Non Randomized Comparative Study With Control

NCT03294824 | Unknown

• 2 other identifiers: P111107IDRCB
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Allogeneic Hematopoietic Stem Cell Transplantation

Keywords

NK cells; Cytomegalovirus; adenovirus; Allogeneic transplantation

Outcome Measures

Primary Outcomes (2)

• Nk cells phenotype (activation, differentiation, memory NK cell) and function (cytoxicity and cytokines production) measured by flow cytometry

  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.

  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"

• NK cells cytoxicity and cytokines production when incubated with standard HLA class I negative K562 target cells

  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.

  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"

Secondary Outcomes (2)

• Effect of CMV and AdV infection compared with healthy donors

  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"

• In vitro Nk cells ligands analyzes on infected cells by CMV

  approximately 18 months after Study Completion Date (last participant's last visit)

Study Arms (3)

patients who reactivate CMV or AdV after allogeneic HSCT

allotransplanted patients who reactivated respectively CMV (n=30) and AdV (n=10)

Other: blood sample

Control group: allogeneic HSC transplanted patients

allotransplanted patients who didn't reactivate CMV

Other: blood sample

Healthy donors group

healthy donors serologically + for CMV

Other: blood sample

Interventions

blood sample OTHER

peripheral blood samples are collected

Control group: allogeneic HSC transplanted patients; Healthy donors group; patients who reactivate CMV or AdV after allogeneic HSCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Allogeneic HSCT for malignant or non malignant hematological disease in adult patients

You may qualify if:

• 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;
• Control group: allogeneic HSC transplanted patients;
• Age\>18 years; no CMV or AdV reactivation ;
• signed informed consent;
• Healthy donors group: HSC donor;
• Age\>18 years;
• signed informed consent

You may not qualify if:

• none

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Pitié Salpêtriere

Paris, 75651, France

RECRUITING

MeSH Terms

Conditions

Adenoviridae Infections

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Stephanie Nguyen Quoc, Doctor

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Nguyen Quoc, Doctor

CONTACT

33142162823; stephanie.nguyen-quoc@aphp.fr

Laetitia Souchet, Doctor

CONTACT

33142162823

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2016
• First Posted: September 27, 2017
• Study Start: September 27, 2013
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: May 29, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)