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

NCT ID: NCT04742582

Last Updated: 2022-06-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 876 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2024-02-01

Brief 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 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.

Conditions

Neonatal Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Preterm Infants - fed fermented formula

Intervention Type: DIETARY_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 formula

Feeding infants with standard formula milk. Preterm infants will be fed either with fermented formula milk or with standard formula

Group Type: PLACEBO_COMPARATOR

Preterm Infants - fed standard formula

Intervention Type: OTHER

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)

Reference Group: Pre-term Infants - breastfed

The breastfeeding infants were the reference group

Group Type: OTHER

Pre-term Infants - breastfed

Intervention Type: OTHER

Breastfeeding infants - Reference group

Interventions

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)

Intervention Type: DIETARY_SUPPLEMENT

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)

Intervention Type: OTHER

Pre-term Infants - breastfed

Breastfeeding infants - Reference group

Intervention Type: OTHER

Eligibility Criteria

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.

• Maximum Eligible Age: 72 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heinz Italia SpA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Unità di Neonatologia e Terapia Intensiva Neonatale, Clinica Mangiagalli

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Fabio Mosca

Role: CONTACT

fabio.mosca@mangiagalli.it

0255032907

Facility Contacts

Paola Roggero

Role: primary

paola.roggero@unimi.it

Other Identifiers

CO-2016-02365100

Identifier Type: -

Identifier Source: org_study_id