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

K

Kraft Heinz

Status

Enrolling

Conditions

Neonatal Sepsis

Treatments

Dietary Supplement: Preterm Infants - fed fermented formula
Other: Pre-term Infants - breastfed
Other: Preterm Infants - fed standard formula

Study type

Interventional

Funder types

Industry

Identifiers

NCT04742582
CO-2016-02365100

Details and patient eligibility

About

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.

Full 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.

Enrollment

876 estimated patients

Sex

All

Ages

Under 72 hours old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

876 participants in 3 patient groups, including a placebo group

Preterm Infants - fed fermented formula
Active Comparator group
Description:
Feeding infants with fermented formula milk. Preterm infants will be fed either with fermented formula milk or with standard formula
Treatment:
Dietary Supplement: Preterm Infants - fed fermented formula
Preterm Infants - fed standard formula
Placebo Comparator group
Description:
Feeding infants with standard formula milk. Preterm infants will be fed either with fermented formula milk or with standard formula
Treatment:
Other: Preterm Infants - fed standard formula
Reference Group: Pre-term Infants - breastfed
Other group
Description:
The breastfeeding infants were the reference group
Treatment:
Other: Pre-term Infants - breastfed

Trial contacts and locations

1

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Central trial contact

Fabio Mosca

Data sourced from clinicaltrials.gov

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