Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by 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: June 24, 2014
Last verified: June 2014
  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; 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 sudy.

Condition Intervention Phase
Infantile Colic
Other: Lactobacillus reuteri DSM 17938
Other: Placebo
Dietary Supplement: L.reuteri + Vit D
Dietary Supplement: Vit D placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna:

Primary Outcome Measures:
  • To evaluate the intestinal microflora of colicky infants before and after the Lactobacillus reuteri or placebo administration (coliforms, Clostridium butyricum, Lactobacilli, Bifidobacteria) with FISH technique. [ Time Frame: time 0 - 21 days ] [ Designated as safety issue: No ]
  • 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 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary Outcome [ Time Frame: 21 day ] [ Designated as safety issue: No ]
    was defined as the number of responders in each group on days 7, 14 and 21. Responders (defined in the protocol) were those who experienced a decrease in the daily average crying time of 50% from baseline. Further, the intestinal microflora of the infants was analyzed the effect of the probiotic on selected intestinal microbiota (Escherichia coli, Clostridium butyricum, Lactobacillus, Bifidobacterium), using fluorescent in situ hybridization (FISH).


Other Outcome Measures:
  • Preventive effects of L.reuteri on infantile colic [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    action on: use of pain relieving agents, switch to infant formula, number of paediatric consultations for infantile colic

  • calprotectin values [ Time Frame: 0-21 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 155
Study Start Date: March 2008
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (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 21 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 21 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
Genders Eligible for Study:   Both
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       francesco.savino@unito.it   
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: Valentina Tarasco, MD         
Ospedale Infantile Regina Margherita Recruiting
Torino, Italy, 10126
Contact: Francesco Savino, MD,PhD         
Principal Investigator: Francesco Savino, Md PhD         
Sponsors and Collaborators
Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
Investigators
Principal Investigator: Francesco Savino, MD, PhD Ospedale Infantile Regina Margherita - Dipartimento di scienze Pediatriche e dell'Adolescenza
  More Information

Publications:

Additional 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: June 24, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna:
infantile colic
lactobacillus
gut microflora
FISH

Additional relevant MeSH terms:
Colic
Abdominal Pain
Pain
Signs and Symptoms
Signs and Symptoms, Digestive
Vitamin D
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Vitamins

ClinicalTrials.gov processed this record on November 19, 2014