Preventive Effect of a Dietary Supplement With Two Probiotic Limosilactobacillus Reuteri Strains on Excessive Crying and Colic in Healthy Newborns.

Official title

Double-blind, Randomized Placebo-controlled Trial for the Preventive Effect of Limosilactobacillus Reuteri (L. Reuteri) on Excessive Crying and Colic in Healthy Infants.

Overview

This study aims to demonstrate that a dietary supplement, which contains two strains of the probiotic L. reuteri is safe, well tolerated and able to reduce the incidence of colic and excessive crying/fussiness in healthy infants. Additionally, the study aims to investigate if children with this probiotic supplement have better stool characteristics and a more beneficial composition of the fecal and skin flora than children given a placebo during the first 3 months of life.

Detailed description

This study is a double-blind, randomized, placebo-controlled trial conducted at UZ Brussel to evaluate the safety and preventive efficacy of a dietary supplement containing two probiotic strains of Limosilactobacillus reuteri on excessive crying and the development of infantile colic in healthy newborns.

Recent systematic reviews and meta-analyses have shown that supplementation with certain strains of L. reuteri significantly reduces crying and fussing time in infants. A novel formulation combining those strains was developed to achieve a potentially enhanced effect on infant distress symptoms. This study investigates whether early supplementation, initiated within the first week of life, is safe and effective during the first three months of life.

Healthy, full-term infants (≥37 weeks' gestation) aged 1-14 days at inclusion are eligible. Participants are randomized to receive either placebo plus vitamin D (400 IU) or L. reuteri plus vitamin D (400 IU) for a maximum of 98 days, until approximately 3 months of age.

Study visits include a baseline visit (day 1-14), a midway visit at 6 weeks, an end-of-intervention visit at 3 months, and a long-term follow-up at 1 year. Additional telephone contacts are triggered by infant day diaries.

The primary outcomes are peak crying and fussing time at 6 weeks of age and the occurrence of infantile colic during the first 3 months of life. Secondary outcomes include infant quality of life (ITQOL™), parental stress, parental satisfaction, crying and fussiness patterns, and the presence of atopic dermatitis. Exploratory outcomes assess changes in the intestinal microbiome, stool characteristics, biomarkers, growth, and allergy-related parameters.

The primary hypothesis is that daily supplementation with the two strains of L. reuteri reduces the incidence of infantile colic and peak crying time at 6 weeks. Secondary hypotheses propose microbiome modulation leading to reduced distress, improved infant quality of life, and lower parental stress.

Interventions

• Dietary supplement Two probiotic Limosilactobacillus reuteri strains
  Each participant in this intervention group gets 5 drops per day, containing the two probiotic Limosilactobacillus reuteri strains and 400 IU of Vitamin D
• Dietary supplement Placebo
  Each participant in this intervention group gets 5 drops per day, containing only 400 IU of Vitamin D.

Primary outcome measures

• Peak measured crying time [Time frame: 6 weeks]
• The occurrence of infant colic at any time in the first 3 months of life. [Time frame: 3 months]

Secondary outcome measures (7)

• Peak measured fussiness time [Time frame: 6 weeks]
• Overall crying and/or fussiness time [Time frame: 3 months]
• Overall unconsolable crying time [Time frame: 3 months]
• Parental stress [Time frame: 3 months]
• Quality of Life score [Time frame: 12 months]
• Parental satisfaction [Time frame: 3 months]
• Atopic dermatitis [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Infant is born at the maternity ward of UZ Brussel with a gestational age of ≥37 weeks.
• Infant is healthy at the time of pre-examination.
• Infant is aged between 1 and 14 days old at the time of inclusion.
• Legal guardian(s) are able and willing to follow the study instructions
• Infant is suitable for participation in the study according to the investigator/ study personnel
• Legal guardian(s) willing to refrain products containing probiotics for their infant, from baseline (visit 1) throughout the study period (visit 3).
• Informed written consent given by parent / legal guardian

Exclusion criteria

• No legal guardian's command of any local language
• Infant with a major congenital anomaly (i.e. anal atresia, trisomy 21) or suspicion of any chronic disorder or disease (i.e. Hirschsprung's disease, metabolic disorder)
• Infant is suffering from congenital or acquired immunodeficiency
• Infant is suffering from an infection at the time of pre-examination or previous 7 days
• Infant is admitted post-partum to the neonatal intensive care unit
• Infant is not suitable for participation in the study according to the study personnel´s opinion

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Belgium · 1 center

• Universitair Ziekenhuis Brussel — Jette

Identifiers

NCT: NCT07347743 · Prot-Prev

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