<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/NCT02205034</url>
  </required_header>
  <id_info>
    <org_study_id>12 391 02</org_study_id>
    <secondary_id>1239102</secondary_id>
    <nct_id>NCT02205034</nct_id>
  </id_info>
  <brief_title>Evaluation of Tolerance, Suckling and Food Intake After Repeated Nasals Administrations of Oxytocin in PWS Infants</brief_title>
  <acronym>OTBB2</acronym>
  <official_title>Evaluation of Tolerance, Suckling and Food Intake After Repeated Nasals Administrations of Oxytocin in PWS Infants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Toulouse</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Toulouse</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Prader-Willi syndrome (PWS) includes severe neonatal hypotonia with impaired suckling&#xD;
      leading to failure to thrive in the most severe cases, subsequently followed by an early&#xD;
      onset of morbid obesity with hyperphagia and deficit of satiety, combined with other&#xD;
      endocrine dysfunction probably due to hypothalamic dysfunction. The pathophysiological&#xD;
      mechanism of the occurrence of the 2 main nutritional phases of PWS is unknown. Swaab&#xD;
      reported a deficit in the oxytocin (OT)-producing neurons of the paraventricular nucleus in&#xD;
      the brain of these patients. In addition of its well-known anorexigenic effect, OT is&#xD;
      involved in establishing and maintaining social codes. Moreover in a PWS mouse model&#xD;
      generated from a MAGEL2 KO gene a single OT injection at 5 hr of life prevent the early death&#xD;
      observed in 50 % of the new born mice by recovering normal suckling. Interestingly this&#xD;
      effect is no longer observed if OT injection takes place later. Our hypothesis is that early&#xD;
      administration of OT in babies with PWS may improve suckling and possibly infant-mother&#xD;
      interactions. In our recent study (manuscript in preparation), we have shown that a single&#xD;
      intranasal administration of OT is well tolerated. This escalating dose study is designed to&#xD;
      evaluate the tolerance of repeated intranasal administration of OT in 3 steps (4IU every&#xD;
      other day, 4 IU daily, 4IU twice daily) in babies younger than 5 months with PWS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prader-Willi syndrome (PWS) is a rare, complex multisystem genetic disorder arising from the&#xD;
      lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. The&#xD;
      syndrome includes severe neonatal hypotonia with impaired suckling leading to failure to&#xD;
      thrive in the most severe cases, subsequently followed by an early onset of morbid obesity&#xD;
      with hyperphagia and deficit of satiety, combined with other endocrine dysfunction probably&#xD;
      due to hypothalamic dysfunction. The pathophysiological mechanism of the occurrence of the 2&#xD;
      main nutritional phases of PWS is unknown. Swaab reported a deficit in the oxytocin&#xD;
      (OT)-producing neurons of the paraventricular nucleus in the brain of these patients. In&#xD;
      addition of its well-known anorexigenic effect, OT is involved in establishing and&#xD;
      maintaining social codes. Moreover in a PWS mouse model generated from a MAGEL2 KO gene a&#xD;
      single OT injection at 5 hr of life prevent the early death observed in 50 % of the new born&#xD;
      mice by recovering normal suckling. Interestingly this effect is no longer observed if OT&#xD;
      injection takes place later. Our hypothesis is that early administration of OT in babies with&#xD;
      PWS may improve suckling and possibly infant-mother interactions. In our recent study&#xD;
      (manuscript in preparation), we have shown that a single intranasal administration of OT is&#xD;
      well tolerated. This escalating dose study is designed to evaluate the tolerance of repeated&#xD;
      intranasal administration of OT in 3 steps (4IU every other day, 4 IU daily, 4IU twice daily)&#xD;
      in babies younger than 5 months with PWS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2013</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurence of adverse event</measure>
    <time_frame>up to day 8 (Visit 8)</time_frame>
    <description>Occurrence of adverse event, description and quantification of their severity, imputability to repeated intranasal administration of OT (4IU every other day, 4 IU daily, 4IU twice daily) during the 7 days following the first administration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy, pathophysiological study</measure>
    <time_frame>Up to day 8</time_frame>
