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Non Randomized Comparative Study With Control (Allo-NK-CMV)

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ClinicalTrials.gov Identifier: NCT03294824
Recruitment Status : Recruiting
First Posted : September 27, 2017
Last Update Posted : May 28, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
NK cells are lymphocytes who play a role in the control of viral infections , tumor and fœtal tolerance. They belong to innate immune cells but they have a link with adaptative immunity. Indeed, after some viral infections such as CMV, Chikungunya, B hepatitis etc, a subset of NKG2C+ NK cells expands and can transfer, in murine models, a " memory " that can better control CMV infections. CMV reactivation is a major cause of morbidity and mortality after allogeneic hematopoietic ste cell transplantation in humans. The aim of this prospective study is to evaluate the role of NK cells, in particular NKG2C+ NK cells in the control of CMV but also Adenovirus after allo HSCT. Peripheral NK cells from 30 and 10 patients who reactivated respectively CMV and AdV are prospectively studied (extensive phenotyping and functional studies before and after administration of anti viral drugs) and compared with 30 allotransplanted patients who didn't reactivate CMV in a pair analysis, and 30 healthy donors serologically + for CMV.

Condition or disease Intervention/treatment
Allogeneic Hematopoietic Stem Cell Transplantation Other: blood sample

Detailed Description:
For both groups: 28ml of peripheral blood samples are collected at different points. Group 1 : before and after anti viral treatment . Control group 2: one point after allo-HSCT; Control group 3: 1 point before transplant. Phenotypical study of NK cells: activating and inhibitory receptors, activation and differentiation's markers. Phenotypical studies of the ligands on infected cells. Genotypic study of KIR receptors (Kirotype); functional studies: polyfunctionality essay (flow cytometry): degranulation CD107a, IFNg, TNFa production).

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Study Type : Observational
Estimated Enrollment : 90 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Study of Natural Killer Immunity During Infections With CMV or AdV After Allogeneic Hematopoietic Stem Cells
Actual Study Start Date : September 27, 2013
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018

Group/Cohort Intervention/treatment
patients who reactivate CMV or AdV after allogeneic HSCT
allotransplanted patients who reactivated respectively CMV (n=30) and AdV (n=10)
Other: blood sample
peripheral blood samples are collected

Control group: allogeneic HSC transplanted patients
allotransplanted patients who didn't reactivate CMV
Other: blood sample
peripheral blood samples are collected

Healthy donors group
healthy donors serologically + for CMV
Other: blood sample
peripheral blood samples are collected




Primary Outcome Measures :
  1. Nk cells phenotype (activation, differentiation, memory NK cell) and function (cytoxicity and cytokines production) measured by flow cytometry [ Time Frame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment" ]

    CD3-CD56+ NK cells will be analyzed by Flow cytometry with an appropriate monoclonal antibodies (mAb) cocktail: anti-CD3 ,CD56, CD16, CD159a/NKG2A , CD85J; HLA-DR ; CD62L , CD161; KIR2DL1 and KIR3DL1, and KIR2DL2/KIR2DL3.

    The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic markers and will be compared with healthy donors.


  2. NK cells cytoxicity and cytokines production when incubated with standard HLA class I negative K562 target cells [ Time Frame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment" ]

    Polyfunctional assay will test the capacity of NK cells degranulation and production of cytokines when incubated with standard HLA class I negative K562 target cells in the presence of anti-CD107a ,IFN-g, or TNF-a mAb.

    The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic and will be compared with healthy donors.



Secondary Outcome Measures :
  1. Effect of CMV and AdV infection compared with healthy donors [ Time Frame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment" ]
    The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic and functional markers and will be compared with healthy donors.

  2. In vitro Nk cells ligands analyzes on infected cells by CMV [ Time Frame: approximately 18 months after Study Completion Date (last participant's last visit) ]

    Monocyte are differentiated in macrophage cells and infected by the CMV strain TB40/E. Nk cell ligands will be analyzed on infected cells. NK cells from infected patients post allogenic transplantation will be tested against in vitro infected cells.

    Being a model in vitro, it is not possible to determine in advance which ligands will be identified.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Allogeneic HSCT for malignant or non malignant hematological disease in adult patients
Criteria

Inclusion Criteria:

  1. patients who reactivate CMV or AdV after allogeneic HSCT ;

    • Age>18 years; indication for a antiviral treatment:
    • at least 1 PCR CMV>1000 copies/ml or 1 PCR ADV>1000 copies/ml or at least 2 ADV PCR positive - sites (stools, throat, urines);
    • signed informed consent;
  2. Control group: allogeneic HSC transplanted patients;

    • Age>18 years; no CMV or AdV reactivation ;
    • signed informed consent;
  3. Healthy donors group: HSC donor;

    • Age>18 years;
    • signed informed consent

Exclusion Criteria:

none


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): NCT03294824


Contacts
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Contact: Stephanie Nguyen Quoc, Doctor 33142162823 stephanie.nguyen-quoc@aphp.fr
Contact: Laetitia Souchet, Doctor 33142162823

Locations
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France
Hôpital Pitié Salpêtriere Recruiting
Paris, France, 75651
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Stephanie Nguyen Quoc, Doctor Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03294824     History of Changes
Other Study ID Numbers: P111107
IDRCB ( Other Identifier: 2013-A00825-40 )
First Posted: September 27, 2017    Key Record Dates
Last Update Posted: May 28, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
NK cells
Cytomegalovirus
adenovirus
Allogeneic transplantation