Sex Differences in Immune ResponseSepsiXNCT04815811
Study of the Sex Differences in Inflammatory Diseases in Children
A study testing Blood collection and Stool collection in people with Sex Differences in Immune Response and Acute Inflammatory Diseases in Children, run by Queen Fabiola Children's University Hospital at 1 site in Belgium.
Trial summary
Sexual differences in innate immune response have been demonstrated and were mainly attributed to the influence of the sex steroids (1-18). However, recent clinical data revealed significant differences in inflammatory markers between boys and girls suffering from acute and chronic inflammatory diseases (19-23). Read more about this study
- Who is it for?
- Ages 6 months to 7 years
- Conditions the study is for
- Sex Differences in Immune Response, Acute Inflammatory Diseases in Children
- What is being tested?
- Blood collection and Stool collection
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteBelgium
- Study dates
- 17 Aug 2019to 31 Dec 2023
- 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 6 months to 7 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male (XY) and female (XX) aged from 6 months to 7 years old.
- Subject hospitalized either for:
- Urinary tract infection caused by Escherichia Coli, with:
- Temperature ≥ to 38,5°C
- Urinalysis
- Leukocyte esterase +
Show all 57Show fewer
- AND/OR Nitrites +
- AND/OR pyuria (≥ 100WBC/mm³)
- AND/OR bacteriuria.
- Urinalysis
- Clean catch voided urine: > 10^4 Escherichia Coli colony form unit (CFU)/mm (urine collection method for children >3 years old or toilet trained children or by stimulation for children <3 years old)
- Transurethral bladder catheterisation: > 10^4 Escherichia Coli colony form unit (CFU)/mm³ (urine collection method for children <3 years old).
- Suprapubic aspiration: > 1 Escherichia Coli colony form unit (CFU)/mm³ (urine collection method for children <3 years old).
- Pneumonia with pleural effusion with :
- Temperature ≥ 38,5°C
- Chest radiography/ultrasound: Pleural effusion
- Streptococcus pneumoniae identified on blood or pleural fluid culture or by PCR
- Sepsis with:
- Documented or suspected infection
- Temperature < 36° or > 38.3°C
- Heart rhythm:
- 2 SD above normal for age
- 6-23 months: >180/min
- 24-71 months: >140/min
- 72-84 months: >130/min
- Respiratory Rate:
- 6-23 months: >35/min
- 24 - 71 months: >30/min
- 72-84 months: >20/min
- WBC:
- 6-23 months: >17500/µL or <5000/µL
- 24-71 months: >15500/µL or <6000/µL
- 72-84 months: >13500/µL or <4500/µL
- and/or CRP (blood) > 2SD above normal
- And at least two of the following:
- PaO2/FiO2 <300
- Proven need for >50% FiO2 to maintain saturation ≥ 92%
- Need for mechanical ventilation
- Glasgow score < 11
- Urine output < 0,5mL/kg/h for at least 2h
- Creatinine:
- 6-11 months: >0,4mg/dL
- 12-23 months: >0,5mg/dL
- 24-59 months: >0,8mg/dL
- 60-84 months: >1mg/dL
- Or creatinine increase more than 0,5 mg/dL
- Platelet count <100000/mL
- Bilirubin >2 mg/dL
- Mean arterial pressure (MAP)
- 6-11 months: <55 mmHg
- 12 -23 months: <60 mmHg
- 24-59 months: <62 mmHg
- 60-84 months: <65 mmHg
- SBP less than two SD below normal for age
- Prolonged capillary refill: > 5 sec
- Male (XY) and female (XX) aged from 6 months to 7 years old.
- Scheduled surgical intervention for a non-infectious pathology.
Who cannot join
- Use of antithrombotic drugs (acetylsalicylic acid, thienopyridines, dipyridamol, glycoprotein IIb / IIIa antagonists, vitamin K antagonists, heparins).
- Congenital or acquired immunodeficiency: immunosuppressive drugs, hematopoietic stem cells transplantation, immunoglobulin therapy, extracorporeal membrane oxygenation (ECMO).
- Hemodialysis.
- 48h following cardiac operation of any type.
- Malignant cancer.
- HIV.
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
HUDERF
Brussels, 1020
Alexandros Popotas, MD, +32 2 477 24 24, alexandros.popotas@ulb.be
Georges Casimir, MD, PhD, + 32 2 477 29 45, georges.casimir@huderf.be
About this study
Sexual differences in innate immune response have been demonstrated and were mainly attributed to the influence of the sex steroids (1-18). However, recent clinical data revealed significant differences in inflammatory markers between boys and girls suffering from acute and chronic inflammatory diseases (19-23). Sex hormone levels in prepubertal children are particularly low and insufficient to explain the gender differences observed in inflammatory conditions from neonates to the elderly, suggesting the contribution of another mechanism, such as the influence of genes situated on the sex chromosomes and involved in the inflammatory response.
The aim of this work is to evaluate the role of the X chromosome in the sex differences in inflammatory diseases in children. In order to discriminate more precisely the role of the X chromosome relatively to the sex steroids in the sex-specific inflammatory response, some innate immune functions related to X-linked genes will be evaluated in whole blood from prepubertal children of both sexes, suffering from acute inflammatory processes such as pyelonephritis caused by Escherichia coli, pneumonia with pleural effusion caused by Streptococcus pneumoniae or sepsis
Read the detailed description
Many studies demonstrated immune differences between men and women suffering from acute and chronic inflammatory processes. In cases of acute inflammatory diseases, such as sepsis, females have better prognosis comparing to males (1,24-28).
On the contrary, worse prognosis for women is observed in chronic inflammatory diseases such as asthma or cystic fibrosis (8-10,12,13,29).
Sex-depended inflammatory response was attributed to the influence of sex hormones on the immune system. (2,15-18). However recent studies revealed differences in the clinical outcome but also in inflammatory markers between boys and girls suffering from acute and chronic inflammatory diseases (19-23). Sex hormone levels in prepubertal children are particularly low and insufficient to explain the gender differences observed in inflammatory conditions from neonates to the elderly, suggesting the contribution of another mechanism, such as the influence of genes situated on the sex chromosomes and involved in the inflammatory response.
The aim of this work is to identify the potential X-linked mechanisms responsible for some of the differences between boys and girls in the inflammatory response, making the girls more at risk of developing complications in chronic inflammatory diseases and the boys more at risk of lethal complications in severe acute inflammatory diseases like sepsis. Several genes coding for innate immunity components are linked to the X chromosome such as diapedesis molecule CD99 or TLR pathway proteins genes. (30-33). X chromosome is also highly enriched in genes encoding micro RNAs (miRNAs) involved in the post-transcriptional regulation of gene expression which play a critical role in immune inflammatory response (34-36).
Thus, in order to discriminate more precisely the role of the X chromosome relatively to the sex steroids in the sex-specific inflammatory response, some innate immune functions related to X-linked genes will be evaluated in whole blood from prepubertal children of both sexes, suffering from acute inflammatory processes such as pyelonephritis caused by Escherichia coli, pneumonia with pleural effusion caused by Streptococcus pneumoniae or sepsis. We will also study the correlations between inflammatory and clinical markers of the disease activity to identify prognosis indicators depending on the sex. Additionally, to delineate microbiome contribution, we will study the gut microbiota in stool samples obtained from the recruited patients.
- Being tested
- Blood collection, Stool collection
- Keywords
- Sex, immunology, inflammation, child, sepsis, UTI, pneumonia
- Medical subject headings
- Coitus, Inflammation, Sepsis, Urinary Tract Infections, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood collectionOther
Blood samples collections to evaluation of the potential role of the sex chromosomes in the innate immune response by analyzing inflammatory cytokine production (IL-1β, IL-6, IL-8, IL-10, TNF-α and IFN-α), studying the cell diapedesis receptor CD99 on PMNs, monocytes, and lymphocytes, analyzing the contribution of X-linked genes of the TLR pathways and the influence of X-linked miRNAs.
