Prevalence of FGIDs and Probiotics Study (PROOF)

Center of Excellence in Thai Pediatric Gastroenterology, Hepatology and Immunology

This is a study to evaluate the prevalence of FGIDs in infants using the Thai version of Rome IV diagnostic questionnaire for functional gastrointestinal disorders in infants and evaluate the efficacy of Limosilactobacillus reuteri DSM 17938 to prevent FGIDs in infants.

Study Overview

• Status: Recruiting
• Conditions: Functional Gastrointestinal Disorders; Infant Conditions
• Intervention / Treatment: Dietary supplement: Biogaia; Other: Placebo

Detailed Description

This is a randomized controlled trial study about the the efficacy of Lactobacillus reuteri DSM 1987 to prevent FGIDs in healthy infants and the effect to gut microbiota diversity. The incidence of FGIDs in Thai infant using Thai version of ROME IV questionnaire (authorized by Rome Foundation) for infant and toddler and the associated factors of FGIDs also evaluate.

Population: target and control populations are the healthy infants born at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, and can come to follow up at the hospital at 1, 2, 4, and 12 months of age Inclusion criteria

1. Healthy and term (GA 37-41 weeks) infants
2. Appropriate weight for age
3. APGAR score more than 8 at 10 minutes of life
4. Normal physical examination

5. Mothers have no previous probiotics use Methodology

   • Participants were double-blinded randomized using computer generation in block of four
   • Target population were received Limosilactobacillus reuteri DSM 17938 5 drops (0.185 mL) per day for 60 days
   • Control population were received mixture of sunflower oil and MCT oil 5 drop (0.185 mL) per day for 60 days
   • There were 5 visits at birth, 1, 2, 4, 12 months of life: the demographic data/Rome IV questionnaire for FGIDs in infant and associated factors with FGIDs record, physical examination and stool collection The study will be analyzed (open the randomized group) after all participants complete the 4-month follow-up period
   • Research assistance will telephone to them to take the Rome IV questionnaire for FGIDs at 3, 6, 9 months of life

Biological specimen collection Stool will be collected by rectal stimulation in each visit. The amount of >5 gm stool will be preserved in DNA and kept at -80 °C. All stool specimen will be processed the DNA extraction (DNA > 40 microlitre with concentration >50 ng/L). The DNA extraction for further amplification 16S rRNA using Illumina. The rest of the specimen will be kept up to 10 years for further evaluation.

• Study Type: Interventional
• Enrollment (Estimated): 512
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Palittiya Sintusek, PhD; Phone Number: +66818288082; Email: palittiya.s@chula.ac.th
• Study Contact Backup: Name: Sittichoke Prachuapthunyachart, MD; Phone Number: +66829740649; Email: sittichoke.p@chula.ac.th

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • Recruiting
    • Maha Chakri Sirindhorn Clinical Research Center (Chula CRC)
    • Contact: Phone Number: 02 251 6704

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy and term (GA 37-41 weeks) infants
2. Appropriate weight for age
3. APGAR score more than 8 at 10 minutes of life
4. Normal physical examination
5. Mothers have no previous probiotics use

Exclusion Criteria:

1. not willing to anticipate in the study
2. cannot come to follow-up until 1 year of age

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotics; Limosilactobacillus reuteri DSM 17938 with sunflower oil and MCT oil were packed into a container. Infants will received 5 drops per day in the morning for 60 +/- 20 days	Dietary supplement: Biogaia; Biogaia is a probiotics product that contain Limosilactobacillus reuteri DSM 17938, sunflower oil and MCT oil
Placebo Comparator: Placebo; Sunflower oit and MCT oil were paced into a container. Infants will received 5 drops per day in the morning for 60+/- 20 days	Other: Placebo; Limosilactobacillus reuteri DSM 17938, sunflower oil and MCT oil; Other Names: Sunflower oil + MCT oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The prevalence of functional gastrointestinal disorders in the treatment group	Functional gastrointestinal disorders (colic, regurgitation, constipation, dyschazia and rumination) were assessed using the Thai version of Rome IV diagnostic questionnaire for neonates and toddlers	at birth, 1 month, 2 months, 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The prevalence of functional gastrointestinal disorders in the placebo group	Functional gastrointestinal disorders (include colic, regurgitation, constipation, dyschazia and rumination) were assessed using the Thai version of Rome IV diagnostic questionnaire for neonates and toddlers	at birth, 1 month, 2 months, 4 months and 1 year (5-time points)
The prevalence of functional gastrointestinal disorders in the treatment group	Functional gastrointestinal disorders (colic, regurgitation, constipation, dyschazia and rumination) were assessed using the Thai version of Rome IV diagnostic questionnaire for neonates and toddlers	at 1 year of age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nutrition associated with functional gastrointestinal disorders in infants	Amount of food composition (carbohydrate, protein, lipid - present as gm per kg body weight)	at 1 year
The sleep quality assessed by Brief Infant Sleep Revise Questionnaire of BISQR	The questionnaire has 33 items in 3 main categories (Infant sleep, parent perception and parent behavior). Scores on each subscale and the total score are scaled from 0 to 100. Higher score denote better sleep quality.	at birth, 1 month, 2 months, 4 months and 1 year (5-time points)
Fluid intake associated with functional gastrointestinal disorders in infants	type of milk (breastfeeding or formula or mixed) and amount (mL per kg body weight)	at birth, 1 month, 2 months and 4 months and 1 year (5-time points)
Stress associated with functional gastrointestinal disorders in infants	stress in family (i.e divorce, family dept present as yes or no)	at birth and 1 year
Antibiotics associated with functional gastrointestinal disorders in infants	antibiotics use (yes or no)	at birth, 1 month, 2 months and 4 months and 1 year (5-time points)
Economic status associated with functional gastrointestinal disorders in infants	Economics status (income in baht)	at birth and 1 year
Education of caregiver associated with functional gastrointestinal disorders in infants	Education (low, high)	at birth and 1 year
Gut microbial profiles associated with functional gastrointestinal disorder in infants	Comparative metagenomic analysis of gut microbial profiles (diversity, relative abundance, species alteration) in fecal samples among different groups of infants	at birth, 1 month, 2 months, and 4 months
Stool metabolomic substances (i.e microbial conjugation of secondary bile acid, aminoacid) and the stool metabolites alteration	Fecal metabolomic substances (i.e microbial conjugation of secondary bile acid, aminoacid) were assesse using liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS) and capillary electrophoresis-mass spectrometry (CE-MS)	at birth, 1 month, 2 months and 4 months
Serious adverse effect during follow-up until end point	admission, cause of admission, treatment details (intravenous fluid, medication, oxygen supplementation)	1 month, 2 months, 4 months, 6 months, 9 months, 1 years
skin problems (seborrheic dermatitis, atopic dermatitis, nonspecific dermatitis)	patient oriented- Scoring atopic dermatitis (it is an application in phone to add the information of skin lesion by doctor or parent examination), examination and record the characteristics and location of skin lesion by doctors	1 month, 2 months, 4 months, 1 year

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Investigators: Study Director: Yong Poovorawan, MD, Center of Excellence in Clinical Virology

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): July 2, 2025
• Last Update Submitted That Met QC Criteria: June 28, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: prevalence; infant; constipation; functional gastrointestinal disorder; regurgitation; colic
• Additional Relevant MeSH Terms: Gastrointestinal Diseases; Digestive System Diseases
• Other Study ID Numbers: 0855/66

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The data were collected anonymous.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No