Effect of Probiotics on Infant's Fecal Microbiota Composition (BABYCARE)

Safety, Tolerability and Effect on Fecal Microbiota Composition of Two Probiotic Strains in Infants

Randomized clinical trial to evaluate the effect of two probiotic strains which belong to Bifidobacterium Longum and Pediococcus pentosaceus species on fecal microbiota composition in healthy infants. Secondary outcomes comprise evaluation of anthropometric growth, digestive tolerance, sleeping habits, incidence of functional gastrointestinal disorders, incidence of gastrointestinal and respiratory infections, allergic reactions and safety and tolerability of the product.

Study Overview

• Status: Recruiting
• Conditions: Microbial Colonization
• Intervention / Treatment: Dietary supplement: Food Supplement 1; Dietary supplement: Food Supplement 2; Dietary supplement: Placebo

Detailed Description

Double-blind, randomized, placebo-controlled clinical trial to determine the effect of the probiotic strains Bifidobacterium longum and Pediococcus pentosaceus on fecal microbiota composition in infants. Healthy babies with ages comprised between 60 and 90 days who meet inclusion and exclusion criteria will be randomized 1:1:1 to one of the following study groups: one group will receive Bifidobacterium longum, another group will receive Pediococcus pentosaceus and the other one will receive placebo for 3 months. Other study outcomes comprise anthropometric growth, frequency and consistency of the stools, digestive tolerance, wellbeing, number, type and duration of infections and functional gastrointestinal disorders, and adverse events.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gerardo Rodríguez Martínez, MD; Phone Number: +34 654633910; Email: gerard@unizar.es
• Study Contact Backup: Name: Meritxell Aguilo Garcia, PhD; Phone Number: +34902903844; Email: aguilo@ab-biotics.com

Study Locations

• Spain
  • Aragón
    • Zaragoza, Aragón, Spain, 50012
      • Recruiting
      • Clínica Viamed Montecanal
      • Contact: Gerardo Rodríguez Martínez, MD; Phone Number: +34 654633910; Email: gerard@unizar.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy infants
• Age between 60 and 90 days
• Gestational age between 37 and 42 weeks
• Appropiate birth weight for gestational age (between P10 and P90)
• APGAR test score for birth normal at 1' and 5' of 7-10
• Whose parents accept the follow-up of the study procedures and sign the informed consent

Exclusion Criteria:

• Infants participating in other clinical study
• Fed with infant formula containing probiotics or other aliments or food supplement based in probiotics 4 weeks prior the start of the study
• Infants who have taken antibiotics 4 weeks prior the start study
• Infants with cow's milk protein allergy, lactose intolerance or other digestive diseases
• Mother's pathological background and during gestation: neurologic disorders, matabolopaties, diabetes mellitus type 1, chronic disease (hypothyroidism), maternal malnutrition
• Acute congenital or acquired diseases which can interfere with the growth and the normal feeding of the infant
• TORCH complex infections
• Every other diseases related with the immune system
• Parents who can not accomplish the follow-up of the study (medical criterium)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental 1; Probiotic single strain formulation comprising Bifidobacterium longum CECT7894 in liquid format suspended in sunflower oil. This probiotic strain has Qualified Presumption of Safety (QPS) status by European Food Safety Authority.	Dietary supplement: Food Supplement 1; Probiotic single strain formulation containing Bifidobacterium longum CECT7894 for 3 months 5 drops/day
Experimental: Experimental 2; Probiotic single strain formulation comprising Pediococcus pentosaceus CECT8330 in liquid format suspended in sunflower oil. This probiotic strain has Qualified Presumption of Safety (QPS) status by European Food Safety Authority.	Dietary supplement: Food Supplement 2; Probiotic single strain formulation containing Pediococcus pentosaceus CECT8330 for 3 months 5 drops/day
Placebo Comparator: Placebo; Sunflower oil	Dietary supplement: Placebo; 5 drops/day for 3 months of sunflower oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Bifidobacterium longum and Pediococcus pentosaceus in feces	Change of total counts of Bifidobacterium longum and Pediococcus pentosaceus in feces determined by qPCR	day 0, month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight change	Change in weight (g per day) between day 0 and month 3	day 0, month 1, month 2, month 3
Length change	Change in length (cm) between day 0 and month 3	day 0, month 1, month 2, month 3
Head circumference change	Change in head circumference (cm) between day 0 and month 3	day 0, month 1, month 2, month 3
BMI change	Change in BMI (kg/m2) between day 0 and month 3	day 0, month 1, month 2, month 3
Frequency of depositions	Frequency of depositions (number stools/day) documented in participants diary	day 0, month 1, month 2, month 3
Consistency of stools	Consistency of stools through a 5-item scale: 1= hard balls, 2=hard-formed, 3=soft-formed, 4=half liquid and 5=liquid	day 0, month 1, month 2, month 3
Infant colic	Incidence of infant colic, defined as prolonged and recurrent periods of crying, agitation, or irritability without apparent cause that cannot be prevented or resolved by your caregivers, for three or more hours daily for three or more days a week	day 0, month 1, month 2, month 3
Vomiting	Incidence of vomiting (n/day)	day 0, month 1, month 2, month 3
Sleeping habits	Nocturnal sleeping (min/day), total sleeping hours (min/day)	day 0, month 1, month 2, month 3
Incidence of infections	Number and duration (in days) of any type of infectious episodes	day 0, month 1, month 2, month 3
Fever	Number of days with fever (axial body temperature higher than 37.5 ºC)	day 0, month 1, month 2, month 3
Antibiotics	Number of days with antibiotic treatment	day 0, month 1, month 2, month 3
Change in fecal microbiota composition	Analysis of α y β biodiversity, relative abundance of bacteria determined by 16S sequencing	day 0, month 3
sIgA in stool samples	Analysis of secretory Immunoglobulin A (sIgA) in stools through ELISA	day 0, month 3
Calprotectin	Analysis of fecal calprotectin through ELISA	day 0, month 3