Stool collectionOther
Fecal sample collection to delineate microbiome contribution, we will study the gut microbiota in faecal samples obtained from the recruited patients.
| Study group | Role | What they receive |
|---|---|---|
| Children suffering from acute inflammatory processes. | Experimental | The study population will consist of male and female children, aged from 6 months to 7 years old, admitted to the hospital for one of the three following types of acute inflammatory processes:
* Urinary tract infection caused by Escherichia coli
* Pneumonia with pleural effusion caused by Streptococcus pneumoniae
* Sepsis Receives: Other: Blood collection; Other: Stool collection |
| Control group | Other | Male and female children, aged from 6 months to 7 years old, admitted to the hospital for a scheduled operation for a non-inflammatory pathology. Receives: Other: Blood collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whole blood production of cytokine IL-6
The production of IL6 is measured by multiplex techniques.
Measured: within 24 hours of hospital admission (Day 0)
Secondary outcomes (38)
Whole blood production of cytokine IL-1β
Measured: within 24 hours of hospital admission (Day 0)
Whole blood production of cytokine IL-8
Measured: within 24 hours of hospital admission (Day 0)
Whole blood production of cytokine IL-10
Measured: within 24 hours of hospital admission (Day 0)
Whole blood production of cytokine TNF-α
Measured: within 24 hours of hospital admission (Day 0)
Whole blood production of cytokine interferon-α
Measured: within 24 hours of hospital admission (Day 0)
Intracellular quantity of the phosphorylated forms of NF-κB p65 in leukocyte population.
Measured: within 24 hours of hospital admission (Day 0)
Intracellular quantity of the phosphorylated forms of ERK1/2 in leukocyte population.
Measured: within 24 hours of hospital admission (Day 0)
Intracellular quantity of the phosphorylated forms of p38 MAPK in leukocyte population.
Measured: within 24 hours of hospital admission (Day 0)
Expression of the cell diapedesis receptor CD99 on PMNs
Measurements of cell diapedesis receptor CD99 on leukocytes will be performed by flow cytometry
Measured: within 24 hours of hospital admission (Day 0)
Expression of the cell diapedesis receptor CD99 on monocytes
Measurements of cell diapedesis receptor CD99 on leukocytes will be performed by flow cytometry
Measured: within 24 hours of hospital admission (Day 0)
Expression of the cell diapedesis receptor CD99 on lymphocytes
Measurements of cell diapedesis receptor CD99 on leukocytes will be performed by flow cytometry
Measured: within 24 hours of hospital admission (Day 0)
Expression of TLR2 on PMNs
Measurements of intracellular phosphorylated forms of TLR pathway proteins as well as the expression of TLR2 and TLR4 will be performed by flow cytometry
Measured: within 24 hours of hospital admission (Day 0)
Expression of TLR2 on monocytes
Measurements of intracellular phosphorylated forms of TLR pathway proteins as well as the expression of TLR2 and TLR4 will be performed by flow cytometry
Measured: within 24 hours of hospital admission (Day 0)
Expression of TLR2 on lymphocytes
Measurements of intracellular phosphorylated forms of TLR pathway proteins as well as the expression of TLR2 and TLR4 will be performed by flow cytometry
Measured: within 24 hours of hospital admission (Day 0)
Expression of TLR4 on PMNs
Measurements of intracellular phosphorylated forms of TLR pathway proteins as well as the expression of TLR2 and TLR4 will be performed by flow cytometry
Measured: within 24 hours of hospital admission (Day 0)
Expression of TLR4 on monocytes
Measurements of intracellular phosphorylated forms of TLR pathway proteins as well as the expression of TLR2 and TLR4 will be performed by flow cytometry
Measured: within 24 hours of hospital admission (Day 0)
Expression of TLR4 on lymphocytes
Measurements of intracellular phosphorylated forms of TLR pathway proteins as well as the expression of TLR2 and TLR4 will be performed by flow cytometry
Measured: within 24 hours of hospital admission (Day 0)
BTK gene expression
Measurements will be performed using the Quantitect Reverse Transcription Kit (Qiagen, Manchester, UK) for quantitative PCR (qPCR) on leucocytes.
Measured: within 24 hours of hospital admission (Day 0)
IRAK1 gene expression
Measurements will be performed using the Quantitect Reverse Transcription Kit (Qiagen, Manchester, UK) for quantitative PCR (qPCR) on leucocytes.
Measured: within 24 hours of hospital admission (Day 0)
NEMO gene expression
Measurements will be performed using the Quantitect Reverse Transcription Kit (Qiagen, Manchester, UK) for quantitative PCR (qPCR) on leucocytes.
