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

Tolerability and Modulatory Action on Neonatal Gastrointestinal Function and Immunity of the Butyrate Releaser N-(1-carbamoyl-2-phenyl-ethyl) Butyramide as New Component for Infant Formula

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.

Study Overview

• Status: Completed
• Conditions: Safety Issues
• Intervention / Treatment: Dietary supplement: FBA; Dietary supplement: placebo

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80131
    • University of Naples Federico II

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: FBA; N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has been developed.	Dietary supplement: FBA; N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has been developed.
PLACEBO_COMPARATOR: placebo; maltodextrins	Dietary supplement: placebo; maltodextrins

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety and tolerability: adverse events	number and proportion of subjects with adverse events	up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of subjects with infantile colics	rate of subjects with infantile colics	up to 28 days
daily number of bowel movements	daily number of bowel movements	up to 28 days
stool consistency	stool consistency	up to 28 days
daily number of regurgitation episodes	daily number of regurgitation episodes	up to 28 days
fecal levels of of β-defensins 2 (HβD-2)		up to 28 days
change of secretory immunoglobulin A (sIgA)		up to 28 days

Collaborators and Investigators

• Sponsor: Federico II University

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 9, 2012
• Primary Completion (ACTUAL): December 31, 2013
• Study Completion (ACTUAL): December 31, 2013

Study Registration Dates

• First Submitted: July 25, 2020
• First Submitted That Met QC Criteria: July 28, 2020
• First Posted (ACTUAL): July 29, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 12, 2020
• Last Update Submitted That Met QC Criteria: August 11, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: 20-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No