<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/NCT03837717</url>
  </required_header>
  <id_info>
    <org_study_id>1183063</org_study_id>
    <nct_id>NCT03837717</nct_id>
  </id_info>
  <brief_title>The Impact of Holding on Stress and Bonding in Mother-Infant Pairs During Therapeutic Hypothermia</brief_title>
  <official_title>The Impact of Holding During Therapeutic Hypothermia on Saliva Oxytocin and Cortisol Levels in Mother-Infant Pairs</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MaineHealth</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>MaineHealth</source>
  <oversight_info>
    <has_dmc>No</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 research is being done to try to improve the experience of mothers and babies during&#xD;
      therapeutic hypothermia. Currently, mothers are not able to hold their baby during&#xD;
      hypothermia treatment. Mothers have reported that not being able to hold their baby during&#xD;
      this time is stressful. Additionally, it is known that holding has many benefits for mothers'&#xD;
      and babies' psychological and physical health.&#xD;
&#xD;
      Therapeutic hypothermia is the standard of care. The experimental interventions of this study&#xD;
      are to have mothers hold their babies during this treatment, collect saliva samples from&#xD;
      mothers and babies, and test the saliva samples for the hormones cortisol and oxytocin. The&#xD;
      investigators will test saliva of infants and their mothers before and after holding. The&#xD;
      investigators hope to demonstrate decreased cortisol, a marker for stress, and increased&#xD;
      oxytocin, a marker for bonding, in infants and mothers while they are held during therapeutic&#xD;
      hypothermia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The inability to hold an infant being treated with therapeutic hypothermia in the neonatal&#xD;
      intensive care unit has been subjectively reported by ours and other research groups as a&#xD;
      significant source of stress for parents. The investigators aim to assess the impact of&#xD;
      holding on endocrinological markers of stress and bonding. Specifically, the investigators&#xD;
      plan to collect salivary cortisol and oxytocin levels from infants undergoing therapeutic&#xD;
      hypothermia and their mothers prior to and immediately after a 30-minute holding period.&#xD;
&#xD;
      The investigators hypothesize that measurable increases in salivary oxytocin levels,&#xD;
      coinciding with the reported qualitative increased levels of bonding, will be observed after&#xD;
      the holding period. The investigators anticipate the reported stress reduction after holding&#xD;
      to be quantified by measurable decreases in salivary cortisol levels. The investigators&#xD;
      hypothesize these hormone changes will be present in both the mother and the infant when&#xD;
      compared to samples taken without the holding intervention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 4, 2018</start_date>
  <completion_date type="Actual">February 8, 2021</completion_date>
  <primary_completion_date type="Actual">February 8, 2020</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>Infants and mothers will be randomly assigned to the holding condition occurring on the second versus the third day of hypothermia.&#xD;
On the day of holding, four samples of saliva will be obtained; two from the mother (pre and post holding) and two from the infant (pre and post holding). The first sample will be collected prior to holding, and the second sample immediately at the end of holding before the infant is placed back in the bed.&#xD;
On the day without holding, four additional samples of saliva will be obtained; two from the mother (pre and post &quot;not holding&quot;) and two from the infant (pre and post &quot;not holding&quot;).</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the level of oxytocin in maternal saliva</measure>
    <time_frame>30-minutes</time_frame>
    <description>To compare the change in the level of oxytocin in maternal saliva between two conditions; one assessing the difference between oxytocin levels before and immediately after a 30-minute period of holding during therapeutic hypothermia compared to the second condition in which pre and post-levels of salivary oxytocin surrounding a 30-minute period of &quot;not holding&quot; are obtained.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the level of cortisol in maternal saliva</measure>
    <time_frame>30-minutes</time_frame>
