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

Not Applicable

• Conditions: Apparent Life-Threatening Event in Infants Under One Year of Age
• Interventions: Biological: Blood sample for specific analyzes

• Registration Number: NCT03278977
• Lead Sponsor: University Hospital, Strasbourg, France

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-08-31
• Study First Submitted QC: 2017-09-07
• Study First Posted: 2017-09-12
• Study Start: 2018-09-15
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-28
• Last Update Posted: 2022-06-30
• Primary Completion: 2022-12
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Muscarinic M2 receptor mRNA expression in blood	At the admission in the hospital, within 24 hours after the inclusion in the study	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.

Secondary Outcome Measures

Name	Time	Method
Acetylcholinesterase mRNA expression in blood	At the admission in the hospital, within 24 hours after the inclusion in the study.	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.

Trial Locations

Locations (4)

Pediatric Intensive Care Unit - Brabois Hospital - Nancy University Hospital; 🇫🇷 Nancy, France

Pediatric unit - Maison Blanche Hospital - Reims University Hospital; 🇫🇷 Reims, France

Pediatric intensive care unit/ Pediatric unit- Strasbourg University Hospital - Hautepierre Hospital; 🇫🇷 Strasbourg, France

Pediatric Intensive Care unit/Emergency unit - Besançon University Hospital; 🇫🇷 Besançon, France