Safety and Efficacy of Infant Formulas Supplemented With Pre- and Probiotic(s)

Healthy Infants Clinical Trial

Official title:

Safety and Efficacy of Starter Infant Formula, Follow-up Formula and Growing-up Milk Supplemented With Pre- and Probiotic(s): a Double-blind, Randomized, Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04962594
• Other study ID #: 20.12.INF
• Status: Completed
• Phase: N/A
• Start date: September 2, 2021
• Est. completion date: April 4, 2024

Study information

• Verified date: June 2024
• Source: Société des Produits Nestlé (SPN)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, controlled, multicenter, double-blind study of healthy term infants. The primary objective of the trial is to demonstrate the safety of a a starter infant formula supplemented with pre- and probiotic(s) by comparing the growth of infants randomized to the experimental formula versus the control formula from enrolment to 4 months of age.

Description:

This is a randomized, controlled, multicenter, double-blind study of healthy term infants, consisting of two randomized formula-fed arms (control and experimental formulas) and a non-randomized breast-fed reference group.

The population under investigation are healthy infants aged ≤14 days at enrollment. The planned sample size for formula-fed infants is 236 (118 per study group). A non-randomized breastfed reference group of 90 healthy, term, exclusively breastfed infants up to 4 months will also be enrolled.

Study formulas are administrated orally, ad libitum, from enrollment until 15 months of age.

The primary objective of the trial is to demonstrate the safety of a starter infant formula supplemented with pre- and probiotic(s) by comparing the growth (weight gain, g/day) of infants randomized to the experimental formula versus the control formula from enrolment to 4 months of age.

In addition fecal microbiome, fecal metabolic profile, fecal markers of immune and gut health, blood markers of immune health (in a subset of 60 infants/group), GI tolerance, bone index (subset of 40 infants/group), other anthropometric measurements, dietary pattern and infant illness and infection outcomes will be assessed/measured.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 318
• Est. completion date: April 4, 2024
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Days to 14 Days

Eligibility

Inclusion Criteria:

1. Evidence of personally signed and dated informed consent document indicating that the infant's parent(s)/ legally accepted representatives LAR have been informed of all pertinent aspects of the study.

2. Infants whose parent(s)/LAR have reached the legal age of majority in the countries where the study is conducted.

3. Infants whose parent(s)/LAR are willing and able to comply with scheduled visits, and the requirements of the study protocol.

4. Infants whose parent(s)/LAR are able to be contacted directly by telephone throughout the study.

5. Infants must meet all of the following inclusion criteria to be eligible for enrollment into the study:

1. Healthy term infant (=37 weeks of gestation)

2. At enrollment visit, post-natal age =14 days/0.5 months

3. Birth weight = 2500g and = 4500g.

4. For formula-fed groups, infants must be exclusively consuming and tolerating a cow's milk infant formula at time of enrollment and their parent(s)/LAR must have independently elected, before enrollment, not to breastfeed.

5. For the breastfed group, infants must have been exclusively consuming breast milk since birth, and their parent(s)/LAR must have made the decision to continue exclusively breastfeeding until at least 4 months of age.

Exclusion Criteria:

1. Infants with conditions requiring infant feedings other than those specified in the protocol.

2. Infants who have a medical condition or history that could increase the risk associated with study participation or interfere with the interpretation of study results, including:

1. Evidence of major congenital malformations (e.g., cleft palate, extremity malformation)

2. Suspected or documented systemic or congenital infections (e.g., human immunodeficiency virus, cytomegalovirus, syphilis)

3. Previous or ongoing severe medical or laboratory abnormality (acute or chronic) which, in the judgment of the investigator, would make the infant inappropriate for entry into the study. Of note, children who are normally healthy but at the time of enrollment suffering from acute illness in a minor condition which are common in childhood and do not require some of the exclusionary medication mentioned below can be enrolled.

3. Infants who are presently receiving or have received prior to enrollment any of the following: medication(s) or supplement(s) which are known or suspected to affect the following: fat digestion, absorption, and/or metabolism (e.g., pancreatic enzymes); stool microbiota and characteristics (e.g., oral or systemic antibiotics, glycerin suppositories, bismuth-containing medications, docusate, Maltsupex, or lactulose); growth (e.g. insulin or growth hormone); gastric acid secretion.

4. Currently participating or having participated in another clinical trial since birth.

5. Subjects or subjects' parent(s) or legal representative who are not willing and not able to comply with scheduled visits and the requirements of the study protocol

Related Conditions & MeSH terms

• Healthy Infants

Intervention

Other:
• Experimental formulas (EF)
First age formula administered orally ad libitum until 6 months of age, switch to second age formula until 12 months and finally to growing-up milk from 12 to 15 months
• Control formulas (CF)
First age formula administered orally ad libitum until 6 months of age, switch to second age formula until 12 months and finally to growing-up milk from 12 to 15 months
• Breast feeding (BF)
Exclusive breast feeding up to 4 months

Locations

Country	Name	City	State
Belgium	AZ Sint-Jan Brugge-Oostende AV	Brugge
Belgium	Universitair Ziekenhuis Brussel	Brussel
Belgium	Kinderartsen Huis	Hasselt
Belgium	CHC-Groupe santé, Clinique MontLégia	Liège
Belgium	CHU de Liège - CHR de la Citadelle	Liège
France	CHU Amiens-Picardie	Amiens
France	Hôpital Femme Mère Enfant	Bron
France	Hôpital de la Croix Rousse	Lyon
France	CHU de Nantes	Nantes
France	CHU Charles Nicolle	Rouen
France	Hôpital Bretonneau, CHRU de Tours	Tours
Germany	Klinikum Südstadt Rostock	Rostock
Germany	Evangelisches Waldkrankenhaus Spandau	Spandau
Spain	Hospital Vithas Castellón	Castellón De La Plana
Spain	Reina Sofía University Hospital	Córdoba
Spain	Instituto Hispalense de Pediatría, Unidad de Investigación	Sevilla
Spain	Hospital Vithas Valencia	Valencia
Spain	Quironsalud Valencia Hospital	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Société des Produits Nestlé (SPN)

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weight	Weight gain measured as mean daily weight gain in g/day	From baseline (=14 days) to 4 months of age
Secondary	Bifidobacteria abundance	Bifidobacteria abundance	At 90 days (3 months of age)
Secondary	Fecal microbiome	Overall fecal microbiota composition, diversity, different bacteria taxa and microbiota community types assessed using next generation sequencing (NGS) technology	Stool sample collected at =14 days (baseline), 3, 6, 12 and 15 months of age
Secondary	Fecal metabolic profile: fecal pH	Fecal pH	Stool sample collected at =14 days (baseline), 3, 6, 12 and 15 months of age
Secondary	Fecal metabolic profile: fecal organic acids	Fecal organic acids (such as, but not restricted to lactate, including indole-lactate, L- and D-lactate, propionate, butyrate, acetate, valerate, and total fecal organic acids)	Stool sample collected at =14 days (baseline), 3, 6, 12 and 15 months of age
Secondary	Fecal markers of immune health and gut barrier	Fecal markers of immune health and gut barrier such as total secretory IgA (sIgA), lipocalin-2, calprotectin, and a-1-antitrypsin assessed by ELISA.	Stool sample collected at =14 days (baseline), 3, 6, 12 and 15 months of age
Secondary	Fecal cytokine profile	Fecal cytokine profile (such as but not restricted to: IL-6, IL-8, IL-1b, IL-22, IFN-?) using multiplex assays	Stool sample collected at =14 days (baseline), 3, 6, 12 and 15 months of age
Secondary	Blood markers of immune health	Vaccine specific antibodies assessed by ELISA and Immuno-phenotyping in a subset of 120 infants (60/group)	At 4 months of age
Secondary	GI-related behavior: stool frequency	Stool frequency recorded via the GI Symptom and Behavior Diary	Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
Secondary	GI-related behavior: stool consistency	Stool consistency recorded via the GI Symptom and Behavior Diary	Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
Secondary	GI-related behavior: incidence of spitting	Incidence of spitting recorded via the GI Symptom and Behavior Diary	Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
Secondary	GI-related behavior: incidence of flatulence	Incidence of flatulence via the GI Symptom and Behavior Diary	Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
Secondary	GI-related behavior: crying time	Crying time via the GI Symptom and Behavior Diary	Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
Secondary	GI-related behavior: sleep time	Sleep time via the GI Symptom and Behavior Diary	Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
Secondary	GI-related behaviour: volume of formula consumed	Volume of formula consumed at each feeding or the number of breast milk feedings recorded via the GI Symptom and Behavior Diary	Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
Secondary	Infant Gastrointestinal Symptom Index	GI symptoms via the Infant Gastrointestinal Symptom Questionnaire (IGSQ-13)	At baseline, 1, 2, 3, 4, 6, 9, 12 and 15 months of infant age
Secondary	Bone index	Bone index measurement will be conducted using a non-invasive and radiation-free ultra-sound sonometer in a subset of 80 children (40/group)	At baseline, 3, 6, 9, 12 and 15 months of infant age
Secondary	Additional growth parameters: weight	Weight in grams and corresponding weight-for-age Z-score according WHO growth standards	At infant age =14 days (baseline), 1, 2, 3, 4, 6, 9, 12 and 15 months of age
Secondary	Additional growth parameters: length	Length in centimeters and corresponding length-for-age Z-score according WHO growth standards	At infant age =14 days (baseline), 1, 2, 3, 4, 6, 9, 12 and 15 months of age
Secondary	Additional growth parameters:head circumference	Head circumference in centimeters and corresponding head circumference-for-age Z-score according WHO growth standards	At infant age =14 days (baseline), 1, 2, 3, 4, 6, 9, 12 and 15 months of age
Secondary	Additional growth parameters: Body Mass Index	BMI (kg/m2) and corresponding BMI-for-age Z-score according WHO growth standards	At infant age =14 days (baseline), 1, 2, 3, 4, 6, 9, 12 and 15 months of age
Secondary	Dietary pattern	Data collected using a food frequency questionnaire including key food groups for infants and young children	At infant age 6, 9, 12 and 15 months
Secondary	Absenteeism (infant and parent)	Time away from daycare (infant) or work (parent) will be recorded during occurrences of illness / infection using a calendar-based electronic Infant Illness Diary (IID)	Data collected continuously from enrollment until 15 months of age