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Tolerability and Modulatory Action of the Butyrate Releaser N-(1-carbamoyl-2-phenyl-ethyl) Butyramide

Not Applicable
Completed
Conditions
Safety Issues
Interventions
Dietary Supplement: placebo
Dietary Supplement: FBA
Registration Number
NCT04491266
Lead Sponsor
Federico II University
Brief Summary

Accumulating evidence is showing that gut microbiota could play a key role in gastrointestinal tract and immune system development and function. Many beneficial effects elicited by gut microbiota are mediated its metabolites. Short chain fatty acids (SCFAs) are major metabolites produced by gut microbiota. Among SCFA, butyrate has emerged as pivotal regulator of many gastrointestinal function and immune system development and function.

Butyrate is produced by intestinal microbial fermentation of resistant starches and dietary fiber. It regulates several beneficial intestinal and extra-intestinal functions, among the first it serves as the primary energy source for the gut epithelium, increases mineral absorption, stimulates proliferation and differentiation of normal colon epithelial cells, improves the gut barrier function by stimulation of the formation of mucin, antimicrobial peptides, and tight-junction proteins, interacts with the immune system and has anti-inflammatory effects.

Butyrate also seems to regulate the expression of antimicrobial peptides in particular upregulating transcription of cathelicidin thanks to his action of histone deacetylase inhibitor and it has been shown to induce human β-defensin 2 (HBD-2) mRNA expression in colonocytes, although there are few publications reporting its regulation of defensins (Berni Canani R et al. W J Gastroenterol. 2011;17(12):1519). Preliminary data showed that breast milk contains butyrate. Butyrate could be an ideal compound for infant formulas for an efficient regulation of a number of protective actions at gastrointestinal tract level and at systemic level.

A new butyrate releaser, useful for all the known applications of butyrate, presenting physiochemical characteristics suitable for easy oral administration (free from unpleasant organoleptic properties of butyrate): N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has been developed. The molecule is a butyrate amide with the amino acid phenylalanine, solid, odourless, tasteless, stable at gastric pH, and able to release butyrate constantly throughout gastrointestinal tract.

The aim of the study was to evaluate tolerability and safety profile of a nutritional intervention with FBA in formula fed at term neonates. The effects on the expression of innate immunity biomarkers as well as on neonatal gut function were also assessed.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
Inclusion Criteria
  • otherwise healthy formula fed-neonates
  • born at term (>37 gestational age)
  • adequate weight for gestational age
Exclusion Criteria
  • twins,
  • infants with history of severe asphyxia,
  • meconium aspiration syndrome,
  • immunodeficiency,
  • congenital infections,
  • genetic diseases and chromosomal abnormalities,
  • malformations,
  • insufficient reliability or presence of conditions that made the patient's compliance with the protocol unlikely,
  • infants with any other condition which, in the opinion of the Investigator, is likely to interfere with the ability of the infant to ingest food, or the normal growth and development of the infant, or the evaluation of the infant.

In addition, as maternal exclusion factors:

  • history of immune diseases,
  • tumors,
  • infectious or inflammatory diseases that required antibiotic therapy during pregnancy,
  • diabetes,
  • gestosis,
  • dyslipidemia,
  • positive vaginal swab for Group B Streptococcus,
  • prolonged rupture of membranes.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placeboplacebomaltodextrins
FBAFBAN-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has been developed.
Primary Outcome Measures
NameTimeMethod
safety and tolerability: adverse eventsup to 28 days

number and proportion of subjects with adverse events

Secondary Outcome Measures
NameTimeMethod
percentage of subjects with infantile colicsup to 28 days

rate of subjects with infantile colics

daily number of regurgitation episodesup to 28 days

daily number of regurgitation episodes

fecal levels of of β-defensins 2 (HβD-2)up to 28 days
daily number of bowel movementsup to 28 days

daily number of bowel movements

stool consistencyup to 28 days

stool consistency

change of secretory immunoglobulin A (sIgA)up to 28 days

Trial Locations

Locations (1)

University of Naples Federico II

🇮🇹

Naples, Italy

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