    <description>Preliminary study of efficacy on suckling and swallowing and quantity of milk intake/day infant-mother interactions before during and after feeding weight gain and growth Pathophysiological study of cerebral metabolism (fMRI bold) plasma levels of ghrelin and other peptides involved in feeding behaviour or energy metabolism</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pharmacokinetic study</measure>
    <time_frame>On day 2, 3, 4, 5, 6, 7, 8</time_frame>
    <description>Pharmacokinetic study : measurement of circulating oxytocin levels before administration and every 48hrs.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Prader Willi Syndrome</condition>
  <arm_group>
    <arm_group_label>first arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>4IU of oxytocin every other day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>second arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>4 IU of oxytocin daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>third arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>4 IU of oxytocin twice daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oxytocin</intervention_name>
    <description>Intranasal administration</description>
    <arm_group_label>first arm</arm_group_label>
    <arm_group_label>second arm</arm_group_label>
    <arm_group_label>third arm</arm_group_label>
    <other_name>Oxytocin (Syntocinon)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infants with PWS genetically confirmed&#xD;
&#xD;
          -  Aged less than 5 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Infants presenting hepatic insufficiency&#xD;
&#xD;
          -  Infants presenting renal insufficiency&#xD;
&#xD;
          -  Infants with abnormal ECG&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>5 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maïthé TAUBER</last_name>
    <role>Principal Investigator</role>
    <affiliation>Endocrinologie pédiatrique, Hospital of Toulouse</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre de réfrence Prader-Willi, Hospital of infants</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <results_reference>
    <citation>Tauber M, Boulanouar K, Diene G, Cabal-Berthoumieu S, Ehlinger V, Fichaux-Bourin P, Molinas C, Faye S, Valette M, Pourrinet J, Cessans C, Viaux-Sauvelon S, Bascoul C, Guedeney A, Delhanty P, Geenen V, Martens H, Muscatelli F, Cohen D, Consoli A, Payoux P, Arnaud C, Salles JP. The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader-Willi Syndrome. Pediatrics. 2017 Feb;139(2):e20162976. doi: 10.1542/peds.2016-2976.</citation>
    <PMID>28100688</PMID>
  </results_reference>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <last_update_submitted>July 26, 2021</last_update_submitted>
  <last_update_submitted_qc>July 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prader Willi</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prader-Willi Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxytocin</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>February 27, 2023</submitted>
  </pending_results>
  <!-- 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/NCT02205034
org study id: 12 391 02
secondary id: 1239102
nct id: NCT02205034
lead sponsor: 
has dmc: Yes
The Prader-Willi syndrome (PWS) includes severe neonatal hypotonia with impaired suckling
      leading to failure to thrive in the most severe cases, subsequently followed by an early
      onset of morbid obesity with hyperphagia and deficit of satiety, combined with other
      endocrine dysfunction probably due to hypothalamic dysfunction. The pathophysiological
      mechanism of the occurrence of the 2 main nutritional phases of PWS is unknown. Swaab
      reported a deficit in the oxytocin (OT)-producing neurons of the paraventricular nucleus in
      the brain of these patients. In addition of its well-known anorexigenic effect, OT is
      involved in establishing and maintaining social codes. Moreover in a PWS mouse model
      generated from a MAGEL2 KO gene a single OT injection at 5 hr of life prevent the early death
      observed in 50 % of the new born mice by recovering normal suckling. Interestingly this
      effect is no longer observed if OT injection takes place later. Our hypothesis is that early
      administration of OT in babies with PWS may improve suckling and possibly infant-mother
      interactions. In our recent study (manuscript in preparation), we have shown that a single
      intranasal administration of OT is well tolerated. This escalating dose study is designed to
      evaluate the tolerance of repeated intranasal administration of OT in 3 steps (4IU every
      other day, 4 IU daily, 4IU twice daily) in babies younger than 5 months with PWS.
Prader-Willi syndrome (PWS) is a rare, complex multisystem genetic disorder arising from the
      lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. The
      syndrome includes severe neonatal hypotonia with impaired suckling leading to failure to
      thrive in the most severe cases, subsequently followed by an early onset of morbid obesity
      with hyperphagia and deficit of satiety, combined with other endocrine dysfunction probably
      due to hypothalamic dysfunction. The pathophysiological mechanism of the occurrence of the 2
      main nutritional phases of PWS is unknown. Swaab reported a deficit in the oxytocin
      (OT)-producing neurons of the paraventricular nucleus in the brain of these patients. In
      addition of its well-known anorexigenic effect, OT is involved in establishing and
      maintaining social codes. Moreover in a PWS mouse model generated from a MAGEL2 KO gene a
      single OT injection at 5 hr of life prevent the early death observed in 50 % of the new born
      mice by recovering normal suckling. Interestingly this effect is no longer observed if OT
      injection takes place later. Our hypothesis is that early administration of OT in babies with
      PWS may improve suckling and possibly infant-mother interactions. In our recent study
      (manuscript in preparation), we have shown that a single intranasal administration of OT is
      well tolerated. This escalating dose study is designed to evaluate the tolerance of repeated
      intranasal administration of OT in 3 steps (4IU every other day, 4 IU daily, 4IU twice daily)
      in babies younger than 5 months with PWS.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurence of adverse event
time frame: up to day 8 (Visit 8)
description: Occurrence of adverse event, description and quantification of their severity, imputability to repeated intranasal administration of OT (4IU every other day, 4 IU daily, 4IU twice daily) during the 7 days following the first administration.
measure: Efficacy, pathophysiological study
time frame: Up to day 8
description: Preliminary study of efficacy on suckling and swallowing and quantity of milk intake/day infant-mother interactions before during and after feeding weight gain and growth Pathophysiological study of cerebral metabolism (fMRI bold) plasma levels of ghrelin and other peptides involved in feeding behaviour or energy metabolism
measure: Pharmacokinetic study
time frame: On day 2, 3, 4, 5, 6, 7, 8
description: Pharmacokinetic study : measurement of circulating oxytocin levels before administration and every 48hrs.
arm group label: first arm
arm group type: Active Comparator
description: 4IU of oxytocin every other day
arm group label: second arm
arm group type: Active Comparator
description: 4 IU of oxytocin daily
arm group label: third arm
arm group type: Active Comparator
description: 4 IU of oxytocin twice daily
intervention type: Drug
intervention name: oxytocin
description: Intranasal administration
arm group label: first arm
arm group label: second arm
arm group label: third arm
other name: Oxytocin (Syntocinon)
criteria: 
gender: All
minimum age: 1 Month
maximum age: 5 Months
healthy volunteers: No
last name: Maïthé TAUBER
role: Principal Investigator
affiliation: Endocrinologie pédiatrique, Hospital of Toulouse
facility: 
country: France
citation: Tauber M, Boulanouar K, Diene G, Cabal-Berthoumieu S, Ehlinger V, Fichaux-Bourin P, Molinas C, Faye S, Valette M, Pourrinet J, Cessans C, Viaux-Sauvelon S, Bascoul C, Guedeney A, Delhanty P, Geenen V, Martens H, Muscatelli F, Cohen D, Consoli A, Payoux P, Arnaud C, Salles JP. The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader-Willi Syndrome. Pediatrics. 2017 Feb;139(2):e20162976. doi: 10.1542/peds.2016-2976.
PMID: 28100688
responsible party type: Sponsor
mesh term: Prader-Willi Syndrome
mesh term: Oxytocin
submitted: February 27, 2023