Implication of UNconventionaL T Lymphocytes in Cystic Fibrosis (UNLOCk) (UNLOCk)
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|ClinicalTrials.gov Identifier: NCT03886350|
Recruitment Status : Recruiting
First Posted : March 22, 2019
Last Update Posted : May 7, 2019
Cystic fibrosis (CF) is characterized by a decrease in mucociliary clearance, recurrent infections and airway inflammation. This inflammatory process in airway mucosa is persistent, uncontrolled, but, somewhat paradoxically, ineffective for pathogen clearance. Neutrophils are chronically recruited in the airway mucosa by proinflammatory mediators such as Interleukin (IL)-17. However, mechanisms involved in this dysregulated and persistent immune response are not well understood.
In this context, a heterogeneous subpopulation of T lymphocytes called "unconventional T cells" (UTC) should deserve greater attention. UTC play a key role in orchestrating the ensuing innate and adaptive immune responses and they are endowed with numerous regulatory and effector properties. UTC mainly establish residency at mucosal sites, including the lung. To date, however, data related to implication and behavior of UTC during cystic fibrosis are extremely limited.
The hypothesis is that, given UTC properties, their functions and behavior are altered in CF, and thus, these cells could be implicated in persistent inflammation and poor response to infections.
The objective is to study UTC properties and functions in cystic fibrosis using blood and sputum samples of patients with CF, in correlation with comprehensive clinical and microbiological data.
The study will enroll adult patients with CF followed-up at University Hospital of Tours, France. For each patient included, blood and sputum samples will be analyzed during 18 months 1/ from routine tests obtained at steady state and 2/ from tests performed during acute exacerbations. UTC will be explored in blood and sputum using flowcytometry approach, to evaluate their relative abundance, activation/inhibition profile and functions (cytokine production and cytotoxic ability). Correlation will be made with clinical status, with longitudinal comparison across the study period for each patient, and comparison with the other patients and healthy volunteers.
This study will add significant knowledge in CF immunopathology by comprehensively assess UTC presence, functions and activation in CF. Indeed, UTC could be explored for disease progression marker, and, in a long-term perspective, explored for therapeutic interventions aiming at modulating their function (by activating or inhibiting UTC), to reshape lung immune response during CF.
|Condition or disease||Intervention/treatment|
|Cystic Fibrosis Innate Immunity Inflammatory Response||Other: blood and sputum samples|
Show Detailed Description
|Study Type :||Observational|
|Estimated Enrollment :||80 participants|
|Official Title:||Implication of UNconventionaL T Lymphocytes in Cystic Fibrosis|
|Actual Study Start Date :||April 3, 2019|
|Estimated Primary Completion Date :||April 2022|
|Estimated Study Completion Date :||October 2023|
Patients with cystic fibrosis
Patients with CF whom follow-up is undertaken at University Hospital of Tours, France
Other: blood and sputum samples
Blood and sputum samples for research purpose collected during routine tests performed at steady state and acute exacerbation
- Blood level of Non-Conventional T Lymphocytes [ Time Frame: 18 months ]Blood UTC expressed as % Cluster of Differenciation 3+ (CD3+) lymphocytes (gamme delta T lymphocytes, MAIT cells, Natural Killer T cells)
- Sputum level of Non-Conventional T Lymphocytes [ Time Frame: 18 months ]Sputum UTC expressed as % CD3+ lymphocytes (gamme delta T lymphocytes, MAIT cells, Natural Killer T cells)
- UTC activation/inhibition profile [ Time Frame: 18 months ]UTC activation/inhibition based on cell surface markers expression such as Cluster of Differenciation (CD) 69 and Programmed cell death 1 (PD-1)
- UTC production of pro-inflammatory cytokines [ Time Frame: 18 months ]Analysis of the level of IL-17, Interferon γ (IFNγ) and Tumor Necrosis Factor α (TNFα) produced by UTC
- UTC capacity to mediate cytotoxicity [ Time Frame: 18 months ]UTC cytotoxic profile based on Granzyme B and Cluster of Differenciation (CD) 107a expression
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03886350
|Contact: Youenn JOUAN, MD||+33 firstname.lastname@example.org|
|Contact: Sylvie LEGUE|
|Cystic Fibrosis Resource and Competence Center, University Hospital, Tours||Recruiting|
|Tours, France, 37044|
|Contact: Julie MANKIKIAN, MD|
|Principal Investigator: Julie MANKIKIAN, MD|
|Pulmonology Department, University Hospital, Tours||Recruiting|
|Tours, France, 37044|
|Contact: Thomas FLAMENT, MD|
|Principal Investigator: Thomas FLAMENT, MD|
|Principal Investigator:||Youenn JOUAN, MD||University Hospital, Tours|