<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/NCT03278977</url>
  </required_header>
  <id_info>
    <org_study_id>6432</org_study_id>
    <nct_id>NCT03278977</nct_id>
  </id_info>
  <brief_title>Apparent Life Threatening Events, Sudden Infant Death Syndrome and Muscarinic Receptors</brief_title>
  <acronym>iALTE</acronym>
  <official_title>Apparent Life Threatening Events, Sudden Infant Death Syndrome and Muscarinic Receptors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Strasbourg, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Groupement Interrégional de Recherche Clinique et d'Innovation Est</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Strasbourg, France</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>
      Apparent Life-Threatening Events (ALTE) in infants often lead to severe neurological&#xD;
      complications or to sudden death. In such situations, cardio-pediatricians and intensive care&#xD;
      physicians have no specific diagnosis or treatment. In a recent translational research&#xD;
      (INSERM-DHOS), our team has reported a myocardiac abnormality in a rabbit model of vagal&#xD;
      hyperreactivity which is also present in the human hearts of infants deceased from sudden&#xD;
      death, i.e. increased M2 muscarinic receptors (M2R) density associated with compensative&#xD;
      increased enzymatic activity and overexpression of acetylcholine esterase (AchE). In a recent&#xD;
      PHRC-I study (article in preparation), these abnormalities have also been observed in the&#xD;
      blood of patients, infants as well as adults, exhibiting severe vagal syncopes. We observed,&#xD;
      even more importantly, similar abnormalities in infants under 1 year of age with very severe&#xD;
      idiopathic ALTE (iALTE) compared with normal subjects and with patients who presented ALTE&#xD;
      with identified etiologies (JAMA Pediatric, 2016 May). The aim of this present study is to&#xD;
      validate the overexpression of M2R as a marker of risk of iALTE in infant under 1 year.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 15, 2018</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Blood sample analysis will be blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Muscarinic M2 receptor mRNA expression in blood</measure>
    <time_frame>At the admission in the hospital, within 24 hours after the inclusion in the study</time_frame>
    <description>Blood sample will be collected not later than 24 hours after the inclusion in the study and will be frozen until centralized analysis.&#xD;
A qRT-PCR will be performed for quantification of CHRM2 gene expression in blood (mRNA expression).&#xD;
Interim analysis with the 7-8 first samples per group together. Final analysis with all samples at the study completion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acetylcholinesterase mRNA expression in blood</measure>
    <time_frame>At the admission in the hospital, within 24 hours after the inclusion in the study.</time_frame>
    <description>Blood sample will be collected not later than 24 hours after the inclusion in the study and will be frozen until centralized analysis..&#xD;
A qRT-PCR will be performed for quantification of ACHE gene expression in blood (mRNA expression).&#xD;
Interim analysis with the 7-8 first samples per group together. Final analysis with all samples at the study completion.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Apparent Life-Threatening Event in Infants Under One Year of Age</condition>
  <arm_group>
    <arm_group_label>ALTE group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Infants aged between 28 days and 12 months presenting severe(s) syncope(s) requiring hospitalization, for which a cause was identified during hospitalization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>iALTE group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Infant aged between 28 days and 12 months presenting a severe syncope(s) requiring hospitalization, for which no etiology was found during hospitalization.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Blood sample for specific analyzes</intervention_name>
    <description>Standard management of ALTE&#xD;
Hospitalization in pediatric intensive care unit or pediatric emergencies&#xD;
Etiologic research&#xD;
Blood volume, 2.5mL in PaxGene® tube, for specific analyzes (M2R, AchE)</description>
    <arm_group_label>ALTE group</arm_group_label>
    <arm_group_label>iALTE group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infant aged between 28 days and 12 months, presenting severe syncope(s) requiring&#xD;
             medical management, hospitalized in a pediatric intensive care unit or pediatric&#xD;
             emergencies&#xD;
&#xD;
          -  Consent signed and dated by the legal representatives&#xD;
&#xD;
          -  Patients affiliated to a social security system&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Infant with known cardiovascular, neurologic, infectious, toxic or metabolic&#xD;
             pathologies before enrollment (before the syncope)&#xD;
&#xD;
          -  Subject on medication for more than 3 months before enrollment&#xD;
&#xD;
          -  Impossibility to clearly inform the legal representatives (comprehension problems)&#xD;
&#xD;
          -  Subject in exclusion period for clinical trial (previous or current study)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>28 Days</minimum_age>
    <maximum_age>12 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Charlie DE MELO, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpitaux Universitaires de Strasbourg</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Pascal BOUSQUET, MD, PhD</last_name>
    <phone>(0)3 68 85 33 89</phone>
    <phone_ext>+33</phone_ext>
    <email>pascal.bousquet@unistra.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Pediatric Intensive Care unit/Emergency unit - Besançon University Hospital</name>
      <address>
        <city>Besançon</city>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Gérard THIRIEZ, MD PhD</last_name>
      <email>gerard.thiriez@univ-fcomte.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Pediatric Intensive Care Unit - Brabois Hospital - Nancy University Hospital</name>
      <address>
        <city>Nancy</city>
        <zip>54500</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mathieu MARIA</last_name>
      <email>m.maria@chru-nancy.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Pediatric unit - Maison Blanche Hospital - Reims University Hospital</name>
      <address>
        <city>Reims</city>
        <zip>51092</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ahmad AKHAVI</last_name>
      <email>aakhavi@chu-reims.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Pediatric intensive care unit/ Pediatric unit- Strasbourg University Hospital - Hautepierre Hospital</name>
      <address>
        <city>Strasbourg</city>
        <zip>67200</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Charlie DE MELO, MD</last_name>
      <email>charlie.demelo@chru-strasbourg.fr</email>
    </contact>
    <investigator>
      <last_name>Charlie DE MELO, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Angelo LIVOLSI, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Pauline HELMS, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>June 28, 2022</last_update_submitted>
  <last_update_submitted_qc>June 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Apparent Life-Threatening Event</keyword>
  <keyword>ALTE</keyword>
  <keyword>Sudden Infant Death</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brief, Resolved, Unexplained Event</mesh_term>
    <mesh_term>Infant Death</mesh_term>
    <mesh_term>Sudden Infant Death</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/NCT03278977
org study id: 6432
nct id: NCT03278977
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Apparent Life-Threatening Events (ALTE) in infants often lead to severe neurological
      complications or to sudden death. In such situations, cardio-pediatricians and intensive care
      physicians have no specific diagnosis or treatment. In a recent translational research
      (INSERM-DHOS), our team has reported a myocardiac abnormality in a rabbit model of vagal
      hyperreactivity which is also present in the human hearts of infants deceased from sudden
      death, i.e. increased M2 muscarinic receptors (M2R) density associated with compensative
      increased enzymatic activity and overexpression of acetylcholine esterase (AchE). In a recent
      PHRC-I study (article in preparation), these abnormalities have also been observed in the
      blood of patients, infants as well as adults, exhibiting severe vagal syncopes. We observed,
      even more importantly, similar abnormalities in infants under 1 year of age with very severe
      idiopathic ALTE (iALTE) compared with normal subjects and with patients who presented ALTE
      with identified etiologies (JAMA Pediatric, 2016 May). The aim of this present study is to
      validate the overexpression of M2R as a marker of risk of iALTE in infant under 1 year.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Outcomes Assessor)
masking description: Blood sample analysis will be blinded
measure: Muscarinic M2 receptor mRNA expression in blood
time frame: At the admission in the hospital, within 24 hours after the inclusion in the study
description: Blood sample will be collected not later than 24 hours after the inclusion in the study and will be frozen until centralized analysis.
A qRT-PCR will be performed for quantification of CHRM2 gene expression in blood (mRNA expression).
Interim analysis with the 7-8 first samples per group together. Final analysis with all samples at the study completion.
measure: Acetylcholinesterase mRNA expression in blood
time frame: At the admission in the hospital, within 24 hours after the inclusion in the study.
description: Blood sample will be collected not later than 24 hours after the inclusion in the study and will be frozen until centralized analysis..
A qRT-PCR will be performed for quantification of ACHE gene expression in blood (mRNA expression).
Interim analysis with the 7-8 first samples per group together. Final analysis with all samples at the study completion.
arm group label: ALTE group
arm group type: Other
description: Infants aged between 28 days and 12 months presenting severe(s) syncope(s) requiring hospitalization, for which a cause was identified during hospitalization.
arm group label: iALTE group
arm group type: Other
description: Infant aged between 28 days and 12 months presenting a severe syncope(s) requiring hospitalization, for which no etiology was found during hospitalization.
intervention type: Biological
intervention name: Blood sample for specific analyzes
description: Standard management of ALTE
Hospitalization in pediatric intensive care unit or pediatric emergencies
Etiologic research
Blood volume, 2.5mL in PaxGene® tube, for specific analyzes (M2R, AchE)
arm group label: ALTE group
arm group label: iALTE group
criteria: 
gender: All
minimum age: 28 Days
maximum age: 12 Months
healthy volunteers: No
last name: Charlie DE MELO, MD
role: Principal Investigator
affiliation: Hôpitaux Universitaires de Strasbourg
last name: Pascal BOUSQUET, MD, PhD
phone: (0)3 68 85 33 89
phone ext: +33
email: pascal.bousquet@unistra.fr
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Brief, Resolved, Unexplained Event
mesh term: Infant Death
mesh term: Sudden Infant Death
sharing ipd: No