Efficacy of Matricariae Chamomilla L., Melissa Officinalis L. and Tyndallized Lactobacillus Acidophilus (H122) for Infantile Colics

Efficacy of a Standardized Extract of Matricariae Chamomilla L., Melissa Officinalis L. and Tyndallized Lactobacillus Acidophilus (H122) Compared With Lactobacillus Reuteri (DSM 17938) and With Simethicone for the Treatment of Infantile Colic

A multicenter prospective, randomized comparative study will be conducted in infants with colic, according to Rome III criteria. Enrolled infants will be assigned at random to receive Chamomilla L., Melissa Officinalis L. and tyndallized L. Acidophilus (H122), L reuteri DSM 17938 (108 CFU) or simethicone. Treatment will be given to subjects for 28 days and they will be followed for 4 weeks. Treatment success will be assessed at the end of study period. Daily crying and fussing times will be recorded in a structured diary, and maternal questionnaires will be completed to monitor changes in infant colic symptoms and adverse events.

Study Overview

• Status: Completed
• Conditions: Infantile Colics
• Intervention / Treatment: Drug: Simethicone; Dietary supplement: Standardized extract of Chamomilla L., Melissa Officinalis L. and tyndallized L. Acidophilus (H122); Dietary supplement: Lactobacillus reuteri DSM 17938 (108 CFU)

Detailed Description

This will be a prospective, multicentre, open label, randomized, controlled trial. All consecutive infants diagnosed with IC, according to Rome III criteria, will be prospectively enrolled in a 12 months period by 3 different Pediatric Gastroenterology units: Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II"; Institute of Pediatrics of the University of Foggia; Endoscopy and Gastroenterology Unit, Department of Pediatrics, University of Messina.

After the enrollment, all children will be randomly assigned to receive Chamomilla L., Melissa Officinalis L. and tyndallized L. Acidophilus (H122) (Group A), L reuteri DSM 17938 (108 CFU) (Group B) or Simethicone (Group C). Treatment will be given to subjects for 28 days. The study's primary outcome is defined as a reduction in the duration of average crying times, from baseline (day 0) to end of treatment (day 28). The secondary outcome measure is the number of participants who respond to treatment on days 28. Infants who experience a decrease in the daily average crying time of 50% from baseline will be considered as responders to the treatment. Parents will be instructed to complete a structured 28-day maternal diary, modified from Barr et al. in order to record the frequency of colic episodes and the daily crying and fussing time (in minutes), feeding schedule, stool frequency and characteristics, and any adverse events experienced (14). Follow-up visits will be conducted on study days 7, 14, 21 and 28 by the same study investigator. At that visit, diaries and unused study products will be returned.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 weeks to 4 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. diagnosis of IC according to Rome III criteria (2);
2. age ≥2 weeks to 4 months;
3. breast-fed or fomula-fed infants;
4. term delivery (≥37 weeks gestation at birth);
5. 5-minute Apgar score ≥7; and 6) birth weight ≥2500 g

Exclusion Criteria:

1. a major medical problem or acute illness;
2. family history of atopy;
3. history of antibiotic treatment before or during the study;
4. history of probiotic supplementation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; All enrolled infants randomized to Group A will receive a standardized extract of Chamomilla L., Melissa Officinalis L. and tyndallized Lactobacillus Acidophilus (H122), administered at the dose of 1 ml twice a day of a commercially available solution	Dietary supplement: Standardized extract of Chamomilla L., Melissa Officinalis L. and tyndallized L. Acidophilus (H122)
Active Comparator: Group B; All enrolled infants randomized to Group B will receive Lactobacillus reuteri DSM 17938 administered at the dose of 108 colony-forming units (CFU)/day in 5 drops of a commercially available oil suspension	Dietary supplement: Lactobacillus reuteri DSM 17938 (108 CFU)
Active Comparator: Group C; All enrolled infants randomized to Group C will receive simethicone, given at a dose of 60 mg in 15 drops two times per day of a commercially available solution	Drug: Simethicone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Daily Crying Time at the End of the Treatment	Median daily crying at the end of treatment (day 28).	28 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Responders	Number of responders defined as the number of patients who experienced a decrease in the daily average crying time of 50% from baseline	28 days of treatment

Collaborators and Investigators

• Sponsor: Federico II University
• Investigators: Principal Investigator: Annamaria Staiano, Prof., Federico II University

Publications and helpful links

General Publications

• Martinelli M, Ummarino D, Giugliano FP, Sciorio E, Tortora C, Bruzzese D, De Giovanni D, Rutigliano I, Valenti S, Romano C, Campanozzi A, Miele E, Staiano A. Efficacy of a standardized extract of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) in infantile colic: An open randomized controlled trial. Neurogastroenterol Motil. 2017 Dec;29(12). doi: 10.1111/nmo.13145. Epub 2017 Jun 30.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: March 4, 2016
• First Submitted That Met QC Criteria: March 14, 2016
• First Posted (Estimate): March 15, 2016

Study Record Updates

• Last Update Posted (Estimate): July 29, 2016
• Last Update Submitted That Met QC Criteria: June 20, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Infantile colics
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Colic; Molecular Mechanisms of Pharmacological Action; Dermatologic Agents; Antifoaming Agents; Emollients; Simethicone
• Other Study ID Numbers: 04032016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Publication