Sepsis, SevereNCT05467605
Effect of Probiotics on Cytokines in Sepsis in Children
A study testing probiotics( Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions), and maltose dissolved in distilled water in people with Sepsis, Severe, run by Cairo University at 1 site in Egypt.
Trial summary
To assess the effect of probiotics on cytokine's level(interleukin 6 and Transforming growth factor-β1)in children admitted to PICU with sepsis. Read more about this study
- Who is it for?
- Ages 30 days to 14 years
- Conditions the study is for
- Sepsis, Severe
- What is being tested?
- probiotics( Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions), and maltose dissolved in distilled water
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteEgypt
- Study dates
- 22 Jul 2022to 5 Feb 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 30 days to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- The study will include children admitted to PICU with sepsis defined as presence of suspected or proven infection with two or more criteria for systemic inflammatory response syndrome (SIRS)
Who cannot join
- Children having contraindications to start enteral feeding.
- Children with known chronic gastrointestinal illness.
- Children known with immunodeficiency.
- Children on prior steroids or immunotherapy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Probiotics on Interleukin 6 and Transforming Growth Factor-βLevels in Critically Ill Children With Sepsis
To assess the effect of probiotics on cytokine's level(interleukin 6 and Transforming growth factor-β1)in children admitted to PICU with sepsis.
Read the detailed description
Sepsis, defined as an infection with deregulated host response leading to life-threatening organ dysfunction. Historically, the term sepsis has been used to characterize life-threatening infections usually caused by bacterial pathogens if untreated progress to shock and death, It contributes to 19% of all deaths globally, with the highest age-specific incidence in children younger than 5 years of age. Pediatric sepsis resulted in 0.7% of all hospital encounters. Epidemiologic studies found an incidence of pediatric sepsis in up to 8% of all pediatric intensive care unit (PICU) admissions, contributing to 1in 4 deaths in PICUs.
Despite many advances in diagnosis and management, sepsis is associated with significant morbidity and mortality in pediatric population. The pathophysiology of systemic inflammatory response syndrome (SIRS)and sepsis is characterized by hyperactive and deregulated endogenous inflammatory mediators in a sequential manner resulting in a cytokine cascade.
Cytokines are regulators of the immune response to infection and play a key role in regulating inflammation and trauma. There are two types of cytokines. Pro-inflammatory cytokines and anti-inflammatory cytokines.
Pro-inflammatory cytokines(tumor necrosis factor [TNF]-α, interferon-γ, interleukin[IL]-1α, IL-1β, IL-6, IL-8, IL-12, IL-17) are important for initiation of an effective inflammatory response against pathogens, whereas their excess production can lead to multiple organ dysfunction syndrome (MODS) and mortality, on the other side, anti-inflammatory cytokines (IL-4, IL-10, IL-13,transforming growth factor [TGF]-β) are required for controlling and down-regulating the inflammatory response and if severe can lead to depression of the immune system.
The levels of these cytokines rise within few hours of onset of sepsis and remain elevated for days together depending on severity and duration of sepsis, baseline host factors, timing of sampling relative to onset of sepsis/septic shock, and inter-individual variation.
The gastrointestinal system seems to play a key role in the pathogenesis MODS owing to a breakdown of intestinal barrier function and increased translocation of bacteria and bacterial components into the systemic circulation.
During critical illness, alterations occur in gut micro flora owing to change in circulating stress hormones, gut ischemia, immune suppression, the use of antibiotics, and lack of nutrients due to delay in starting enteral feeding.
Probiotics are living micro-organisms that, when administered in adequate amounts, can help maintain the integrity of the intestinal barrier function by modulating the immune response. Such administration has been included in the management of critically ill patients as a therapeutic approach.
Various studies highlighted that probiotics can modulate intestinal micro biota by colonizing human GIT, preventing overgrowth of pathogens, normalizing altered intestinal flora, reducing bacterial translocation, influencing immune system, and balancing control of pro-inflammatory and anti-inflammatory Cytokines.
- Conditions
- Sepsis, Severe
- Being tested
- probiotics( Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions),, maltose dissolved in distilled water
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
probiotics( Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions),Dietary supplement
Also called LACTEOL FORTE
therapeutic intervention, Children will be randomized into two groups using sealed envelopes on admission after meeting inclusion criteria, group ONE will receive multi strain probiotic product which contains(Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions),
maltose dissolved in distilled waterOther
the other group placebo (GROUP TWO ) will receive maltose dissolved in 10 ml distilled water .
| Study group | Role | What they receive |
|---|---|---|
| CASE, GROUP ONE | Active comparator | Group 1 (group who will receive probiotics): one sachet contains(Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions), dissolved in 10 ml distilled water twice a day for 7days orally or through nasogastric/orogastric tube depending on clinical status of patients. Receives: Dietary Supplement: probiotics( Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions), |
| CONTROL, GROUP 2 | Placebo comparator | GROUP 2 will receive only maltose dissolved in 10 ml of distilled water twice a day for 7 days orally or though nasogastric/orogastric tube depending on clinical status of patients. Receives: Other: maltose dissolved in distilled water |
What is being measured
The primary outcome is the main question the study is designed to answer.
1- To assess the effect of probiotics on cytokine levels(interleukin 6 and Transforming growth factor-β1) in probiotic group
To assess the effect of probiotics on cytokine levels(interleukin 6 and Transforming growth factor-β1) in probiotic group and To assess the change on cytokine levels (interleukin 6 and Transforming growth factor-β1) from day 1 to 7 in critically ill children with sepsis in two groups.
Measured: one week
Secondary outcomes (3)
assessment of other sepsis parameters
Assessment of other sepsis parameters like C-reactive protein ( CRP ) level in relation to prognosis of sepsis in the two groups.
Measured: up to 2 weeks
assessment of patient general condition during pediatric intensive care admission
The duration of ventilation, will be assessed in the two groups.
Measured: through admission till discharge from PICU up to one month
assessment of patient general condition during pediatric intensive care admission
length of stay in the PICU, will be assessed in the two groups.
Measured: through admission till discharge from PICU up to one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2022
- Study start22 Jul 2022
- Primary completion20 Jan 2023
- Study completion5 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sepsis, SevereStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Heba Ibrahim Abdallah, Cairo University
- Investigators
- AYMAN EMIL, MD, Study director, Professor of Pediatrics, Cairo UniversityHANAA RADY, MD, Study director, Professor of Pediatrics, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05467605
- Sponsor's protocol ID
- probiotics in pediatric sepsis
- Status last verified
- Feb 2023
- First submitted
- 27 Jun 2022
- Last updated
- 9 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Angurana SK, Bansal A, Singhi S, Aggarwal R, Jayashree M, Salaria M, Mangat NK. Evaluation of Effect of Probiotics on Cytokine Levels in Critically Ill Children With Severe Sepsis: A Double-Blind, Placebo-Controlled Trial. Crit Care Med. 2018 Oct;46(10):1656-1664. doi: 10.1097/CCM.0000000000003279.
PubMed 29957709Chaudhry H, Zhou J, Zhong Y, Ali MM, McGuire F, Nagarkatti PS, Nagarkatti M. Role of cytokines as a double-edged sword in sepsis. In Vivo. 2013 Nov-Dec;27(6):669-84.
PubMed 24292568
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Probiotics on Interleukin 6 and Transforming Growth Factor-βLevels in Critically Ill Children With Sepsis
- ClinicalTrials.gov ID
- NCT05467605
- Acronym / sponsor ID
- probiotics in pediatric sepsis
- Conditions
- Sepsis, Severe
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 22 Jul 2022 (actual)
- Primary completion
- 20 Jan 2023 (actual)
- Study completion
- 5 Feb 2023 (actual)
- First posted
- 20 Jul 2022 (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.
To assess the effect of probiotics on cytokine's level(interleukin 6 and Transforming growth factor-β1)in children admitted to PICU with sepsis.
Detailed description
Sepsis, defined as an infection with deregulated host response leading to life-threatening organ dysfunction. Historically, the term sepsis has been used to characterize life-threatening infections usually caused by bacterial pathogens if untreated progress to shock and death, It contributes to 19% of all deaths globally, with the highest age-specific incidence in children younger than 5 years of age. Pediatric sepsis resulted in 0.7% of all hospital encounters. Epidemiologic studies found an incidence of pediatric sepsis in up to 8% of all pediatric intensive care unit (PICU) admissions, contributing to 1in 4 deaths in PICUs.
Despite many advances in diagnosis and management, sepsis is associated with significant morbidity and mortality in pediatric population. The pathophysiology of systemic inflammatory response syndrome (SIRS)and sepsis is characterized by hyperactive and deregulated endogenous inflammatory mediators in a sequential manner resulting in a cytokine cascade.
Cytokines are regulators of the immune response to infection and play a key role in regulating inflammation and trauma. There are two types of cytokines. Pro-inflammatory cytokines and anti-inflammatory cytokines.
Pro-inflammatory cytokines(tumor necrosis factor [TNF]-α, interferon-γ, interleukin[IL]-1α, IL-1β, IL-6, IL-8, IL-12, IL-17) are important for initiation of an effective inflammatory response against pathogens, whereas their excess production can lead to multiple organ dysfunction syndrome (MODS) and mortality, on the other side, anti-inflammatory cytokines (IL-4, IL-10, IL-13,transforming growth factor [TGF]-β) are required for controlling and down-regulating the inflammatory response and if severe can lead to depression of the immune system.
The levels of these cytokines rise within few hours of onset of sepsis and remain elevated for days together depending on severity and duration of sepsis, baseline host factors, timing of sampling relative to onset of sepsis/septic shock, and inter-individual variation.
The gastrointestinal system seems to play a key role in the pathogenesis MODS owing to a breakdown of intestinal barrier function and increased translocation of bacteria and bacterial components into the systemic circulation.
During critical illness, alterations occur in gut micro flora owing to change in circulating stress hormones, gut ischemia, immune suppression, the use of antibiotics, and lack of nutrients due to delay in starting enteral feeding.
Probiotics are living micro-organisms that, when administered in adequate amounts, can help maintain the integrity of the intestinal barrier function by modulating the immune response. Such administration has been included in the management of critically ill patients as a therapeutic approach.
Various studies highlighted that probiotics can modulate intestinal micro biota by colonizing human GIT, preventing overgrowth of pathogens, normalizing altered intestinal flora, reducing bacterial translocation, influencing immune system, and balancing control of pro-inflammatory and anti-inflammatory Cytokines.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CASE, GROUP ONE | Active comparator | Dietary Supplement: probiotics( Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions),Group 1 (group who will receive probiotics): one sachet contains(Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions), dissolved in 10 ml distilled water twice a day for 7days orally or through nasogastric/orogastric tube depending on clinical status of patients. |
| CONTROL, GROUP 2 | Placebo comparator | Other: maltose dissolved in distilled waterGROUP 2 will receive only maltose dissolved in 10 ml of distilled water twice a day for 7 days orally or though nasogastric/orogastric tube depending on clinical status of patients. |
Who may qualify
- Ages
- 30 days to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- The study will include children admitted to PICU with sepsis defined as presence of suspected or proven infection with two or more criteria for systemic inflammatory response syndrome (SIRS)
Key exclusion criteria (4 listed)
- Children having contraindications to start enteral feeding.
- Children with known chronic gastrointestinal illness.
- Children known with immunodeficiency.
- Children on prior steroids or immunotherapy.
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 |
|---|---|---|
| probiotics( Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions),Also: LACTEOL FORTEtherapeutic intervention, Children will be randomized into two groups using sealed envelopes on admission after meeting inclusion criteria, group ONE will receive multi strain probiotic product which contains(Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions), | Dietary supplement | CASE, GROUP ONE |
| maltose dissolved in distilled waterthe other group placebo (GROUP TWO ) will receive maltose dissolved in 10 ml distilled water . | Other | CONTROL, GROUP 2 |
Primary outcome
1- To assess the effect of probiotics on cytokine levels(interleukin 6 and Transforming growth factor-β1) in probiotic group
Time frame: one week
To assess the effect of probiotics on cytokine levels(interleukin 6 and Transforming growth factor-β1) in probiotic group and To assess the change on cytokine levels (interleukin 6 and Transforming growth factor-β1) from day 1 to 7 in critically ill children with sepsis in two groups.
3 secondary outcomes
assessment of other sepsis parameters
Time frame: up to 2 weeks
assessment of patient general condition during pediatric intensive care admission
Time frame: through admission till discharge from PICU up to one month
assessment of patient general condition during pediatric intensive care admission
Time frame: through admission till discharge from PICU up to one month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2023.
- Results publication: PubMed 29957709Angurana SK, Bansal A, Singhi S, Aggarwal R, Jayashree M, Salaria M, Mangat NK. Evaluation of Effect of Probiotics on Cytokine Levels in Critically Ill Children With Severe Sepsis: A Double-Blind, Placebo-Controlled Trial. Crit Care Med. 2018 Oct;46(10):1656-1664. doi: 10.1097/CCM.0000000000003279.
- Results publication: PubMed 24292568Chaudhry H, Zhou J, Zhong Y, Ali MM, McGuire F, Nagarkatti PS, Nagarkatti M. Role of cytokines as a double-edged sword in sepsis. In Vivo. 2013 Nov-Dec;27(6):669-84.
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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.
AYMAN EMIL, MD study director
Professor of Pediatrics, Cairo University
HANAA RADY, MD study director
Professor of Pediatrics, Cairo University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing probiotics( Lactobacillus acidophilus, lactobacillus delbruekii and lactobacillus fermentum 10 billions), and maltose dissolved in distilled water in people with Sepsis, Severe, run by Cairo University at 1 site in Egypt.
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 1 inclusion and 4 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: finished, as of the sponsor's last update on 9 Feb 2023. 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 Egypt. 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. Some participants in this study may receive a placebo. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
1- To assess the effect of probiotics on cytokine levels(interleukin 6 and Transforming growth factor-β1) in probiotic group (time frame: one week). 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 NCT05467605, which also lists 2 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 9 Feb 2023.