Clinical trial NCT04962594: Safety and Efficacy of Infant Formulas Supplemented With Pre- and Probiotic(s)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Infants
Lead sponsor: Société des Produits Nestlé (SPN)
Sponsor class: INDUSTRY
First posted: 2021-07-15
Enrollment: 318
Sex: ALL
Minimum age (years): 0
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized, controlled trial plus a non-randomized breastfed reference group
Primary purpose: OTHER

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Weight
timeFrame: From baseline (≤14 days) to 4 months of age
Secondary outcomes:
measure: Bifidobacteria abundance
timeFrame: At 90 days (3 months of age)
measure: Fecal microbiome
timeFrame: Stool sample collected at ≤14 days (baseline), 3, 6, 12 and 15 months of age
measure: Fecal metabolic profile: fecal pH
timeFrame: Stool sample collected at ≤14 days (baseline), 3, 6, 12 and 15 months of age
measure: Fecal metabolic profile: fecal organic acids
timeFrame: Stool sample collected at ≤14 days (baseline), 3, 6, 12 and 15 months of age
measure: Fecal markers of immune health and gut barrier
timeFrame: Stool sample collected at ≤14 days (baseline), 3, 6, 12 and 15 months of age
measure: Fecal cytokine profile
timeFrame: Stool sample collected at ≤14 days (baseline), 3, 6, 12 and 15 months of age
measure: Blood markers of immune health
timeFrame: At 4 months of age
measure: GI-related behavior: stool frequency
timeFrame: Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
measure: GI-related behavior: stool consistency
timeFrame: Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
measure: GI-related behavior: incidence of spitting
timeFrame: Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
measure: GI-related behavior: incidence of flatulence
timeFrame: Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
measure: GI-related behavior: crying time
timeFrame: Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
measure: GI-related behavior: sleep time
timeFrame: Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
measure: GI-related behaviour: volume of formula consumed
timeFrame: Retrospective 1-day (at baseline) and prospective for 3 days prior to 1, 2, 3, 4, 6, 9, 12 and 15 months of age
measure: Infant Gastrointestinal Symptom Index
timeFrame: At baseline, 1, 2, 3, 4, 6, 9, 12 and 15 months of infant age
measure: Bone index
timeFrame: At baseline, 3, 6, 9, 12 and 15 months of infant age
measure: Additional growth parameters: weight
timeFrame: At infant age ≤14 days (baseline), 1, 2, 3, 4, 6, 9, 12 and 15 months of age
measure: Additional growth parameters: length
timeFrame: At infant age ≤14 days (baseline), 1, 2, 3, 4, 6, 9, 12 and 15 months of age
measure: Additional growth parameters:head circumference
timeFrame: At infant age ≤14 days (baseline), 1, 2, 3, 4, 6, 9, 12 and 15 months of age
measure: Additional growth parameters: Body Mass Index
timeFrame: At infant age ≤14 days (baseline), 1, 2, 3, 4, 6, 9, 12 and 15 months of age
measure: Dietary pattern
timeFrame: At infant age 6, 9, 12 and 15 months
measure: Absenteeism (infant and parent)
timeFrame: Data collected continuously from enrollment until 15 months of age
Other outcomes:
Locations:
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge-Oostende AV
city: Brussel
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Hasselt
country: Belgium
facility: Kinderartsen Huis
city: Liège
country: Belgium
facility: CHC-Groupe santé, Clinique MontLégia
city: Liège
country: Belgium
facility: CHU de Liège - CHR de la Citadelle
city: Amiens
country: France
facility: CHU Amiens-Picardie
city: Bron
country: France
facility: Hôpital Femme Mère Enfant
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Nantes
country: France
facility: CHU de Nantes
city: Rouen
country: France
facility: CHU Charles Nicolle
city: Tours
country: France
facility: Hôpital Bretonneau, CHRU de Tours
city: Rostock
country: Germany
facility: Klinikum Südstadt Rostock
city: Spandau
country: Germany
facility: Evangelisches Waldkrankenhaus Spandau
city: Castellón De La Plana
country: Spain
facility: Hospital Vithas Castellón
city: Córdoba
country: Spain
facility: Reina Sofía University Hospital
city: Sevilla
country: Spain
facility: Instituto Hispalense de Pediatría, Unidad de Investigación
city: Valencia
country: Spain
facility: Hospital Vithas Valencia
city: Valencia
country: Spain
facility: Quironsalud Valencia Hospital
Study officials:
References: