NCT00893711

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
155

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Mar 2008

Longer than P75 for not_applicable

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2008

Completed
1.2 years until next milestone

First Submitted

Initial submission to the registry

May 5, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 6, 2009

Completed
12.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2021

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2022

Completed
Last Updated

March 3, 2021

Status Verified

March 1, 2021

Enrollment Period

13.7 years

First QC Date

May 5, 2009

Last Update Submit

March 2, 2021

Conditions

Infantile Colic

Keywords

infantile coliclactobacillusgut microfloraFISHtoll like receptorT regmessenger RNACC-chemokine receptor 7interleukin 10

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Responders to treatment

    30 day

  • To analyze intestinal microflora

    day 0 and day 30

  • Assay of Th17/Treg balance

    time 0- 30 days

Other Outcomes (3)

  • Preventive effects of L.reuteri on infantile colic

    5 months

  • Fecal calprotectin values

    0-30 days

  • Parental satisfacion

    day 30

Study Arms (4)

Lactobacillus reuteri

ACTIVE COMPARATOR

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.

Other: Lactobacillus reuteri DSM 17938

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

L.reuteri + vit D

ACTIVE COMPARATOR

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

Dietary Supplement: L.reuteri + Vit D

Vit D Placebo

PLACEBO COMPARATOR

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

Dietary Supplement: Vit D placebo

Interventions

Lactobacillus reuteri DSM 17938OTHER

Lactobacillus reuteri is administered at a dose of 1.000.000.000 colony forming units (CFU) in V drops/day for 21 days

Also known as: Reuterin,Noos - Italy; BIOGAIA drops - Sweden
Lactobacillus reuteri
PlaceboOTHER

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.

Also known as: Placebo BIOGAIA Sweden
Placebo
L.reuteri + Vit DDIETARY_SUPPLEMENT
Also known as: Reuterin D3 drops, Noos Italy, Reuflor D3 drops, Recordati Italy
L.reuteri + vit D
Vit D placeboDIETARY_SUPPLEMENT
Vit D Placebo

Eligibility Criteria

Age4 Weeks - 16 Weeks
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Ospedale Infantile Regina Margherita

Torino, TO, 10126, Italy

RECRUITING

Ospedale Infantile Regina Margherita

Torino, 10126, Italy

RECRUITING

Ospedale Infantile Regina Margherita

Torino, 10126, Italy

RECRUITING

Related Publications (11)

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

    PMID: 17718777BACKGROUND

  • 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.

    PMID: 17498186BACKGROUND

  • 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.

    PMID: 17200238BACKGROUND

  • 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.

    PMID: 16754557BACKGROUND

  • 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.

    PMID: 16736065BACKGROUND

  • 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.

    PMID: 16214780BACKGROUND

  • 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.

    PMID: 16041731BACKGROUND

  • 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.

    PMID: 15693915BACKGROUND

  • 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.

    PMID: 15244234BACKGROUND

  • 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.

    PMID: 28969887DERIVED

  • 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.

    PMID: 23468874DERIVED

MeSH Terms

Conditions

Colic

Condition Hierarchy (Ancestors)

Infant, Newborn, DiseasesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

  • Francesco Savino, MD, PhD

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

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Francesco Savino, MD, PhD

CONTACT

00390113135618francesco.savino@unito.it

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

May 5, 2009

First Posted

May 6, 2009

Study Start

March 1, 2008

Primary Completion

November 1, 2021

Study Completion

December 1, 2022

Last Updated

March 3, 2021

Record last verified: 2021-03

Data Sharing

IPD Sharing
Will share

to partecipe to an individual partecipant data meta- analysis.

Locations

IT(3)