Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
Trial record 23 of 33 for:    klinefelter

Impact of Gender and Pubertal Status on Human Plasmacytoid Dendritic Cells. PLASMACYTOKID

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02956980
Recruitment Status : Terminated (recruitment target not obtained)
First Posted : November 6, 2016
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse

Tracking Information
First Submitted Date  ICMJE November 3, 2016
First Posted Date  ICMJE November 6, 2016
Last Update Posted Date July 15, 2019
Actual Study Start Date  ICMJE June 21, 2017
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 9, 2016)
percentage of IFN1 producing pDCs [ Time Frame: 1 day ]
Assessment of the percentage of IFN1 producing pDCs after ex vivo stimulation with TLR 7, 9 and 8 ligands.
Original Primary Outcome Measures  ICMJE
 (submitted: November 4, 2016)
percentage of IFN1 producing pDCs [ Time Frame: 1 day ]
Our primary outcome will be the assessment of the percentage of IFN1 producing pDCs after ex vivo stimulation with TLR 7, 9 and 8 ligands.
Change History Complete list of historical versions of study NCT02956980 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2016)
  • Percentage of IFN1 producing tumor necrosis factor(TNF)-alpha [ Time Frame: 1 day ]
    Innate immune functions of pDCs present in the circulating blood of healthy children will be assessed by the percentage of pDCs producing TNF-alpha.
  • IFN1 concentration in the peripheral blood mononuclear cells circulating (PBMC) culture supernatant. [ Time Frame: 1 day ]
    The innate immune functions of pDCs present in the circulating blood of healthy children will also be assessed by measuring the concentration IFN1 present in the culture supernatant of PBMC stimulated with TLR 7 or TLR 9 ligands.
  • percentage of cells producing TNF alpha and Interleukin(IL)-12p40 [ Time Frame: 1 day ]
    Innate immune functions of conventional dendritic cells (cDC) and monocytes present in the circulating blood of healthy children will be assessed by the percentage of cells producing TNF alpha and IL-12p40.
  • percentage of pDc, cDC and monocytes in circulating blood [ Time Frame: 1 day ]
    Innate immune functions of pDCs, cDC and Monocytes present in the circulating blood of boys with Klinefelter syndrome or girls with Turner syndrome will be evaluated identically to healthy children.
  • Number of DC (cDC and pDC) by milliliter of blood [ Time Frame: 1 day ]
    The number of DCs (pDCs CDC) / ml of blood flowing will be quantified and expressed in blood and percentage of PBMCs.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2016)
  • percentage of IFN1 producing TNF-alpha [ Time Frame: 1 day ]
    Innate immune functions of pDCs present in the circulating blood of healthy children will be assessed by the percentage of pDCs producing TNF-alpha.
  • IFN1 concentration in the peripheral blood mononuclear cells circulating (PBMC) culture supernatant. [ Time Frame: 1 day ]
    The innate immune functions of pDCs present in the circulating blood of healthy children will also be assessed by measuring the concentration IFN1 present in the culture supernatant of PBMC stimulated withTLR7 or TLR9 ligands.
  • percentage of cells producing TNF alpha and Il-12p40 [ Time Frame: 1 day ]
    Innate immune functions of conventional dendritic cells (cDC) and monocytes present in the circulating blood of healthy children will be assessed by the percentage of cells producing TNF alpha and IL-12p40.
  • percentage of pDc, cDC and monocytes in circulating blood [ Time Frame: 1 day ]
    Innate immune functions of pDCs, cDC and Monocytes present in the circulating blood of boys with Klinefelter syndrome or girls with Turner syndrome will be evaluated identically to healthy children.
  • Number of DC (cDC and pDC) by milliliter of blood [ Time Frame: 1 day ]
    The number of DCs (pDCs CDC) / ml of blood flowing will be quantified and expressed in blood and percentage of PBMCs.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Impact of Gender and Pubertal Status on Human Plasmacytoid Dendritic Cells. PLASMACYTOKID
Official Title  ICMJE Impact of Gender and Pubertal Status on Human Plasmacytoid Dendritic Cells - PLASMACYTOKID Study
