Human Milk Oligosaccharide (HMO) Supplementation in Colic Management

Efficacy and Tolerability of a Composition Comprising of HMO in a Supplement Format on Colic Management: a Double-blind, Randomized, Placebo-controlled Trial

Efficacy and tolerability of a composition comprising of HMO in a supplement format on colic management: a double-blind, randomized, placebo-controlled trial

Study Overview

• Status: Recruiting
• Conditions: Colic
• Intervention / Treatment: Dietary supplement: HMO; Behavioral: Parental reassurance and support; Dietary supplement: Placebo

Detailed Description

This is a double-blinded, randomized, placebo-controlled trial. The purpose of this trial is to investigate the efficacy and tolerability of a composition comprising of HMO in a supplement format in the management of colicky infants aged 2-12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cecilia L Fumero, PhD; Phone Number: +41 21 785 8328; Email: CECILIA.FUMERO@RDLS.NESTLE.COM

Study Locations

• Italy
  • Bari, Italy, 70126
    • Recruiting
    • Ospedale Pediatrico Giovanni XXIII, Policlinico di Bari
    • Principal Investigator: Ruggiero Francavilla, MD, PhD
  • Milano, Italy
    • Recruiting
    • ASST FBF Sacco
    • Principal Investigator: Elvira Verduci, MD.
  • Palermo, Italy
    • Recruiting
    • AOUP Paolo Giaccone
    • Principal Investigator: Giuffrè P Mario, MD.
  • Pisa, Italy
    • Recruiting
    • Azienda Ospedaliero -Universitaria Pisana
    • Principal Investigator: Diego Perioni, MD.
• Spain
  • Murcia, Spain, 30009
    • Recruiting
    • Centro de Salud El Ranero
    • Principal Investigator: Antonio Iofrío De Arce, Dr.
  • Santiago de Compostela, Spain, 15706
    • Recruiting
    • Hospital Clínico Universitario de Santiago de Compostela
    • Principal Investigator: Maria Rosaura Leis Trabazo, Dr.
  • Sevilla, Spain, 41014
    • Recruiting
    • Unidad de Estudios e Investigación IHP
    • Principal Investigator: Ignacio Salamanca, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 weeks to 1 month (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Infants 2 weeks - 12 weeks of age at enrolment

2. Infants diagnosed with colic according to Rome IV criteria: Diagnostic criteria for research purposes (infant must meet all Rome IV criteria):

   1. An infant who is less than 5 months of age (in the current clinical trial, only infants 2 weeks to 8 weeks of age will be enrolled) when the symptoms start and stop
   2. Recurrent and prolonged periods of infant crying, fussing, or irritability reported by caregivers that occur without obvious cause and cannot be prevented or resolved by caregivers
   3. No evidence of infant failure to thrive, fever, or illness
   4. Excessive crying/fussiness for 3 or more hours per day during 3 or more days in the past 7 days as reported by parents to the clinician
   5. Total 24-hour crying plus fussing is 3 hours or more when measured by at least one prospectively kept 24-hour behavior diary. (The Structured Infant Crying and Fussing Diary will be dispensed at the screening visit (V0), completed for two 24-hour periods at H0 (days -3 to -1), and returned at V1 to be used as part of the diagnostic criteria for infantile colic.)
3. Term infants (≥ 37 weeks) generally healthy with normal birth weight (≥2.5kg) and singleton born
4. Predominantly formula fed* (formula fed ≥ 80% of the time) for at least 7 days before randomization and the choice of formula feeding has been made by the parents before the beginning of the trial.
5. Infants who have been on the same formula for the past 5 days
6. Signed informed consent obtained for infant's and parents'/Legally Acceptable Representative (LAR) participation in the study
7. Parent/LAR of infant agrees not to enroll infant in another interventional clinical research study while participating in this study
8. Parent of the infant/LAR is willing and able to fulfill the requirements of the study protocol

9. Parent of infant can be contacted throughout the study

   • Predominantly formula feeding defined in the study means that the infant's predominant source of nourishment is formula. Specifically, infants are fed with formula for at least 80% of total milk feeds per day.

Exclusion criteria:

1. Presence of any congenital condition and/or previous or current illness/infection and (or) medication use that could interfere with the main study outcomes.
2. Clinical evidence of chronic illness or gastrointestinal disorders, major medical problems (e.g. ill, immunocompromised, major developmental or genetic abnormality).
3. Known cow's milk protein allergy, lactose intolerance, or galactosaemia; including presence of any allergic manifestations.
4. Received any special formula (e.g. lactose-free, hydrolyzed protein) within 5 days before randomization or switched formulas within 5 days before randomization.

5. Received any of the following products/medication within 5 days before randomization:

   • Antibiotics
   • Alginate
   • Prokinetics
   • Proton pump inhibitors
   • Simethicone
   • L. reuteri probiotic
   • Formula containing Human milk Oligosaccharides
6. Other infant(s) <6months of age living in the same household.
7. Current participation in another interventional clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liquid oral supplement comprising HMO; 2 ampules/day for 21 days	Dietary supplement: HMO; Composition comprising of HMO; Behavioral: Parental reassurance and support; Both groups will receive standardized written materials to provide parental reassurance and support, in alignment with local clinical practice
Placebo Comparator: Placebo; 2 ampules/day for 21 days	Behavioral: Parental reassurance and support; Both groups will receive standardized written materials to provide parental reassurance and support, in alignment with local clinical practice; Dietary supplement: Placebo; Placebo supplementation having the same appearance and dosing regimen as the intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in average infant daily crying and fussing duration	Difference in average infant daily crying and fussing duration at the end of the intervention in the Intervention Group (IG) versus the Control Group (CG). The crying and fussing duration is measured using a structured infant crying and fussing diary.	At the end of the intervention period (day 21)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modulation of infant gut microbiota (communities of microbes, their taxonomy, strain composition, diversity, ecology, functionalities, and the metabolites produced)	Modulation of infant gut microbiota in the intervention group versus the control group assessed using metagenomics	V1 (day 0), V2 (day 7), and V4 (day 21)
Difference in average infant daily crying duration	Difference in average infant daily crying duration at the end of the intervention in the IG versus the CG assessed using a structured infant crying and fussing diary.	Change from baseline (V1) to intervention end (V4)
Difference in average infant daily fussing duration	Difference in average infant daily fussing duration at the end of the intervention in the IG versus the CG assessed using a structured infant crying and fussing diary.	Change from baseline (V1) to intervention end (V4)
Difference in average infant daily crying and fussing duration in the IG	Difference in average infant daily crying duration and fussing duration combined from baseline (V1) to intervention end (V4) in the IG assessed using a structured infant crying and fussing diary.	Change from baseline (V1) to intervention end (V4)
Difference in average infant daily crying duration in the Intervention group	Difference in average infant daily crying duration from baseline (V1) to intervention end (V4) in the Intervention group assessed using a structured infant crying and fussing diary.	Change from baseline (V1) to intervention end (V4)
Difference in average infant daily fussing duration in the Intervention group	Difference in average infant daily fussing duration from baseline (V1) to intervention end (V4) in the interventional group assessed using a structured infant crying and fussing diary.	Change from baseline (V1) to intervention end (V4)
Infant daily crying and fussing duration assessed longitudinally	Infant daily crying and fussing duration combined assessed longitudinally across the intervention assessed using a structured infant crying and fussing diary.	Longitudinal changes across specific visits V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
Infant crying/fussing per 24 hours	Episodes of infant crying/fussing per 24 hours assessed using a structured infant crying and fussing diary.	At specific visits V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
Percentage of children achieving a reduction in daily crying and fussing	Percentage of children achieving a reduction in daily crying, fussing, crying and fussing time combined of ≤ 25 % and ≤ 50 % assessed using a structured infant crying and fussing diary.	At specific visits V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
Incidence of infantile colic	Incidence of infantile colic assessed using a structured infant crying and fussing diary.	At specific visits V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
Parental perception of colic severity	Parental perception of colic severity assessed using a 10-cm visual analog scale (VAS)	At specific visits V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
Overall GI tolerance and individual GI symptoms	Overall infant GI tolerance and individual GI and GI-related symptoms (stooling, spitup/ vomiting, gassiness, crying, fussiness) assessed using IGSQ-13	V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
Overall GI tolerance and individual GI symptoms	Change in IGSQ-13 scores assessed using IGSQ-13	Baseline to intervention end (day 21)
Overall GI tolerance and individual GI symptoms	Functional GI symptoms (regurgitation, consistency of stools), crying, allergic symptoms (atopic eczema) and respiratory symptoms assessed using CoMiSS	At V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
Overall GI tolerance and individual GI symptoms	Change in CoMiSS scores assessed using CoMiSS	From baseline to intervention end (day 21)
