Clinical trial NCT00486148: Safety and Efficacy of an Infant Formula Supplemented With Galacto-oligosaccharides (GOS)
Official title: Randomized, Double Blind Study to Evaluate the Safety and Efficacy of an Infant Formula Supplemented With Galacto-oligosaccharides (GOS) in Healthy, Full Term Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nutritional Safety
Keywords: Formula
Feeding
Healthy
Full
Term
Infants
Lead sponsor: Heinz Italia SpA
Sponsor class: INDUSTRY
First posted: 2007-06-13
Enrollment: 360
Sex: ALL
Minimum age (years): 1
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and efficacy of an infant formula supplemented with a "prebiotic" component (GOS) in improving the gut microflora balance, mimicking that of breast-fed infants.

Detailed description: Oligosaccharides are one of the major breast milk components. They are not digested and reach the colon where they're used by selected groups of microflora positive bacteria, specifically bifidobacteria and lactobacilli.

Therefore, oligosaccharides have prebiotic effects accountable for health benefits in infants.

Over the last years the supplementation of infant formulae has been studied to mimic breast milk prebiotic functions enhancing gut microflora growth similar to that of breast fed infants.

However further scientific data are necessary to support the efficacy of the supplementation of oligosaccharide in infant formulae.

Eligibility criteria: Inclusion Criteria:

1. Healthy infants of both sexes, born at term with natural labor or cesarean birth
2. Single birth
3. Infant born between 37th - 42th gestation week (included)
4. Infant with birth weight ≥ 2500 g
5. APGAR score after 5 minutes of life \> 7
6. Infant born from parents of Caucasian race
7. Exclusive breast feeding or formula feeding within 15 days from birth.
8. Consensus form signed by both parents or by the legal tutor properly informed of the study.
9. Parents able to understand the protocol requirements and to fill out the infants Diary.

Exclusion Criteria:

1. Infant with inborn malformation and with hereditary and/or chronic and/or inborn diseases requiring hospital care superior to 7 days.
2. Diseases jeopardizing intrauterine growth.
3. Infant born from mother suffering from dismetabolic and/or chronic diseases.
4. Unknown father
5. Infant with parents who might not report at hospital controls or not follow the protocol.
6. Infant already enrolled or selected for another clinical trial.

Primary outcomes:
measure: The nutritional safety through anthropometric controls. Adverse events: diarrhea, crying, gaseous colics, regurgitation, vomit, skin rashes, fever.
timeFrame: Anthropometric controls at birth, on enrolment, after 1, 2, 3, 4 months of life and just before starting weaning. Adverse events daily.
Secondary outcomes:
measure: The prebiotic effect through the control of the feces consistency and frequency, the incidence of gaseous colics and microbiological analyses of the fecal samples.
timeFrame: Feces consistency and frequency, and incidence of gaseous colics, microbiological analyses of the fecal samples on enrolment and after 1 and 2 months of life.
Other outcomes:
Locations:
city: Cernusco sul Naviglio (Milan)
country: Italy
facility: "Casa Pia Ospitaliera Uboldo" Unità Operativa di Pediatria e Neonatologia
city: Erba (Como)
country: Italy
facility: Ospedale "Sacra Famiglia del Fatebenefratelli" Unità Operativa di Pediatria e Neonatologia
city: Melzo (MI)
country: Italy
facility: Ospedale "Santa Maria delle Stelle" Unità Operativa di Pediatria e Neonatologia
city: Milan
country: Italy
facility: Azienda ospedaliera "San Paolo", Dipartimento di Pediatria
city: Milan
country: Italy
facility: Ospedale "San Carlo Borromeo" Unità Operativa di Pediatria
city: Milan
country: Italy
facility: Azienda Ospedaliera "Luigi Sacco" Unità Operativa di Pediatria
city: Piacenza
country: Italy
facility: Ospedale Civile "G. da Saliceto" Unità Operativa di Pediatria
Study officials:
affiliation: Azienda Ospedaliera San Paolo
name: Carlo Agostoni, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera "Luigi Sacco"
name: Gian Vincenzo Zuccotti, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Civile "G. da Saliceto"
name: Giacomo Biasucci, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale San Carlo Borromeo
name: Fabio Alberto Podestà, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: "Casa Pia Ospitaliera Uboldo" - Ospedale "Santa Maria delle Stelle"
name: Amilcare Rottoli, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale "Sacra Famiglia del Fatebenefratelli"
name: Cino Galluzzo, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mountzouris KC, McCartney AL, Gibson GR. Intestinal microflora of human infants and current trends for its nutritional modulation. Br J Nutr. 2002 May;87(5):405-20. doi: 10.1079/BJNBJN2002563.
citation: Agostoni C, Axelsson I, Goulet O, Koletzko B, Michaelsen KF, Puntis JW, Rigo J, Shamir R, Szajewska H, Turck D; ESPGHAN Committee on Nutrition. Prebiotic oligosaccharides in dietetic products for infants: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2004 Nov;39(5):465-73. doi: 10.1097/00005176-200411000-00003.
citation: Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995 Jun;125(6):1401-12. doi: 10.1093/jn/125.6.1401.
citation: Macfarlane GT, Cummings JH. Probiotics and prebiotics: can regulating the activities of intestinal bacteria benefit health? BMJ. 1999 Apr 10;318(7189):999-1003. doi: 10.1136/bmj.318.7189.999. No abstract available.
citation: Moro G, Minoli I, Mosca M, Fanaro S, Jelinek J, Stahl B, Boehm G. Dosage-related bifidogenic effects of galacto- and fructooligosaccharides in formula-fed term infants. J Pediatr Gastroenterol Nutr. 2002 Mar;34(3):291-5. doi: 10.1097/00005176-200203000-00014.
citation: Boehm G, Lidestri M, Casetta P, Jelinek J, Negretti F, Stahl B, Marini A. Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2002 May;86(3):F178-81. doi: 10.1136/fn.86.3.f178.
citation: Schmelzle H, Wirth S, Skopnik H, Radke M, Knol J, Bockler HM, Bronstrup A, Wells J, Fusch C. Randomized double-blind study of the nutritional efficacy and bifidogenicity of a new infant formula containing partially hydrolyzed protein, a high beta-palmitic acid level, and nondigestible oligosaccharides. J Pediatr Gastroenterol Nutr. 2003 Mar;36(3):343-51. doi: 10.1097/00005176-200303000-00008.
citation: Long SS, Swenson RM. Development of anaerobic fecal flora in healthy newborn infants. J Pediatr. 1977 Aug;91(2):298-301. doi: 10.1016/s0022-3476(77)80836-6.
citation: Rotimi VO, Duerden BI. The development of the bacterial flora in normal neonates. J Med Microbiol. 1981 Feb;14(1):51-62. doi: 10.1099/00222615-14-1-51.
citation: Orrhage K, Nord CE. Factors controlling the bacterial colonization of the intestine in breastfed infants. Acta Paediatr Suppl. 1999 Aug;88(430):47-57. doi: 10.1111/j.1651-2227.1999.tb01300.x.
citation: Benno Y, Sawada K, Mitsuoka T. The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol Immunol. 1984;28(9):975-86. doi: 10.1111/j.1348-0421.1984.tb00754.x.
citation: Lundequist B, Nord CE, Winberg J. The composition of the faecal microflora in breastfed and bottle fed infants from birth to eight weeks. Acta Paediatr Scand. 1985 Jan;74(1):45-51. doi: 10.1111/j.1651-2227.1985.tb10919.x.
citation: Howie PW. Protective effect of breastfeeding against infection in the first and second six months of life. Adv Exp Med Biol. 2002;503:141-7. doi: 10.1007/978-1-4615-0559-4_16. No abstract available.
citation: Heine W, Mohr C, Wutzke KD. Host-microflora correlations in infant nutrition. Prog Food Nutr Sci. 1992;16(2):181-97.
citation: Kunz C, Rodriguez-Palmero M, Koletzko B, Jensen R. Nutritional and biochemical properties of human milk, Part I: General aspects, proteins, and carbohydrates. Clin Perinatol. 1999 Jun;26(2):307-33.
citation: Kunz C, Rudloff S, Baier W, Klein N, Strobel S. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr. 2000;20:699-722. doi: 10.1146/annurev.nutr.20.1.699.
citation: Engfer MB, Stahl B, Finke B, Sawatzki G, Daniel H. Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract. Am J Clin Nutr. 2000 Jun;71(6):1589-96. doi: 10.1093/ajcn/71.6.1589.
citation: Erney RM, Malone WT, Skelding MB, Marcon AA, Kleman-Leyer KM, O'Ryan ML, Ruiz-Palacios G, Hilty MD, Pickering LK, Prieto PA. Variability of human milk neutral oligosaccharides in a diverse population. J Pediatr Gastroenterol Nutr. 2000 Feb;30(2):181-92. doi: 10.1097/00005176-200002000-00016.
citation: Giovannini M, Riva E, Banderali G, Scaglioni S, Veehof SH, Sala M, Radaelli G, Agostoni C. Feeding practices of infants through the first year of life in Italy. Acta Paediatr. 2004 Apr;93(4):492-7. doi: 10.1080/08035250410025591.
citation: Howie PW, Forsyth JS, Ogston SA, Clark A, Florey CD. Protective effect of breast feeding against infection. BMJ. 1990 Jan 6;300(6716):11-6. doi: 10.1136/bmj.300.6716.11.
citation: Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev. 2002;(1):CD003517. doi: 10.1002/14651858.CD003517.