NCT04811274

Brief Summary

Mutations in the MARS gene encoding methionyl-tRNA synthetase are responsible for a genetic form of alveolar proteinosis (PAP), but the pathophysiological mechanisms of the respiratory phenotype are not known. The main hypothesis is that the PAP phenotype in these patients is secondary to a defective clearance of the surfactant by the alveolar macrophages. The main objective of the study is to study the clearance capacity of lipoproteinaceous material by macrophages of patients with MARS related PAP. This will be investigate in cultured macrophages derived from peripheral blood monocytes of patients (patients with MARS related PAP) and controls (patients without MARS related PAP).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Jun 2021

Shorter than P25 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 19, 2021

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 23, 2021

Completed
3 months until next milestone

Study Start

First participant enrolled

June 7, 2021

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 6, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 6, 2021

Completed
Last Updated

September 15, 2025

Status Verified

September 1, 2025

Enrollment Period

5 months

First QC Date

March 19, 2021

Last Update Submit

September 8, 2025

Conditions

Pulmonary Alveolar Proteinosis (PAP)MARSGenetic Mutation

Keywords

Pulmonary alveolar proteinosis (PAP)Mutations in the MARS geneMethionyl-tRNA synthetaseSurfactant clearanceAlveolar macrophages

Outcome Measures

Primary Outcomes (1)

  • Measurement of the clearance

    Measurement of the clearance of abnormal lipo-proteinaceous material (from patients) at 48h of culture by cultured macrophages derived from peripheral blood monocytes from patients and controls. Microscopic examination of cell samples prepared on slide after cytospin and stained with oil red'O.

    Day 0

Secondary Outcomes (2)

  • Measurement of the clearance after supplementation with methionine

    Day 0

  • Cellular phenotyping and study of the GM-CSF pathway

    Day 0

Study Arms (2)

Patients

Minor patients with alveolar proteinosis by mutations of the MARS gene.

Biological: Blood collectionBiological: Bronchoalveolar lavage fluid collection

Controls

Minors patients without alveolar proteinosis.

Biological: Blood collectionBiological: Bronchoalveolar lavage fluid collection

Interventions

Blood collectionBIOLOGICAL

2 to 5 ml

ControlsPatients
Bronchoalveolar lavage fluid collectionBIOLOGICAL

5 to 25 ml

ControlsPatients

Eligibility Criteria

AgeUp to 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)
Sampling MethodNon-Probability Sample
Study Population

Minor patients with alveolar proteinosis by mutations of the MARS gene and minor patients without alveolar proteinosis, hospitalized for their care at Necker Enfants Malades hospital and for whom a blood sample and a bronchoscopy with bronchoalveolar lavage must be performed for their care.

You may qualify if:

  • Minors from 0 to 17 years hospitalized for their care at Necker Enfants Malades hospital and for whom a blood sample and a bronchoscopy with bronchoalveolar lavage must be performed as part of their care
  • Information and consent of the holders of parental authority and the patient

You may not qualify if:

  • \- Refusal of holders of parental authority or patient

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hôpital Necker-Enfants Malades

Paris, 75015, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood Bronchoalveolar lavage fluid (BALF)

MeSH Terms

Conditions

Pulmonary Alveolar Proteinosis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Alice HADCHOUEL

    Assistance Publique - Hôpitaux de Paris

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 19, 2021

First Posted

March 23, 2021

Study Start

June 7, 2021

Primary Completion

November 6, 2021

Study Completion

November 6, 2021

Last Updated

September 15, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations

FR(1)