Clinical trial NCT06869499: Study of the Prevalence of Acid Sphingomyelinase Deficiency/Niemann Pick AB and B Disease in Patients With Diffuse Interstitial Lung Disease
Official title: Niemann-PID: Study of the Prevalence of Acid Sphingomyelinase Deficiency/Niemann Pick AB and B Disease in Patients With Diffuse Interstitial Lung Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Splenomegaly
Splenectomy
Thrombopenia
Interstitial Lung Disease (ILD)
Hypocholesterolemia
Keywords: Acid sphingomyelinase deficiency
Ground glass lesions
Niemann Pick A/B, B
lysoSM
smpd1
splenomegaly
interstitial lung disease
screening
acid sphingomyelinase
Lead sponsor: Groupe Hospitalier Diaconesses Croix Saint-Simon
Sponsor class: OTHER
Collaborators: name: Bichat Hospital
name: Hospital Avicenne
name: Rennes University Hospital
name: Bicetre Hospital
name: University Hospital, Marseille
name: Tenon Hospital, Paris
name: CHU Dijon Bourgogne
name: University Hospital, Lille
name: Hospices Civils de Lyon
First posted: 2025-03-11
Enrollment: 200
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study is a multicenter prospective interventional research involving humans with minimal risks and constraints.

The minimal risks and study add-ons are:

-4ml blood sample for acid sphingomyelinase enzyme activity and LysoSM, if required.
Primary purpose: SCREENING

Brief summary: The goal of this clinical trial is to optimise and facilitate screening for Acid SphingoMyelinase Deficiency (ASMD) disease, by evaluating acid sphingomyelinase activity and, where appropriate, LysoSM levels in a cohort of 200 participants with diffuse interstitial lund disease (ILD) at risk of developing ASMD disease.

ILD is common in the general population, so in order to limit the number of differential diagnoses, the population to be studied will be restricted to participants aged between 15 years and 3 months and 60 years, with ILD plus ground-glass opacities on chest CT scan certified by a pulmonologist/radiologist or internist, AND splenomegaly or splenectomy, and/or thrombocytopenia, and/or low HDL cholesterol, and/or parental consanguinity which increase the sensitivity of ASMD screening.

In this clinical trail, two procedures are added, participants will be asked for :

* a blood sample to measure the acid sphingomyelinase enzyme activity and LysoSM, if required.
* a follow-up visit at 6 months

Detailed description: With the prevalence of ASMD estimated to be between 0.4 and 0.6/100,000 births, is probably under-diagnosed because it is not well known. Based on the current literature, no prevalence studies have been carried out, particularly in patients with interstitial lung disease (ILD). Similarly, no decision-making algorithm has been established for screening for ASMD in this participant population. Therefore, we aim to conduct this multicenter clinical trial to assess the relevance of implementing a decision algorithm to optimise screening for ASMD. Validation of this algorithm could provide clinicians with an additional diagnostic tool to improve the management of this disease and prevent its progression. Olipudase-alfa, a specific treatment for ASMD available from 2022, could thus benefit a greater number of people with disease who have been under-diagnosed.

The literature reports an association between chronic visceral ASMD (type B) and the presence of ILD, usually accompanied by splenomegaly or splenectomy (whatever the medical reason or cause), low HDL cholesterol, thrombocytopenia, with a higher frequency in cases of parental consanguinity.

ILD is common in the general population, therefore, in order to limit the number of differential diagnoses, the population to be studied will consist of participants aged between 15 years and 3 months and 60 years, with diffuse interstitial lung disease with ground-glass opacities on chest CT scan certified by a pulmonologist/radiologist or internist. We will propose acid sphingomyelinase activity testing in this population in case of splenomegaly (palpable spleen or craniocaudal length ≥ 13 cm) or splenectomy and/or thrombocytopenia (platelets \< 150 G/L) and/or low HDL cholesterol (\<0.4 g/l or 1. 03 mmol/l) and/or parental consanguinity increase the sensitivity of ASMD screening.

Considering that detection of ASMD after the age of 60 would not lead to a modification in current management, it was decided to limit the population to 60 years of age. Screening for ASMD, a very rare disease, can only be reasonably performed in a limited and selected population.

Description of actions and procedures added by the research :

* Venous blood collection (4ml EDTA tube) for the determination of :

  * acid sphingomyelinase enzyme activity in all participants included in the study. The determination of acid sphigomyelinase enzyme activity will be performed using a multiplex blotting assay that allows simultaneous determination of acid sphigomyelinase activity (ASMD) by tandem MS/MS mass spectrometry, but also Beta-glucocerebrosidase (Gaucher disease), alpha-galactosidase (Fabry disease), Maltase Acid (Pompe disease), Galactocerebrosidase (Krabbe disease), Alpha-L iduronidase (control enzyme) (MPSI)).
  * if acid sphingomyelinase activity \< 1.82 μmol/h/l (decreased) is detected, the concentration of lysoSM should be determined on the same sample.
* Appropriate participant management in the event of a positive ASMD screening.

Eligibility criteria: Inclusion Criteria:

1. Interstitial lung disease with ground-glass lesions on a chest CT scan certified by a pneumologist/radiologist or internist.
2. At least one of the following criteria :

   * Splenomegaly (palpable spleen or craniocaudal length ≥ 13 cm)
   * Splenectomy
   * Thrombocytopenia (platelets \< 150 G/L)
   * Low HDL-cholesterol (\<0.4 g/l or 1.03 mmol/l)
   * Notion of parental consanguinity
3. Have given their written informed consent, in accordance with regulations.
4. Affiliated to the social security system or entitled beneficiary (excluding AME).

Exclusion Criteria:

1. Inability to understand the information provided.
2. Under guardianship, curatorship or legal protection.
3. Under restraint or deprived of liberty by judicial or administrative decision.

Primary outcomes:
measure: Optimising screening for ASMD in a population of adult patients with diffuse interstitial pneumopathy
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Diaconesses Croix Saint-Simon
Study officials:
affiliation: Groupe Hospitalier Diaconesses Croix Saint-Simon
name: Wladimir MAUHIN, Doctor
role: PRINCIPAL_INVESTIGATOR
References: