Evolution of Functional Gastrointestinal Disorders in Infants Fed With a New Infant Formula

Assessment of the Evolution of functIonal Gastrointestinal Disorders in Infants During Their Dietary Management With a New Infant Formula

This study aims to assess the evolution of functional gastrointestinal disorders (FGIDs) in infants fed with a new infant formula, using the Gastrointestinal (GI) and gastroesophageal reflux (GER) (GIGER) scale through an interventional, open-label, non-comparative multicenter study.

Study Overview

• Status: Recruiting
• Conditions: Functional Gastrointestinal Disorders
• Intervention / Treatment: Dietary supplement: New infant formula

Detailed Description

The study comprises a first period of 30 days followed by an optional intervention period of 90 days.

• Study Type: Interventional
• Enrollment (Estimated): 139
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne-Sophie Garreau; Phone Number: 0033-155372222; Email: as.garreau@novalac.com
• Study Contact Backup: Name: Caroline Thevret, Dr.; Phone Number: 0033-155372222; Email: c.thevret@novalac.com

Study Locations

• France
  • Nice, France
    • Not yet recruiting
    • Site 02
  • Paris, France
    • Not yet recruiting
    • Site 04
  • Toulon, France
    • Recruiting
    • Site 03
  • Vincennes, France
    • Recruiting
    • Site 01

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Infants presenting with at least one of the FGIDs below, defined based on adapted Rome IV criteria as follows:

   1.1 Regurgitations: 1.2 Colic: 1.3 Constipation:

2. Infants born at 35 weeks or more of gestational age
3. Infants up to 4 months of age

Exclusion Criteria:

1. Exclusively or partially breastfed infants (i.e. > 2 breast feeds per day) with maternal willingness to continue breastfeeding
2. Diversified infants or whose parents intend to start diversification within the first 2 weeks of the study
3. Use of antibiotics at inclusion visit (V0) and within 7 days before the inclusion visit (V0)
4. The willingness to take additional pre-, probiotics or thickening agents during the study
5. Known allergy/intolerance to any of the product ingredients or suspected allergy to cow's milk requiring an eviction diet
6. Infants presenting with any other situation including the participation in another clinical trial, which, according to the investigator, may interfere with the study participation, or lead to a particular risk for the patient

