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

NCT ID: NCT00893711

Last Updated: 2021-03-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

155 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-03-31

Study Completion Date

2022-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Infantile Colic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Lactobacillus reuteri

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.

Group Type ACTIVE_COMPARATOR

Lactobacillus reuteri DSM 17938

Intervention Type OTHER

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 30 days. Placebo is inactive, similar to the studied treatment with the same package, taste, characteristics of colour and consistency.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

L.reuteri + vit D

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

Group Type ACTIVE_COMPARATOR

L.reuteri + Vit D

Intervention Type DIETARY_SUPPLEMENT

Vit D Placebo

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

Group Type PLACEBO_COMPARATOR

Vit D placebo

Intervention Type DIETARY_SUPPLEMENT

Interventions

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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

Intervention Type OTHER

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.

Intervention Type OTHER

L.reuteri + Vit D

Intervention Type DIETARY_SUPPLEMENT

Vit D placebo

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Reuterin,Noos - Italy; BIOGAIA drops - Sweden Placebo BIOGAIA Sweden Reuterin D3 drops, Noos Italy Reuflor D3 drops, Recordati Italy

Eligibility Criteria

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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
Minimum Eligible Age

4 Weeks

Maximum Eligible Age

16 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna

OTHER

Sponsor Role lead

Responsible Party

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Dr. SAVINO Francesco

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Francesco Savino, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Ospedale Infantile Regina Margherita - Dipartimento di Pediatria.S.S.D. SAPI, Torino

Locations

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Ospedale Infantile Regina Margherita

Torino, TO, Italy

Site Status RECRUITING

Ospedale Infantile Regina Margherita

Torino, , Italy

Site Status RECRUITING

Ospedale Infantile Regina Margherita

Torino, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Francesco Savino, MD, PhD

Role: CONTACT

00390113135618

Facility Contacts

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Francesco Savino, MD PhD

Role: primary

+39 0113135618

Francesco Savino, MD, PhD

Role: primary

00390113135224

Francesco Savino, MD, PhD

Role: primary

+390113135618

References

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Savino F. Focus on infantile colic. Acta Paediatr. 2007 Sep;96(9):1259-64. doi: 10.1111/j.1651-2227.2007.00428.x.

Reference Type BACKGROUND
PMID: 17718777 (View on PubMed)

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. doi: 10.1111/j.1651-2227.2007.00328.x. Epub 2007 May 10. No abstract available.

Reference Type BACKGROUND
PMID: 17498186 (View on PubMed)

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. doi: 10.1542/peds.2006-1222.

Reference Type BACKGROUND
PMID: 17200238 (View on PubMed)

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. doi: 10.1080/08035250500522654.

Reference Type BACKGROUND
PMID: 16754557 (View on PubMed)

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. doi: 10.1038/sj.ejcn.1602457. Epub 2006 May 31.

Reference Type BACKGROUND
PMID: 16736065 (View on PubMed)

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. doi: 10.1111/j.1651-2227.2005.tb02169.x.

Reference Type BACKGROUND
PMID: 16214780 (View on PubMed)

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. doi: 10.1002/ptr.1668.

Reference Type BACKGROUND
PMID: 16041731 (View on PubMed)

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. doi: 10.1111/j.1399-3038.2005.00207.x.

Reference Type BACKGROUND
PMID: 15693915 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15244234 (View on PubMed)

Savino F, Garro M, Montanari P, Galliano I, Bergallo M. Crying Time and RORgamma/FOXP3 Expression in Lactobacillus reuteri DSM17938-Treated Infants with Colic: A Randomized Trial. J Pediatr. 2018 Jan;192:171-177.e1. doi: 10.1016/j.jpeds.2017.08.062. Epub 2017 Sep 29.

Reference Type DERIVED
PMID: 28969887 (View on PubMed)

Roos S, Dicksved J, Tarasco V, Locatelli E, Ricceri F, Grandin U, Savino F. 454 pyrosequencing analysis on faecal samples from a randomized DBPC trial of colicky infants treated with Lactobacillus reuteri DSM 17938. PLoS One. 2013;8(2):e56710. doi: 10.1371/journal.pone.0056710. Epub 2013 Feb 28.

Reference Type DERIVED
PMID: 23468874 (View on PubMed)

Other Identifiers

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FS-2009

Identifier Type: -

Identifier Source: org_study_id

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