Measured: within 24 hours of hospital admission (Day 0)
Expression of X-linked miRNAs in leucocytes
Expression of X-linked miRNAs is measured by sequencing and qRT-PCR on leucocytes and/or plasma samples.
Measured: within 24 hours of hospital admission (Day 0)
Expression of X-linked miRNAs in plasma
Expression of X-linked miRNAs is measured by sequencing and qRT-PCR on leucocytes and/or plasma samples.
Measured: within 24 hours of hospital admission (Day 0)
Leukocyte population
White blood cell count including neutrophils, monocytes, monocytes subtypes and lymphocytes.
Measured: within 24 hours of hospital admission (Day 0)
Leukocyte population
White blood cell count including neutrophils, monocytes, monocytes subtypes and lymphocytes. Only applicable for the sepsis sub-group
Measured: Day 1
Leukocyte population
White blood cell count including neutrophils, monocytes, monocytes subtypes and lymphocytes. Only applicable for the sepsis sub-group
Measured: Day 2
Leukocyte population
White blood cell count including neutrophils, monocytes, monocytes subtypes and lymphocytes. Only applicable for the sepsis sub-group
Measured: Day 3
CRP
Measured: within 24 hours of hospital admission (Day 0)
CRP
Only applicable for the sepsis sub-group
Measured: Day 1
CRP
Only applicable for the sepsis sub-group
Measured: Day 2
CRP
Only applicable for the sepsis sub-group
Measured: Day 3
Total 17β-estradiol
Measured: within 24 hours of hospital admission (Day 0)
Testosterone
Measured: within 24 hours of hospital admission (Day 0)
IGF1
Measured: within 24 hours of hospital admission (Day 0)
Microbiome analysis
Measured: During subject hospitalisation
pSOFA score
Only applicable for the sepsis sub-group. The pSOFA will be evaluated every 24 hours in order to compare laboratory and clinical data. The score will be based on the PaO2: FiO2 or SpO2: FiO2 ratio, the platelet count, the bilirubin level, the Mean Arterial Pressure (MAP), the Glasgow score and the creatinine level.
Measured: within 24 hours of hospital admission (Day 0)
pSOFA score
Only applicable for the sepsis sub-group. The pSOFA will be evaluated every 24 hours in order to compare laboratory and clinical data. The score will be based on the PaO2: FiO2 or SpO2: FiO2 ratio, the platelet count, the bilirubin level, the Mean Arterial Pressure (MAP), the Glasgow score and the creatinine level.
Measured: Day 1
pSOFA score
Only applicable for the sepsis sub-group. The pSOFA will be evaluated every 24 hours in order to compare laboratory and clinical data. The score will be based on the PaO2: FiO2 or SpO2: FiO2 ratio, the platelet count, the bilirubin level, the Mean Arterial Pressure (MAP), the Glasgow score and the creatinine level.
Measured: Day 2
pSOFA score
Only applicable for the sepsis sub-group. The pSOFA will be evaluated every 24 hours in order to compare laboratory and clinical data. The score will be based on the PaO2: FiO2 or SpO2: FiO2 ratio, the platelet count, the bilirubin level, the Mean Arterial Pressure (MAP), the Glasgow score and the creatinine level.
Measured: Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2021
- Study start17 Aug 2019
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (35)Papers the sponsor has linked to this study.
- Other trials for Sex Differences in Immune ResponseStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Queen Fabiola Children's University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Belgium Kid's Fund
- Responsible party
- Sponsor
- Investigators
- Alexandros Popotals, MD, Principal investigator, HUDERF
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04815811
- Sponsor's protocol ID
- P2019/LABO/SepsiX
- Acronym
- SepsiX
- Status last verified
- Oct 2020
- First submitted
- 21 Oct 2020
- Last updated
- 25 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schroder J, Kahlke V, Staubach KH, Zabel P, Stuber F. Gender differences in human sepsis. Arch Surg. 1998 Nov;133(11):1200-5. doi: 10.1001/archsurg.133.11.1200.
PubMed 9820351Angele MK, Pratschke S, Hubbard WJ, Chaudry IH. Gender differences in sepsis: cardiovascular and immunological aspects. Virulence. 2014 Jan 1;5(1):12-9. doi: 10.4161/viru.26982. Epub 2013 Nov 5.
PubMed 24193307Wichmann MW, Inthorn D, Andress HJ, Schildberg FW. Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome. Intensive Care Med. 2000 Feb;26(2):167-72. doi: 10.1007/s001340050041.
PubMed 10784304Schoeneberg C, Kauther MD, Hussmann B, Keitel J, Schmitz D, Lendemans S. Gender-specific differences in severely injured patients between 2002 and 2011: data analysis with matched-pair analysis. Crit Care. 2013 Nov 29;17(6):R277. doi: 10.1186/cc13132.
PubMed 24289182Moss M, Mannino DM. Race and gender differences in acute respiratory distress syndrome deaths in the United States: an analysis of multiple-cause mortality data (1979- 1996). Crit Care Med. 2002 Aug;30(8):1679-85. doi: 10.1097/00003246-200208000-00001.
PubMed 12163776Carr MJ, Moss E, Waters A, Dean J, Jin L, Coughlan S, Connell J, Hall WW, Hassan J. Molecular epidemiological evaluation of the recent resurgence in mumps virus infections in Ireland. J Clin Microbiol. 2010 Sep;48(9):3288-94. doi: 10.1128/JCM.00434-10. Epub 2010 Jul 21.
PubMed 20660212McClelland EE, Smith JM. Gender specific differences in the immune response to infection. Arch Immunol Ther Exp (Warsz). 2011 Jun;59(3):203-13. doi: 10.1007/s00005-011-0124-3. Epub 2011 Mar 26.
PubMed 21442309Vink NM, Postma DS, Schouten JP, Rosmalen JG, Boezen HM. Gender differences in asthma development and remission during transition through puberty: the TRacking Adolescents' Individual Lives Survey (TRAILS) study. J Allergy Clin Immunol. 2010 Sep;126(3):498-504.e1-6. doi: 10.1016/j.jaci.2010.06.018.
PubMed 20816186Venn A, Lewis S, Cooper M, Hill J, Britton J. Questionnaire study of effect of sex and age on the prevalence of wheeze and asthma in adolescence. BMJ. 1998 Jun 27;316(7149):1945-6. doi: 10.1136/bmj.316.7149.1945. No abstract available.
PubMed 9641931Chen W, Mempel M, Schober W, Behrendt H, Ring J. Gender difference, sex hormones, and immediate type hypersensitivity reactions. Allergy. 2008 Nov;63(11):1418-27. doi: 10.1111/j.1398-9995.2008.01880.x.
PubMed 18925878Raghavan D, Varkey A, Bartter T. Chronic obstructive pulmonary disease: the impact of gender. Curr Opin Pulm Med. 2017 Mar;23(2):117-123. doi: 10.1097/MCP.0000000000000353.
PubMed 27977622Fogarty A, Hubbard R, Britton J. International comparison of median age at death from cystic fibrosis. Chest. 2000 Jun;117(6):1656-60. doi: 10.1378/chest.117.6.1656.
PubMed 10858398Sweezey NB, Ratjen F. The cystic fibrosis gender gap: potential roles of estrogen. Pediatr Pulmonol. 2014 Apr;49(4):309-17. doi: 10.1002/ppul.22967. Epub 2013 Dec 11.
PubMed 24339235Betteridge JD, Armbruster SP, Maydonovitch C, Veerappan GR. Inflammatory bowel disease prevalence by age, gender, race, and geographic location in the U.S. military health care population. Inflamm Bowel Dis. 2013 Jun;19(7):1421-7. doi: 10.1097/MIB.0b013e318281334d.
PubMed 23518811Ahmed SA, Talal N. Sex hormones and the immune system--Part 2. Animal data. Baillieres Clin Rheumatol. 1990 Apr;4(1):13-31. doi: 10.1016/s0950-3579(05)80241-9.
PubMed 2282659
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Sex Differences in Inflammatory Diseases in Children
- ClinicalTrials.gov ID
- NCT04815811
- Acronym / sponsor ID
- SepsiX / P2019/LABO/SepsiX
- Keywords
- Sex, immunology, inflammation, child, sepsis, UTI, pneumonia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Queen Fabiola Children's University HospitalUniversity, hospital or other
- Collaborators
- Belgium Kid's Fund
- Study start
- 17 Aug 2019 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 25 Mar 2021 (actual)
- 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.
