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Recruitment of breastfed infants was very slow. Decision with PI (05/2018): Termination (80/100); no implication on primary outcome. Predetermined number of breastfed infants (n=100) was arbitray choice. Formula groups completed (460/460) 12/2017.
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| Name | Class |
|---|---|
| Biofortis Mérieux NutriSciences | OTHER |
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The primary objective of this study is to demonstrate that a synbiotic formula, fed for the duration of the first year of life (infant and follow-on formula) reduces the incidence rate of episodes of infectious diarrhea in infants during the first year of life compared to a standard infant formula.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Synbiotic formula | Experimental | Synbiotic formula : standard formula enriched with a prebiotic fiber and a probiotic strain Dose : variable number of powder scoops, adapted to the infant's age and weight, and addition of the defined amount of water, according to the Dose and Drinking Amount table. Route : oral, ad libitum Duration of product intake:
|
|
| Control formula | Placebo Comparator | Control formula : standard formula without pre and probiotic Dose : variable number of powder scoops, adapted to the infant's age and weight, and addition of the defined amount of water according to the Dose and Drinking Amount table. Route: oral, ad libitum Duration of product intake:
|
|
| Breast-fed group | No Intervention | - Breast milk as exclusive feeding (no more than one formula meal per day), from birth until at least 4 months of age. Then, when the mother decides to stop breastfeeding, the infants can consume any formula on parent's choice respecting forbidden products list. Dose:
Route : oral, ad libitum Duration of product intake:
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Synbiotic formula | Dietary Supplement | Standard milk formula enriched with a prebiotic fiber and a probiotic strain |
|
| Measure | Description | Time Frame |
|---|---|---|
| (Cumulative) number of infectious diarrhea episodes per subject during the first year of life. | Difference between formula groups are evaluated via incidence rate based on number of subjects. In formula-fed infants, diarrhea is defined as three or more loose or watery stools in 24 hours with or without fever or vomiting (according to WHO and ESPGHAN definition). For breast-fed infants, a change in stool consistency versus previous stool consistency is more indicative of diarrhea than stool number. Diarrhea episode is considered as ended as soon as 2 consecutive non-watery stools are observed or no stools are observed in 24 hours. | one year |
| Measure | Description | Time Frame |
|---|---|---|
| Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples | Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile | 4 months |
| Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples |
| Measure | Description | Time Frame |
|---|---|---|
| Microbiota results | Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only | 1 year |
| Urinary D-Lactate and creatinine |
Inclusion Criteria:
Additionnaly , criteria of inclusion in one of the formula-fed groups or in the breast-fed group, respectively, are the following:
or
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hugues Piloquet, Pediatrician | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Elie JABBOUR | Gémozac | Charente-Maritime | 17260 | France | ||
| Christophe VIEL |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38462218 | Derived | Piloquet H, Vrignaud B, Gillaizeau F, Capronnier O, Berding K, Gunther J, Hecht C, Regimbart C; GOLF III Study Group. Efficacy and safety of a synbiotic infant formula for the prevention of respiratory and gastrointestinal infections: a randomized controlled trial. Am J Clin Nutr. 2024 May;119(5):1259-1269. doi: 10.1016/j.ajcnut.2024.03.005. Epub 2024 Mar 10. | |
| 36811568 |
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| ID | Term |
|---|---|
| D003967 | Diarrhea |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Control formula | Dietary Supplement | Standard milk formula without pre and probiotic |
|
Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile |
| 1 year |
| Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples | Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile | 2 years |
| Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples | Levels of total lactobacilli, Lactobacillus fermentum species (and if possible the strain CECT 5716 will be quantified too), total bifidobacteria, enterobacteriaceae, clostridium difficile | 3 years |
| Analysis of fecal microbiota by molecular analysis from frozen stools in diarrhea samples | levels of potential pathogens causing diarrhea including rotavirus, norovirus, Salmonella enterica, Campylobacter jejuni, Clostridium difficile, Clostridium perfringens, Escherichia coli (potential pathogenic bacteria will be screened only in case of negative testing for viruses on sample collected within 72 hours after beginning of the diarrhea episode); | 1 year |
| Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples | short chain fatty acids (SCFA): acetate, propionate, butyrate; | 4 months |
| Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples | short chain fatty acids (SCFA): acetate, propionate, butyrate; | 1 year |
| Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples | short chain fatty acids (SCFA): acetate, propionate, butyrate; | 2 years |
| Fecal pH and levels of short chain fatty acids (SCFA) in planned stool samples | short chain fatty acids (SCFA): acetate, propionate, butyrate; | 3 years |
| Characteristics of bowel movements and stools | - assessed through a 3-day diary filled in by parents
| 4 months |
| Characteristics of bowel movements and stools | - assessed through a 3-day diary filled in by parents
| 6 months |
| Characteristics of bowel movements and stools | - assessed through a 3-day diary filled in by parents
| 9 months |
| Characteristics of bowel movements and stools | - assessed through a 3-day diary filled in by parents
| 1 year |
| Characteristics of bowel movements and stools | - assessed through a 3-day diary filled in by parents
| 2 years |
| Characteristics of bowel movements and stools | - assessed through a 3-day diary filled in by parents
| 3 years |
| Characteristics of bowel movements during diarrhea episodes | - assessed through a diary filled in by parents during diarrhea episodes
| 1 year |
| Levels of fecal IgA and fecal calprotectin in planned stool samples | 4 months |
| Levels of fecal IgA and fecal calprotectin in planned stool samples | 1 year |
| Levels of fecal IgA and fecal calprotectin in planned stool samples | 2 years |
| Levels of fecal IgA and fecal calprotectin in planned stool samples | 3 years |
| Number and duration of infectious diseases | Especially: otitis media, infections of upper and lower respiratory tract and of urinary tract; | 3 years |
| Number and duration of fever episodes; | 3 years |
| Number and duration of antibiotic treatment. | 3 years |
| Infants growth measured by anthropometric measurements | weight, size, head circumference; | 4 weeks |
| Infants growth measured by anthropometric measurements | weight, size, head circumference; | 4 months |
| Infants growth measured by anthropometric measurements | weight, size, head circumference; | 6 months |
| Infants growth measured by anthropometric measurements | weight, size, head circumference; | 9 months |
| Infants growth measured by anthropometric measurements | weight, size, head circumference; | 1 year |
| Infants growth measured by anthropometric measurements | weight, size, head circumference; | 2 years |
| Infants growth measured by anthropometric measurements | weight, size, head circumference; | 3 years |
| Child's behavior | Assessed through a 3-day diary filled in by parents - Average sleep duration and crying duration per 24 hours; | 4 months |
| Child's behavior | Assessed through a 3-day diary filled in by parents - Average sleep duration and crying duration per 24 hours; | 6 months |
| Child's behavior | Assessed through a 3-day diary filled in by parents - Average sleep duration and crying duration per 24 hours; | 9 months |
| Child's behavior | Assessed through a 3-day diary filled in by parents - Average sleep duration and crying duration per 24 hours; | 1 year |
| Child's behavior | Assessed through a 3-day diary filled in by parents - Average sleep duration and crying duration per 24 hours; | 2 years |
| Child's behavior | Assessed through a 3-day diary filled in by parents - Average sleep duration and crying duration per 24 hours; | 3 years |
| Minor gastrointestinal disorders (digestive tolerance) | Assessed through a 3-day diary filled in by parents - average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition); | 4 months |
| Minor gastrointestinal disorders (digestive tolerance) | Assessed through a 3-day diary filled in by parents - average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition); | 6 months |
| Minor gastrointestinal disorders (digestive tolerance) | Assessed through a 3-day diary filled in by parents - average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition); | 9 months |
| Minor gastrointestinal disorders (digestive tolerance) | Assessed through a 3-day diary filled in by parents - average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition); | 1 year |
| Minor gastrointestinal disorders (digestive tolerance) | Assessed through a 3-day diary filled in by parents - average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition); | 2 years |
| Minor gastrointestinal disorders (digestive tolerance) | Assessed through a 3-day diary filled in by parents - average daily vomiting, regurgitation/reflux, flatulence, constipation (according to WHO definition); | 3 years |
