Second Generation Human Milk Oligosaccharides Blend Study

Healthy Infants Clinical Trial

Official title:

Growth, Safety and Efficacy of a Starter Infant Formula, Follow-up Formula, and Growing-up Milk Supplemented With a Blend of Five Human Milk Oligosaccharides: a Double-blind, Randomized, Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03722550
• Other study ID #: 1624INF
• Status: Completed
• Phase: N/A
• Start date: September 19, 2018
• Est. completion date: January 19, 2022

Study information

• Verified date: February 2022
• Source: Nestlé
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 789
• Est. completion date: January 19, 2022
• Est. primary completion date: November 5, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 21 Days

Eligibility

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

Related Conditions & MeSH terms

• Healthy Infants

Intervention

Other:
• Starter Infant Formula, Follow-up Formula, and Growing-up Milk Supplemented With a Blend of Five Human Milk Oligosaccharides
Study formulas are administered orally, ad libitum, from enrollment until 15 months of age
• Breast-feeding
Exclusive Breast-feeding up to 4 months of age
• Standard Starter Infant Formula, Follow-up Formula, and Growing-up Milk
Standard Study formulas are administered orally, ad libitum, from enrollment until 15 months of age

Locations

Country	Name	City	State
Bulgaria	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	Ruse
Bulgaria	Medical Center-1-Sevlievo EOOD	Sevlievo
Bulgaria	1st Pediatric Consultative Clinic	Sofia
Bulgaria	Alitera-Med-Medical Center EOOD	Sofia
Bulgaria	Medical Center Excelsior	Sofia
Bulgaria	Medical Centre - Izgrev EOOD	Sofia
Bulgaria	Diagnostic-consultative center Ritam TR'' OOD	Stara Zagora
Bulgaria	SMA Dr Stefan Banov	Stara Zagora
Hungary	Dr. Kenessey Albert Kórház-Rendelointézet Csecsemo és Gyermekosztály	Balassagyarmat
Hungary	Clinexpert Kft.	Budapest
Hungary	Clinexpert Gyöngyös Egészségügyi Szolgáltató Kft.	Gyöngyös
Hungary	Futurenest Kft.	Miskolc
Hungary	Kanizsai Dorottya Kórház Csecsemo és Gyermekgyógyászati Osztály	Nagykanizsa
Hungary	Házi Gyermekorvosi Rendelo / Babadoki Kft.	Szeged
Hungary	Mentaház Magánorvosi Központ Kft.	Székesfehérvár
Hungary	Csolnoky Ferenc Kórház	Veszprém
Poland	Poliklinika Ginekolo.-Poloznicza	Bialystok
Poland	Szpital Uniwersytecki nr 2	Bydgoszcz
Poland	Clinical Vitae Sp z o.o. Poradnia Podstawowej Opieki Zdrowotnej	Gdansk
Poland	Gdanskie Centrum Zdrowia Sp. Z o.o	Gdansk
Poland	Centrum Medyczne Plejady	Kraków
Poland	Centrum Medyczne PROMED	Kraków
Poland	Grazyna Jasieniak-Pinis ATOPIA Niepubliczny Zaklad Opieki Zdrowotnej Poradnie Specjalistyczne	Kraków
Poland	Uniwersytecki Szpital Dzieciecy w Lublinie	Lublin
Poland	Centrum Medyczne Pratia Ostroleka	Ostroleka
Poland	Centrum Innowacyjnych Terapii Sp. z o.o.	Piaseczno
Poland	Korczowski Bartosz Gabinet Lekarski	Rzeszów
Poland	ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. Z o.o	Tarnów
Poland	Centrum Medyczne Pratia Warszawa	Warsaw

Sponsors (1)

Lead Sponsor	Collaborator
Nestlé

Countries where clinical trial is conducted

Bulgaria,  Hungary,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	From Study Day 1 to 4 months of age
Primary	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)	From Study Day 1 to 15 months of age
Secondary	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)	at different stages of feeding 1st age Infant Formula, 2nd age Follow-up Formula, and 3rd age Growing-up Milk when applicable
Secondary	Medication use (specifically antimicrobials and antipyretics)	Medication type and duration of intake will be combined to report the medication use	From enrollment until 15 months of age
Secondary	Absenteeism: Time away from daycare (infant) or work (parent)	Time away from daycare (infant) or work (parent)	From enrollment until 15 months of age
Secondary	Fecal microbiome composition, diversity, community type	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	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)
Secondary	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)	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)
Secondary	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.	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)
Secondary	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	At 6 months of age
Secondary	Gastrointestinal tolerance	Stool patterns (stool frequency and consistency), Gastrointestinal symptoms, Gastrointestinal-related behaviors, and milk intake will be combined to report the gastrointestinal tolerance	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)
Secondary	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	At 15 months of age
Secondary	DNA Genotyping of fucosyltransferase 2 and 3 (secretor status)	Association between secretor status and illnesses/infections via microbiome modulation will be evaluated.	At Study Day 60 +/- 5 days
Secondary	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	At Study Day 90 +/- 5 days
Secondary	Anthropometric measurements: Weight	Weight measurements in grams to report anthropometric measurements.	From enrollment until 15 months of age
Secondary	Anthropometric measurements: Length	Length measurements in centimeters to report anthropometric measurements.	From enrollment until 15 months of age
Secondary	Anthropometric measurements: Head circumference	Head circumference measurements in centimeters to report anthropometric measurements.	From enrollment until 15 months of age
Secondary	Anthropometric measurements: BMI	BMI measurements in kg/m^2 to report anthropometric measurements.	From enrollment until 15 months of age
Secondary	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.	From enrollment until 15 months of age
Secondary	Vital signs: Infant respiration	Infant respiration in breaths per minute will also be measured to report vital signs	From enrollment until 15 months of age
Secondary	Vital signs: Heart rate	Heart rate in beasts per minute will also be measured to report vital signs	From enrollment until 15 months of age
Secondary	Vital signs: Body temperature	Body temperature in Celsius degree will also be measured to report vital signs	From enrollment until 15 months of age
Secondary	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	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
Secondary	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	From enrollment until 15 months of age
Secondary	Dietary pattern	Dietary pattern will be evaluated using a Food frequency questionnaire including sixteen key food groups for infants and young children	From 6 months of age until 15 months of age