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

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

Sponsors

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

Source Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
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.

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.

Overall Status Recruiting
Start Date March 2008
Completion Date December 2019
Primary Completion Date November 2019
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
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 0 - 7 - 21 - 30 days
Secondary Outcome
Measure Time Frame
Responders to treatment 30 day
To analyze intestinal microflora day 0 and day 30
Assay of Th17/Treg balance time 0- 30 days
Enrollment 155
Condition
Intervention

Intervention Type: Other

Intervention Name: Lactobacillus reuteri DSM 17938

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

Arm Group Label: Lactobacillus reuteri

Other Name: Reuterin,Noos - Italy; BIOGAIA drops - Sweden

Intervention Type: Other

Intervention Name: Placebo

Description: 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.

Arm Group Label: Placebo

Other Name: Placebo BIOGAIA Sweden

Intervention Type: Dietary Supplement

Intervention Name: L.reuteri + Vit D

Arm Group Label: L.reuteri + vit D

Intervention Type: Dietary Supplement

Intervention Name: Vit D placebo

Arm Group Label: Vit D Placebo

Eligibility

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

Gender: All

Minimum Age: N/A

Maximum Age: 16 Weeks

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Francesco Savino, MD, PhD Principal Investigator Ospedale Infantile Regina Margherita - Dipartimento di Pediatria.S.S.D. SAPI, Torino
Overall Contact

Last Name: Francesco Savino, MD, PhD

Phone: 00390113135618

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
Ospedale Infantile Regina Margherita | Torino, TO, 10126, Italy Recruiting Francesco Savino, MD PhD +39 0113135618 [email protected] Francesco Savino, MD PhD Principal Investigator
Ospedale Infantile Regina Margherita | Torino, 10126, Italy Recruiting Francesco Savino, MD, PhD 00390113135224 [email protected] Valentina Tarasco, MD Sub-Investigator Elisabetta Palumeri, MD Sub-Investigator Emanuela Locatelli, MD Sub-Investigator Diego Matteuzzi, Professor Sub-Investigator Lisa Cordisco, PhD Sub-Investigator Roberto Oggero, MD Sub-Investigator Emanuele Castagno, MD Sub-Investigator Roberto Calabrese, PhD Sub-Investigator Stefan Roos, PhD Sub-Investigator Simone Ceratto, MD Sub-Investigator Angela De Marco, MD Sub-Investigator Maria Garro, MD Sub-Investigator Massimiliano Bergallo, BS Sub-Investigator Paola Montanari, BS Sub-Investigator Ilaria Galliano, BS Sub-Investigator Silvia Nicoli, MD Sub-Investigator Cristina Calvi, BS Sub-Investigator Valentina Daprà, BS Sub-Investigator
Ospedale Infantile Regina Margherita | Torino, 10126, Italy Recruiting Francesco Savino, MD, PhD +390113135618 [email protected] Francesco Savino, MD, PhD Principal Investigator Maria Garrro, MD Sub-Investigator Massimiliano Bergallo, BS Sub-Investigator
Location Countries

Italy

Verification Date

February 2019

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna

Investigator Full Name: Dr. SAVINO Francesco

Investigator Title: MD, PhD

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Lactobacillus reuteri

Type: Active Comparator

Description: 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.

Label: Placebo

Type: Placebo Comparator

Description: 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.

Label: L.reuteri + vit D

Type: Active Comparator

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

Label: Vit D Placebo

Type: Placebo Comparator

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

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov