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

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Dr. SAVINO Francesco, Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
Sponsor:
Information provided by (Responsible Party):
Dr. SAVINO Francesco, Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
ClinicalTrials.gov Identifier:
NCT00893711
First received: May 5, 2009
Last updated: April 4, 2017
Last verified: April 2017
  Purpose

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.
  • Parental satisfaction at the end of the study period ( 30 day ) with a numerc scale from 1 to 10.

Condition Intervention
Infantile Colic Other: Lactobacillus reuteri DSM 17938 Other: Placebo Dietary Supplement: L.reuteri + Vit D Dietary Supplement: Vit D placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Lactobacillus Reuteri Versus Placebo in the Treatment and Prevention of Infantile Colic: a Clinical and Microbiological, Double-blind, Prospective, Randomised, Controlled Study

Resource links provided by NLM:


Further study details as provided by Dr. SAVINO Francesco, Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna:

Primary Outcome Measures:
  • 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 [ Time Frame: time 0 - 7 - 21 - 30 days ]
    diary crying Barr


Secondary Outcome Measures:
  • Responders to treatment [ Time Frame: 30 day ]
    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.

  • To analyze intestinal microflora [ Time Frame: day 0 and day 30 ]
    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.

  • Assay of Th17/Treg balance [ Time Frame: time 0- 30 days ]
    For the analyses of mRNA FOXP3 and RORγ in peripheral blood RT-PCR Real Time Taqman will be used


Other Outcome Measures:
  • Preventive effects of L.reuteri on infantile colic [ Time Frame: 5 months ]
    action on: use of pain relieving agents, switch to infant formula, number of paediatric consultations for infantile colic

  • Fecal calprotectin values [ Time Frame: 0-30 days ]
    BÜHLMANN Quantum Blue® Calprotectin High Range (Schönenbuch, Switzerland). It is a quantitative determination of fecal calprotectin through a sandwich immunoassay.

  • Parental satisfacion [ Time Frame: day 30 ]
    numeric scale from 1to 10


Estimated Enrollment: 155
Study Start Date: March 2008
Estimated Study Completion Date: November 2017
Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
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
Other Name: Reuterin, BIOGAIA - Sweden
Placebo Comparator: 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.
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.
Other Name: Placebo BIOGAIA Sweden
Active Comparator: L.reuteri + vit D
L. reuteri DSM 17938 (10^8 CFU) plus vitamin D3 (400 UI) five drops/day for 3 months
Dietary Supplement: L.reuteri + Vit D
Other Names:
  • Reuterin D3 drops, Noos Italy
  • Reuflor D3 drops, Italchimici Italy
Placebo Comparator: Vit D Placebo
vitamin D3 (400 UI) five drops/day for 3 months
Dietary Supplement: Vit D placebo

Detailed 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.
  Eligibility

Ages Eligible for Study:   up to 16 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00893711

Contacts
Contact: Francesco Savino, MD, PhD 00390113135618 francesco.savino@unito.it

Locations
Italy
Ospedale Infantile Regina Margherita Completed
Piazza polonia 94 - Torino, Torino, Italy, 10126
Ospedale Infantile Regina Margherita Recruiting
Torino, TO, Italy, 10126
Contact: Francesco Savino, MD PhD    +39 0113135618    francesco.savino@unito.it   
Principal Investigator: Francesco Savino, MD PhD         
Ospedale Infantile Regina Margherita Recruiting
Torino, Italy, 10126
Contact: Francesco Savino, MD, PhD    +390113135618    francesco.savino@unito.it   
Principal Investigator: Francesco Savino, MD, PhD         
Sub-Investigator: Maria Garrro, MD         
Sub-Investigator: Massimiliano Bergallo, BS         
Sponsors and Collaborators
Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
Investigators
Principal Investigator: Francesco Savino, MD, PhD Ospedale Infantile Regina Margherita - Dipartimento di Pediatria Generale e Specialistica. S.S. D. Sub Intensiva Allargata della Prima Infanzia
  More Information

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. SAVINO Francesco, MD, PhD, Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
ClinicalTrials.gov Identifier: NCT00893711     History of Changes
Other Study ID Numbers: FS-2009
Study First Received: May 5, 2009
Last Updated: April 4, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: to partecipe to an individual partecipant data meta- analysis.

Keywords provided by Dr. SAVINO Francesco, Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna:
infantile colic
lactobacillus
gut microflora
FISH

Additional relevant MeSH terms:
Colic
Infant, Newborn, Diseases
Vitamin D
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 21, 2017