Clinical trial NCT04880083: Feeding Tolerance and Gut Maturation of Infants Consuming a Formula Rich in Glycoprotein
Official title: Feeding Tolerance and Gut Maturation of Infants Consuming a Formula Rich in Glycoprotein: A Single-arm, Open-label, Prospective Interventional Study Including a Breastfed Reference Group
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Digestion
Gut Microbiota
Keywords: gut tolerance
gut microbiota
gut immunity
Lead sponsor: Société des Produits Nestlé (SPN)
Sponsor class: INDUSTRY
Collaborators: name: Medrio, Inc
name: SAS Institute
name: Veeva Systems
First posted: 2021-05-10
Enrollment: 120
Sex: ALL
Minimum age (years): 3
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This is a non-randomized, single-arm, open-label, prospective interventional study using a commercially available starter infant formula in healthy term formula-fed infants with a parallel group of healthy term breast-fed infants as reference group. Approximately 120 male and female infants (60 per group) who are 3-28 days old and are exclusively or predominately formula-feeding or breastfeeding will be enrolled.

Detailed description: Breastmilk contains an abundance of structurally diverse compounds having important physiologic roles. These include glycoproteins which are biologically active and involved in infant gut, immune and brain development (Jiang and Lönnerdal 2016).

The overall purpose of this study is to study the effectiveness of a term infant formula rich in glycoprotein (formula-fed group) on gastrointestinal tolerance, and gastrointestinal health in healthy term infants compared to a breast-fed reference group. We hypothesize that there will be comparable gastrointestinal tolerance in formula-fed and breast-fed and that fecal bifidobacteria changes in early infancy in the formula-fed group are similar to that of breast-fed infants.

Eligibility criteria: Inclusion Criteria:

1. Evidence of personally signed and dated informed consent document indicating that the infant's parent(s)/ legally accepted representatives LAR have been informed of all pertinent aspects of the study.
2. Infants whose parent(s)/LAR have reached the legal age of majority in the countries where the study is conducted.
3. Infants whose parent(s)/LAR are willing and able to comply with scheduled visits, and the requirements of the study protocol.
4. Infants whose parent(s)/LAR can be contacted directly by telephone throughout the study.
5. Infants whose parent(s)/LAR have a working freezer.
6. Infants must meet all the following inclusion criteria to be eligible for enrolment into the study:

   * Healthy term infant (37-42 weeks of gestation).
   * At enrolment visit, post-natal age 3-28 days (date of birth = day 0)
   * Birth weight ≥ 2500g and ≤ 4500g.
   * Formula-fed infants only: Infants must predominantly consume and tolerate a standard cow's milk infant formula prior to enrolment and their parent(s)/LAR must have independently elected, before enrolment, not to exclusively breastfeed. Predominantly formula feeding means that the infant's predominant source of nourishment has been formula. Specifically, infants are fed with formula for at least 75% of total milk feeds per day.
   * Breastfed infants only: Infants must have been predominantly breastfed since birth, and their parent(s)/LAR must have made the decision to continue predominant breastfeeding for the duration of the study. Predominant breastfeeding allows infants to be mix fed with breastmilk and other milks. It means that the infant's predominant source of nourishment has been breastmilk. Specifically, infants are fed with breast milk for at least 75% of total milk feeds per day.

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:

   * Evidence of major congenital malformations (e.g., cleft palate, extremity malformation).
   * 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.
4. Infants who are presently receiving or have received prior to enrollment probiotic supplements or 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 and microbiota (e.g., oral and systemic antibiotics, glycerin suppositories, bismuth-containing medications, docusate, Maltsupex, or lactulose); growth (e.g. insulin or growth hormone); gastric acid secretion.
5. Currently participating or having participated in another clinical trial since birth.
6. Subjects or subjects' parent(s) or legal representative who are not willing and not able to comply with scheduled visits and the requirements of the study protocol.

Primary outcomes:
measure: Overall gastrointestinal (GI) tolerance
timeFrame: Day 39-45
Secondary outcomes:
measure: Change in Bifidobacteria abundance
timeFrame: Day 1, Day 36-44
measure: Fecal microbiota
timeFrame: Day 1, Day 36-44
measure: Fecal metabolism
timeFrame: Day 1, Day 36-44
measure: GI immunity assessed from fecal markers
timeFrame: Day 1, Day 36-44
measure: GI maturation assessed from fecal markers
timeFrame: Day 1, Day 36-44
measure: Stool characteristics: Stool frequency
timeFrame: Day 0, Day 36-44
measure: Stool characteristics: Difficulty in passing stool
timeFrame: Day 0, Day 36-44
measure: Stool characteristics: Stool consistency
timeFrame: Day 0, Day 36-44
measure: GI-related behaviors: Stooling
timeFrame: Day 0, Day 39-45
measure: GI-related behaviors: Incidence of spitting-up
timeFrame: Day 0, Day 39-45
measure: GI-related behaviors: Crying time
timeFrame: Day 0, Day 39-45
measure: GI-related behaviors: Fussiness
timeFrame: Day 0, Day 39-45
measure: GI-related behaviors: Incidence of flatulence
timeFrame: Day 0, Day 39-45
measure: Milk intake (Breast-Fed infants)
timeFrame: Day 0, Day 36-44
measure: Milk intake (Formula-Fed infants)
timeFrame: Day 0, Day 36-44
measure: Infant quality of life
timeFrame: Day 0, Day 39-45
measure: Growth: Weight of the infant
timeFrame: Day 0, Day 39-45
measure: Growth: Length of the infant
timeFrame: Day 0, Day 39-45
measure: Growth: Weight-for-length of the infant
timeFrame: Day 0, Day 39-45
measure: Growth: Head circumference of the infant
timeFrame: Day 0, Day 39-45
measure: Growth: Body mass index (BMI) of the infant
timeFrame: Day 0, Day 39-45
measure: Safety assessment: Infant illness
timeFrame: Day 0 through 14 days after Day 39-45
measure: Safety assessment: Infection outcomes
timeFrame: Day 0 through 14 days after Day 39-45
measure: Safety assessment: Medication use
timeFrame: Day 0 through 14 days after Day 39-45
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
Study officials:
affiliation: Shanghai Institute for Pediatric Research at Xinhua Hospital, Shanghai Jiao Tong University
name: Ying Wang
role: PRINCIPAL_INVESTIGATOR
References: