Efficacy of Methylprednisolone Pulses in Neuroendocrine Celles Hyperplasia of Infancy : An Early Phase Study
NCT Number: NCT06471556
Acronym: CORTICONEHI
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Neuroendocrine Cell Hyperplasia of Infancy
Interventions: DRUG: IV Methylprednisolone pulses
Sponsor: Assistance Publique - Hôpitaux de Paris
Sex: ALL
Age: CHILD
Enrollment: 18
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2028-04
Locations: Pediatric Pulmonology Department and Reference centre for rare lung diseases, Paris, 75012, France

Summary:
Childhood interstitial lung diseases (chILD) are a heterogeneous group of rare and severe disorders with an estimated prevalence of 1/100,000. Among them, neuroendocrine cells hyperplasia of infancy (NEHI), also called persistent tachypnoea of infancy (PTI), is one of the most common aetiology (up to 16% of the cases). NEHI involves young infants (median age at onset 3 to 6 months) with tachypnoea, hypoxemia, crackles, retractions, failure to thrive and specific localizations of ground glass opacities (GGO) on chest CT-scan (paramediastinal areas and anterior lobes (right middle lobe and lingula). At diagnosis, most patients (50 to 100%) require oxygen supplementation that usually lasts for months to years, sometimes associated with nutritional support with eventual enteral nutrition. NEHI is believed to be related to an increased number of neuroendocrine cells in airway epithelial area. These cells are abundant in foetal life, when they play a role in regulating the lung development and decrease before birth.

There is no specific treatment for NEHI. The main treatment of chILD is corticosteroids. However, in NEHI, their efficacy is matter of debate. There is only a few NEHI cases series or cohorts all over the world, accounting for a maximum of 500 reported cases within only retrospective studies. Among them, United States and Argentina teams report supportive care only (oxygen therapy and nutritional support) whereas other teams, like the French ones largely uses IV corticosteroid pulses.

Unlike the majority of chILD, NEHI prognosis is usually good. However, at school-age, 26% of the patients remain symptomatic or have an abnormal lung function. Moreover, oxygen therapy significantly affects quality of life (QoL) of the children with ILD (-10.43/100 points, p=0.02) but also QoL and mood of their parents (unpublished data).

The present study hypothesis that corticosteroids are associated with a reduction of the length of oxygen support in infants with NEHI.

Primary Outcome Measures: Number of children still requiring oxygen therapy, To evaluate the efficacy on oxygen therapy need of a 6 months methylprednisolone pulses in NEHI patients at M18., Month 18
Secondary Outcome Measures: Time to achieve the oxygen therapy weaning, Duration between randomization and the absence of oxygen therapy requirement at M18, Month 18|The number of patients requiring continuous oxygen therapy (meaning sleep and awake oxygen therapy by opposition to sleep oxygen only) over time, Number of children still requiring oxygen therapy/ Number of children requiring only sleep oxygen, Month 18|The number of patients requiring only sleep oxygen over time, Number of children requiring only sleep oxygen, Month 18|The number of patients with a normal respiratory rate, Number of children with a normal respiratory rate at rest, Month 18|ChILD healing (reduction of severity) over time, Difference of Fan's severity score assessing the severity of children with ILD (respiratory symptoms, SpO2\<90% at sleep or exertion, SpO2\<90% at rest and pulmonary hypertension), Between Month 0 and Month 18|Parents QoL, Family impact PedsQL score and a parents QoL score (submitted for publication), Month 0 and Month 18|Patient's QoL, Patients impact PedsQL and the chILD QoL scores; the chILDPQoL score., Month 0 and Month 18|Impact of NEHI on feeding and growth status, Number of patients requiring at least one enteral nutrition episode (based on the physician appreciation in case of abnormal weight curve), Between Month 0 and Month 18|Safety of methylprednisolone pulses, Number of unexpected hospitalizations for a respiratory exacerbation, Between Month 0 and Month 18|Number of antibiotic courses for an infectious lung exacerbation, Safety of methylprednisolone pulses, Between Month 0 and Month 18|Safety of methylprednisolone pulses, * the number of patients with at least once systolic or diastolic arterial blood pressure (AP) over 2SD for the age at the days of methylprednisolone pulses
* the number of patients with at least one elevated fasting glycaemia before the first day of methylprednisolone pulses., At Month 6|Safety of methylprednisolone pulses, - the number of patients with at least one elevated fasting glycaemia before the first day of methylprednisolone pulses., At Month 6|To compare the family impact PedsQL questionnaire to the newly described chILD-PQoL questionnaire, Correlation between family impact PedsQL questionnaire and the newly described chILD-PQoL questionnaire, Month 0, Month 6, Month 12, Month 18|To study thoracic CT-scan evolution, Number of patients with an extension, a stability, a decrease or an absence of the GGO lesions on the CT-scan, at Month 6 and Month 18