Second Generation Human Milk Oligosaccharides Blend Study

Société des Produits Nestlé (SPN)789 enrolled

Overview

The aim of this trial is to show that infants fed these new formulas, containing a blend of 5 Human Milk Oligosaccharides (HMOs), allow for growth in line with infants fed formulas without HMOs. There will be different groups in the trial: three formula-fed groups and a breastfed group.

These 5 HMOs are identical to the ones found naturally in human milk. They are natural prebiotics (or complex sugars) with potential health benefits. Prebiotics are natural compounds that help the establishment of beneficial gut bacteria (such as bifidobacteria), while preventing bad bacteria from doing harm. Supplementing diets with certain prebiotics has been shown to be well tolerated in adults and infants and to provide potential benefits.Therefore, the trial also aims to understand if consuming HMOs supplemented formulas could strengthen immunity and prevent common illnesses (for example, respiratory illnesses) in infants and toddlers. Furthermore, stool frequency and consistency will be monitored, so as to evaluate digestive tolerance to the formula.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Enrollment

789

Conditions

Healthy Infants

Interventions

Starter Infant Formula, Follow-up Formula, and Growing-up Milk Supplemented With a Blend of Five Human Milk OligosaccharidesOTHER

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

Breast-feedingOTHER

Exclusive Breast-feeding up to 4 months of age

Standard Starter Infant Formula, Follow-up Formula, and Growing-up MilkOTHER

Standard Study formulas are administered orally, ad libitum, from enrollment until 15 months of age

Eligibility

Sex: ALLMin age: 7 DaysMax age: 21 DaysHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Evidence of personally signed and dated informed consent document indicating that the infant's parent(s)/Legally Acceptable Representative has been informed of all pertinent aspects of the study. 2. Infants whose parent(s)/Legally Acceptable Representative have reached the legal age of majority in the countries where the study is conducted. 3. Infants whose parent(s)/Legally Acceptable Representative are willing and able to comply with scheduled visits, and the requirements of the study protocol. 4. Infants whose parent(s)/Legally Acceptable Representative are able to be contacted directly by telephone throughout the study. 5. Infants whose parent(s)/Legally Acceptable Representative have a working freezer. 6. Infants must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Healthy term (37-42 weeks of gestation) infant at birth. 2. At enrollment visit, post-natal age ≥ 7 days and ≤ 21 days (date of birth = day 0, 0.25 - 0.75 months old). 3. At enrollment, birth weight ≥ 2500g and ≤ 4500g. 4. For formula-fed group, infants must be exclusively consuming and tolerating a cow's milk infant formula at time of enrollment and their parent(s)/Legally Acceptable Representative must have independently elected, before enrollment, not to breastfeed. 5. For breastfed group, infants must have been exclusively consuming breast milk since birth, and their parent(s)/Legally Acceptable Representative must have made the decision to continue exclusively breastfeeding until at least 4 month of age. Exclusion Criteria: 1. Infants with conditions requiring infant feedings other than those specified in the protocol. 2. Infants receiving complementary foods or liquids defined as 4 or more teaspoons per day or approximately 20 g per day of complementary foods or liquids at or prior to enrollment. 3. 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. History of admission to the Neonatal Intensive Care Unit (NICU), with the exception of admission for jaundice phototherapy. 4. Other 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. 4. 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 characteristics (e.g., glycerin suppositories, bismuth-containing medications, docusate, Maltsupex, or lactulose); growth (e.g. insulin or growth hormone); gastric acid secretion; or any study outcomes. 5. Currently participating or having participated in another clinical trial since birth

Locations (34)

Outcomes

Primary Outcomes

To compare the growth of infants between the groups

To compare the growth (weight gain, g/day) of infants randomized to Test Groups (TG1 or TG2) versus Control Group (CG)

Time frame: From Study Day 1 to 4 months of age

To compare recurrent incidences of illness of infants between the groups

To compare recurrent incidences of illness (specifically lower and upper respiratory tract illnesses including bronchitis/bronchiolitis), of infants randomized to Test Groups (TG1 or TG2) versus Control Group (CG)

Time frame: From Study Day 1 to 15 months of age

Secondary Outcomes

Infant illness and infection outcomes

Specific parent-reported infant illness symptoms and physician confirmed diagnoses of lower respiratory tract infection (LRTI), upper respiratory tract infection (URTI), total respiratory tract infection (TRTI), gastrointestinal infection (GII), ear illness \[including: otitis media (OM), ear infection, ear inflammation, and ear pain\], and fever will be combined to report infant illness and infection outcomes (Episode, incidence, duration, severity, and recurrence)

Time frame: at different stages of feeding 1st age Infant Formula, 2nd age Follow-up Formula, and 3rd age Growing-up Milk when applicable

Medication use (specifically antimicrobials and antipyretics)

Medication type and duration of intake will be combined to report the medication use

Time frame: From enrollment until 15 months of age

Absenteeism: Time away from daycare (infant) or work (parent)

Time away from daycare (infant) or work (parent)

Time frame: From enrollment until 15 months of age

Fecal microbiome composition, diversity, community type

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Sveti Ivan Rilski - Chudotvorets

Blagoevgrad, Bulgaria

University Hospital Deva Maria, Department for Naonatology

Burgas, Bulgaria

Multiprofile Hospital for Active Treatment Sveti Ivan Rilski Kozloduy,Department of Pediatrics

Kozloduy, Bulgaria

Multiprofile Hospital for Active Treatment City Clinic - Sveti Georgi EOOD,Department of Paediatrics

Montana, Bulgaria

University Multiorofile Hospital for active treatment Sveti Georgi EAD, Pediatric clinic

Plovdiv, Bulgaria

Multiprofile Hospital for Active treatment- Ruse AD, Department of Paediatrics

Rousse, Bulgaria

Medical Center-1-Sevlievo EOOD

Sevlievo, Bulgaria

1st Pediatric Consultative Clinic

Sofia, Bulgaria

Medical Center Excelsior

Sofia, Bulgaria

Medical Centre - Izgrev EOOD

Sofia, Bulgaria

...and 24 more locations

Fecal microbiota composition, diversity, and microbiota community type will be assessed using cutting-edge next generation sequencing technology and combined to report the Fecal microbiome

Time frame: Stool sample collected at infant age less than 0.75, 3, 6, 12, and 15 months of age (a subset of 105 infants per formula group; 90 breastfed infants)

Fecal metabolic profile

Measures of fecal metabolism will be combined to report fecal metabolic profile (fecal pH, fecal organic acids, as well as additional targeted/untargeted metabolomics and cell-based functional assays)

Time frame: Stool sample collected at infant age less than 0.75, 3, 6, 12, and 15 months of age (a subset of 105 infants per formula group; 90 breastfed infants)

Markers of immune and gut health

Fecal markers of immune and gut health will include secretory immunoglobulin A IgA \[total\], alpha-1 antitrypsin, and calprotectin.

Time frame: Stool sample collected at infant age less than 0.75, 3, 6, 12, and 15 months of age (a subset of 105 infants per formula group; 90 breastfed infants)

Blood Markers of immune health

Plasma and peripheral blood mononuclear cells, Extracellular in vivo and ex vivo circulating cytokine levels will be measured in plasma

Time frame: At 6 months of age

Gastrointestinal tolerance

Stool patterns (stool frequency and consistency), Gastrointestinal symptoms, Gastrointestinal-related behaviors, and milk intake will be combined to report the gastrointestinal tolerance

Time frame: Stool sample collected at infant age less than 0.75, 3, 6, 12, and 15 months of age (a subset of 105 infants per formula group; 90 breastfed infants)

Cognitive and behavioral outcomes

Assessment at 15 months through the use of the MacArthur-Bates Communicative Development Inventories (MCDI) and the Early Childhood Behavior Questionnaire (ECBQ), two parent-reported questionnaires that evaluate early language/vocabulary and development of communication skills, that will be combined to report the cognitive and behavioral outcomes

Time frame: At 15 months of age

DNA Genotyping of fucosyltransferase 2 and 3 (secretor status)

Association between secretor status and illnesses/infections via microbiome modulation will be evaluated.

Time frame: At Study Day 60 +/- 5 days

Breastmilk collection for Human Milk Oligosaccharides profile analysis (breastfeeding mothers only)

A small sample of milk (1ml) will be hand pumped, collected in an Eppendorf tube and stored frozen

Time frame: At Study Day 90 +/- 5 days

Anthropometric measurements: Weight

Weight measurements in grams to report anthropometric measurements.

Time frame: From enrollment until 15 months of age

Anthropometric measurements: Length

Length measurements in centimeters to report anthropometric measurements.

Time frame: From enrollment until 15 months of age

Anthropometric measurements: Head circumference

Head circumference measurements in centimeters to report anthropometric measurements.

Time frame: From enrollment until 15 months of age

Anthropometric measurements: BMI

BMI measurements in kg/m\^2 to report anthropometric measurements.

Time frame: From enrollment until 15 months of age

Anthropometric measurements: World Health Organization (WHO) growth standard calculated z-scores

WHO growth standard z-scores including weight-for-age, length-for-age, weight-for-length, head-circumference-for-age, BMI-for-age and weight velocity will be calculated and combined to report anthropometric measurements.

Time frame: From enrollment until 15 months of age

Vital signs: Infant respiration

Infant respiration in breaths per minute will also be measured to report vital signs

Time frame: From enrollment until 15 months of age

Vital signs: Heart rate

Heart rate in beasts per minute will also be measured to report vital signs

Time frame: From enrollment until 15 months of age

Vital signs: Body temperature

Body temperature in Celsius degree will also be measured to report vital signs

Time frame: From enrollment until 15 months of age

Standard adverse events (AEs) reporting for safety assessment

Reported adverse events (AEs) and Serious Adverse Events (SAEs) include type, incidence, severity, seriousness and relation to feeding

Time frame: From the time the informed consent form has been signed at enrollment infant age less than 21 days or 0.75 months through the 2 weeks post-study telephone contact at infant age 464 days

Bone index measurement

Bone index measurement will be conducted using a non-invasive and radiation-free ultra-sound sonometer measuring bone transmission time and speed of sound at the radius and tibia site, including also the measurement of the femur and radius length

Time frame: From enrollment until 15 months of age

Dietary pattern

Dietary pattern will be evaluated using a Food frequency questionnaire including sixteen key food groups for infants and young children

Time frame: From 6 months of age until 15 months of age