Brainstem Dysfunction Involvement in the Pathogenesis of Pierre Robin Sequence

Pierre Robin Sequence Clinical Trial

— DYSROBIN  

Official title:

Brainstem Dysfunction Involvement in the Pathogenesis of Pierre Robin Sequence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03423017
• Other study ID #: 69HCL17_0816
• Status: Completed
• Phase: N/A
• Start date: May 24, 2018
• Est. completion date: March 23, 2023

Study information

• Verified date: January 2024
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Introduction Pierre Robin Sequence, PRS, incidence is about one hundred births per year in France. The main neonatal clinical manifestations are secondary to airway obstruction and food difficulties related to swallowing disorders. Despite recent progress, the pathogenesis of PRS is not fully understood.

The hypothesis is that brainstem dysfunction, BSD, plays a central role in the pathogenesis of PRS.

The purpose of the study is to achieve a complete evaluation of BSD to specify its role in the pathogenesis of PRS.

The primary objective is to compare central apnea index (CAI) of infants with PRS with those of infants with isolated airway obstruction (AWO) and those of healthy infants in order to clarify the direct role of BSD.

Material and Methods This prospective interventional study will be carried out in Lyon at the Hôpital Femme-Mère-Enfant and in Paris at the Hôpital Necker-Enfants Malades for 2 years. 3 groups of patients will be studied: PRS, 50 patients, AWO, 50 patients and healthy, 30 patients, included before 2 months of life. Infants will be followed for a maximum of 10 months. The evaluations will be carried out for 48 hours between birth and 2 months of life and then for 24 hours between 6 and 10 months of life for PRS and AWO group. Concerning the healthy group, the evaluation will be carried out during 48h during a single hospitalization before 2 months. Polysomnography, holter-ECG, 24h gas exchange, impedance-pH monitoring and mental region EEG will be performed. The central apnea index (mean number per hour), obstructive apnea index, non-nutritive swallowing index (NNS), gastroesophageal reflux and NNS-respiration coordination will be assessed for each stage of sleep and compared between the three groups of patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 113
• Est. completion date: March 23, 2023
• Est. primary completion date: March 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 2 Months

Eligibility

Inclusion Criteria for the group 1

• infants with PRS

Inclusion Criteria for the group 2 - infant with isolated airway obstruction

Inclusion Criteria for the group 3

• healthy infant : siblings of sudden unexpected death of the infant or with any known pathology

Inclusion Criteria for the 3 groups

• During one hospitalization or program for one hospitalization

• Parental consent

• Social safety affiliation

Exclusion Criteria:

• Birth before 37 SA

• Neonatal complication

• Group 2 only: AWO with neurological disease including brainstem dysfunction

• Group 3 only : AWO, ENT disease or syndromic disease, neurological disease including brainstem dysfunction, Intra uterine growth retardation

Related Conditions & MeSH terms

• Brainstem Dysfunction
• Pierre Robin Sequence
• Pierre Robin Syndrome

Intervention

Other:
• Recording of data
Recording during one hospitalization of 48 hours between birth and 2 months of life and one hospitalization of 24 hours between 6 and 10 months of life General data: age, term of birth, birth weight, gender, diseases, weight and size at recording, cranial perimeter, food, drugs : first and second visit Respiratory rate, respiratory signs, stridor : first and second visit 24h holter-ECG : first and second visit 24h impedance pH-metry : first visit Nocturne polysomnography : 50% prone position, 50% supine : sleep analyze, obstructive apnea hypopnea index (OAHI), central apnea index (CAI), periodical breathing, micro arousals index, non-nutritive swallowing analyze,(mental region electromyogram) : first and second visit 24 h gaz exchanges : mean, maximal PtcCO2 and % of time spent above 50 mmHg , SpO2 under 90%, 85% et 80% and desaturations index : first and second visit succimetry procedure : at first visit only between birth and 2 months
• Recording of data
Recording during one hospitalization of 48 hours between birth and 2 months of life General data: age, term of birth, birth weight, gender, diseases, weight and size at recording, cranial perimeter, food, drugs Respiratory rate, respiratory signs, stridor 24h holter-ECG 24h impedance pH-metry Nocturne polysomnography : 100% supine position : sleep analyze, obstructive apnea hypopnea index (OAHI), central apnea index (CAI), periodical breathing, micro arousals index, non-nutritive swallowing analyze,(mental region electromyogram) 24 h gas exchanges : mean, maximal PtcCO2 and % of time spent above 50 mmHg , SpO2 under 90%, 85% et 80% and desaturations index Succimetry procedure : at first visit only between birth and 2 months

Locations

Country	Name	City	State
France	Hopital Femme Mère Enfant	Bron
France	APHP-Necker	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Central apnea index (CAI) (mean number per hour)	To compare central apnea index (CAI) (mean number per hour), according to the ASSM guidelines 2007, recording by one nocturne polysomnography, between 3 groups of infants by sleep step, between birth and 2 months of life, in order to clarify the direct role of BSD.; According to the ASSM guidelines 2007, the central apnea index is measured : mean number of central apnea per hour.	2 months of life during one nocturne polysomnography
Secondary	Obstructive apnea hypopnea index (OAHI)(mean number per hour)	To compare obstructive apnea hypopnea index (OAHI)(mean number per hour) according to the guidelines ASSM 2007, recording by one nocturne polysomnography, between 3 groups of infants by sleep step, between birth and 2 months of life According to the ASSM guidelines 2007, the obstructive apnea hypopnea index is measured: mean number of obstructive apnea and hypopnea per hour.	2 months
Secondary	Comparison of OAHI(mean number per hour) and CAI	To compare obstructive apnea hypopnea index (OAHI)(mean number per hour) and central apnea index (CAI) (mean number per hour), between PRS group and AWO group by sleep step between 6 and 10 months of life; According to the ASSM guidelines 2007, the obstructive apnea hypopnea index, mean number of obstructive apnea and hypopnea per hour, and the central apnea index are measured, mean number of central apnea per hour.	between 6 and 10 months of life
Secondary	Micro arousals index (mean number per hour)	To compare micro arousals index (mean number per hour) between the 3 groups by sleep step between birth and 2 months of life and between PRS group and AWO group between 6 and 10 months of life to clarify the role of BSD in sleep microstructure; According to the ASSM guidelines 2007, micro arousals index (mean number per hour) are measured.	up to 2 months of life
Secondary	Micro arousals index (mean number per hour)	To compare micro arousals index (mean number per hour) between the 3 groups by sleep step between birth and 2 months of life and between PRS group and AWO group between 6 and 10 months of life to clarify the role of BSD in sleep microstructure; According to the ASSM guidelines 2007, micro arousals index (mean number per hour) are measured.	up to 10 months of life
Secondary	Non-nutritive swallowing index (NNS) and apnea secondary to non-nutritive swallowing	To compare non-nutritive swallowing index (NNS) and apnea secondary to non-nutritive swallowing between the 3 groups by sleep step between birth and 2 months of life and between PRS group and AWO group between 6 and 10 months of life to clarify the role of BSD in swallowing disorders and NNS-respiration coordination; non-nutritive swallowing index (NNS), mean number per hour, and apnea secondary to non-nutritive swallowing, mean number per hour, monitoring by the mental region EEG and the one nocturne polysomnography	up to 2 months of life
Secondary	Non-nutritive swallowing index (NNS) and apnea secondary to non-nutritive swallowing	To compare non-nutritive swallowing index (NNS) and apnea secondary to non-nutritive swallowing between the 3 groups by sleep step between birth and 2 months of life and between PRS group and AWO group between 6 and 10 months of life to clarify the role of BSD in swallowing disorders and NNS-respiration coordination; non-nutritive swallowing index (NNS), mean number per hour, and apnea secondary to non-nutritive swallowing, mean number per hour, monitoring by the mental region EEG and the one nocturne polysomnography	up to 10 months of life
Secondary	Positive and negative pressures, their temporal organizations evaluated using succimetry procedure between the 3 groups of patients at 0 and 2 months of life	Compare the positive and negative pressures, their temporal organizations evaluated using succimetry procedure between the 3 groups of patients at 0 and 2 months of life.	up to 2 months of life