Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Implication of UNconventionaL T Lymphocytes in Cystic Fibrosis (UNLOCk) (UNLOCk)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03886350
Recruitment Status : Recruiting
First Posted : March 22, 2019
Last Update Posted : May 7, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Tours

Brief Summary:

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

Layout table for study information
Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Case-Control
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Group/Cohort Intervention/treatment
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




Primary Outcome Measures :
  1. 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)

  2. 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)


Secondary Outcome Measures :
  1. 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)

  2. 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

  3. 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
Blood samples Sputum samples


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Adult patients with cystic fibrosis whom follow-up is undertaken at University Hospital of Tours.
Criteria

Inclusion Criteria:

  • Patients with a genetic diagnosis of cystic fibrosis
  • Older than 18 years old
  • Be followed-up at University Hospital of Tours

Exclusion Criteria:

  • Pregnant or breastfeeding women
  • Patient under judicial protection
  • Patient having objected to the processing of his data

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Youenn JOUAN, MD +33 247479861 youenn.jouan@univ-tours.fr
Contact: Sylvie LEGUE

Locations
Layout table for location information
France
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         
Sponsors and Collaborators
University Hospital, Tours
Investigators
Layout table for investigator information
Principal Investigator: Youenn JOUAN, MD University Hospital, Tours

Layout table for additonal information
Responsible Party: University Hospital, Tours
ClinicalTrials.gov Identifier: NCT03886350     History of Changes
Other Study ID Numbers: RIPH3-RNI18 / UNLOCk
2019-A00290-57 ( Other Identifier: IdRCB )
First Posted: March 22, 2019    Key Record Dates
Last Update Posted: May 7, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Tours:
Unconventional T cells
Cystic fibrosis
gamma delta T cell
Mucosal Associated Invariant T cell
Natural Killer T cell
Additional relevant MeSH terms:
Layout table for MeSH terms
Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases