Cystic Fibrosis Blood Neutrophils

Not Applicable

Recruiting

• Conditions: Cystic Fibrosis
• Interventions: Other: 2 blood samples; Other: 1 blood sample

• Registration Number: NCT04970225
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The purpose of this prospective study is to analyze function and phenotype of blood neutrophils in cystic fibrosis patients and the impact of Pseudomonas aeruginosa chronic infection, treatment with CFTR modulators and acute exacerbation on blood neutrophils phenotype and function.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-01-17
• Study Start: 2021-07-08
• Study First Submitted QC: 2021-07-09
• Study First Posted: 2021-07-21
• Status Verified: 2023-09
• Last Update Submitted: 2024-07-15
• Last Update Posted: 2024-07-16
• Primary Completion: 2025-01
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

• Patient over the age of 18 who is not under legal protection

• Patients with CF according to the diagnostic criteria of the Cystic Fibrosis Foundation including:

  • 15 patients with severe mutation but not chronically infected with PA and not treated with lumacaftor / ivacaftor
  • 15 patients homozygous phe508del, chronically infected with PA and not treated with lumacaftor / ivacaftor
  • 15 patients homozygous phe508del, chronically infected with PA and treated with lumacaftor / ivacaftor
  • 15 hospitalized patients for respiratory exacerbation
  • 40 patients initiating Ivacaftor-Tezacaftor-Elexacaftor treatment.

• No change in baseline treatment for 15 days (including antibiotic treatment).

• Patient affiliated to a social security system

• Free, informed and written consent, dated and signed by the patient and the investigator, at the latest on the day of inclusion and before any action required by the study.

Exclusion Criteria

• Informed consent impossible to obtain
• Involvement in an interventional research protocol in the previous 3 months if exclusion directive was given in this protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exacerbation	2 blood samples	15 adult cystic fibrosis patients followed in the respiratory medicine department of Cochin hospital, paris, France and hospitalized for respiratory exacerbation
Stable state	1 blood sample	45 adult cystic fibrosis patients followed in the respiratory medicine department of Cochin hospital, paris, France: * With severe cftr mutations * With or without PA chronic infection * Treated or not with Ivacaftor-Lumacaftor
Starting Ivacaftor-Tezacaftor-Elexacaftor	2 blood samples	40 adult cystic fibrosis patients followed in the respiratory medicine department of Cochin hospital, paris, France: * With at least one severe cftr mutation * With or without PA chronic infection * Initiating Ivacaftor-Tezacaftor-Elexacaftor

Primary Outcome Measures

Name	Time	Method
Effector function analysis of blood neutrophils in CF.	Through study completion, an average of 1 year	Comparison of effector function analysis of blood neutrophils of CF patients versus control blood-donors.
Phagocytosis potential of blood neutrophils in CF.	Through study completion, an average of 1 year	Comparison of phagocytosis potential of blood neutrophils of CF patients versus control blood-donors.
Quantification of blood low density neutrophils in cystic fibrosis (CF)	Through study completion, an average of 1 year	Quantitative flow cytometric evaluation of neutrophil membrane markers that differ according to whether they are : * mature neutrophils : CD16high, CD15high, CD33high, CD10high; * or Low density neutrophils (LDG) : CD16low, CD15neg, CD33 neg, CD10 neg. Comparison of neutrophil membrane markers profile in CF patients versus control blood-donors.
Survival/apoptosis balance analysis in CF	Through study completion, an average of 1 year	Survival / apoptosis balance analysis : (PCNA localization) in CF patients blood neutrophils versus control blood-donors.
Transcriptomic analysis of blood neutrophils in cystic fibrosis (CF)	Through study completion, an average of 1 year	Transcriptomic analysis of blood neutrophil proinflammatory or immunomodulatory potential.; Comparison of transcriptomic blood neutrophil profile in CF patients versus control blood-donors.

Secondary Outcome Measures

Name	Time	Method
Transcriptomic analysis of blood neutrophils in CF according to different clinical situations.	Through study completion, an average of 1 year	Transcriptomic analysis of blood neutrophil proinflammatory or immunomodulatory potential.; * At stable state: * presence or absence of airway chronic infection with PA; * whether or not patients are treated Ivacaftor-Lumacaftor; * At beginning of exacerbation or after antibiotic treatment.; * Before or after Ivacaftor-Tezacaftor-Elexacaftor treatment
Quantification of blood low density neutrophils in CF vs other chronic inflammatory disorders.	Through study completion, an average of 1 year	Quantitative flow cytometric evaluation of neutrophil membrane markers that differ according to whether they are: * mature neutrophils : CD16high, CD15high, CD33high, CD10high; * Low density neutrophils (LDG) : CD16low, CD15neg, CD33 neg, CD10 neg. Comparison of neutrophil membrane markers profile in CF patients versus patients with other chronic inflammatory disease (eg. Rheumatoid arthritis, inflammatory bowel disease).
Quantification of blood low density neutrophils in CF according to different clinical situations.	Through study completion, an average of 1 year	Quantitative flow cytometric evaluation of neutrophil membrane markers.; * At stable state: * presence or absence of airway chronic infection with PA; * whether or not patients are treated Ivacaftor-Lumacaftor; * At beginning of exacerbation or after antibiotic treatment.; * Before or after Ivacaftor-Tezacaftor-Elexacaftor treatment
Phagocytosis potential of blood neutrophils in CF according to different clinical situations.	Through study completion, an average of 1 year	Phagocytosis potential analysis of blood neutrophils in CF: * At stable state: * presence or absence of airway chronic infection with PA; * whether or not patients are treated Ivacaftor-Lumacaftor; * At beginning of exacerbation or after antibiotic treatment.; * Before or after Ivacaftor-Tezacaftor-Elexacaftor treatment
Effector function analysis of blood neutrophils in CF according to different clinical situations.	Through study completion, an average of 1 year	Effector function analysis of blood neutrophils: * At stable state: * presence or absence of airway chronic infection with PA; * whether or not patients are treated Ivacaftor-Lumacaftor; * At beginning of exacerbation or after antibiotic treatment.; * Before or after Ivacaftor-Tezacaftor-Elexacaftor treatment
Survival/apoptosis balance analysis in CF according to different clinical situations.	Through study completion, an average of 1 year	Survival / apoptosis balance analysis (PCNA localization): * At stable state: * presence or absence of airway chronic infection with PA; * whether or not patients are treated Ivacaftor-Lumacaftor; * At beginning of exacerbation or after antibiotic treatment.; * Before or after Ivacaftor-Tezacaftor-Elexacaftor treatment.

Trial Locations

Locations (1)

Cochin hospital, AP-HP; 🇫🇷 Paris, France