The Effect of Probiotics in Infantile Colic (CSUB0214)

Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Evaluate the Effect of L. Reuteri on Crying and Fussing Time in Infants With Infantile Colic

Academic, independent, non-commercial, multicenter study sponsored by the Department of Translational Medical Sciences (DISMET), University of Naples Federico II. The study evaluates whether daily oral supplementation with L reuteri reduces crying and fussing time more rapidly than an indistinguishable placebo in otherwise healthy infants with Rome IV infantile colic.

Study Overview

• Status: Recruiting
• Conditions: Infantile Colic
• Intervention / Treatment: Dietary supplement: Probiotic: L. reuteri total 2 × 10⁸ CFU/day; Dietary supplement: Placebo: matching oil formulation without L. reuteri

Detailed Description

Eligible participants will meet the clinical description for having infant colic. Participants will be assessed for eligibility at the screening visit and must meet all specified inclusion and exclusion criteria. Based on screening examinations, the individual Family Pediatrician (PLS) is solely responsible for determining clinical eligibility and making the final enrollment decision, which will be documented on the Participant Screening and Enrolment Log. The Scientific Coordinator will exclusively monitor aggregate screening logs and enrollment targets across all active sites, without direct involvement in the clinical selection. Fifty infants will be randomized 1:1 to probiotic or placebo. Each participant will complete a 7-day run-in, 21 days of treatment and 7 days of safety follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Robeto Berni Canani, PhD, MD; Phone Number: +390817462680; Email: berni@unina.it

Study Locations

• Italy
  • Naples, Italy, 80100
    • Recruiting
    • Family pediatricians
    • Contact: Roberto Berni Canani, MD, PhD; Phone Number: +390817462680; Email: berni@unina.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 weeks to 2 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 3-12 weeks at screening;
• gestational age 37+0 to 42+0 weeks;
• birth weight appropriate or large for gestational age;
• parent/caregiver/legal guardian older than 18 years;
• exclusive or predominant breastfeeding (>50%);
• willingness to maintain feeding pattern and complete diaries and questionnaires;
• physician-confirmed Rome IV infantile colic, parental report of ≥3 hours of crying/fussing per day on ≥3 days in the prior week, and ≥3 hours in at least one 24-hour period documented in the run-in diary;
• written informed consent; mother available for scheduled visits; infant otherwise clinically healthy.

Exclusion Criteria:

• Severe gastroesophageal reflux (as defined in the protocol);
• failure to thrive;
• intrauterine growth restriction;
• hematochezia;
• significant diarrhea or fever ≥38 °C;
• congenital heart disease, immunodeficiency, asplenia, malignancy, cystic fibrosis or liver disease;
• probiotic or systemic/oral antibiotic use in the 7 days before screening or anticipated use during the study;
• use of treatments for infantile colic; including proton pump inhibitors; in the 7 days before screening or during the study.
• Infant and mother must not participate concurrently in another interventional clinical study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Probiotic; Probiotic: L. reuteri total 2 × 10⁸ CFU/day, 5 oral drops once daily for 21 days	Dietary supplement: Probiotic: L. reuteri total 2 × 10⁸ CFU/day; 5 oral drops once daily for 21 days.
Placebo Comparator: Placebo; Placebo: matching oil formulation without L. reuteri, 5 oral drops once daily for 21 days.	Dietary supplement: Placebo: matching oil formulation without L. reuteri; 5 oral drops once daily for 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily total crying and fussing time at day 7	Total infant crying and fussing time, expressed as hours per 24-hour period, recorded daily by parents on baby's day diary	7 days after initiation of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in daily total crying and fussing time from baseline to day 7	Total infant crying duration and fussing time, expressed as hours per 24-hour period, recorded daily by parents on baby's day diary	At Day 0 and at day 7 of intervention
Change in daily total crying and fussing time from baseline to every day during 21days of treatment	Total infant crying duration and fussing time, expressed as hours per 24-hour period, recorded daily by parents on baby's day diary	During 21 days of treatment
Proportion of responder patients assessed using a parent-completed daily sleep diary (Baby's Day Diary)	Proportion of patients responders to the treatment, defined as the number of infants with ≥50% reduction in crying and fussing time, expressed as hours per 24-hour period, recorded daily by parents on baby's day diary	During the first 21 days of treatment
Sleeping time	Total infant sleep duration, expressed as hours per 24-hour period, recorded daily by parents on baby's day diary	During the first 21 days of treatment
PedsQL Family Impact Module	Changes in PedsQL Family Impact Module range 0-100 (with higher scores reflecting better functioning) from baseline to Days 7 and 21	During 21 days of treatment
Maternal Edinburgh Postnatal Depression Scale score	Changes in Maternal Edinburgh Postnatal Depression Scale score evaluation Total score range: 0 to 30 (higher score on the Edinburgh Postnatal Depression Scale (EPDS) indicates a greater severity of symptoms) from baseline to Days 7 and 21	During 21 days of treatment
Number of participants experiencing adverse events and serious adverse events.	Number of participants experiencing at least one adverse event (AE) or serious adverse event (SAE) during the study. Events will be recorded and characterized according to type, severity, seriousness, and relationship to the study intervention.	From initiation of the intervention (Day 1) through Day 28.Adverse events, serious adverse events
Body temperature	body temperature (°C)	At day 0 and 21
Heart rate	heart rate (BPM)	At day 0 and 21
Respiratory rate	Respiratory rate/minute	At day 0 and 21
Blood pressure	blood pressure (mmHg)	At day 0 and 21
Height	Height in cm	At day 0 and 21
Weight	Weight in Kg	At day 0 and 21

Collaborators and Investigators

• Sponsor: Federico II University

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: September 24, 2026
• First Submitted That Met QC Criteria: October 23, 2026
• First Posted (Actual): October 26, 2026

Study Record Updates

• Last Update Posted (Actual): November 9, 2026
• Last Update Submitted That Met QC Criteria: November 5, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: infants; probiotics
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Colic
• Other Study ID Numbers: 204/26

Drug and device information, study documents

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