Condition category
Signs and Symptoms
Date applied
14/05/2020
Date assigned
16/05/2020
Last edited
08/06/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Colic is when a baby cries a lot and is difficult to console, without an obvious cause. This is a common problem that should get better on its own, but can be distressing and exhausting for parents. The exact causes of infantile colic are not fully understood. Likely causes could be problems with gut motility and food intolerance. Growing evidence suggests that the gut microbiota (the microorganisms that live in the gut) could be also involved in colic.

Certain compositions of the gut microbiota, where a type of bacteria called Coliforms are in high concentrations and a type of bacteria called Lactobacilli are in a low concentration, have been found to be more common in infants with colic than in infants without colic.

Probiotic supplementation with Lactobacilli has been shown to be effective in treating this condition in some clinical trials of breastfed infants. However, changing the composition of the gut bacteria during the early stages of gut development can induce lasting shifts in immunity as a result of inflammation of the gut.

A specific bacterial species called Lactobacillus rhamnosus may have anti-inflammatory properties. Supplementation with a probiotic of this bacteria may improve colic and reduce inflammation. The aim of this study was to investigate how effective a Lactobacillus rhamnosus probiotic was in treating infantile colic, in addition to maternal diet avoidance of cow’s milk.

Who can participate?
Newborns with colic aged between 2 and 10 weeks who are breastfed.

What does the study involve?
Participants are randomly allocated to one of two groups. Infants will either have normal care and breastfeeding or they will take 5 drops of the probiotic each day for 28 days and their mother will avoid consuming cow's milk over this period. Fecal samples will be collected from nappies before the trial starts and after 28 days. Their mother will also report how often the infant is crying at the start and end of the study.

What are the possible benefits and risks of participating?
This probiotic is well know and safe. There could be a reduction in colic symptoms of crying and fussing of the baby and parental discomfort.

Where is the study run from?
University Hospital City of Health and Science of Turin (Italy)

When is the study starting and how long is it expected to run for?
April 2017 to October 2019

Who is funding the study?
Office of the Governer (USA)

Who is the main contact?
Dr Francesco Savino
francesco.savino@unito.it

Trial website

https://www.cittadellasalute.to.it/

Contact information

Type

Scientific

Primary contact

Dr Francesco Savino

ORCID ID

https://orcid.org/0000-0001-9163-1016

Contact details

Department of Pediatrics
Ospedale Infantile Regina Margherita
Azienda Ospedaliera Citta' Della Salute E Della Scienza Di Torino
Piazza Polonia
94
Italy
10126
Italy
+39 (0)113135618
francesco.savino@unito.it

Additional identifiers

EudraCT number

2020-002496-35

ClinicalTrials.gov number

Nil known

Protocol/serial number

Nil known

Study information

Scientific title

Supplementation with the probiotic L rhamnosus GG to reduce the crying time and modify gut microbiota, or fecal calprotectin values in a group of infants with colic (Lactobacillus GG): a randomized controlled pilot study

Acronym

Lactobacillus GG

Study hypothesis

The aim of this study is to investigate whether supplementation with the probiotic Lactobacillus rhamnosus ATCC 53103 and maternal dietary elimination of cow's milk is effective in treating infantile colic of breastfed infants and reducing gut inflammation by measuring fecal calprotectin levels and composition of gut microbiota compared to placebo control.

Ethics approval

Approved 05/04/ 2017, Ethics Committee of the University Hospital City of Health and Science of Turin (Ospedale Mauriziano di Torino , Corso Spezia 60, Torino 10126 Italy; +39 (0)113134079), ref: 7/2017

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional file in Italian ISRCTN16554977_PIS_Italian (added 08/06/2020)

Condition

Infantile colic

Intervention

At enrollment, each infant underwent a medical examination by a pediatrician, and parents completed a questionnaire to obtain data concerning type of delivery, birth weight, and gestational age. The pediatrician asked the parents to report full-force crying by means of a well-validated three-day diary before the faecal sample collection at baseline and again after the 28 day intervention. The mean daily minutes of crying were calculated as a sum of crying, fussing, and unsuitable crying using a parental diary.

Eligible participants will be randomized to either receive the intervention or placebo control:
1. The intervention arm received Lactobacillus rhamnosus GG (5 x10⁹ colony units per day). The probiotic study product consisted of a suspension of freeze-dried L rhamnosus ATCC53103 in a mixture of mais oil and mono and diglyceride oil supplied in a 5 mL dark bottle fitted with a dropper cap.
2. The control arm received a placebo. The placebo was a mixture of mais oil and mono and diglyceride oil supplied in a 5 mL dark bottle fitted with a dropper cap, without probiotic.

Both arms were instructed to take 5 drops of either the probiotic or placebo in the morning 30 minutes before feeding each day for 28 days. For both arms, maternal avoidance of cow's milk was requested for the 28 days study period.

Randomization was performed by the random-digit method, on the basis of a computer-generated numbers. A two treatments randomization scheme with random block of varying size was used (Stata Statistical Software: Release 9. StataCorp LP, College Station, TX. Ralloc Procedure).

Intervention type

Supplement

Phase

Drug names

Primary outcome measure

Colic measured by changes in the parent-reported crying time per day of infants at baseline and 28 days

Secondary outcome measures

Gut inflammation assessed using real-time PCR analysis of gut microbiota from fecal samples, and fecal calprotectin levels measured via a quantitative assay at baseline and 28 days

Overall trial start date

05/04/2017

Overall trial end date

30/11/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged between 2 and 10 weeks
2. Gestational age between 37 and 40 weeks
3. Birth weight between 2700 g and 4200 g,
4. Exclusively breastfed
5. Colic, as diagnosed according to the Wessel definition modified by Roma IV criteria (infants have at least three episodes of unexplained full-force crying lasting more than three hours per day on at least three days a week for at least one week)
6. Maternal willingness and ability to avoid dietary cow’s milk

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

20

Total final enrolment

57

Participant exclusion criteria

1. Clinical evidence of chronic illness or gastrointestinal disorders
2. Antibiotic or probiotic treatment in the week preceding recruitment

Recruitment start date

01/03/2018

Recruitment end date

31/10/2019

Locations

Countries of recruitment

Italy

Trial participating centre

Ospedale Infantile Regina Margherita (ORIM)
Children's Hospital Regina Margherita University Hospital City of Health and Science of Turin Piazza Polonia, 94
Torino
10126
Italy

Sponsor information

Organisation

Azienda Ospedaliera Citta' Della Salute E Della Scienza Di Torino

Sponsor details

Piazza Polonia
94
Torino
10126
Italy
+39 (0)113135059
fsavino@cittadellasalute.to.it

Sponsor type

Hospital/treatment centre

Website

https://www.cittadellasalute.to.it/

Funders

Funder type

Government

Funder name

Office of the Governer

Alternative name(s)

Funding Body Type

unknown

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD Sharing statement:
The datasets generated during and/or analysed during the current study will be available upon request from Dr Francesco Savino, francesco.savino@unito.it.

Intention to publish date

01/06/2020

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

08/06/2020: The participant information sheet has been uploaded as an additional file. 15/05/2020: Trial’s existence confirmed by Ethics Committee of the University Hospital City of Health and Science of Turin.