Starter Infant Formula With Synbiotics

Study Overview
=================
Brief Summary
-----------------
This randomized, double-blind, controlled intervention trial aims to evaluate the safety and efficacy of a starter infant formula supplemented with a blend of 7 HMOs, MOS and B. infantis and will provide evidence on the safety and efficacy of the innovative prebiotic/ probiotic blend to support age-appropriate infant growth, a healthy gut microbiome, gastrointestinal (GI) tolerance and GI health, and immune development.

Official Title
-----------------
Safety and Efficacy of a Starter Infant Formula With Synbiotics: a Double-blind, Randomized, Controlled Trial

Conditions
-----------------
Healthy Infants

Intervention / Treatment
-----------------
* Other: Control 1st age starter infant formula
* Other: Experimental1st age starter infant formula


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Evidence of personally signed and dated informed consent document indicating that at least one of the infant's parent(s)/LAR(s), as per local regulation, have been informed of all pertinent aspects of the study. Infants whose parent(s)/LAR(s) have reached the legal age of majority in the countries where the study is conducted. Able to temporarily store stool samples in a household freezer. Infants whose parent(s)/LAR(s) are willing and able to comply with scheduled visits, and the requirements of the study protocol. Infants whose parent(s)/LAR(s) are able to be contacted directly by telephone throughout the study. Infants must meet all of the following inclusion criteria to be eligible for enrollment into the study: Healthy term infant (≥37 weeks of gestation). At enrollment visit, post-natal age ≥14 to ≤35 days / 0.75 - 1 month (date of birth = day 0) Birth weight ≥ 2500g and ≤ 4500g. 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(s) must have independently elected, before enrollment, not to breastfeed. For the breastfed group, infants must have been exclusively consuming breastmilk since birth (small amounts of other feedings allowed during the first three days of life before breastfeeding is well-established), and their parent(s)/LAR(s) must have made the decision to continue exclusively breastfeeding until at least 4 months of age. Exclusion Criteria: Infants with conditions requiring infant feedings other than those specified in the protocol. 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: Evidence of major congenital malformations (e.g., cleft palate, extremity malformation). Suspected or documented systemic or congenital infections (e.g., human immunodeficiency virus, cytomegalovirus, syphilis). 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 enrolment 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. Infants who are presently receiving or have received prior to enrolment 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. Currently participating or having participated in another interventional clinical trial since birth.

Ages Eligible for Study
-----------------
Minimum Age: 14 Days
Maximum Age: 35 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control formula group<br>The Control Formula group will receive 1st age infant formula exclusively for the first four months. | Other: Control 1st age starter infant formula<br>* A standard bovine milk-based term infant formula.<br>|
| Experimental: Experimental formula group<br>The Experimental Formula group will receive 1st age infant formula identical to Control formula, but supplemented with 7 HMOs, MOS and B. infantis exclusively for the first four months. | Other: Experimental1st age starter infant formula<br>* Same content as Control formula plus supplemented 7 HMOs, MOS and B. infantis.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of experimental formula demonstrated by growth | Weight gain comparison between infants from experimental and control group | Baseline Visit 1 to 4 months of age Visit 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of experimental formula demonstrated by fecal sIgA concentration. | Concentration of sIgA in fecal samples | Baseline Visit 1 to 4 months of age Visit 5 | 
| Fecal microbiome | Fecal microbiota modulating effect | Baseline Visit 1 to 6 month of age Visit 6 | 
| Fecal metabolic profile | Fecal pH, fecal organic acids measurement from fecal samples | Baseline Visit 1 to 6 month of age Visit 6 | 
| Immune health and gut barrier function | Fecal markers and cytokine profile from fecal samples | Baseline Visit 1 to 6 month of age Visit 6 | 
| Gut barrier function | Fecal markers and cytokine profile from fecal samples | Baseline Visit 1 to 6 month of age Visit 6 | 
| Blood markers of systemic immunity | Immunotyping and plasma immune proteomics and Vaccine specific antibodies measurement from blood samples | Baseline Visit 1 to 4 months of age Visit 5 | 
| 3-day GI Symptom and Behavior Diary | GI tolerance, GI symptoms and GI-related behaviors | Baseline Visit 1 to 6 month of age Visit 6 | 
| Infant Gastrointestinal Symptom Questionnaire (IGSQ-13) Index questionnaire | GI tolerance, GI symptoms and GI-related behaviors | Baseline Visit 1 to 6 month of age Visit 6 | 
| Weight (g) | Anthropometric measurement. Weight and height will be combined to report BMI in kg/m^2 | Baseline Visit 1 to 6 month of age Visit 6 | 
| Length (cm) | Anthropometric measurement. Weight and height will be combined to report BMI in kg/m^2 | Baseline Visit 1 to 6 month of age Visit 6 | 
| Head circumference (cm) | Anthropometric measurement | Baseline Visit 1 to 6 month of age Visit 6 | 
| Respiration | Vital signs | Baseline Visit 1 to 6 month of age Visit 6 | 
| Heart rate | Vital signs | Baseline Visit 1 to 6 month of age Visit 6 | 
| Body temperature | Vital signs | Baseline Visit 1 to 6 month of age Visit 6 | 
| Physical examination | Infant illness and infection outcomes | Baseline Visit 1 to 3 years of age Observational Follow Up Visit 5 | 
| Pediatric Immune System Index and Infant Illness Questionnaire | Infant illness and infection outcomes | Baseline Visit 1 to 3 years of age Observational Follow Up Visit 5 | 
| Antibiotic and antipyretic use | Concomitant medication reporting | Baseline Visit 1 to 6 month of age Phone visit 7 |