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

• Sponsor: Federico II University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02708238
• Collaborator: (none)
• Enrollment: 180
• Arms: 3
• Duration (Months): 15

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infantile Colics	Dietary Supplement: Standardized extract of Chamomilla L., Melissa Officinalis L. and tyndallized L. Acidophilus (H122); Dietary Supplement: Lactobacillus reuteri DSM 17938 (108 CFU); Drug: Simethicone	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Median Daily Crying Time at the End of the Treatment [28 days of treatment]

   Median daily crying at the end of treatment (day 28).

Secondary Outcome Measures

1. Number of Responders [28 days of treatment]

   Number of responders defined as the number of patients who experienced a decrease in the daily average crying time of 50% from baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: 14 Days to 4 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Federico II University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Erasmo Miele, Researcher, Federico II University
• ClinicalTrials.gov Identifier: NCT02708238
• Other Study ID Numbers: 04032016
• First Posted: Mar 15, 2016
• Last Update Posted: Jul 29, 2016
• Last Verified: Jun 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Erasmo Miele, Researcher, Federico II University: Infantile colics
• Additional relevant MeSH terms: Colic; Simethicone

Study Results

Participant Flow

Arm/Group Title	Group A	Group B	Group C
Arm/Group Description	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 Standardized extract of Chamomilla L., Melissa Officinalis L. and tyndallized L. Acidophilus (H122)	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 Lactobacillus reuteri DSM 17938 (108 CFU)	All enrolled infants randomized to Group C will receive simethicone, given at a dose of 60 mg in 20 drops four times per day of a commercially available solution Simethicone
Period Title: Overall Study
STARTED	60	60	60
COMPLETED	60	59	57
NOT COMPLETED	0	1	3

Baseline Characteristics

Arm/Group Title	Group A	Group B	Group C	Total
Arm/Group Description	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 Standardized extract of Chamomilla L., Melissa Officinalis L. and tyndallized L. Acidophilus (H122)	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 Lactobacillus reuteri DSM 17938 (108 CFU)	All enrolled infants randomized to Group C will receive simethicone, given at a dose of 60 mg in 20 drops four times per day of a commercially available solution Simethicone	Total of all reporting groups
Overall Participants	60	59	57	176
Age (Count of Participants)
<=18 years	60 100%	59 100%	57 100%	176 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (Days) [Median (Full Range) ]
Median (Full Range) [Days]	38	35	30	35
Sex: Female, Male (Count of Participants)
Female	31 51.7%	21 35.6%	39 68.4%	91 51.7%
Male	29 48.3%	38 64.4%	18 31.6%	85 48.3%
Region of Enrollment (participants) [Number]
Italy	60 100%	59 100%	57 100%	176 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B	Group C
Arm/Group Description	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 Standardized extract of Chamomilla L., Melissa Officinalis L. and tyndallized L. Acidophilus (H122)	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 Lactobacillus reuteri DSM 17938 (108 CFU)	All enrolled infants randomized to Group C will receive simethicone, given at a dose of 60 mg in 20 drops four times per day of a commercially available solution Simethicone
Measure Participants	60	59	57
Median (Full Range) [minutes]	50	55	80

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B	Group C
Arm/Group Description	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 Standardized extract of Chamomilla L., Melissa Officinalis L. and tyndallized L. Acidophilus (H122)	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 Lactobacillus reuteri DSM 17938 (108 CFU)	All enrolled infants randomized to Group C will receive simethicone, given at a dose of 60 mg in 20 drops four times per day of a commercially available solution Simethicone
Measure Participants	60	59	57
Number [number of responders]	57	47	38

Adverse Events

Arm/Group Title	Group A		Group B		Group C
Arm/Group Description	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 Standardized extract of Chamomilla L., Melissa Officinalis L. and tyndallized L. Acidophilus (H122)		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 Lactobacillus reuteri DSM 17938 (108 CFU)		All enrolled infants randomized to Group C will receive simethicone, given at a dose of 60 mg in 20 drops four times per day of a commercially available solution Simethicone
All Cause Mortality
	Group A		Group B		Group C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group A		Group B		Group C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/59 (0%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	Group A		Group B		Group C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/59 (0%)		0/57 (0%)

Limitations/Caveats

The absence of a placebo group and the open label design represent the main limitations of this study

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.