Brainstem Dysfunction Involvement in the Pathogenesis of Pierre Robin Sequence

NCT03423017 | Completed

• 1 other identifier: 69HCL17_0816
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Pierre Robin Sequence; Brainstem Dysfunction

Keywords

Pierre Robin sequence; Brainstem; pathogenesis; swallowing; apnea

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Obstructive apnea hypopnea index (OAHI)(mean number per hour)

  2 months

• Comparison of OAHI(mean number per hour) and CAI

  between 6 and 10 months of life

• Micro arousals index (mean number per hour)

  up to 2 months of life

• Micro arousals index (mean number per hour)

  up to 10 months of life

• Non-nutritive swallowing index (NNS) and apnea secondary to non-nutritive swallowing

  up to 2 months of life

Study Arms (3)

Pierre Robin sequence

OTHER

Infants with PRS : retrognathism, glossoptosis, cleft palate Group 1a : isolated PRS Group 1b : PRS with bone disease or collagen disease (Stickler) Group 1c : syndromic PRS or associated PRS without bone disease or collagen disease

Other: Recording of data

Superior airway obstruction, AWO

OTHER

Infants with AWO : laryngomalacia, tracheal stenosis, laryngeal stenosis, others etiology

Other: Recording of data

Healthy infants

OTHER

Healthy infants : siblings of sudden unexpected death of the infant

Other: Recording of data

Interventions

Recording of data OTHER

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

Pierre Robin sequence; Superior airway obstruction, AWO

Eligibility Criteria

• Age: 1 Day - 2 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \- infants with PRS
• \- healthy infant : siblings of sudden unexpected death of the infant or with any known pathology
• During one hospitalization or program for one hospitalization
• Parental consent
• Social safety affiliation

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Hopital Femme Mère Enfant

Bron, 69500, France

Location

APHP-Necker

Paris, 75015 Paris, France

Location

MeSH Terms

Conditions

Pierre Robin Syndrome; Apnea

Condition Hierarchy (Ancestors)

Jaw Abnormalities; Jaw Diseases; Musculoskeletal Diseases; Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Stomatognathic Diseases; Stomatognathic System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2018
• First Posted: February 6, 2018
• Study Start: May 24, 2018
• Primary Completion: March 23, 2023
• Study Completion: March 23, 2023
• Last Updated: January 10, 2024

Record last verified: 2024-01

Locations

FR (2)