Collaborators and Investigators

• Sponsor: AB Biotics, SA
• Collaborators: Centre for the Development of Industrial Technology, Ministry of Science and Innovation, Spain

Publications and helpful links

General Publications

• Chen K, Liu C, Li H, Lei Y, Zeng C, Xu S, Li J, Savino F. Infantile Colic Treated With Bifidobacterium longum CECT7894 and Pediococcus pentosaceus CECT8330: A Randomized, Double-Blind, Placebo-Controlled Trial. Front Pediatr. 2021 Sep 10;9:635176. doi: 10.3389/fped.2021.635176. eCollection 2021.
• Hoy-Schulz YE, Jannat K, Roberts T, Zaidi SH, Unicomb L, Luby S, Parsonnet J. Safety and acceptability of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 in Bangladeshi infants: a phase I randomized clinical trial. BMC Complement Altern Med. 2016 Feb 2;16:44. doi: 10.1186/s12906-016-1016-1.
• Radke M, Picaud JC, Loui A, Cambonie G, Faas D, Lafeber HN, de Groot N, Pecquet SS, Steenhout PG, Hascoet JM. Starter formula enriched in prebiotics and probiotics ensures normal growth of infants and promotes gut health: a randomized clinical trial. Pediatr Res. 2017 Apr;81(4):622-631. doi: 10.1038/pr.2016.270. Epub 2016 Dec 21. Erratum In: Pediatr Res. 2018 Jan;83(1-1):190.
• Braegger C, Chmielewska A, Decsi T, Kolacek S, Mihatsch W, Moreno L, Piescik M, Puntis J, Shamir R, Szajewska H, Turck D, van Goudoever J; ESPGHAN Committee on Nutrition. Supplementation of infant formula with probiotics and/or prebiotics: a systematic review and comment by the ESPGHAN committee on nutrition. J Pediatr Gastroenterol Nutr. 2011 Feb;52(2):238-50. doi: 10.1097/MPG.0b013e3181fb9e80.
• Navarro-Tapia E, Sebastiani G, Sailer S, Toledano LA, Serra-Delgado M, Garcia-Algar O, Andreu-Fernandez V. Probiotic Supplementation During the Perinatal and Infant Period: Effects on Gut Dysbiosis and Disease. Nutrients. 2020 Jul 27;12(8):2243. doi: 10.3390/nu12082243.
• Castanet M, Costalos C, Haiden N, Hascoet JM, Berger B, Sprenger N, Grathwohl D, Brussow H, De Groot N, Steenhout P, Pecquet S, Benyacoub J, Picaud JC. Early Effect of Supplemented Infant Formulae on Intestinal Biomarkers and Microbiota: A Randomized Clinical Trial. Nutrients. 2020 May 20;12(5):1481. doi: 10.3390/nu12051481.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: August 26, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Microbiota; Probiotics; Infants
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: AB-BABYCARE-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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