Neonatal SepsisNCT04742582
Potential Protective Effect of a Formula Supplemented With Fermented Matrices on the Risk of Developing Neonatal Sepsis
A study testing Preterm Infants - fed fermented formula, Preterm Infants - fed standard formula and Pre-term Infants - breastfed in people with Neonatal Sepsis, run by Heinz Italia SpA at 1 site in Italy.
Trial summary
This is a multicenter, randomized, double-blind, placebo controlled trial, with parallel groups and reference group. The aim of the study was to evaluate the hypothesis that an immunonutritional strategy, based on use of Lactobacillus paracasei CBA L74-fermented formula, prevents or limits the development of… Read more about this study
- Who is it for?
- Ages Up to 72 hours
- Conditions the study is for
- Neonatal Sepsis
- What is being tested?
- Preterm Infants - fed fermented formula, Preterm Infants - fed standard formula and Pre-term Infants - breastfed
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 876 participants
- Where
- 1 siteItaly
- Study dates
- 1 Mar 2021to 1 Feb 2024
- 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 72 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Newborns weighing less than 1500 grams
- Gestational age <32 weeks
- Artificial feeding or Human milk not available < 30%
Who cannot join
- Voluntary interruption;
- Suspension decided by PI or PDF
- Adverse events
- Gastrointestinal disease that prevent oral feeding
- Congenital or maternal infections
- Immunodeficiencies
Show all 9Show fewer
- Malformations
- Syndromes
- Genetic or metabolic diseases.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Unità di Neonatologia e Terapia Intensiva Neonatale, Clinica Mangiagalli
Milan, 20122
Paola Roggero, paola.roggero@unimi.it
About this study
Official title: The Potential Protective Effect of a Formula Supplemented With Fermented Matrices on the Risk of Developing Neonatal Sepsis
This is a multicenter, randomized, double-blind, placebo controlled trial, with parallel groups and reference group.
The aim of the study was to evaluate the hypothesis that an immunonutritional strategy, based on use of Lactobacillus paracasei CBA L74-fermented formula, prevents or limits the development of late-onset-sepsis in preterm infants.
Read the detailed description
15-20% of infant born weighing less than 1500 grams develop late-onset-sepsis. The prevention of sepsis is based on hygiene measures, on the prudent use of invasive procedures, on drug management and on early diagnosis. However, no intervention is fully effective in reducing the burden of the disease, prolonged hospitalizations in neonatal intensive care units, high costs or delayed neurodevelopmental impairment. The immunonutrition is defined as the potential to modulate the activity of the immune system throught use of specific nutrients. Many immunonutritional approaches in pediatric age act in part with a modulation of the microbiota. Functional foods derived from fermentation with probiotic strains can be used and their activity is considered specific for each strain and dose dependent.
A new functional food derived from fermentation of cow's milk with Lactobacillus paracasei CBA L74 has recently been de-veloped. The fermentation was started in the presence of 106 bacteria, reaching 5.9 X 109 colony-forming units/g after a 15-h incubation at 37 C°. After heating at 85 C° for 20 s in order to inactivate the live bacteria, the formula was spray-dried. Thus, the final fermented milk powder contained only bacterial bodies and fermentation products and no living microorganisms. Lactobacillus paracasei CBA L74 was registered in the Belgian Collection BCCM/LMG and was included in the EFSA list be-tween the "Qualified Presumption of Safety microorganisms".
Pre-clinical studies showed anti-infective and anti-inflammatory properties of this new fermented food. More recently, a similar effect for the L. paracasei supernatant was noted after 24 and 6 h before the LPS treatment. The supernatant protects against the release of inflammatory mediators IFN-ɣ and IL-12p40 and increases the anti-inflammatory cytokine IL-10.
In a randomized controlled clinical trial, the daily supplementation of this fermented food was shown to protect children from infectious diseases and induces immunoregulatory effects. These clinical results are supported by the significant inverse correlation between the concentrations of alpha-defensins, betadefensins, cathelecidins and the secretory levels of IgA with the number of infectious diseases. In another clinical trial it was shown that a daily supplementation of this new fermented food in healthy full-term infants can stimulate the production of innate and acquired immune peptides. Finally, it was reported that milk fermented by L. paracasei CBA L74 stimultes the immune and non-immune defense mechanisms against sepsis, through a direct interaction with human enterocytes.
Although currently available data suggest a positive impact on morbidity, mortality and costs related to neonatal sepsis, there is little knowledge on the use of this fermented functional food in neonatal age. In particular, there are no studies on the effects of this immunonutritional approach on pre-term infants.
- Conditions
- Neonatal Sepsis
- Being tested
- Preterm Infants - fed fermented formula, Preterm Infants - fed standard formula, Pre-term Infants - breastfed
- Medical subject headings
- Neonatal Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Preterm Infants - fed fermented formulaDietary supplement
Feeding infants with fermented formula supplemented with the fermentation products of the probiotic L. paracasei CBA L74 (800 mg / 100 ml of milk) (84 kcal and 2.9 g protein per 100 ml)
Preterm Infants - fed standard formulaOther
Feeding infants with standard formula with the addition of skimmed milk powder in order to provide the same protein and energy amount of the supplemented formula (84 kcal and 2.9 g protein per 100 ml)
Pre-term Infants - breastfedOther
Breastfeeding infants - Reference group
| Study group | Role | What they receive |
|---|---|---|
| Preterm Infants - fed fermented formula | Active comparator | Feeding infants with fermented formula milk. Preterm infants will be fed either with fermented formula milk or with standard formula Receives: Dietary Supplement: Preterm Infants - fed fermented formula |
| Preterm Infants - fed standard formula | Placebo comparator | Feeding infants with standard formula milk. Preterm infants will be fed either with fermented formula milk or with standard formula Receives: Other: Preterm Infants - fed standard formula |
| Reference Group: Pre-term Infants - breastfed | Other | The breastfeeding infants were the reference group Receives: Other: Pre-term Infants - breastfed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Monitoring of the number of confirmed episodes of late-onset-sepsis during hospitalization period and potential complications of the sepsis
Data collection concerning the appearance during hospitalization of episodes of sepsis from Gram positive, Gram negative bacteria and from fungi; the occurrence of comorbidities: necrotizing enterocolitis (NEC); bronchopulmonary dysplasia (BPD); intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), the mortality rate.
Measured: from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
Monitoring the number of days required to achieve complete enteral feeding, presence and duration of central vascular access
Data collection concerning the number of days required to achieve complete enteral feeding, presence and duration of central vascular access
Measured: from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
Monitoring the growth rate
Data collection concerning the growth rate (g/ kg/ day)
Measured: from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
Monitoring the length of hospital stay
Data collection concerning the lenght of the hospital stay
Measured: from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
Psychomotor development with the Griffiths III
Evaluation of the psychomotor development through development quotient using the Griffiths III. General quotient: A scale: learning basis; B scale: language and communication; C scale: eye-manual coordination; D scale: personal-social-emotional; E scale: gross-motor; average 100, DS 15.
Measured: at 180 days of life
Secondary outcomes (5)
Fecal dosage of cathelicidines, alfa and beta defensins, sIgA
Dosage of biomarkers levels of innate and acquired immunity (cathelicidines, alfa and beta defensins, sIgA ) on fecal samples, using ELISA kits
Measured: at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Microbiota
The V region of the 16S rRNA will be amplified using specific primers and the obtained amplicons will be used for sequencing library preparation, multiplexing and paired-end sequencing on the Illumina MiSeq platform. The alpha and beta diversity at the level of the phylum, genus and species among groups and their separation in a principal coordinate analysis will be evaluated.
Measured: at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Cytokines production assessment on infants blood sample
Cytokines (IL-6, IL-12p40, TNF-a) production assessment on infants blood sample, using CBA (cytokine bead array)
Measured: at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Cytokines production assessment on dendritic cells culture medium
Cytokines (IL-6, IL-12p40, TNF-a) production assessment on murine dendritic cells culture medium
Measured: at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Cell surface activation markers (MHC and costimulatory molecules)
Determination of cell surface activation markers (MHC and costimulatory molecules) on dendritic cell after infant serum treatment and strong inflammatory stimulus (LPS or Salmonella typhimurium)
Measured: at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2021
- Study start1 Mar 2021
- Primary completion1 Feb 2024 (estimated)
- Study completion1 Feb 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neonatal SepsisStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 876 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heinz Italia SpA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04742582
- Sponsor's protocol ID
- CO-2016-02365100
- Status last verified
- Jun 2022
- First submitted
- 31 Dec 2020
- Last updated
- 2 Jun 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Potential Protective Effect of a Formula Supplemented With Fermented Matrices on the Risk of Developing Neonatal Sepsis
- ClinicalTrials.gov ID
- NCT04742582
- Acronym / sponsor ID
- CO-2016-02365100
- Conditions
- Neonatal Sepsis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 876 participants (estimated)
- Lead sponsor
- Heinz Italia SpAIndustry (pharma, biotech, devices)
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 1 Feb 2024 (estimated)
- Study completion
- 1 Feb 2024 (estimated)
- First posted
- 8 Feb 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.
This is a multicenter, randomized, double-blind, placebo controlled trial, with parallel groups and reference group.
The aim of the study was to evaluate the hypothesis that an immunonutritional strategy, based on use of Lactobacillus paracasei CBA L74-fermented formula, prevents or limits the development of late-onset-sepsis in preterm infants.
Detailed description
15-20% of infant born weighing less than 1500 grams develop late-onset-sepsis. The prevention of sepsis is based on hygiene measures, on the prudent use of invasive procedures, on drug management and on early diagnosis. However, no intervention is fully effective in reducing the burden of the disease, prolonged hospitalizations in neonatal intensive care units, high costs or delayed neurodevelopmental impairment. The immunonutrition is defined as the potential to modulate the activity of the immune system throught use of specific nutrients. Many immunonutritional approaches in pediatric age act in part with a modulation of the microbiota. Functional foods derived from fermentation with probiotic strains can be used and their activity is considered specific for each strain and dose dependent.
A new functional food derived from fermentation of cow's milk with Lactobacillus paracasei CBA L74 has recently been de-veloped. The fermentation was started in the presence of 106 bacteria, reaching 5.9 X 109 colony-forming units/g after a 15-h incubation at 37 C°. After heating at 85 C° for 20 s in order to inactivate the live bacteria, the formula was spray-dried. Thus, the final fermented milk powder contained only bacterial bodies and fermentation products and no living microorganisms. Lactobacillus paracasei CBA L74 was registered in the Belgian Collection BCCM/LMG and was included in the EFSA list be-tween the "Qualified Presumption of Safety microorganisms".
Pre-clinical studies showed anti-infective and anti-inflammatory properties of this new fermented food. More recently, a similar effect for the L. paracasei supernatant was noted after 24 and 6 h before the LPS treatment. The supernatant protects against the release of inflammatory mediators IFN-ɣ and IL-12p40 and increases the anti-inflammatory cytokine IL-10.
In a randomized controlled clinical trial, the daily supplementation of this fermented food was shown to protect children from infectious diseases and induces immunoregulatory effects. These clinical results are supported by the significant inverse correlation between the concentrations of alpha-defensins, betadefensins, cathelecidins and the secretory levels of IgA with the number of infectious diseases. In another clinical trial it was shown that a daily supplementation of this new fermented food in healthy full-term infants can stimulate the production of innate and acquired immune peptides. Finally, it was reported that milk fermented by L. paracasei CBA L74 stimultes the immune and non-immune defense mechanisms against sepsis, through a direct interaction with human enterocytes.
Although currently available data suggest a positive impact on morbidity, mortality and costs related to neonatal sepsis, there is little knowledge on the use of this fermented functional food in neonatal age. In particular, there are no studies on the effects of this immunonutritional approach on pre-term infants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Preterm Infants - fed fermented formula | Active comparator | Dietary Supplement: Preterm Infants - fed fermented formulaFeeding infants with fermented formula milk. Preterm infants will be fed either with fermented formula milk or with standard formula |
| Preterm Infants - fed standard formula | Placebo comparator | Other: Preterm Infants - fed standard formulaFeeding infants with standard formula milk. Preterm infants will be fed either with fermented formula milk or with standard formula |
| Reference Group: Pre-term Infants - breastfed | Other | Other: Pre-term Infants - breastfedThe breastfeeding infants were the reference group |
Who may qualify
- Ages
- Up to 72 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Newborns weighing less than 1500 grams
- Gestational age <32 weeks
- Artificial feeding or Human milk not available < 30%
Key exclusion criteria (9 listed)
- Voluntary interruption;
- Suspension decided by PI or PDF
- Adverse events
- Gastrointestinal disease that prevent oral feeding
- Congenital or maternal infections
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 |
|---|---|---|
| Preterm Infants - fed fermented formulaFeeding infants with fermented formula supplemented with the fermentation products of the probiotic L. paracasei CBA L74 (800 mg / 100 ml of milk) (84 kcal and 2.9 g protein per 100 ml) | Dietary supplement | Preterm Infants - fed fermented formula |
| Preterm Infants - fed standard formulaFeeding infants with standard formula with the addition of skimmed milk powder in order to provide the same protein and energy amount of the supplemented formula (84 kcal and 2.9 g protein per 100 ml) | Other | Preterm Infants - fed standard formula |
| Pre-term Infants - breastfedBreastfeeding infants - Reference group | Other | Reference Group: Pre-term Infants - breastfed |
Primary outcome
Monitoring of the number of confirmed episodes of late-onset-sepsis during hospitalization period and potential complications of the sepsis
Time frame: from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
Data collection concerning the appearance during hospitalization of episodes of sepsis from Gram positive, Gram negative bacteria and from fungi; the occurrence of comorbidities: necrotizing enterocolitis (NEC); bronchopulmonary dysplasia (BPD); intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), the mortality rate.
Monitoring the number of days required to achieve complete enteral feeding, presence and duration of central vascular access
Time frame: from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
Data collection concerning the number of days required to achieve complete enteral feeding, presence and duration of central vascular access
Monitoring the growth rate
Time frame: from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
Data collection concerning the growth rate (g/ kg/ day)
Monitoring the length of hospital stay
Time frame: from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
Data collection concerning the lenght of the hospital stay
Psychomotor development with the Griffiths III
Time frame: at 180 days of life
Evaluation of the psychomotor development through development quotient using the Griffiths III. General quotient: A scale: learning basis; B scale: language and communication; C scale: eye-manual coordination; D scale: personal-social-emotional; E scale: gross-motor; average 100, DS 15.
5 secondary outcomes
Fecal dosage of cathelicidines, alfa and beta defensins, sIgA
Time frame: at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Microbiota
Time frame: at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Cytokines production assessment on infants blood sample
Time frame: at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Cytokines production assessment on dendritic cells culture medium
Time frame: at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Cell surface activation markers (MHC and costimulatory molecules)
Time frame: at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2022.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Preterm Infants - fed fermented formula, Preterm Infants - fed standard formula and Pre-term Infants - breastfed in people with Neonatal Sepsis, run by Heinz Italia SpA at 1 site in Italy.
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 3 inclusion and 9 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 2 Jun 2022. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fabio Mosca (0255032907, fabio.mosca@mangiagalli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Monitoring of the number of confirmed episodes of late-onset-sepsis during hospitalization period and potential complications of the sepsis (time frame: from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)). The study lists 5 primary outcomes in all. 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 2 Jun 2022.