| Suitability for daily use | Assessed through a 3-day diary filled in by parents - average daily consumption: drinking amounts and formula acceptance; | 4 months |
| Suitability for daily use | Assessed through a 3-day diary filled in by parents - average daily consumption: drinking amounts and formula acceptance; | 6 months |
| Suitability for daily use | Assessed through a 3-day diary filled in by parents - average daily consumption: drinking amounts and formula acceptance; | 9 months |
| Suitability for daily use | Assessed through a 3-day diary filled in by parents - average daily consumption: drinking amounts and formula acceptance; | 1 year |
| Suitability for daily use | Assessed through a 3-day diary filled in by parents - average daily consumption: drinking amounts and formula acceptance; | 2 years |
| Suitability for daily use | Assessed through a 3-day diary filled in by parents - average daily consumption: drinking amounts and formula acceptance; | 3 years |
| Adverse events (AE) | Assessed through a 3-day diary filled in by parents - Number of events, number of subjects showing adverse events, intensity and relationship of AE. | 4 months |
| Adverse events (AE) | Assessed through a 3-day diary filled in by parents - Number of events, number of subjects showing adverse events, intensity and relationship of AE. | 6 months |
| Adverse events (AE) | Assessed through a 3-day diary filled in by parents - Number of events, number of subjects showing adverse events, intensity and relationship of AE. | 9 months |
| Adverse events (AE) | Assessed through a 3-day diary filled in by parents - Number of events, number of subjects showing adverse events, intensity and relationship of AE. | 1 year |
| Adverse events (AE) | Assessed through a 3-day diary filled in by parents - Number of events, number of subjects showing adverse events, intensity and relationship of AE. | 2 years |
| Adverse events (AE) | Assessed through a 3-day diary filled in by parents - Number of events, number of subjects showing adverse events, intensity and relationship of AE. | 3 years |
| Number and duration of fever episodes; | 1 year |
| Number and duration of antibiotic treatment. | 1 year |
| Number and duration of infectious diseases | Especially: otitis media, infections of upper and lower respiratory tract and of urinary tract; | 1 year |
To assess change in the urinary lactate and creatinine (in a subgroup of 96 infants only) via ratio after 3 months of consumption of the supplemented infant formula, compared to the control formula
| 4 weeks |
| Urinary D-Lactate and creatinine | To assess change in the urinary lactate and creatinine (in a subgroup of 96 infants only) via ratio after 3 months of consumption of the supplemented infant formula, compared to the control formula | 4 months |
| Microbiota results | Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only | 4 months |
| Microbiota results | Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only | 2 years |
| Microbiota results | Phyla and families of bacteria in planned stools using 16S taxonomical metasequencing compared to the control formula in a sub-group of 96 infants only | 3 years |
| La Rochelle |
| Charente-Maritime |
| 17000 |
| France |
| C.I.C Pédiatrique - C.H.U. de Grenoble - Hôpital Couple-Enfant | Grenoble | Isère | 38043 | France |
| C.I.C pédiatrique - C.H.U. de Nantes - Hôpital Mère-Enfant | Nantes | Loire-Atlantique | 44093 | France |
| Alain PALOMBA | Angers | Maine-et-Loire | 49000 | France |
| Christophe RONDEAU | Angers | Maine-et-Loire | 49000 | France |
| Damien GODIN | Angers | Maine-et-Loire | 49000 | France |
| Daniel GOMBAUD | Angers | Maine-et-Loire | 49000 | France |
| Jean-François FOUCAULT | Angers | Maine-et-Loire | 49000 | France |
| Michel LAMBERT | Angers | Maine-et-Loire | 49000 | France |
| Nolwenn RONCERAY | Angers | Maine-et-Loire | 49000 | France |
| Philippe REMAUD | Angers | Maine-et-Loire | 49000 | France |
| Pierre-André FERRAND | Angers | Maine-et-Loire | 49000 | France |
| Vanessa BERNAND | Angers | Maine-et-Loire | 49000 | France |
| Francisco MARTINEZ-CORTES | Angers | Maine-et-Loire | 49100 | France |
| Damien GUILLON | Angers | Maine-et-Loire | 49120 | France |
| Christine REGIMBART | Bécon-les-Granits | Maine-et-Loire | 49370 | France |
| Antoine LEPELLETIER | Montreuil | Maine-et-Loire | 49460 | France |
| Benoit DAGUZAN | Segré | Maine-et-Loire | 49500 | France |
| Didier NOURRY | Tiercé | Maine-et-Loire | 49125 | France |
| Philippe IGIGABEL | Tiercé | Maine-et-Loire | 49125 | France |
| Alain BATY | Laval | Mayenne | 53000 | France |
| Christian DUROY | Laval | Mayenne | 53000 | France |
| François RICHARD | Laval | Mayenne | 53000 | France |
| Patrick ROBERT | Laval | Mayenne | 53000 | France |
| Lagkouvardos I, Intze E, Schaubeck M, Rooney JP, Hecht C, Piloquet H, Clavel T. Early life gut microbiota profiles linked to synbiotic formula effects: a randomized clinical trial in European infants. Am J Clin Nutr. 2023 Feb;117(2):326-339. doi: 10.1016/j.ajcnut.2022.11.012. Epub 2022 Dec 21. |