Brief Summary Differences in pDCs function related to gender have been demonstrated in adults but have never been addressed in children. Yet, differences in immune responses related to gender also exist in children, both in responses to pathogens and susceptibility to autoimmune diseases. The investigators suppose that these differences are partly linked to difference in pDCs functions. This study aim is to compare pDCs functions in children based on gender and pubertal status. This study will be performed in healthy children, boys with Klinefelter syndrome and girls with Turner syndrome.
Detailed Description There are differences in immune responses according to gender. Women have stronger responses against pathogens, especially viruses but are also more susceptible to develop autoimmune diseases. These points reflect more robust innate and adaptive responses in women. Plasmacytoid dendritic cells (pDCs) are key actor of innate immune responses through their ability to produce large amounts of type 1 Interferons (IFN1) secondary to stimulation of their toll like receptors (TLR) 7 and 9 by nucleic acids. Thus, pDCs play a major beneficial role in antiviral responses. In autoimmune diseases like Systemic Erythematous Lupus, pDCs also play a role, mostly deleterious, through inappropriate production of IFN1 upon stimulation of their TLR's by self nucleic acids. In these diseases, pDCs from women have been demonstrated to produce more IFN1 as compared to men, a phenomenon that can be linked to both hormonal and genetic factors. Indeed, the investigators research team demonstrated that IFN1 production by human pDCs can be increased by oestradiol through a specific receptor present in pDCs. Regarding genetics, some studies recently shown in a humanized mouse model, that pDCs developing from female hematopoietic precursor cells have an enhanced TLR 7 mediated IFN1 response as compared to male ones. These results indicate that X chromosome dosage could contribute independently to the enhanced TLR 7 mediated response of pDCs from women. Although some genes implicated in IFN1 production are on the X chromosome, including TLR 7, the mechanism underlying this observation are presently unknown.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Condition  ICMJE Innate Immune Responses
Intervention  ICMJE Biological: Blood Plasmacytoid dendritic cells (pDCs) absolute number
Two 7 ml tubes will be necessary to perform the functional assays as well as the quantification of blood pDCs absolute number. Functional assays will be performed on isolated PBMC by Ficoll procedure. Quantification of blood pDCs absolute number will be performed on whole blood. After written parental consent, blood sample will be performed on children participating to the study.
Study Arms  ICMJE
  • Experimental: Group 1: non-pubescent children
    70 non-pubescent children (25 healthy boys, 25 healthy girls, 10 boys with Klinefelter syndrome and 10 girls with Turner syndrome) Two 7 ml tubes of blood will be taken to perform the functional assays as well as the quantification of Blood Plasmacytoid dendritic cells (pDCs) absolute number in this 70 non-pubescent children.
    Intervention: Biological: Blood Plasmacytoid dendritic cells (pDCs) absolute number
  • Experimental: Group 2: pubescent healthy children
    50 pubescent healthy children (25 boys and 25 girls) Two 7 ml tubes of blood will be taken to perform the functional assays as well as the quantification of Blood Plasmacytoid dendritic cells (pDCs) absolute number in this 50 pubescent healthy children.
    Intervention: Biological: Blood Plasmacytoid dendritic cells (pDCs) absolute number
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 11, 2019)
78
Original Estimated Enrollment  ICMJE
 (submitted: November 4, 2016)
120
Actual Study Completion Date  ICMJE December 31, 2018
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Pediatric patients (0-18 years old):

    • Group 1 : Age<8 years old
    • Group 2 : Age>12 years old
  2. Body weight >10kgs
  3. Pubescent (group 2) or non-pubescent (group 1)
  4. Written consent of parents

Exclusion Criteria:

  1. Active infectious disease
  2. Known perturbations of immune and/or inflammatory systems
  3. Oral or subcutaneous contraception in pubescent girls
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02956980
Other Study ID Numbers  ICMJE RC31/16/8251
AOL 2016 ( Other Grant/Funding Number: University Hospital Toulouse )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Toulouse
Study Sponsor  ICMJE University Hospital, Toulouse
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Arnaud Garnier, MD CHU Toulouse, Hôpital des Enfants
PRS Account University Hospital, Toulouse
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP