Macrophages, GM-CSF and MARS Proteinosis (MacroMARS)

March 30, 2026 updated by: Assistance Publique - Hôpitaux de Paris

Study of Macrophage Function and of the GM-CSF Signaling Pathway in Alveolar Proteinosis by Mutations of the MARS Gene

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Pulmonary alveolar proteinosis (PAP) is a rare respiratory disease characterized by the accumulation of lipoproteinaceous material within the pulmonary alveoli, resulting in the majority of cases from a defective clearance of the surfactant by intra-alveolar macrophages.

Mutations in the MARS gene encoding methionyl-tRNA synthetase are responsible for a genetic form of alveolar proteinosis, but the pathophysiological mechanisms leading to mutations in the respiratory phenotype are not known.

The main hypothesis is that the alveolar proteinosis 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).

The subjects and the controls will be included during a hospitalization during which a blood sample and a bronchoscopy with broncoalveolar lavage must be performed as part of their care.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Paris, France, 75015
        • Hôpital Necker-Enfants Malades

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 13 years (Child)

Accepts Healthy Volunteers

No

Sampling Method

Non-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.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

- Refusal of holders of parental authority or patient

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Patients
Minor patients with alveolar proteinosis by mutations of the MARS gene.
Biological: Blood collection
2 to 5 ml
Biological: Bronchoalveolar lavage fluid collection
5 to 25 ml
Controls
Minors patients without alveolar proteinosis.
Biological: Blood collection
2 to 5 ml
Biological: Bronchoalveolar lavage fluid collection
5 to 25 ml

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Measurement of the clearance
Time Frame: Day 0

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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Measurement of the clearance after supplementation with methionine
Time Frame: Day 0

Measurement of the clearance of abnormal lipo-proteinaceous material (from patients) at 48h culture with methionine supplementation in culture medium 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
Cellular phenotyping and study of the GM-CSF pathway
Time Frame: Day 0

Description : Study the impact of mutations on the cell phenotype and the GM-CSF signalling pathway.

(i) CD11b and CD49d cell immunostaining which are surface markers of healthy alveolar macrophages ; (ii) measurement of the level of intracellular phosphorylation of STAT5 by flow cytometry; and (iii) measurement of the level of expression of the SPI1, PPARγ and ABCG1 genes by quantitative PCR.

These measurements will be performed in cultured macrophages derived from peripheral blood monocytes of patients and controls, but also in alveolar macrophages directly isolated from the BAL fluid of patients and controls. All these measurements will be performed in response to incubation with GM-CSF.
Day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
URC-CIC Paris Descartes Necker Cochin

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Alice HADCHOUEL, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 7, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 6, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 6, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 19, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 23, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 30, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APHP201476
  • 2020-A02750-39 (Other Identifier: IDRCB number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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