Potential Protective Effect of a Formula Supplemented With Fermented Matrices on the Risk of Developing Neonatal Sepsis

June 1, 2022 updated by: Heinz Italia SpA

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
876

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Italy
      • Milano, Italy, 20122
        • Recruiting
        • Unità di Neonatologia e Terapia Intensiva Neonatale, Clinica Mangiagalli
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 3 days (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Newborns weighing less than 1500 grams
  • Gestational age <32 weeks
  • Artificial feeding or Human milk not available < 30%

Exclusion Criteria:

  • Voluntary interruption;
  • Suspension decided by PI or PDF
  • Adverse events
  • Gastrointestinal disease that prevent oral feeding
  • Congenital or maternal infections
  • Immunodeficiencies
  • Malformations
  • Syndromes
  • Genetic or metabolic diseases.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Preterm Infants - fed fermented formula
Feeding infants with fermented formula milk. Preterm infants will be fed either with fermented formula milk or with standard formula
Dietary supplement: Preterm Infants - fed fermented formula
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)
Placebo Comparator: Preterm Infants - fed standard formula
Feeding infants with standard formula milk. Preterm infants will be fed either with fermented formula milk or with standard formula
Other: Preterm Infants - fed standard formula
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)
Other: Reference Group: Pre-term Infants - breastfed
The breastfeeding infants were the reference group
Other: Pre-term Infants - breastfed
Breastfeeding infants - Reference group

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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
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
from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
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)
from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
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
from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
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.
at 180 days of life

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Dosage of biomarkers levels of innate and acquired immunity (cathelicidines, alfa and beta defensins, sIgA ) on fecal samples, using ELISA kits
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
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.
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 (IL-6, IL-12p40, TNF-a) production assessment on infants blood sample, using CBA (cytokine bead array)
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
Cytokines (IL-6, IL-12p40, TNF-a) production assessment on murine dendritic cells culture medium
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
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)
at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Heinz Italia SpA

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2024

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 31, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 2, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 8, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 2, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 1, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CO-2016-02365100

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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