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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Safety Issues

Intervention / Treatment
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* Dietary Supplement: FBA
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 3 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FBA<br>N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has been developed. | Dietary Supplement: FBA<br>* N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) has been developed.<br>|
| Placebo Comparator: placebo<br>maltodextrins | Dietary Supplement: placebo<br>* maltodextrins<br>|

What is the study measuring?
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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 |