Growth, Safety and Efficacy of a Probiotic Supplement

Study Overview
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Brief Summary
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The primary objective of the study is to demonstrate the safety of a daily high dose of a probiotic supplement by comparing the growth (weight gain, g/day) of formula-fed and/or breastfed infants in high dose group versus placebo group from enrolment to 8 weeks of intervention

Detailed Description
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This is a randomized, placebo-controlled, double-blind study of healthy term infants, consisting of three randomized arms: placebo control group, high dose experimental group, and low dose experimental group. The study population, approximately 228, are infants 14 - 21 days of age who are formula-fed and/or breastfed who is aligned with the intended target population for a probiotic supplement. Placebo and probiotic supplements will be mixed with formula or breastmilk and fed orally using a feeding cup or syringe. All enrolled infants will participate in the trial for approximately 8 weeks.

Official Title
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Growth, Safety and Efficacy of a Probiotic Supplement: a Double-blind, Randomized, Placebo-controlled Trial

Conditions
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Probiotic Supplement

Intervention / Treatment
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* Other: High dose probiotic supplement
* Other: Low dose probiotic supplement
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Infants whose parent(s)/LAR have reached the legal age of majority in the countries where the study is conducted. Infants whose parent(s)/LAR are willing and able to comply with scheduled visits, and the requirements of the study protocol. Infants whose parent(s)/LAR can be contacted directly by telephone throughout the study. Infants whose parent(s)/LAR have access to a working freezer. Infants must meet all the following inclusion criteria to be eligible for enrolment into the study: Healthy term (37-42 weeks of gestation) infant at birth. At enrolment visit, post-natal age 14-21 days (date of birth = day 0) Birth weight ≥ 2500g and ≤ 4500g. Breastfed and/or formula-fed infants (including exclusively and mixed fed breast- and formula-fed infants) whose parent(s)/LAR intent not to change the feeding regimen until the study end at 8 weeks of intervention. Formula-fed infants and their parent(s)/LAR must have independently elected, before enrolment not to breastfeed and their infant must tolerate a standard cow's milk infant formula not containing any probiotics at time of enrolment. Exclusion Criteria: Infants with conditions requiring specific infant feeding regimens other than those specified in the protocol. 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. 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). History of admission to the Neonatal Intensive Care Unit (NICU), except for admission for jaundice phototherapy. 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. 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 (e.g., 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 clinical trial since birth.

Ages Eligible for Study
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Minimum Age: 14 Days
Maximum Age: 21 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group 1<br>High dose probiotic supplement and maltodextrin as the excipient | Other: High dose probiotic supplement<br>* One probiotic stick pack will be dissolved in 10 mL lukewarm formula milk or breastmilk at body temperature. The dissolved supplement will be fed orally, preferably in the morning, starting on Day 1 until Day 56.<br>|
| Experimental: Experimental Group 2<br>Low dose probiotic supplement and maltodextrin as the excipient | Other: Low dose probiotic supplement<br>* One probiotic stick pack will be dissolved in 10 mL lukewarm formula milk or breastmilk at body temperature. The dissolved supplement will be fed orally, preferably in the morning, starting on Day 1 until Day 56.<br>|
| Placebo Comparator: Control Group<br>Placebo supplement containing only maltodextrin but having the same appearance as the probiotic supplements | Other: Placebo<br>* One placebo stick pack will be dissolved in 10 mL lukewarm formula milk or breastmilk at body temperature. The dissolved supplement will be fed orally, preferably in the morning, starting on Day 1 until Day 56.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of high dose probiotic supplement (weight gain) | Compare the growth (weight gain, g/day) of formula-fed and/or breastfed infants in EG 1 vs. CG from enrolment to 8 weeks of intervention | Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of two different doses of probiotic supplement | Bifidobacteria abundance measured in the fecal sample collected at home after 8 weeks of intervention (V3) analyzed by next generation sequencing (NGS) technology. | Day 0, Day 25-27, Day 53-55 |