother's voice recording, contiguous but not simultaneous with PAM NNS sessions without suck-contingent reinforcement (no voice).
intervention type: Device
intervention name: pacifier-activated device
description: The utilization of the pacifier-activated-music player combines the sound of the mother's voice with a pacifier routinely used with each patient during their inpatient NICU stay
arm group label: Intervention Group
other name: PAL
criteria: 
gender: All
minimum age: 32 Weeks
maximum age: 12 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Nathalie L Maitre, MD, PhD
role: Principal Investigator
affiliation: Nationwide Children's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Nationwide Children's Hospital
investigator full name: Kristen Benninger, MD
investigator title: Principle Investigator
mesh term: Cerebral Palsy
mesh term: Brain Diseases
mesh term: Hydrocephalus
mesh term: Thrombosis
mesh term: Infarction
mesh term: Hemorrhage
sharing ipd: Undecided