Comparative Effects of a2 Platinum Stage 1 Infant Formula on Infant Digestion and Comfort

Study Overview
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Brief Summary
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This trial is a single-blind, randomized, controlled, parallel-designed trial to compare the effects of a2 Platinum® stage 1 infant formula versus conventional, A1 and A2 β-casein-containing stage 1 infant formula versus breastfeeding on crying, tolerance, gut health, and immune function.

Detailed Description
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The protocol was updated from V8.2 to V9.1 and was approved by the Ethical Committee of Shanghai First Maternity and Infant Hospital, the main site. The major changes are: from blind to participants to non-blind to participants; from Single-Centre to Multi-Centre; number of subjects from 270 to 180; trial period from 3 weeks to 4 weeks; and number of visits from 6 to 4.

Official Title
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Protocol Title: Comparative Effects of a2 Platinum® Stage 1 Infant Formula Versus Conventional Stage 1 Infant Formula Containing A1 and A2 β-casein Versus Breast Feeding on Infant Digestion and Comfort: A Single-blind Randomized Controlled Trial

Conditions
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Healthy Infants

Intervention / Treatment
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* Other: a2 Platinum® stage 1 infant formula
* Other: Conventional, A1 and A2 β-casein containing stage 1 infant formula


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 0-76 days of age after birth, inclusive (day of birth is considered day 0) Singleton birth Gestational age of 37-42 weeks (36 weeks and six days is considered 36 weeks gestational age) Birth weight of 2,500 g to 4,500 g Signed informed consent obtained for infant's participation in the survey Parent or guardian of infant agrees not to enrol infant in another interventional clinical survey while participating in this survey Parent or guardian agrees to formula-feed the baby as per the randomization schedule For the formula-fed groups, participants in addition to the above-listed criteria, must also meet the following criterion: - Parent or guardian agrees that the baby will be fed with standardized formula upon enrolment and switched to randomized formula at baseline (90-105 days of age) For the breastfed group, participants in addition to the above-listed criteria, must also meet the following criterion: - Parent or guardian agrees that the baby will be breast-fed Exclusion Criteria: Infant with inborn malformation and with hereditary and/or chronic and/or inborn diseases that could interfere with the survey (e.g. being unable to breast-feed or formula-fed) Diseases jeopardizing intrauterine growth Known or increased risk of IgE-mediated cow's milk protein allergy (i.e. one of the biological parents and/or siblings diagnosed with similar allergy, asthma, hay fever, etc.) Infant with an acute infection or gastroenteritis at time of randomization Evidence of feeding difficulties or formula intolerance, such as vomiting or poor intake at time of randomization Participation in another clinical trial Investigator's uncertainty about the willingness or ability of the parents to comply with the protocol requirements (including to fill in the diaries and to wait with introducing weaning foods until 4 months of age, and capability and willingness to do stool sample collection, handling, processing, and storage as instructed) Infant is immunocompromised (according to a doctor's diagnosis of immunodeficiencies such as combined immunodeficiencies, DiGeorge Syndrome, Wiskott-Aldrich syndrome, severe congenital neutropenia and secondary immunodeficiencies linked to HIV infection, Down Syndrome or others) and children with known head/brain disease/injury such as microcephaly, macrocephaly or others Exit Criteria: Ineligibility (either arising during the trial or retrospectively having been overlooked at screening) Significant protocol deviation Significant non-compliance with product regimen or trial requirements An adverse event (including one occurring before the start of the trial period) which requires discontinuation of the trial product or results in inability to continue to comply with trial procedures Disease progression which requires discontinuation of the trial product or results in inability to continue to comply with trial procedures Withdrawal of Consent Lost to follow up Weight at Visit 2 is <95% of birth weight [(weight at Visit 2÷birth weight) x 100 <95%] Use of antibiotics, steroids or prebiotics/probiotics anytime between 14 days before baseline and trial completion Participant whose mother has used any form of antibiotics or steroids while breastfeeding More than 1 feed of formula milk per day for the breastfed group More than 2 feeds of breast milk per day for the formula groups

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 76 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: a2 Group<br>The infant group consuming a2 Platinum® stage 1 infant formula | Other: a2 Platinum® stage 1 infant formula<br>* Upon randomization (if not included in the breastfed group), each participant will be provided with up to 105 days' supply of the standardized formula and up to 28 days' supply of the allocated formula. Participants and study investigators will conduct the trial via a pre-determined randomization schedule.<br>|
| Active Comparator: Control Group<br>The infant group consuming conventional, A1 and A2 β-casein containing stage 1 infant formula | Other: Conventional, A1 and A2 β-casein containing stage 1 infant formula<br>* Upon randomization (if not included in the breastfed group), each participant will be provided with up to 105 days' supply of the standardized formula and up to 28 days' supply of the allocated formula. Participants and study investigators will conduct the trial via a pre-determined randomization schedule.<br>|
| No Intervention: breast feeding<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of crying frequency at each follow up visit compared to baseline | Record frequency of crying (times/d) | Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 days after baseline); Visit 4 (28 days after baseline) | 
| Changes of crying duration at each follow up visit compared to baseline | Record duration of crying (min) | Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline) | 
| Changes in fecal MPO levels at each follow up visit compared to baseline | Record fecal MPO (in Unit) as markers of inflammation | Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in salivary cortisol levels at each follow up visit compared to baseline | Record salivary cortisol (nmol/L) as markers of immune function | Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline) | 
| Changes in body length | Differences in length gain (cm/d) | Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 days after baseline); Visit 4 (28 days after baseline) | 
| Changes in body weight | Differences in weight gain (kg/d) | Visit 1 (screening/randomization); Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline) | 
| Changes in head circumference | Differences in head circumference (cm/d) | Visit 1 (screening/randomization); Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline) | 
| Number of adverse events at each follow up visit compared to baseline | Record number of adverse events as a measure of safety and tolerability | Visit 1 (screening/randomization); Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline) | 
| Abundance analysis of gut microflora species | Differences in abundance of gut microflora species | Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 days after baseline); Visit 4 (28 days after baseline) |