Neuroendocrine Cell Hyperplasia of InfancyPhase 2CORTICONEHINCT06471556
Efficacy of Methylprednisolone Pulses in Neuroendocrine Celles Hyperplasia of Infancy : An Early Phase Study
A Phase 2 study testing IV Methylprednisolone pulses in people with Neuroendocrine Cell Hyperplasia of Infancy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 12 years
- Conditions the study is for
- Neuroendocrine Cell Hyperplasia of Infancy
- What is being tested?
- IV Methylprednisolone pulses
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteFrance
- Study dates
- 30 Jun 2025to 28 Feb 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infant aged under 12 months
- NEHI diagnosis based on:
- The recently validated clinical Liptzin score ≥7/10 associated with a suggestive thoracic CT pattern with ground glass opacities confined to middle lobe, lingula, and paramediastinal lung areas OR
- a clinical and thoracic CT suspicion and a lung biopsy showing an increased number of neuroendocrine cells in the epithelial airways area (at least one bronchiole with at least 10% of neuroendocrine cells)
- Oxygen requirement (awake and/or asleep) based on the usual pediatric recommendations (see section 4.1.1)
- Followed in one of the RespiRare participating centers
- Written informed consent of the holder(s) of its legal representative at the inclusion
Who cannot join
- Other cause of chILD assessed by lab biology tests, genetic analysis for surfactant genes (if available), bronchoalveolar lavage, and/or lung biopsy.
- Patient treated with IV methylprednisolone pulses before (any time)
- Diabetes
- Uncontrolled arterial hypertension
- Absence of Health care insurance
- Ongoing infection
Show all 9Show fewer
- Immunization with a live attenuated vaccine within the past two weeks
- Long term treatment with Azithromycin and/or Hydroxychloroquine
- Patients already included in an interventional study (RIPH1, clinical investigation or clinical trial)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Pediatric Pulmonology Department and Reference centre for rare lung diseases
Paris, 75012
Nadia NATHAN, 00 33 1 44 73 66 18, nadia.nathan@aphp.fr
Ralph EPAUD, 00 33 1 45 17 53 98, ralph.epaud@chicreteil.fr
About this study
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.
Read more
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.
Read the detailed description
This study aims at assessing the beneficial effect of IV methylprednisolone pulses on oxygen therapy in infants with NEHI. It applies to all hypoxic NEHI patients aged below 12 months and followed in one of the centres of the RespiRare network. 18 patients will be recruited.
CORTICO-NEHI is designed as an early phase study following an A'Hern's Single Stage Phase II design.
All the patients are included in a single group receiving as a standard of care a maximum of 6 IV pulses of 3 days each.
12 visits will be performed as a standard of care:
- Screening visit (M-1 at maximum) :follow-up routine visit, (usually the hospitalization for NEHI diagnosis). If the patient is eligible, parents are informed of the study and an informed note is given. Information on the study protocol is given to obtain their written consent as soon as possible, and at the latest at the inclusion.
- Inclusion (M0) : After checking of the inclusion criteria and the absence of exclusion criteria, information and collection of parental consent. Following these investigations, the patient's first IV methylprednisolone pulse (D1) is administrated within the limit of 10 days.
- Treatment visits (M0 - M5): During a hospitalization, 6 pulses are performed at a 4 weeks interval (+/- 10 days). Each pulse is a 3-days-6h-perfusions of Methylprednisolone (500mg and 120mg) 10mg/kg/day diluted in 50ml of saline under supervision of SpO2, heart rate, blood pressure / 30min. If oxygen can be stopped (2 oxymetries with a 1-week interval +/- 10 days): The endpoint is reached and the methylprednisolone pulses are definitively stopped.
