Pulmonary Alveolar Proteinosis (PAP)MacroMARSNCT04811274
Macrophages, GM-CSF and MARS Proteinosis
An observational study of Pulmonary Alveolar Proteinosis (PAP) and MARS, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Pulmonary Alveolar Proteinosis (PAP), MARS, Genetic Mutation
- What is being tested?
- Blood collection and Bronchoalveolar lavage fluid collection
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- 7 Jun 2021to 6 Nov 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
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 17 years
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- 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
Who cannot join
- Refusal of holders of parental authority or patient
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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).
Read the 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.
- Conditions
- Pulmonary Alveolar Proteinosis (PAP), MARS, Genetic Mutation
- Being tested
- Blood collection, Bronchoalveolar lavage fluid collection
- Keywords
- Pulmonary alveolar proteinosis (PAP), Mutations in the MARS gene, Methionyl-tRNA synthetase, Surfactant clearance, Alveolar macrophages
- Medical subject headings
- Pulmonary Alveolar Proteinosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood collectionBiological
2 to 5 ml
Bronchoalveolar lavage fluid collectionBiological
5 to 25 ml
| Study group | Role | What they receive |
|---|---|---|
| Patients | Minor patients with alveolar proteinosis by mutations of the MARS gene. Receives: Biological: Blood collection; Biological: Bronchoalveolar lavage fluid collection | |
| Controls | Minors patients without alveolar proteinosis. Receives: Biological: Blood collection; Biological: Bronchoalveolar lavage fluid collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 0
Secondary outcomes (2)
Measurement of the clearance after supplementation with methionine
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.
Measured: Day 0
Cellular phenotyping and study of the GM-CSF pathway
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.
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2021
- Study start7 Jun 2021
- Primary completion6 Nov 2021
- Study completion6 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Alveolar Proteinosis (PAP)Studies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Alice HADCHOUEL, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04811274
- Sponsor's protocol ID
- APHP201476
- Other IDs
- 2020-A02750-39
- Acronym
- MacroMARS
- Status last verified
- Mar 2026
- First submitted
- 19 Mar 2021
- Last updated
- 3 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Macrophage Function and of the GM-CSF Signaling Pathway in Alveolar Proteinosis by Mutations of the MARS Gene
- ClinicalTrials.gov ID
- NCT04811274
- Acronym / sponsor ID
- MacroMARS / APHP201476
- Conditions
- Pulmonary Alveolar Proteinosis (PAP), MARS, Genetic Mutation
- Keywords
- Pulmonary alveolar proteinosis (PAP), Mutations in the MARS gene, Methionyl-tRNA synthetase, Surfactant clearance, Alveolar macrophages
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 7 Jun 2021 (actual)
- Primary completion
- 6 Nov 2021 (actual)
- Study completion
- 6 Nov 2021 (actual)
- First posted
- 23 Mar 2021 (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.
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).
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | – | Biological: Blood collection, Biological: Bronchoalveolar lavage fluid collectionMinor patients with alveolar proteinosis by mutations of the MARS gene. |
| Controls | – | Biological: Blood collection, Biological: Bronchoalveolar lavage fluid collectionMinors patients without alveolar proteinosis. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (1 listed)
- Refusal of holders of parental authority or patient
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 |
|---|---|---|
| Blood collection2 to 5 ml | Biological | Controls, Patients |
| Bronchoalveolar lavage fluid collection5 to 25 ml | Biological | Controls, Patients |
Primary outcome
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.
2 secondary outcomes
Measurement of the clearance after supplementation with methionine
Time frame: Day 0
Cellular phenotyping and study of the GM-CSF pathway
Time frame: Day 0
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2026.
- Individual participant dataSharing planned: No
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. This study is not recruiting at the moment.
Alice HADCHOUEL 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?
An observational study of Pulmonary Alveolar Proteinosis (PAP) and MARS, 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 2 inclusion and 1 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: finished, as of the sponsor's last update on 3 Apr 2026. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of the clearance (time frame: Day 0). 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 3 Apr 2026.