Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04742582
Other study ID # CO-2016-02365100
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date March 1, 2021
Est. completion date February 1, 2024

Study information

Verified date June 2022
Source Heinz Italia SpA
Contact Fabio Mosca
Phone 0255032907
Email fabio.mosca@mangiagalli.it
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 late-onset-sepsis in preterm infants.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 876
Est. completion date February 1, 2024
Est. primary completion date February 1, 2024
Accepts healthy volunteers No
Gender All
Age group N/A to 72 Hours
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

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)
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)
Pre-term Infants - breastfed
Breastfeeding infants - Reference group

Locations

Country Name City State
Italy Unita` di Neonatologia e Terapia Intensiva Neonatale, Clinica Mangiagalli Milano

Sponsors (1)

Lead Sponsor Collaborator
Heinz Italia SpA

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
Primary 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 from enrollment (from 0 to 72 hours of life) to discharge (estimated average 40 weeks of corrected age)
Primary Monitoring the growth rate 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)
Primary Monitoring the length of hospital stay 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)
Primary 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. at 180 days of life
Secondary 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 at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Secondary 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. at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Secondary 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) at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
Secondary Cytokines production assessment on dendritic cells culture medium 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
Secondary 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) at the enrollment (from 0 to 72 hours of life), at 30 days of life, and discharge or 40 weeks of correct age
See also
  Status Clinical Trial Phase
Not yet recruiting NCT05692128 - Frequency and Severity of Thrombocytopenia in Neonatal Sepsis
Completed NCT00942084 - A Study to Describe the Pharmacokinetics of Acyclovir in Premature Infants (PTN_Acyclo) Phase 1
Completed NCT06002295 - A Comparative Analysis of 4% Chlorhexidine Versus Methylated Spirit as Prophylaxis of Omphalitis and Sepsis in Newborns Phase 2
Not yet recruiting NCT05114057 - Use of NGAL for Fluid Dosing and CRRT Initiation in Pediatric and Neonatal AKI N/A
Recruiting NCT04528251 - Comparison of the Effectiveness of Two Different Antibiotic Regimens of the Treatment of Pregnant Women With Preterm Rupture of Membranes
Active, not recruiting NCT03871491 - Azithromycin-Prevention in Labor Use Study (A-PLUS) Phase 3
Completed NCT03746743 - Severity Index of Neonatal Septicemia Using Score for Neonatal Acute Physiology (SNAP) II
Completed NCT02386592 - Prevention of Nosocomial Bacteremia Among Zambian Neonates N/A
Not yet recruiting NCT06113653 - Outcomes and Predictors of Mortality Among Preterm Infants With Neonatal Sepsis
Completed NCT03199547 - Pre-delivery Administration of Azithromycin to Prevent Neonatal Sepsis & Death Phase 3
Completed NCT02147327 - Effects of Cord Blood 25-hydroxy-vitamin D Level on Early Neonatal Morbidities N/A
Completed NCT01005589 - CD64 Measurement in Neonatal Infection and Necrotising Enterocolitis N/A
Completed NCT00866567 - Defects in Opsonophagocytosis in Premature Infants N/A
Completed NCT02281890 - Neurodevelopmental Outcomes After Suspected or Proven Sepsis: Secondary Analysis of INIS Trial Database N/A
Suspended NCT05156333 - Probiotics and GBS Colonization in Pregnancy N/A
Recruiting NCT05127070 - Evaluating the NeoTree in Malawi and Zimbabwe
Completed NCT03755635 - Neonatal Sepsis at Neonatal Intensive Care Units in Ghana N/A
Completed NCT03247920 - Reduction of Intravenous Antibiotics In Neonates Phase 4
Completed NCT03295162 - Effects of Melatonin as a Novel Antioxidant and Free Radicals Scavenger in Neonatal Sepsis Phase 1/Phase 2
Completed NCT02954926 - Intravenous Immunoglobulin in Prevention of Preterm Neonatal Sepsis Phase 3