- Follow-up visits (M6, M9, M12, M15 and M18)
For the research needs,
- CT scan and Echocardiography will be done at inclusion if not performed in the past 3 months
- QoL questionnaires will be performed at inclusion, M6, M12 and M18
- Dipstick for sugar will be performed at M6, M9, M12, M15, M18 (in addition to M0 - M5 according to the standard of care)
- Being tested
- IV Methylprednisolone pulses
- Keywords
- neuroendocrine cells hyperplasia of infancy (NEHI), Persistent tachypnoea of infancy (PTI), Childhood interstitial lung diseases (chILD), IV Corticosteroids pulses, Methylprednisolone, Oxygen therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV Methylprednisolone pulsesDrug
Six (6) pulses (max) are performed at a 4 weeks interval (+/- 10 days). Each pulse is a 3-days-6h-perfusions of Methylprednisolone (500mg and 120mg) 10mg/kg/day diluted in 50ml of saline under supervision of SpO2, heart rate, blood pressure /
| Study group | Role | What they receive |
|---|---|---|
| IV Methylprednisolone pulses | Experimental | Not described Receives: Drug: IV Methylprednisolone pulses |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Month 18
Secondary outcomes (14)
Time to achieve the oxygen therapy weaning
Duration between randomization and the absence of oxygen therapy requirement at M18
Measured: 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
Measured: Month 18
The number of patients requiring only sleep oxygen over time
Number of children requiring only sleep oxygen
Measured: Month 18
The number of patients with a normal respiratory rate
Number of children with a normal respiratory rate at rest
Measured: 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)
Measured: Between Month 0 and Month 18
Parents QoL
Family impact PedsQL score and a parents QoL score (submitted for publication)
Measured: Month 0 and Month 18
Patient's QoL
Patients impact PedsQL and the chILD QoL scores; the chILDPQoL score.
Measured: 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)
Measured: Between Month 0 and Month 18
Safety of methylprednisolone pulses
Number of unexpected hospitalizations for a respiratory exacerbation
Measured: Between Month 0 and Month 18
Number of antibiotic courses for an infectious lung exacerbation
Safety of methylprednisolone pulses
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: at Month 6 and Month 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2024
- Study start30 Jun 2025
- Primary completion28 Feb 2029 (estimated)
- Study completion28 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine Cell Hyperplasia of InfancyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nadia NATHAN, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06471556
- Sponsor's protocol ID
- APHP230821
- Other IDs
- 2023-508132-65-00, 2023
- Acronym
- CORTICONEHI
- Status last verified
- Aug 2025
- First submitted
- 13 Jun 2024
- Last updated
- 27 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Methylprednisolone Pulses in Neuroendocrine Celles Hyperplasia of Infancy : An Early Phase Study
- ClinicalTrials.gov ID
- NCT06471556
- Acronym / sponsor ID
- CORTICONEHI / APHP230821
- Keywords
- neuroendocrine cells hyperplasia of infancy (NEHI), Persistent tachypnoea of infancy (PTI), Childhood interstitial lung diseases (chILD), IV Corticosteroids pulses, Methylprednisolone, Oxygen therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 30 Jun 2025 (actual)
- Primary completion
- 28 Feb 2029 (estimated)
- Study completion
- 28 Feb 2029 (estimated)
- First posted
- 24 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study aims at assessing the beneficial effect of IV methylprednisolone pulses on oxygen therapy in infants with NEHI. It applies to all hypoxic NEHI patients aged below 12 months and followed in one of the centres of the RespiRare network. 18 patients will be recruited.
CORTICO-NEHI is designed as an early phase study following an A'Hern's Single Stage Phase II design.
All the patients are included in a single group receiving as a standard of care a maximum of 6 IV pulses of 3 days each.
12 visits will be performed as a standard of care:
- Screening visit (M-1 at maximum) :follow-up routine visit, (usually the hospitalization for NEHI diagnosis). If the patient is eligible, parents are informed of the study and an informed note is given. Information on the study protocol is given to obtain their written consent as soon as possible, and at the latest at the inclusion.
