- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04811274
Macrophages, GM-CSF and MARS Proteinosis (MacroMARS)
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
Intervention / Treatment
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
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Alice HADCHOUEL, MD, PhD
- Phone Number: +33 1 44 49 48 47
- Email: alice.hadchouel-duverge@aphp.fr
Study Locations
-
-
-
Paris, France, 75015
- Recruiting
- Hopital Necker-Enfants Malades
-
Contact:
- Alice HADCHOUEL, MD, PhD
- Phone Number: +33 1 44 49 48 47
- Email: alice.hadchouel-duverge@aphp.fr
-
Sub-Investigator:
- Isabelle SERMET-GAUDELUS, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
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
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Patients
Minor patients with alveolar proteinosis by mutations of the MARS gene.
|
2 to 5 ml
5 to 25 ml
|
Controls
Minors patients without alveolar proteinosis.
|
2 to 5 ml
5 to 25 ml
|
What is the study measuring?
Primary Outcome Measures
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
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
Investigators
- Principal Investigator: Alice HADCHOUEL, Assistance Publique - Hôpitaux de Paris
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- APHP201476
- 2020-A02750-39 (Other Identifier: IDRCB number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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