Clinical trial NCT04733937: Comparative Effects of A2 Platinum Stage 1 Infant Formula on Infant Digestion and Comfort
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Infants
Lead sponsor: a2 Milk Company Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai First Maternity and Infant Hospital
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Edanz Group Japan Ltd
name: Women & Children's Health Care Hospital of Linyi, China
name: Beijing Esmile Technology Co. Ltd.
name: Nanjing Maternity and Child Health Care Hospital
name: First Teaching Hospital of Tianjin University of Traditional Chinese Medicine
name: Second Hospital of Jilin University
First posted: 2021-02-02
Enrollment: 180
Sex: ALL
Minimum age (years): 0
Maximum age (years): 76
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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".

Eligibility criteria: Inclusion Criteria:

1. 0-76 days of age after birth, inclusive (day of birth is considered day 0)
2. Singleton birth
3. Gestational age of 37-42 weeks (36 weeks and six days is considered 36 weeks gestational age)
4. Birth weight of 2,500 g to 4,500 g
5. Signed informed consent obtained for infant's participation in the survey
6. Parent or guardian of infant agrees not to enrol infant in another interventional clinical survey while participating in this survey
7. 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:

1. 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)
2. Diseases jeopardizing intrauterine growth
3. Known or increased risk of IgE-mediated cow's milk protein allergy

   1. (i.e. one of the biological parents and/or siblings diagnosed with similar allergy,
   2. asthma, hay fever, etc.)
4. Infant with an acute infection or gastroenteritis at time of randomization
5. Evidence of feeding difficulties or formula intolerance, such as vomiting or poor intake at time of randomization
6. Participation in another clinical trial
7. 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)
8. 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:

1. Ineligibility (either arising during the trial or retrospectively having been overlooked at screening)
2. Significant protocol deviation
3. Significant non-compliance with product regimen or trial requirements
4. 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
5. Disease progression which requires discontinuation of the trial product or results in inability to continue to comply with trial procedures
6. Withdrawal of Consent
7. Lost to follow up
8. Weight at Visit 2 is \<95% of birth weight \[(weight at Visit 2÷birth weight) x 100 \<95%\]
9. Use of antibiotics, steroids or prebiotics/probiotics anytime between 14 days before baseline and trial completion
10. Participant whose mother has used any form of antibiotics or steroids while breastfeeding
11. More than 1 feed of formula milk per day for the breastfed group
12. More than 2 feeds of breast milk per day for the formula groups

Primary outcomes:
measure: Changes of crying frequency at each follow up visit compared to baseline
timeFrame: Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 days after baseline); Visit 4 (28 days after baseline)
measure: Changes of crying duration at each follow up visit compared to baseline
timeFrame: Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline)
measure: Changes in fecal MPO levels at each follow up visit compared to baseline
timeFrame: Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline)
Secondary outcomes:
measure: Changes in salivary cortisol levels at each follow up visit compared to baseline
timeFrame: Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline)
measure: Changes in body length
timeFrame: Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 days after baseline); Visit 4 (28 days after baseline)
measure: Changes in body weight
timeFrame: Visit 1 (screening/randomization); Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline)
measure: Changes in head circumference
timeFrame: Visit 1 (screening/randomization); Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline)
measure: Number of adverse events at each follow up visit compared to baseline
timeFrame: Visit 1 (screening/randomization); Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 day after baseline); Visit 4 (28 days after baseline)
measure: Abundance analysis of gut microflora species
timeFrame: Visit 2 (baseline [90-105 days since birth]); Visit 3 (14 days after baseline); Visit 4 (28 days after baseline)
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing Maternity and Child Health Care Hospital
state: Jiangsu
city: Changchun
country: China
facility: Second Hospital of Jilin University
state: Jilin
city: Linyi
country: China
facility: Women & Children's Health Care Hospital of Linyi, China
state: Shandong
city: Shanghai
country: China
facility: Shanghai First Maternity and Infant Hospital
state: Shanghai
city: Tianjin
country: China
facility: First Teaching Hospital of Tianjin University of Traditional Chinese Medicine
state: Tianjin
Study officials:
affiliation: Shanghai First Maternity and Infant Hospital
name: Jiangqin Liu, MD
role: PRINCIPAL_INVESTIGATOR
References: