Lactobacillus Reuteri Versus Placebo in the Treatment and Prevention of Infantile Colic

Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna

Status

Unknown

Conditions

Infantile Colic

Treatments

Other: Lactobacillus reuteri DSM 17938

Other: Placebo

Dietary Supplement: Vit D placebo

Dietary Supplement: L.reuteri + Vit D

Study type

Interventional

Funder types

Other

Identifiers

NCT00893711

FS-2009

Details and patient eligibility

About

The purpose of this study is:

to study the intestinal microflora of colicky infants before and after L. reuteri or placebo administration, evaluating the effect of Lactobacillus reuteri on the growth of the main intestinal microbiota (coliforms, Clostridium butyricum, Lactobacilli, Bifidobacteria) with fluorescent in situ hybridization (FISH) technique or with Real-Time PCR Taqman; Further, the global intestinal microflora composition, using large-scale DNA sequencing of 16S rRNA genes ( 454-pyrosequencing technique.
to evaluate the improvement of colicky symptoms by the oral administration of Lactobacillus reuteri (primary outcome: reduction of the daily average crying time from baseline to the end of the treatment period, to less than 3 hours a day, the cut-off proposed by Wessel; secondary outcome: number of responders versus non-responders in each group at the end of the treatment).
to evaluate fecal calprotectin values at the beginning and at the end of the study. BÜHLMANN Quantum Blue® Calprotectin High Range (Schönenbuch, Switzerland). A quantitative immunoassay.
to evaluate Th17/Treg balance at time 0 and t 30 ( days) investigating mRNA FOXP3 and RORγ in peripheral blood using RT-PCR Real Time Taqman.
the measurement of the expression level of CC-chemokine receptor 7 messenger RNA using the real-time TaqMan reverse transcription polymerase chain reaction method.
the measurement of expression of interleukin 10 (IL-10) messenger RNA using the real-time TaqMan reverse transcription polymerase chain reaction method.
Parental satisfaction at the end of the study period ( 30 day ) with a numerc scale from 1 to 10.

Full description

Infantile colic is one of the most common problems within the first three months of life. It consists of a behavioural syndrome characterised by paroxysmal, excessive and inconsolable crying without identifiable cause. Although infantile colic is commonly reported and causes appreciable distress for both parents and paediatricians, despite forty years of research, its aetiology still remains unclear. Recently the role of intestinal microflora has growing importance, and a lower count of intestinal lactobacilli has been observed in colicky infants compared to healthy ones. In a recent study we have observed that Lactobacillus reuteri improved colicky symptoms in breast-fed infants within one week of treatment compared to Simethicone, suggesting that probiotics may play a role in infantile colic (Savino F, Pelle E, Palumeri E, Oggero R, Miniero R.Lactobacillus reuteri (American Type Culture Collection Strain 55730) versus simethicone in the treatment of infantile colic: a prospective randomized study. Pediatrics 2007; 119:e124-30). The mechanism involved in such finding is only partially understood and, for this reason, we have planned this new study to evaluate not only the clinical improvement but also the microbiological data.

Enrollment

155 estimated patients

Sex

All

Ages

4 to 16 weeks old

Volunteers

No Healthy Volunteers

Inclusion criteria

clinical diagnosis of infantile colic according to Wessel's criteria
gestational age between 37 and 42 weeks
age between 4 and 16 weeks
birth weight between 2500 and 4000 g
exclusively breastfed

Exclusion criteria

clinical evidence of chronic illness or gastrointestinal disorders
administration of probiotics and antibiotics

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

155 participants in 4 patient groups, including a placebo group

Lactobacillus reuteri

Active Comparator group

Description:

Lactobacillus reuteri DSM 17938 is administered at a dose of 1.000.000.000 colony forming units (CFU) in V drops of a commercially available oil suspension, 30 min before feeding, once a day for 30 days.

Treatment:

Other: Lactobacillus reuteri DSM 17938

Placebo

Placebo Comparator group

Description:

Placebo is administered in V drops once a day for 30 days. Placebo is inactive, similar to the studied treatment with the same package, taste, characteristics of colour and consistency.

Treatment:

Other: Placebo

L.reuteri + vit D

Active Comparator group

Description:

L. reuteri DSM 17938 (10\^8 CFU) plus vitamin D3 (400 UI) five drops/day for 3 months

Treatment:

Dietary Supplement: L.reuteri + Vit D

Vit D Placebo

Placebo Comparator group

Description:

vitamin D3 (400 UI) five drops/day for 3 months