(non exhaustive list)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test formula; The test product is a thickened infant formula containing symbiotic (fibers and probiotics)	Dietary supplement: New infant formula; The new formula will be given to infants during the 4-month study period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of the Gastrointestinal and Gastroesophageal Reflux (GIGER) scale score	The main outcome will be the evolution of the sum score of the Gastrointestinal and Gastroesophageal Reflux (GIGER) scale (Pados et al., 2021). The GIGER score varies from 0 to 180 being the worst.	Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of FGIDs (regurgitations, colic and constipation)	FGIDs such as regurgitation, colic and constipation will be assessed according to adapted Rome IV criteria. The improvement and complete resolution timeframe of each FGID present at inclusion and/or occurring during the study will be determined.	Day 14, Day 30, Day 60, Day 90, Day 120
Regurgitation frequency	The number of daily regurgitation episodes and the daily volume of regurgitation will be assessed on average over the last 3 days. The frequency of regurgitations away from meals and of continuous regurgitations of small volumes after feeding will be assessed on average over the last 3 days via a 4-point scale [Never; Rarely; Often; Always].	Day 7, Day 14, Day 30, Day 60, Day 90, Day 120
Regurgitation severity	The regurgitation severity will be assessed using the adapted Vandenplas regurgitation score (from 0 to 6 being the worst) (Vandenplas et al., 1994) over the last 3 days preceding each visit.	Day 14, Day 30, Day 60, Day 90, Day 120
Stool frequency and consistency in non constipated infant	If the infant is not constipated at inclusion and during the study, the average main stool consistency will be assessed based on the BITSS scale (Brussels Infant and Toddler Stool Scale) as well as the daily average number of stools over the last 3 days. The BITTS scale is a reliable instrument to assess stools of non-toilet trained children. It consists of 7 color photographs of diapers containing stools from infants and toddlers categorized as Hard, Formed, Loose, or Watery (Huysentruyt et al., 2019).	Day 7, Day 14, Day 30, Day 60, Day 90, Day 120
Stool frequency and consistency in constipated infant	If the infant is constipated at one visit during the study, the total number of each stool consistency will be assessed for the next visit based on the BITSS scale over the last 7 days. The total number of stools over the last 7 days will be calculated.	Day 7, Day 14, Day 30, Day 60, Day 90, Day 120
Defecation pain frequency in constipated infant	If the infant is constipated at one visit during the study, the frequency of defecation pain will be assessed for the next visit based on a 3-point scale (No; Yes, only 1 time; Yes, >1 time) over the last 7 days.	Day 7, Day 14, Day 30, Day 60, Day 90, Day 120
Colic	Colic will be assessed through unexplained crying duration and fussing/irritability duration on average over the last 3 days and reported based on a 4-point scale (< 1h; 1h-2h; 2h-3h; > 3h).	Day 7, Day 14, Day 30, Day 60, Day 90, Day 120
Gas/flatulence severity	Gas/flatulence severity will be assessed on average over the last 3 days using a visual analog scale (from 0=No symptom to 10=Very severe symptoms).	Day 7, Day 14, Day 30, Day 60, Day 90, Day 120
Abdominal distension severity	Abdominal distension is defined as a swollen, tense and hard to the touch stomach. Its severity will be assessed on average over the last 3 days using a visual analog scale (from 0=No symptom to 10=Very severe symptoms).	Day 7, Day 14, Day 30, Day 60, Day 90, Day 120
GIGER score	Evolution of Gastrointestinal and Gastroesophageal Reflux (GIGER) scale total score (from 0 to 180) and 3 subscores (subscore 1: from 0 to 75; subscore 2: from 0 to 65; subscore 3: from 0 to 40) from baseline. The higher the GIGER is, the worst the symptoms are.	Day 7, Day 14, Day 60, Day 90, Day 120
Investigator's evaluation of the evolution of FGIDs	The investigator will evaluate the evolution of each FGID (i.e. regurgitations, constipation, colic) using a 4-point scale (Improvement; Worsening; No evolution; Not applicable) over the past period.	Day 14, Day 30, Day 60, Day 90, Day 120
Number of bottles at night	The number of bottles at night will be recorded on average over the last 3 days.	D7, D14, D30, D60, D90, D120
Sleep	The average sleep duration will be reported over the last 3 days and sleep quality will be assessed using a visual analog scale (from 0= Difficult to fall asleep, frequent awakenings to 10= Easy and quick falling asleep, no awakenings without obvious cause).	Day 7, Day 14, Day 30, Day 60, Day 90, Day 120
Infant's quality of life	Parents will complete the QUALIN questionnaire (score from -68 to +68) (Manificat et al., 2000) over the last week.	Day 7, Day 14, Day 30, Day 60, Day 90, Day 120
Weight	Weight will be expressed in kg and in z scores according to the World Health Organization (WHO) Child Growth Standards.	Day 30, Day 60, Day 90, Day 120
Height	Height will be expressed in cm and in z scores according to the WHO Child Growth Standards.	Day 30, Day 60, Day 90, Day 120
Head circumference	Head circumference will be expressed in cm and in z scores according to the WHO Child Growth Standards.	Day 30, Day 60, Day 90, Day 120
BMI	BMI will be expressed in value and z scores according to the WHO Child Growth Standards.	Day 30, Day 60, Day 90, Day 120
Adverse events	Any untoward medical reaction occuring from the signatture of the consent until the end of the participant's participation	Through study completion (up to 30 days or 120 days if participation to the optional intervention period)
Parents' satisfaction	Parents' satisfaction will be assessed on the product use and acceptability using a 5-point Likert scale and more specifically on the evolution of each FGID (i.e. regurgitations, constipation, colic) using a 4-point scale (Improvement; Worsening; No evolution; Not applicable) over the past period.	Day 7, Day 14, Day 30, Day 60, Day 90, Day 120

Collaborators and Investigators

• Sponsor: United Pharmaceuticals
• Collaborators: Axiodis CRO
• Investigators: Study Director: Christophe Batard, Dr., Ambulatory pediatrician in Vincennes (France); Study Chair: Camille Jung, Prof., Centre Hospitalier Intercommunal (CHI) in Créteil (France)

Publications and helpful links

General Publications

• Manificat S, Dazord A, Langue J, Danjou G, Bauche P, Bovet F, Cubells J, Luchelli R, Tockert E, Conway K. [Evaluation of the quality of life of infants and very young children: validation of a questionnaire. Multicenter European study]. Arch Pediatr. 2000 Jun;7(6):605-14. doi: 10.1016/s0929-693x(00)80127-x. French.
• Pados BF, Repsha C, Hill RR. The Gastrointestinal and Gastroesophageal Reflux (GIGER) Scale for Infants and Toddlers. Glob Pediatr Health. 2021 Jul 14;8:2333794X211033130. doi: 10.1177/2333794X211033130. eCollection 2021.
• Vandenplas Y, Hachimi-Idrissi S, Casteels A, Mahler T, Loeb H. A clinical trial with an "anti-regurgitation" formula. Eur J Pediatr. 1994 Jun;153(6):419-23. doi: 10.1007/BF01983405.
• Huysentruyt K, Koppen I, Benninga M, Cattaert T, Cheng J, De Geyter C, Faure C, Gottrand F, Hegar B, Hojsak I, Miqdady M, Osatakul S, Ribes-Koninckx C, Salvatore S, Saps M, Shamir R, Staiano A, Szajewska H, Vieira M, Vandenplas Y; BITSS working group. The Brussels Infant and Toddler Stool Scale: A Study on Interobserver Reliability. J Pediatr Gastroenterol Nutr. 2019 Feb;68(2):207-213. doi: 10.1097/MPG.0000000000002153.

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: June 21, 2024
• First Submitted That Met QC Criteria: June 27, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 2, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Constipation; Infant formula; Nutrition; Infants; Colic; Regurgitations; GIGER scale
• Additional Relevant MeSH Terms: Gastrointestinal Diseases; Digestive System Diseases
• Other Study ID Numbers: UP2022_FGID

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