Sexual differences in innate immune response have been demonstrated and were mainly attributed to the influence of the sex steroids (1-18). However, recent clinical data revealed significant differences in inflammatory markers between boys and girls suffering from acute and chronic inflammatory diseases (19-23). Sex hormone levels in prepubertal children are particularly low and insufficient to explain the gender differences observed in inflammatory conditions from neonates to the elderly, suggesting the contribution of another mechanism, such as the influence of genes situated on the sex chromosomes and involved in the inflammatory response.
The aim of this work is to evaluate the role of the X chromosome in the sex differences in inflammatory diseases in children. In order to discriminate more precisely the role of the X chromosome relatively to the sex steroids in the sex-specific inflammatory response, some innate immune functions related to X-linked genes will be evaluated in whole blood from prepubertal children of both sexes, suffering from acute inflammatory processes such as pyelonephritis caused by Escherichia coli, pneumonia with pleural effusion caused by Streptococcus pneumoniae or sepsis
Detailed description
Many studies demonstrated immune differences between men and women suffering from acute and chronic inflammatory processes. In cases of acute inflammatory diseases, such as sepsis, females have better prognosis comparing to males (1,24-28).
On the contrary, worse prognosis for women is observed in chronic inflammatory diseases such as asthma or cystic fibrosis (8-10,12,13,29).
Sex-depended inflammatory response was attributed to the influence of sex hormones on the immune system. (2,15-18). However recent studies revealed differences in the clinical outcome but also in inflammatory markers between boys and girls suffering from acute and chronic inflammatory diseases (19-23). Sex hormone levels in prepubertal children are particularly low and insufficient to explain the gender differences observed in inflammatory conditions from neonates to the elderly, suggesting the contribution of another mechanism, such as the influence of genes situated on the sex chromosomes and involved in the inflammatory response.
The aim of this work is to identify the potential X-linked mechanisms responsible for some of the differences between boys and girls in the inflammatory response, making the girls more at risk of developing complications in chronic inflammatory diseases and the boys more at risk of lethal complications in severe acute inflammatory diseases like sepsis. Several genes coding for innate immunity components are linked to the X chromosome such as diapedesis molecule CD99 or TLR pathway proteins genes. (30-33). X chromosome is also highly enriched in genes encoding micro RNAs (miRNAs) involved in the post-transcriptional regulation of gene expression which play a critical role in immune inflammatory response (34-36).
Thus, in order to discriminate more precisely the role of the X chromosome relatively to the sex steroids in the sex-specific inflammatory response, some innate immune functions related to X-linked genes will be evaluated in whole blood from prepubertal children of both sexes, suffering from acute inflammatory processes such as pyelonephritis caused by Escherichia coli, pneumonia with pleural effusion caused by Streptococcus pneumoniae or sepsis. We will also study the correlations between inflammatory and clinical markers of the disease activity to identify prognosis indicators depending on the sex. Additionally, to delineate microbiome contribution, we will study the gut microbiota in stool samples obtained from the recruited patients.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Children suffering from acute inflammatory processes. | Experimental | Other: Blood collection, Other: Stool collectionThe study population will consist of male and female children, aged from 6 months to 7 years old, admitted to the hospital for one of the three following types of acute inflammatory processes: * Urinary tract infection caused by Escherichia coli * Pneumonia with pleural effusion caused by Streptococcus pneumoniae * Sepsis |
| Control group | Other | Other: Blood collectionMale and female children, aged from 6 months to 7 years old, admitted to the hospital for a scheduled operation for a non-inflammatory pathology. |
Who may qualify
- Ages
- 6 months to 7 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (57 listed)
- Male (XY) and female (XX) aged from 6 months to 7 years old.
- Subject hospitalized either for:
- Temperature ≥ to 38,5°C
- Urinalysis
- Urinalysis
Key exclusion criteria (6 listed)
- Use of antithrombotic drugs (acetylsalicylic acid, thienopyridines, dipyridamol, glycoprotein IIb / IIIa antagonists, vitamin K antagonists, heparins).
- Congenital or acquired immunodeficiency: immunosuppressive drugs, hematopoietic stem cells transplantation, immunoglobulin therapy, extracorporeal membrane oxygenation (ECMO).
- Hemodialysis.
- 48h following cardiac operation of any type.
- Malignant cancer.
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 collectionBlood samples collections to evaluation of the potential role of the sex chromosomes in the innate immune response by analyzing inflammatory cytokine production (IL-1β, IL-6, IL-8, IL-10, TNF-α and IFN-α), studying the cell diapedesis receptor CD99 on PMNs, monocytes, and lymphocytes, analyzing the contribution of X-linked genes of the TLR pathways and the influence of X-linked miRNAs. | Other | Children suffering from acute inflammatory processes., Control group |
| Stool collectionFecal sample collection to delineate microbiome contribution, we will study the gut microbiota in faecal samples obtained from the recruited patients. | Other | Children suffering from acute inflammatory processes. |
Primary outcome
Whole blood production of cytokine IL-6
Time frame: within 24 hours of hospital admission (Day 0)
The production of IL6 is measured by multiplex techniques.
38 secondary outcomes
Whole blood production of cytokine IL-1β
Time frame: within 24 hours of hospital admission (Day 0)
Whole blood production of cytokine IL-8
Time frame: within 24 hours of hospital admission (Day 0)
Whole blood production of cytokine IL-10
Time frame: within 24 hours of hospital admission (Day 0)
Whole blood production of cytokine TNF-α
Time frame: within 24 hours of hospital admission (Day 0)
Whole blood production of cytokine interferon-α
Time frame: within 24 hours of hospital admission (Day 0)
Intracellular quantity of the phosphorylated forms of NF-κB p65 in leukocyte population.
Time frame: within 24 hours of hospital admission (Day 0)
Intracellular quantity of the phosphorylated forms of ERK1/2 in leukocyte population.
Time frame: within 24 hours of hospital admission (Day 0)
Intracellular quantity of the phosphorylated forms of p38 MAPK in leukocyte population.
Time frame: within 24 hours of hospital admission (Day 0)
Expression of the cell diapedesis receptor CD99 on PMNs
Time frame: within 24 hours of hospital admission (Day 0)
Expression of the cell diapedesis receptor CD99 on monocytes
Time frame: within 24 hours of hospital admission (Day 0)
Expression of the cell diapedesis receptor CD99 on lymphocytes
Time frame: within 24 hours of hospital admission (Day 0)
Expression of TLR2 on PMNs
Time frame: within 24 hours of hospital admission (Day 0)
Expression of TLR2 on monocytes
Time frame: within 24 hours of hospital admission (Day 0)
Expression of TLR2 on lymphocytes
Time frame: within 24 hours of hospital admission (Day 0)
Expression of TLR4 on PMNs
Time frame: within 24 hours of hospital admission (Day 0)
Expression of TLR4 on monocytes
Time frame: within 24 hours of hospital admission (Day 0)
Expression of TLR4 on lymphocytes
Time frame: within 24 hours of hospital admission (Day 0)
BTK gene expression
Time frame: within 24 hours of hospital admission (Day 0)
IRAK1 gene expression
Time frame: within 24 hours of hospital admission (Day 0)
NEMO gene expression
Time frame: within 24 hours of hospital admission (Day 0)
Expression of X-linked miRNAs in leucocytes
Time frame: within 24 hours of hospital admission (Day 0)
Expression of X-linked miRNAs in plasma
Time frame: within 24 hours of hospital admission (Day 0)
Leukocyte population
Time frame: within 24 hours of hospital admission (Day 0)
Leukocyte population
Time frame: Day 1
Leukocyte population
Time frame: Day 2
Leukocyte population
Time frame: Day 3
CRP
Time frame: within 24 hours of hospital admission (Day 0)
CRP
Time frame: Day 1
CRP
Time frame: Day 2
CRP
Time frame: Day 3
Total 17β-estradiol
Time frame: within 24 hours of hospital admission (Day 0)
Testosterone
Time frame: within 24 hours of hospital admission (Day 0)
IGF1
Time frame: within 24 hours of hospital admission (Day 0)
Microbiome analysis
Time frame: During subject hospitalisation
pSOFA score
Time frame: within 24 hours of hospital admission (Day 0)
pSOFA score
Time frame: Day 1
pSOFA score
Time frame: Day 2
pSOFA score
Time frame: Day 3
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2021.
