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

Infantile Colic Clinical Trial

Official title:

Lactobacillus Reuteri Versus Placebo in the Treatment and Prevention of Infantile Colic: a Clinical and Microbiological, Double-blind, Prospective, Randomised, Controlled Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00893711
• Other study ID #: FS-2009
• Status: Recruiting
• Phase: N/A
• Start date: March 2008
• Est. completion date: December 2022

Study information

• Verified date: March 2021
• Source: Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
• Contact: Francesco Savino, MD, PhD
• Phone: 00390113135618
• Email: francesco.savino[@]unito.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 155
• Est. completion date: December 2022
• Est. primary completion date: November 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 16 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Colic
• Infantile Colic

Intervention

Other:
• Lactobacillus reuteri DSM 17938
Lactobacillus reuteri is administered at a dose of 1.000.000.000 colony forming units (CFU) in V drops/day for 21 days
• Placebo
Placebo is administered in V drops once a day for 21 days. Placebo is inactive, similar to the studied treatment with the same package, taste, characteristics of colour and consistency.

Dietary Supplement:
• L.reuteri + Vit D

• Vit D placebo

Locations

Country	Name	City	State
Italy	Ospedale Infantile Regina Margherita	Torino	TO
Italy	Ospedale Infantile Regina Margherita	Torino
Italy	Ospedale Infantile Regina Margherita	Torino

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Savino F, Bailo E, Oggero R, Tullio V, Roana J, Carlone N, Cuffini AM, Silvestro L. Bacterial counts of intestinal Lactobacillus species in infants with colic. Pediatr Allergy Immunol. 2005 Feb;16(1):72-5. — View Citation

Savino F, Castagno E, Bretto R, Brondello C, Palumeri E, Oggero R. A prospective 10-year study on children who had severe infantile colic. Acta Paediatr Suppl. 2005 Oct;94(449):129-32. — View Citation

Savino F, Cresi F, Castagno E, Silvestro L, Oggero R. A randomized double-blind placebo-controlled trial of a standardized extract of Matricariae recutita, Foeniculum vulgare and Melissa officinalis (ColiMil) in the treatment of breastfed colicky infants. Phytother Res. 2005 Apr;19(4):335-40. — View Citation

Savino F, Cresi F, Pautasso S, Palumeri E, Tullio V, Roana J, Silvestro L, Oggero R. Intestinal microflora in breastfed colicky and non-colicky infants. Acta Paediatr. 2004 Jun;93(6):825-9. — View Citation

Savino F, Grassino EC, Guidi C, Oggero R, Silvestro L, Miniero R. Ghrelin and motilin concentration in colicky infants. Acta Paediatr. 2006 Jun;95(6):738-41. — View Citation

Savino F, Palumeri E, Castagno E, Cresi F, Dalmasso P, Cavallo F, Oggero R. Reduction of crying episodes owing to infantile colic: A randomized controlled study on the efficacy of a new infant formula. Eur J Clin Nutr. 2006 Nov;60(11):1304-10. Epub 2006 May 31. — View Citation

Savino F, Pelle E, Castagno E, Palumeri E, Oggero R. Must infants with colic really be hospitalized? Acta Paediatr. 2007 Jul;96(7):1109; author reply 1110. Epub 2007 May 10. — View Citation

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 Jan;119(1):e124-30. — View Citation

Savino F. Focus on infantile colic. Acta Paediatr. 2007 Sep;96(9):1259-64. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Preventive effects of L.reuteri on infantile colic	action on: use of pain relieving agents, switch to infant formula, number of paediatric consultations for infantile colic	5 months
Other	Fecal calprotectin values	BÜHLMANN Quantum Blue® Calprotectin High Range (Schönenbuch, Switzerland). It is a quantitative determination of fecal calprotectin through a sandwich immunoassay.	0-30 days
Other	Parental satisfacion	numeric scale from 1to 10	day 30
Primary	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 and number of responders versus non-responders in each group at the end of the treatment	diary crying Barr	time 0 - 7 - 21 - 30 days
Secondary	Responders to treatment	was defined as the number of responders in each group on days 7, 14 , 21 and 30 . Responders (defined in the protocol) were those who experienced a decrease in the daily average crying time of 50% from baseline. Diary Crying Barr.	30 day
Secondary	To analyze intestinal microflora	The intestinal microflora of the infants will be analyzed the effect of the probiotic on selected intestinal microbiota (Escherichia coli, Clostridium butyricum, Lactobacillus, Bifidobacterium), using fluorescent in situ hybridization (FISH) or using with Real-Time PCR Taqman.	day 0 and day 30
Secondary	Assay of Th17/Treg balance	For the analyses of mRNA FOXP3 and ROR? in peripheral blood RT-PCR Real Time Taqman will be used	time 0- 30 days