Study of the Prevalence of Acid Sphingomyelinase Deficiency/Niemann Pick AB and B Disease in Patients With Diffuse Interstitial Lung Disease (Niemann-PID)

Niemann-PID: Study of the Prevalence of Acid Sphingomyelinase Deficiency/Niemann Pick AB and B Disease in Patients With Diffuse Interstitial Lung Disease

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

Study Overview

• Status: Not yet recruiting
• Conditions: Splenomegaly; Thrombopenia; Interstitial Lung Disease (ILD); Splenectomy; Hypocholesterolemia
• Intervention / Treatment: Procedure: Blood sampling for dosage

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.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Djazia BOUZELMAT Clinical Research Assistant; Phone Number: + 33 01 44 64 30 98; Email: dbouzelmat@hopital-dcss.org

Study Locations

• France
  • Paris, France, 75020
    • Groupe Hospitalier Diaconesses Croix Saint-Simon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental Cohort; The participants will be asked for a : 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 care management in the event of a positive ASMD screening.

Procedure: Blood sampling for dosage; 4ml blood sample to measure acid sphingomyelinase enzyme activity and LysoSM, if required.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimising screening for ASMD in a population of adult patients with diffuse interstitial pneumopathy	To optimise and facilitate screening for ASMD by evaluating acid sphingomyelinase activity and, where appropriate, LysoSM levels in a cohort of 200 patients with diffuse interstitial pneumopathy disease at risk of developing ASMD.	12 months

Collaborators and Investigators

• Sponsor: Wladimir MAUHIN, Dr
• Collaborators: Hospices Civils de Lyon; Rennes University Hospital; University Hospital, Lille; Bicetre Hospital; University Hospital, Marseille; Tenon Hospital, Paris; Bichat Hospital; Hospital Avicenne; CHU Dijon Bourgogne
• Investigators: Principal Investigator: Wladimir MAUHIN, Doctor, Groupe Hospitalier Diaconesses Croix Saint-Simon

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: February 19, 2025
• First Submitted That Met QC Criteria: March 5, 2025
• First Posted (Actual): March 11, 2025

Study Record Updates

• Last Update Posted (Actual): May 18, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: screening; interstitial lung disease; splenomegaly; Acid sphingomyelinase deficiency; Ground glass lesions; Niemann Pick A/B, B; lysoSM; smpd1; acid sphingomyelinase
• Additional Relevant MeSH Terms: Cytopenia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathological Conditions, Anatomical; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Respiratory Tract Diseases; Hematologic Diseases; Lymphatic Diseases; Lipid Metabolism Disorders; Lysosomal Storage Diseases; Blood Platelet Disorders; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Sphingolipidoses; Lipidoses; Hypertrophy; Lung Diseases; Lung Diseases, Interstitial; Thrombocytopenia; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C; Splenomegaly
• Other Study ID Numbers: 2024-A00050-47

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: not yet decided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No