    <description>To compare the change in the level of cortisol in maternal saliva between two conditions; one assessing the difference between cortisol levels before and immediately after a 30-minute period of holding during therapeutic hypothermia compared to the second condition in which pre and post-levels of salivary cortisol surrounding a 30-minute period of &quot;not holding&quot; are obtained.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the level of oxytocin and cortisol in infant saliva</measure>
    <time_frame>30-minutes</time_frame>
    <description>To compare the change in the level of oxytocin and cortisol in infant saliva between the same two conditions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of infant temperature before, during and after holding</measure>
    <time_frame>30 minutes prior to holding, 30 minutes during holding, and 45 minutes after holding.</time_frame>
    <description>Comparison between the holding and &quot;not holding&quot; conditions of infant temperature in °C, collected 30 minutes prior to holding, every 2 minutes during, and 45 minutes after holding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of infant heart rate before, during and after holding</measure>
    <time_frame>30 minutes prior to holding, 30 minutes during holding, and 45 minutes after holding.</time_frame>
    <description>Comparison between the holding and &quot;not holding&quot; conditions of infant heart rate in beats per minute, collected 30 minutes prior to holding, every 2 minutes during, and 45 minutes after holding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of infant blood pressure before, during and after holding</measure>
    <time_frame>30 minutes prior to holding, 30 minutes during holding, and 45 minutes after holding.</time_frame>
    <description>Comparison between the holding and &quot;not holding&quot; conditions of infant mean arterial blood pressure, measured with an arterial line, or, if none present, with systolic and diastolic cuff pressures, collected 30 minutes prior to holding, every 2 minutes during, and 45 minutes after holding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of infant oxygen saturation before, during and after holding</measure>
    <time_frame>30 minutes prior to holding, 30 minutes during holding, and 45 minutes after holding.</time_frame>
    <description>Comparison between the holding and &quot;not holding&quot; conditions of infant percent oxygen saturation collected 30 minutes prior to holding, every 2 minutes during, and 45 minutes after holding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective maternal reports</measure>
    <time_frame>Immediately after 30-minutes of holding</time_frame>
    <description>Subjective maternal reports of the experience of holding the infant during hypothermia and responses to questions about stress level and bonding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective nurse reports</measure>
    <time_frame>Immediately after 30-minutes of holding</time_frame>
    <description>Subjective nurse report about the experience of assisting with holding.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Hypoxic-Ischemic Encephalopathy</condition>
  <condition>Neonatal Encephalopathy</condition>
  <arm_group>
    <arm_group_label>Holding First</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Holding will occur on the second day of hypothermia treatment. Saliva will be collected on Day 2 and Day 3</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Holding First</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Holding will occur on the third day of hypothermia treatment. Saliva will be collected on Day 2 and Day 3</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Holding</intervention_name>
    <description>Mothers will be assisted with holding their infants (and the cooling blanket) for a single 30-minute period, with the use of a thin foam barrier for thermal protection. Mothers and infants will not be skin-to-skin.</description>
    <arm_group_label>Holding First</arm_group_label>
    <arm_group_label>No Holding First</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Saliva collection</intervention_name>
    <description>Saliva will be collected from infants (via syringe suction) and mothers (via passive drool), and tested for levels of cortisol and oxytocin</description>
    <arm_group_label>Holding First</arm_group_label>
    <arm_group_label>No Holding First</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>No Holding</intervention_name>
    <description>Saliva will be collected from Mothers and infants, and vital sign information will be collected from infants in the same manner as the Holding intervention, with the exception of having mother's hold their infants.</description>
    <arm_group_label>Holding First</arm_group_label>
    <arm_group_label>No Holding First</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  gestational age at birth of 35 weeks or greater&#xD;
&#xD;
          -  absence of clinical or electrographic seizures during the first 24 hours of&#xD;
             therapeutic hypothermia&#xD;
&#xD;
          -  designation as &quot;clinically stable&quot; by the attending neonatologist on service&#xD;
&#xD;
          -  respiratory status of: room air, nasal cannula, continuous positive airway pressure or&#xD;
             intubated on conventional ventilator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  designation as &quot;clinically unstable&quot; by the a member of the medical team&#xD;
&#xD;
          -  use of inhaled nitric oxide for persistent pulmonary hypertension of the newborn&#xD;
&#xD;
          -  high frequency oscillator ventilation&#xD;
&#xD;
          -  presence of electrographic seizures&#xD;
&#xD;
          -  use of vasopressors or paralytic agents, presence of chest tubes, wound vacuums, or&#xD;
             drains&#xD;
&#xD;
          -  in utero opiate exposure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>24 Hours</minimum_age>
    <maximum_age>2 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexa K Craig, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MaineHealth</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maine Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Maine</state>
        <zip>04103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Vittner D, McGrath J, Robinson J, Lawhon G, Cusson R, Eisenfeld L, Walsh S, Young E, Cong X. Increase in Oxytocin From Skin-to-Skin Contact Enhances Development of Parent-Infant Relationship. Biol Res Nurs. 2018 Jan;20(1):54-62. doi: 10.1177/1099800417735633. Epub 2017 Oct 11.</citation>
    <PMID>29017336</PMID>
  </reference>
  <reference>
    <citation>Craig AK, James C, Bainter J, Evans S, Gerwin R. Parental perceptions of neonatal therapeutic hypothermia; emotional and healing experiences. J Matern Fetal Neonatal Med. 2020 Sep;33(17):2889-2896. doi: 10.1080/14767058.2018.1563592. Epub 2019 Jan 8.</citation>
    <PMID>30585100</PMID>
  </reference>
  <reference>
    <citation>Craig AK, Gerwin R, Bainter J, Evans S, James C. Exploring parent expectations of neonatal therapeutic hypothermia. J Perinatol. 2018 Jul;38(7):857-864. doi: 10.1038/s41372-018-0117-8. Epub 2018 May 8.</citation>
    <PMID>29740186</PMID>
  </reference>
  <reference>
    <citation>Craig AK, Gerwin R, Bainter J, Evans S, James C. Exploring Parent Experience of Communication About Therapeutic Hypothermia in the Neonatal Intensive Care Unit. Adv Neonatal Care. 2018 Apr;18(2):136-143. doi: 10.1097/ANC.0000000000000473.</citation>
    <PMID>29595551</PMID>
  </reference>
  <reference>
    <citation>Craig A, Deerwester K, Fox L, Jacobs J, Evans S. Maternal holding during therapeutic hypothermia for infants with neonatal encephalopathy is feasible. Acta Paediatr. 2019 Sep;108(9):1597-1602. doi: 10.1111/apa.14743. Epub 2019 Mar 5.</citation>
    <PMID>30721531</PMID>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>February 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>December 2, 2021</last_update_submitted>
  <last_update_submitted_qc>December 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>MaineHealth</investigator_affiliation>
    <investigator_full_name>Alexa Craig</investigator_full_name>
    <investigator_title>Attending Pediatric Neurologist</investigator_title>
  </responsible_party>
  <keyword>Saliva</keyword>
  <keyword>Neonatal Encephalopathy</keyword>
  <keyword>Hypoxic-Ischemic Encephalopathy</keyword>
  <keyword>Bonding</keyword>
  <keyword>Oxytocin</keyword>
  <keyword>Stress</keyword>
  <keyword>Cortisol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Brain Ischemia</mesh_term>
    <mesh_term>Hypoxia-Ischemia, Brain</mesh_term>
    <mesh_term>Hypothermia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 17, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT03837717/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03837717
org study id: 1183063
nct id: NCT03837717
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This research is being done to try to improve the experience of mothers and babies during
      therapeutic hypothermia. Currently, mothers are not able to hold their baby during
      hypothermia treatment. Mothers have reported that not being able to hold their baby during
      this time is stressful. Additionally, it is known that holding has many benefits for mothers'
      and babies' psychological and physical health.

      Therapeutic hypothermia is the standard of care. The experimental interventions of this study
      are to have mothers hold their babies during this treatment, collect saliva samples from
      mothers and babies, and test the saliva samples for the hormones cortisol and oxytocin. The
      investigators will test saliva of infants and their mothers before and after holding. The
      investigators hope to demonstrate decreased cortisol, a marker for stress, and increased
      oxytocin, a marker for bonding, in infants and mothers while they are held during therapeutic
      hypothermia.
The inability to hold an infant being treated with therapeutic hypothermia in the neonatal
      intensive care unit has been subjectively reported by ours and other research groups as a
      significant source of stress for parents. The investigators aim to assess the impact of
      holding on endocrinological markers of stress and bonding. Specifically, the investigators
      plan to collect salivary cortisol and oxytocin levels from infants undergoing therapeutic
      hypothermia and their mothers prior to and immediately after a 30-minute holding period.

      The investigators hypothesize that measurable increases in salivary oxytocin levels,
      coinciding with the reported qualitative increased levels of bonding, will be observed after
      the holding period. The investigators anticipate the reported stress reduction after holding
      to be quantified by measurable decreases in salivary cortisol levels. The investigators
      hypothesize these hormone changes will be present in both the mother and the infant when
      compared to samples taken without the holding intervention.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Infants and mothers will be randomly assigned to the holding condition occurring on the second versus the third day of hypothermia.
On the day of holding, four samples of saliva will be obtained; two from the mother (pre and post holding) and two from the infant (pre and post holding). The first sample will be collected prior to holding, and the second sample immediately at the end of holding before the infant is placed back in the bed.
On the day without holding, four additional samples of saliva will be obtained; two from the mother (pre and post "not holding") and two from the infant (pre and post "not holding").
primary purpose: Supportive Care
masking: None (Open Label)
measure: Change in the level of oxytocin in maternal saliva
time frame: 30-minutes
description: To compare the change in the level of oxytocin in maternal saliva between two conditions; one assessing the difference between oxytocin levels before and immediately after a 30-minute period of holding during therapeutic hypothermia compared to the second condition in which pre and post-levels of salivary oxytocin surrounding a 30-minute period of "not holding" are obtained.
measure: Change in the level of cortisol in maternal saliva
time frame: 30-minutes
description: To compare the change in the level of cortisol in maternal saliva between two conditions; one assessing the difference between cortisol levels before and immediately after a 30-minute period of holding during therapeutic hypothermia compared to the second condition in which pre and post-levels of salivary cortisol surrounding a 30-minute period of "not holding" are obtained.
measure: Change in the level of oxytocin and cortisol in infant saliva
time frame: 30-minutes
description: To compare the change in the level of oxytocin and cortisol in infant saliva between the same two conditions
measure: Comparison of infant temperature before, during and after holding
time frame: 30 minutes prior to holding, 30 minutes during holding, and 45 minutes after holding.
description: Comparison between the holding and "not holding" conditions of infant temperature in °C, collected 30 minutes prior to holding, every 2 minutes during, and 45 minutes after holding.
measure: Comparison of infant heart rate before, during and after holding
time frame: 30 minutes prior to holding, 30 minutes during holding, and 45 minutes after holding.
description: Comparison between the holding and "not holding" conditions of infant heart rate in beats per minute, collected 30 minutes prior to holding, every 2 minutes during, and 45 minutes after holding.
measure: Comparison of infant blood pressure before, during and after holding
time frame: 30 minutes prior to holding, 30 minutes during holding, and 45 minutes after holding.
description: Comparison between the holding and "not holding" conditions of infant mean arterial blood pressure, measured with an arterial line, or, if none present, with systolic and diastolic cuff pressures, collected 30 minutes prior to holding, every 2 minutes during, and 45 minutes after holding.
measure: Comparison of infant oxygen saturation before, during and after holding
time frame: 30 minutes prior to holding, 30 minutes during holding, and 45 minutes after holding.
description: Comparison between the holding and "not holding" conditions of infant percent oxygen saturation collected 30 minutes prior to holding, every 2 minutes during, and 45 minutes after holding.
measure: Subjective maternal reports
time frame: Immediately after 30-minutes of holding
description: Subjective maternal reports of the experience of holding the infant during hypothermia and responses to questions about stress level and bonding.
measure: Subjective nurse reports
time frame: Immediately after 30-minutes of holding
description: Subjective nurse report about the experience of assisting with holding.
arm group label: Holding First
arm group type: Experimental
description: Holding will occur on the second day of hypothermia treatment. Saliva will be collected on Day 2 and Day 3
arm group label: No Holding First
arm group type: Experimental
description: Holding will occur on the third day of hypothermia treatment. Saliva will be collected on Day 2 and Day 3
intervention type: Behavioral
intervention name: Holding
description: Mothers will be assisted with holding their infants (and the cooling blanket) for a single 30-minute period, with the use of a thin foam barrier for thermal protection. Mothers and infants will not be skin-to-skin.
arm group label: Holding First
arm group label: No Holding First
intervention type: Other
intervention name: Saliva collection
description: Saliva will be collected from infants (via syringe suction) and mothers (via passive drool), and tested for levels of cortisol and oxytocin
arm group label: Holding First
arm group label: No Holding First
intervention type: Behavioral
intervention name: No Holding
description: Saliva will be collected from Mothers and infants, and vital sign information will be collected from infants in the same manner as the Holding intervention, with the exception of having mother's hold their infants.
arm group label: Holding First
arm group label: No Holding First
criteria: 
gender: All
minimum age: 24 Hours
maximum age: 2 Days
healthy volunteers: No
last name: Alexa K Craig, MD
role: Principal Investigator
affiliation: MaineHealth
facility: 
country: United States
citation: Vittner D, McGrath J, Robinson J, Lawhon G, Cusson R, Eisenfeld L, Walsh S, Young E, Cong X. Increase in Oxytocin From Skin-to-Skin Contact Enhances Development of Parent-Infant Relationship. Biol Res Nurs. 2018 Jan;20(1):54-62. doi: 10.1177/1099800417735633. Epub 2017 Oct 11.
PMID: 29017336
citation: Craig AK, James C, Bainter J, Evans S, Gerwin R. Parental perceptions of neonatal therapeutic hypothermia; emotional and healing experiences. J Matern Fetal Neonatal Med. 2020 Sep;33(17):2889-2896. doi: 10.1080/14767058.2018.1563592. Epub 2019 Jan 8.
PMID: 30585100
citation: Craig AK, Gerwin R, Bainter J, Evans S, James C. Exploring parent expectations of neonatal therapeutic hypothermia. J Perinatol. 2018 Jul;38(7):857-864. doi: 10.1038/s41372-018-0117-8. Epub 2018 May 8.
PMID: 29740186
citation: Craig AK, Gerwin R, Bainter J, Evans S, James C. Exploring Parent Experience of Communication About Therapeutic Hypothermia in the Neonatal Intensive Care Unit. Adv Neonatal Care. 2018 Apr;18(2):136-143. doi: 10.1097/ANC.0000000000000473.
PMID: 29595551
citation: Craig A, Deerwester K, Fox L, Jacobs J, Evans S. Maternal holding during therapeutic hypothermia for infants with neonatal encephalopathy is feasible. Acta Paediatr. 2019 Sep;108(9):1597-1602. doi: 10.1111/apa.14743. Epub 2019 Mar 5.
PMID: 30721531
responsible party type: Principal Investigator
investigator affiliation: MaineHealth
investigator full name: Alexa Craig
investigator title: Attending Pediatric Neurologist
mesh term: Brain Diseases
mesh term: Brain Ischemia
mesh term: Hypoxia-Ischemia, Brain
mesh term: Hypothermia
sharing ipd: No
provided document: 