- Background: PubMed 9820351Schroder J, Kahlke V, Staubach KH, Zabel P, Stuber F. Gender differences in human sepsis. Arch Surg. 1998 Nov;133(11):1200-5. doi: 10.1001/archsurg.133.11.1200.
- Background: PubMed 24193307Angele MK, Pratschke S, Hubbard WJ, Chaudry IH. Gender differences in sepsis: cardiovascular and immunological aspects. Virulence. 2014 Jan 1;5(1):12-9. doi: 10.4161/viru.26982. Epub 2013 Nov 5.
- Background: PubMed 10784304Wichmann MW, Inthorn D, Andress HJ, Schildberg FW. Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome. Intensive Care Med. 2000 Feb;26(2):167-72. doi: 10.1007/s001340050041.
- Background: PubMed 24289182Schoeneberg C, Kauther MD, Hussmann B, Keitel J, Schmitz D, Lendemans S. Gender-specific differences in severely injured patients between 2002 and 2011: data analysis with matched-pair analysis. Crit Care. 2013 Nov 29;17(6):R277. doi: 10.1186/cc13132.
- Background: PubMed 12163776Moss M, Mannino DM. Race and gender differences in acute respiratory distress syndrome deaths in the United States: an analysis of multiple-cause mortality data (1979- 1996). Crit Care Med. 2002 Aug;30(8):1679-85. doi: 10.1097/00003246-200208000-00001.
- Background: PubMed 20660212Carr MJ, Moss E, Waters A, Dean J, Jin L, Coughlan S, Connell J, Hall WW, Hassan J. Molecular epidemiological evaluation of the recent resurgence in mumps virus infections in Ireland. J Clin Microbiol. 2010 Sep;48(9):3288-94. doi: 10.1128/JCM.00434-10. Epub 2010 Jul 21.
- Background: PubMed 21442309McClelland EE, Smith JM. Gender specific differences in the immune response to infection. Arch Immunol Ther Exp (Warsz). 2011 Jun;59(3):203-13. doi: 10.1007/s00005-011-0124-3. Epub 2011 Mar 26.
- Background: PubMed 20816186Vink NM, Postma DS, Schouten JP, Rosmalen JG, Boezen HM. Gender differences in asthma development and remission during transition through puberty: the TRacking Adolescents' Individual Lives Survey (TRAILS) study. J Allergy Clin Immunol. 2010 Sep;126(3):498-504.e1-6. doi: 10.1016/j.jaci.2010.06.018.
- Background: PubMed 9641931Venn A, Lewis S, Cooper M, Hill J, Britton J. Questionnaire study of effect of sex and age on the prevalence of wheeze and asthma in adolescence. BMJ. 1998 Jun 27;316(7149):1945-6. doi: 10.1136/bmj.316.7149.1945. No abstract available.
- Background: PubMed 18925878Chen W, Mempel M, Schober W, Behrendt H, Ring J. Gender difference, sex hormones, and immediate type hypersensitivity reactions. Allergy. 2008 Nov;63(11):1418-27. doi: 10.1111/j.1398-9995.2008.01880.x.
- Background: PubMed 27977622Raghavan D, Varkey A, Bartter T. Chronic obstructive pulmonary disease: the impact of gender. Curr Opin Pulm Med. 2017 Mar;23(2):117-123. doi: 10.1097/MCP.0000000000000353.
- Background: PubMed 10858398Fogarty A, Hubbard R, Britton J. International comparison of median age at death from cystic fibrosis. Chest. 2000 Jun;117(6):1656-60. doi: 10.1378/chest.117.6.1656.
- Individual participant dataSharing planned: No
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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.
Alexandros Popotals, MD principal investigator
HUDERF
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 collection and Stool collection in people with Sex Differences in Immune Response and Acute Inflammatory Diseases in Children, run by Queen Fabiola Children's University Hospital at 1 site in Belgium.
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 57 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 25 Mar 2021. 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 Belgium. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alexandros Popotas, MD (+32 2 477 24 24, alexandros.popotas@ulb.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Whole blood production of cytokine IL-6 (time frame: within 24 hours of hospital admission (Day 0)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04815811, which also lists 35 linked publications.
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 25 Mar 2021.