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
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
Funders
Funder type
Government
Funder name
Office of the Governer
Alternative name(s)
Funding Body Type
government organisation
Funding Body Subtype
Local government
Location
United States of America
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
- ISRCTN16554977_PIS_Italian.pdf Uploaded 08/06/2020