- Inclusion (M0) : After checking of the inclusion criteria and the absence of exclusion criteria, information and collection of parental consent. Following these investigations, the patient's first IV methylprednisolone pulse (D1) is administrated within the limit of 10 days.
- Treatment visits (M0 - M5): During a hospitalization, 6 pulses are performed at a 4 weeks interval (+/- 10 days). Each pulse is a 3-days-6h-perfusions of Methylprednisolone (500mg and 120mg) 10mg/kg/day diluted in 50ml of saline under supervision of SpO2, heart rate, blood pressure / 30min. If oxygen can be stopped (2 oxymetries with a 1-week interval +/- 10 days): The endpoint is reached and the methylprednisolone pulses are definitively stopped.
- Follow-up visits (M6, M9, M12, M15 and M18)
For the research needs,
- CT scan and Echocardiography will be done at inclusion if not performed in the past 3 months
- QoL questionnaires will be performed at inclusion, M6, M12 and M18
- Dipstick for sugar will be performed at M6, M9, M12, M15, M18 (in addition to M0 - M5 according to the standard of care)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IV Methylprednisolone pulses | Experimental | Drug: IV Methylprednisolone pulses |
Who may qualify
- Ages
- Up to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Infant aged under 12 months
- NEHI diagnosis based on:
- Oxygen requirement (awake and/or asleep) based on the usual pediatric recommendations (see section 4.1.1)
- Followed in one of the RespiRare participating centers
- Written informed consent of the holder(s) of its legal representative at the inclusion
Key exclusion criteria (9 listed)
- Other cause of chILD assessed by lab biology tests, genetic analysis for surfactant genes (if available), bronchoalveolar lavage, and/or lung biopsy.
- Patient treated with IV methylprednisolone pulses before (any time)
- Diabetes
- Uncontrolled arterial hypertension
- Absence of Health care insurance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IV Methylprednisolone pulsesSix (6) pulses (max) are performed at a 4 weeks interval (+/- 10 days). Each pulse is a 3-days-6h-perfusions of Methylprednisolone (500mg and 120mg) 10mg/kg/day diluted in 50ml of saline under supervision of SpO2, heart rate, blood pressure / | Drug | IV Methylprednisolone pulses |
Primary outcome
Number of children still requiring oxygen therapy
Time frame: Month 18
To evaluate the efficacy on oxygen therapy need of a 6 months methylprednisolone pulses in NEHI patients at M18.
14 secondary outcomes
Time to achieve the oxygen therapy weaning
Time frame: Month 18
The number of patients requiring continuous oxygen therapy (meaning sleep and awake oxygen therapy by opposition to sleep oxygen only) over time
Time frame: Month 18
The number of patients requiring only sleep oxygen over time
Time frame: Month 18
The number of patients with a normal respiratory rate
Time frame: Month 18
ChILD healing (reduction of severity) over time
Time frame: Between Month 0 and Month 18
Parents QoL
Time frame: Month 0 and Month 18
Patient's QoL
Time frame: Month 0 and Month 18
Impact of NEHI on feeding and growth status
Time frame: Between Month 0 and Month 18
Safety of methylprednisolone pulses
Time frame: Between Month 0 and Month 18
Number of antibiotic courses for an infectious lung exacerbation
Time frame: Between Month 0 and Month 18
Safety of methylprednisolone pulses
Time frame: At Month 6
Safety of methylprednisolone pulses
Time frame: At Month 6
To compare the family impact PedsQL questionnaire to the newly described chILD-PQoL questionnaire
Time frame: Month 0, Month 6, Month 12, Month 18
To study thoracic CT-scan evolution
Time frame: at Month 6 and Month 18
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2025.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nadia NATHAN principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IV Methylprednisolone pulses in people with Neuroendocrine Cell Hyperplasia of Infancy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nadia NATHAN (00 33 1 44 73 66 18, nadia.nathan@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of children still requiring oxygen therapy (time frame: Month 18). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2025.