Innate Immune ResponsesNCT02956980
Impact of Gender and Pubertal Status on Human Plasmacytoid Dendritic Cells. PLASMACYTOKID
A study testing Blood Plasmacytoid dendritic cells (pDCs) absolute number in people with Innate Immune Responses, run by University Hospital, Toulouse at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Innate Immune Responses
- What is being tested?
- Blood Plasmacytoid dendritic cells (pDCs) absolute number
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteFrance
- Study dates
- 21 Jun 2017to 31 Dec 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Pediatric patients (0-18 years old):
- Group 1 : Age<8 years old
- Group 2 : Age>12 years old
- Body weight >10kgs
- Pubescent (group 2) or non-pubescent (group 1)
- Written consent of parents
Who cannot join
- Active infectious disease
- Known perturbations of immune and/or inflammatory systems
- Oral or subcutaneous contraception in pubescent girls
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Gender and Pubertal Status on Human Plasmacytoid Dendritic Cells - PLASMACYTOKID Study
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.
Read the 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.
- Conditions
- Innate Immune Responses
- Being tested
- Blood Plasmacytoid dendritic cells (pDCs) absolute number
- Keywords
- type 1 interferons, children, gender, pubertal status, sex difference
- Medical subject headings
- Coitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood Plasmacytoid dendritic cells (pDCs) absolute numberBiological
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 group | Role | What they receive |
|---|---|---|
| Group 1: non-pubescent children | Experimental | 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. Receives: Biological: Blood Plasmacytoid dendritic cells (pDCs) absolute number |
| Group 2: pubescent healthy children | Experimental | 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. Receives: Biological: Blood Plasmacytoid dendritic cells (pDCs) absolute number |
What is being measured
The primary outcome is the main question the study is designed to answer.
percentage of IFN1 producing pDCs
Assessment of the percentage of IFN1 producing pDCs after ex vivo stimulation with TLR 7, 9 and 8 ligands.
Measured: 1 day
Secondary outcomes (5)
Percentage of IFN1 producing tumor necrosis factor(TNF)-alpha
Innate immune functions of pDCs present in the circulating blood of healthy children will be assessed by the percentage of pDCs producing TNF-alpha.
Measured: 1 day
IFN1 concentration in the peripheral blood mononuclear cells circulating (PBMC) culture supernatant.
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.
Measured: 1 day
percentage of cells producing TNF alpha and Interleukin(IL)-12p40
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.
Measured: 1 day
percentage of pDc, cDC and monocytes in circulating blood
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.
Measured: 1 day
Number of DC (cDC and pDC) by milliliter of blood
The number of DCs (pDCs CDC) / ml of blood flowing will be quantified and expressed in blood and percentage of PBMCs.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2016 (estimated)
- Study start21 Jun 2017
- Primary completion31 Dec 2018
- Study completion31 Dec 2018
Why it stopped: recruitment target not obtained
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Innate Immune ResponsesStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Arnaud Garnier, MD, Principal investigator, CHU Toulouse, Hôpital des Enfants
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02956980
- Sponsor's protocol ID
- RC31/16/8251
- Other IDs
- AOL 2016
- Status last verified
- Jul 2019
- First submitted
- 3 Nov 2016
- Last updated
- 15 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Gender and Pubertal Status on Human Plasmacytoid Dendritic Cells - PLASMACYTOKID Study
- ClinicalTrials.gov ID
- NCT02956980
- Acronym / sponsor ID
- RC31/16/8251
- Conditions
- Innate Immune Responses
- Keywords
- type 1 interferons, children, gender, pubertal status, sex difference
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: recruitment target not obtained
- Enrolment
- 78 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 21 Jun 2017 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 7 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: non-pubescent children | Experimental | Biological: Blood Plasmacytoid dendritic cells (pDCs) absolute number70 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. |
| Group 2: pubescent healthy children | Experimental | Biological: Blood Plasmacytoid dendritic cells (pDCs) absolute number50 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. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Pediatric patients (0-18 years old):
- Body weight >10kgs
- Pubescent (group 2) or non-pubescent (group 1)
- Written consent of parents
Key exclusion criteria (3 listed)
- Active infectious disease
- Known perturbations of immune and/or inflammatory systems
- Oral or subcutaneous contraception in pubescent girls
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood Plasmacytoid dendritic cells (pDCs) absolute numberTwo 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. | Biological | Group 1: non-pubescent children, Group 2: pubescent healthy children |
Primary outcome
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.
5 secondary outcomes
Percentage of IFN1 producing tumor necrosis factor(TNF)-alpha
Time frame: 1 day
IFN1 concentration in the peripheral blood mononuclear cells circulating (PBMC) culture supernatant.
Time frame: 1 day
percentage of cells producing TNF alpha and Interleukin(IL)-12p40
Time frame: 1 day
percentage of pDc, cDC and monocytes in circulating blood
Time frame: 1 day
Number of DC (cDC and pDC) by milliliter of blood
Time frame: 1 day
Results and safety
The study was stopped early (reason given: recruitment target not obtained). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2019.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arnaud Garnier, MD principal investigator
CHU Toulouse, Hôpital des Enfants
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood Plasmacytoid dendritic cells (pDCs) absolute number in people with Innate Immune Responses, run by University Hospital, Toulouse at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: recruitment target not obtained). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
percentage of IFN1 producing pDCs (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2019; AzTrials last refreshed its copy on 7 Nov 2026.