Apparent Life Threatening Events, Sudden Infant Death Syndrome and Muscarinic Receptors (iALTE)

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.

Study Overview

• Status: Recruiting
• Conditions: Apparent Life-Threatening Event in Infants Under One Year of Age
• Intervention / Treatment: Biological: Blood sample for specific analyzes

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pascal BOUSQUET, MD, PhD; Phone Number: +33 (0)3 68 85 33 89; Email: pascal.bousquet@unistra.fr

Study Locations

• France
  • Besançon, France, 25030
    • Not yet recruiting
    • Pediatric Intensive Care unit/Emergency unit - Besançon University Hospital
    • Contact: Gérard THIRIEZ, MD PhD; Email: gerard.thiriez@univ-fcomte.fr
  • Nancy, France, 54500
    • Recruiting
    • Pediatric Intensive Care Unit - Brabois Hospital - Nancy University Hospital
    • Contact: Mathieu MARIA; Email: m.maria@chru-nancy.fr
  • Reims, France, 51092
    • Recruiting
    • Pediatric unit - Maison Blanche Hospital - Reims University Hospital
    • Contact: Ahmad AKHAVI; Email: aakhavi@chu-reims.fr
  • Strasbourg, France, 67200
    • Recruiting
    • Pediatric intensive care unit/ Pediatric unit- Strasbourg University Hospital - Hautepierre Hospital
    • Contact: Charlie DE MELO, MD; Email: charlie.demelo@chru-strasbourg.fr
    • Principal Investigator: Charlie DE MELO, MD
    • Sub-Investigator: Angelo LIVOLSI, MD
    • Sub-Investigator: Pauline HELMS, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infant aged between 28 days and 12 months, presenting severe syncope(s) requiring medical management, hospitalized in a pediatric intensive care unit or pediatric emergencies
• Consent signed and dated by the legal representatives
• Patients affiliated to a social security system

Exclusion Criteria:

• Infant with known cardiovascular, neurologic, infectious, toxic or metabolic pathologies before enrollment (before the syncope)
• Subject on medication for more than 3 months before enrollment
• Impossibility to clearly inform the legal representatives (comprehension problems)
• Subject in exclusion period for clinical trial (previous or current study)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ALTE group; Infants aged between 28 days and 12 months presenting severe(s) syncope(s) requiring hospitalization, for which a cause was identified during hospitalization.	Biological: Blood sample for specific analyzes; 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)
Other: iALTE group; Infant aged between 28 days and 12 months presenting a severe syncope(s) requiring hospitalization, for which no etiology was found during hospitalization.	Biological: Blood sample for specific analyzes; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscarinic M2 receptor mRNA expression in blood	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.	At the admission in the hospital, within 24 hours after the inclusion in the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acetylcholinesterase mRNA expression in blood	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.	At the admission in the hospital, within 24 hours after the inclusion in the study.

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France
• Collaborators: Groupement Interrégional de Recherche Clinique et d'Innovation Est
• Investigators: Principal Investigator: Charlie DE MELO, MD, Hôpitaux Universitaires de Strasbourg

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2018
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: August 31, 2017
• First Submitted That Met QC Criteria: September 7, 2017
• First Posted (Actual): September 12, 2017

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Sudden Infant Death; Apparent Life-Threatening Event; ALTE
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Death, Sudden; Death; Respiratory Insufficiency; Cyanosis; Infant Death; Sudden Infant Death; Brief, Resolved, Unexplained Event
• Other Study ID Numbers: 6432 (Other Identifier: LSHTM ethics reference number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No