Overall GI tolerance and individual GI symptoms	Stool consistency, spitting up/vomiting and flatulence assessed using 1-day retrospective GI diary at V1 (day 0) and prospective 3-Day GI symptom diary diaries at home (H2, H3 and H4) just prior to V2 (day 7), V3 (day 14) and V4 (day 21)	1-day retrospective GI diary at V1 (day 0) and prospective 3-Day GI symptom diary diaries at home (H2, H3 and H4) just prior to V2 (day 7), V3 (day 14) and V4 (day 21)
Infant sleep	Infant sleep duration and nighttime wakings per 24 hours assessed using Brief infant sleep questionnaire (BISQ)	V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
Infant Quality of life	Infant quality of life assessed using an Infant Quality of Life instrument. The tool includes IQI includes questions on 7 health items such as sleeping, crying, feeding , skin, breathing, playfulness and Interaction, and stooling. Each item consists of 4 levels, most of which are ranked by severity.	V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
Parental and family quality of life	Parental/family quality of life will be assessed using a Quality of Life Visual Analog Scale that rates the parent / family's quality of life based on a 10-point Likert scale.	V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
Infant fecal gut microbiota	Microbiome of fecal samples to investigate the communities of microbes, their taxonomy, strain composition, diversity, ecology, functionalities, and the metabolites produced assessed using metagenomics.	V1 (day 0), V2 (day 7), and V4 (day 21)
Fecal metabolism	Fecal metabolism (pH, organic acids)	V1 (day 0), V2 (day 7), and V4 (day 21)
Fecal markers of inflammation calprotectin	Inflammation biomarkers calprotectin assessed using ELISA.	V1 (day 0) and V4 (day 21)
Fecal markers of inflammation lipocalin	Inflammation biomarkers lipocalin assessed using ELISA.	V1 (day 0) and V4 (day 21)
Infant anthropometry weight	Weight in grams	V1 (day 0), V2 (day 7), V3 (day 14) (optional if V3 is a phone call) and V4 (day 21)
Infant anthropometry length	Length in cm	V1 (day 0), V2 (day 7), V3 (day 14) (optional if V3 is a phone call) and V4 (day 21)
Infant anthropometry head circumference	Head circumference in cm	V1 (day 0), V2 (day 7), V3 (day 14) (optional if V3 is a phone call) and V4 (day 21)
Infant anthropometry weight gain	Weight gain in g/d	V1 (day 0), V2 (day 7), V3 (day 14) (optional if V3 is a phone call) and V4 (day 21)
Infant anthropometry length gain	Length gain in cm/d	V1 (day 0), V2 (day 7), V3 (day 14) (optional if V3 is a phone call) and V4 (day 21)
Infant illness and infection and medication usage	Data collected using a calendar-based electronic Infant Illness Diary (IID)	V1 (day 0) until V4 (day 21)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration and number of episodes of infant crying type based on a crying-type classification of the audio recording	Duration and number of episodes of each infant crying type (pain, fussiness, hunger) based on a crying-type classification of the audio recording	24 hours after V1 (day 0), V2 (day 7), V3 (day 14) and for 3 days prior to V4 (day 21)
Proportion of children with a specific crying type based on a crying-type classification of the audio recording	Proportion of children with a specific crying type (pain, fussiness, hunger) based on a crying-type classification of the audio recording	24 hours after V1 (day 0), V2 (day 7), V3 (day 14) and for 3 days prior to V4 (day 21)
Duration of crying based on a crying-type classification of the audio recording	Duration of crying based on a crying-type classification of the audio recording	24 hours after V1 (day 0), V2 (day 7), V3 (day 14) and for 3 days prior to V4 (day 21)
Duration of fussing based on a crying-type classification of the audio recording	Duration of fussing based on a crying-type classification of the audio recording	24 hours after V1 (day 0), V2 (day 7), V3 (day 14) and for 3 days prior to V4 (day 21)
Duration of crying and fussing combined based on a crying-type classification of the audio recording	Duration of crying and fussing combined based on a crying-type classification of the audio recording	24 hours after V1 (day 0), V2 (day 7), V3 (day 14) and for 3 days prior to V4 (day 21)
Crying and fussing comparison between the structured infant crying and fussing diary and the crying-type classification of the recording of infant crying/fussing across the intervention	Infant daily crying and fussing duration compared between the structured infant crying and fussing diary and the crying-type classification of the recording of infant crying/fussing across the intervention	V1 (day 0), V2 (day 7), V3 (day 14) and V4 (day 21)
Maternal Postpartum depression/ anxiety	Maternal postpartum depressive and anxiety symptoms assessed using an Edinburgh postnatal depression scale (EPDS)	V1 (day 0) and V4 (day 21)

Collaborators and Investigators

• Sponsor: Société des Produits Nestlé (SPN)

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2022
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 28, 2022
• First Submitted That Met QC Criteria: September 22, 2022
• First Posted (Actual): September 26, 2022

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Colic
• Other Study ID Numbers: 20.28.INF

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
• product manufactured in and exported from the U.S.: No