Growth, Safety and Efficacy of a Probiotic Supplement (Clara)

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

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

Study Overview

• Status: Completed
• Conditions: Probiotic Supplement
• Intervention / Treatment: Other: High dose probiotic supplement; Other: Low dose probiotic supplement; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 228
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Philippines
  • Muntinlupa, Philippines, 1781
    • Asian Foundation for Tropical Medicine, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 weeks to 3 weeks (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 access to a working freezer.

6. Infants must meet all the following inclusion criteria to be eligible for enrolment into the study:

   1. Healthy term (37-42 weeks of gestation) infant at birth.
   2. At enrolment visit, post-natal age 14-21 days (date of birth = day 0)
   3. Birth weight ≥ 2500g and ≤ 4500g.
   4. 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.
   5. 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:

1. Infants with conditions requiring specific infant feeding regimens 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:

   1. Evidence of major congenital malformations (e.g., cleft palate, extremity malformation).
   2. Suspected or documented systemic or congenital infections (e.g., human immunodeficiency virus, cytomegalovirus, syphilis).
   3. History of admission to the Neonatal Intensive Care Unit (NICU), except for admission for jaundice phototherapy.
   4. 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.
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 (e.g., 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group 1; High dose probiotic supplement and maltodextrin as the excipient	Other: High dose probiotic supplement; 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.
Experimental: Experimental Group 2; Low dose probiotic supplement and maltodextrin as the excipient	Other: Low dose probiotic supplement; 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.
Placebo Comparator: Control Group; Placebo supplement containing only maltodextrin but having the same appearance as the probiotic supplements	Other: Placebo; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional growth parameters: weight	Weight in grams and corresponding weight-for-age Z-score according WHO growth standards	Day 0, Day 28, Day 56
Additional growth parameters: length	Length in centimeters and corresponding length-for-age Z-score according WHO growth standards	Day 0, Day 28, Day 56
Additional growth parameters: head circumference	Head circumference in centimeters and corresponding head circumference-for-age Z-score according WHO growth standards	Day 0, Day 28, Day 56
Additional growth parameters: body mass index	BMI and corresponding BMI-for-age Z-score according WHO growth standards	Day 0, Day 28, Day 56
Fecal microbiome composition	Overall fecal microbiota composition, diversity, and microbiota community types will be assessed using NGS technology (including relative abundance of beneficial bifidobacteria bacteria species and pathogenic bacteria species) and	Day 0, Day 28, Day 56
Bifidobacteria colonization	Bifidobacteria colonization using a newly developed rapid diagnostic kit	Day 0, Day 28, Day 56
Fecal microbiome: Continuation of bifidobacteria colonization	Continuation of bifidobacteria colonization 4 weeks after intervention stop using NGS technology and DNAFoil® technology	Day 84
Fecal metabolic profile: Fecal pH	Fecal pH	Day 0, Day 28, Day 56
Fecal metabolic profile: Fecal organic acids	Fecal organic acids (such as, but not restricted to lactate, propionate, butyrate, acetate, valerate, and total fecal organic acids)	Day 0, Day 28, Day 56
Fecal metabolic profile: gut microbiota-derived metabolites	Concentration of gut microbiota-derived metabolites using mass spectrometry and/or nuclear magnetic resonance	Day 0, Day 28, Day 56
Biological response of selected fecal metabolites	Biological response using cultured cell lines or combinations of cell lines (Cell-based functional assays)	Day 0, Day 28, Day 56
Fecal markers of immune health and gut barrier	Total secretory IgA, calprotectin, and α-1-antitrypsin assessed by ELISA and Fecal cytokine levels (such as, but not restricted to: IL-1ra, IL-1α, IL-1β, IL-6, IFN- γ, and TNF-α) will be measured by multiplex assays	Day 0, Day 28, Day 56
GI tolerance	Infant Gastrointestinal Symptom Questionnaire (IGSQ-13) Index Score for overall GI tolerance calculated from the IGSQ-13	Day 0, Day 28, Day 56
GI-related behaviors: Stool frequency	GI endpoints will be recorded via the 1-day and 3-day GI Symptom and Behavior Diary	Day 0, Day 25-27, Day 53-55
GI-related behaviors: Stool consistency	Stool consistency using a validated 5-point scale in the 1-day and 3-day GI Symptom and Behavior Diary	Day 0, Day 25-27, Day 53-55
GI-related behaviors: Incidence of spitting-up	Incidence of spitting-up using a Likert scale via the 1-day and 3-day GI Symptom and Behavior Diary	Day 0, Day 25-27, Day 53-55
GI-related behaviors: Incidence of flatulance	Flatulence of spitting-up using a Likert scale via the 1-day and 3-day GI Symptom and Behavior Diary	Day 0, Day 25-27, Day 53-55
GI-related behaviors: Crying time	Crying time (hours/min) via the 1-day and 3-day GI Symptom and Behavior Diary	Day 0, Day 25-27, Day 53-55
GI-related behaviors: Sleep time	Sleep time (hours/min) using a Likert scale via the 1-day and 3-day GI Symptom and Behavior Diary	Day 0, Day 25-27, Day 53-55

Collaborators and Investigators

• Sponsor: Société des Produits Nestlé (SPN)

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2021
• Primary Completion (Actual): August 23, 2021
• Study Completion (Actual): October 12, 2021

Study Registration Dates

• First Submitted: November 12, 2020
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 20.11.INF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No