Clinical trial NCT02577133: Prevention of Colic With the Probiotic Lactobacillus Reuteri
Official title: Prevention of Colic With the Probiotic Lactobacillus Reuteri in Mexican Infants: Randomized, Double-blind Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Colic
Keywords: colic
probiotic
Lactobacillus reuteri
prevention
Lead sponsor: Hospital General Naval de Alta Especialidad - Escuela Medico Naval
Sponsor class: OTHER_GOV
First posted: 2015-10-16
Enrollment: 478
Sex: ALL
Minimum age (years): 1
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Colic is a term for inconsolable crying happened in the first months of life. Its etiology is multifactorial and caregiver and pediatrician generates among other problems: anxiety, risk of child abuse as well as economic costs.

There is now enough evidence for the treatment of colic using probiotics, especially Lactobacillus reuteri.

The investigators study aims to demonstrate the utility for the prevention of colic with L. reuteri and thereby avoid the problems caused by this pathology.

Objective: Compare the number of events of colic among infants with oral probiotic Lactobacillus reuteri during the first month of life versus infants with placebo

Study Design. Double blind, randomized, controlled, 492 neonates of 37-42 gestational age, breast or formula fed, will receive L. reuteri 5 drops (1x108 CFU) daily or placebo for 28 days. The investigators trial will be performed at Naval Hospital in Mexico City.

Detailed description: Methods:

This study is planned for October 2015 to October 2016 aiming newborns born population in Naval Hospital

Inclusion:

* Term Healthy Newborns (RN) ≥38 weeks and ≤ 41 weeks of gestation
* Appropriate weight for gestational age
* ≥than 8 Apgar at 5 minutes
* Egress at the first 24-48 hours of life of the newborn with the mother of hospital
* No congenital or physical abnormalities on physical examination at birth.
* Availability during the study period.
* Thorough understanding of the protocol by parents
* Informed Consent is signed by both parents.

Exclusion:

* Administration of antibiotics to the mother for a week before the birth of the newborn.
* Administration of probiotics newborn before inclusion or consumption by the mother during these last two trimesters.
* Medication Management newborn different routine prescribed at birth.

Elimination

* Loss of monitoring
* Abandonment by parents
* Diagnosis of allergy to cow's milk protein (confirmed by resolution of symptoms after switching to Formula hypo allergenic or free feeding cow's milk by the mother in breastfed children).
* Diagnosis of structural alterations or gastrointestinal illness to explain the symptoms of colic in the following months after the inclusion

Interventions:

The patients enrolled will receive probiotics (1000000000 CFU per day) or placebo every days for 28 days

Weekly, each patient will be called twice to interrogate the number of events colic as well as the different variables under study

After birth, on 15, 30, 45 and 60 of life will be cited for clinical examination and review and weight dropper bottle of probiotic

• Principal: Number of events or inconsolable crying

• Secondary: Average or evacuations / day Average or regurgitation / day Drugs to decrease excessive crying Medical reviews for excessive crying Changes feeding for excessive crying Level of satisfaction with the care of the newborn (numerical scale from 0: the worst possible, 10: completely satisfied)

• Universal variables

Weight:

Size:

Gender Weeks gestation Type of birth Feeding of formula / breast-

Eligibility criteria: Inclusion Criteria:

* Term Healthy Newborns (RN) ≥38 weeks and ≤ 41 weeks of gestation.
* Appropriate weight for gestational age
* ≥than 8 Apgar at 5 minutes
* Egress at the first 24-48 hours of life of the newborn with the mother of hospital
* No congenital or physical abnormalities on physical examination at birth.
* Availability during the study period.
* Thorough understanding of the protocol by parents
* Informed Consent is signed by both parents.

Exclusion Criteria:

* Administration of antibiotics to the mother for a week before the birth of the newborn.
* Administration of probiotics newborn before inclusion or consumption by the mother during these last two trimesters.
* Medication Management newborn different routine prescribed at birth.

Primary outcomes:
measure: Event number of colic
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Secretaria de Marina-Armada de México (Mexican Navy)
name: Héctor Javier Varona Bobadilla, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hyman PE, Milla PJ, Benninga MA, Davidson GP, Fleisher DF, Taminiau J. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology. 2006 Apr;130(5):1519-26. doi: 10.1053/j.gastro.2005.11.065.
citation: WESSEL MA, COBB JC, JACKSON EB, HARRIS GS Jr, DETWILER AC. Paroxysmal fussing in infancy, sometimes called colic. Pediatrics. 1954 Nov;14(5):421-35. No abstract available.
citation: Douglas P, Hill P. Managing infants who cry excessively in the first few months of life. BMJ. 2011 Dec 15;343:d7772. doi: 10.1136/bmj.d7772. No abstract available.
citation: E. Ortega Páeza , D. Barroso Espaderob Flashes pediátricos AEpap Cólico del lactante Rev Pediatr Aten Primaria Supl. 2013;(22):81-7
citation: Wolke D, Samara M, Alvarez Wolke M. Meta-analysis of fuss/cry durations and colic prevalence across countries: Proceedings of the11th International Infant Cry Research Workshop, June, 2011, The Netherlands.
citation: Cohen GM, Albertini LW. Colic. Pediatr Rev. 2012 Jul;33(7):332-3; discussion 333. doi: 10.1542/pir.33-7-332. No abstract available.
citation: Barr RG, Rotman A, Yaremko J, Leduc D, Francoeur TE. The crying of infants with colic: a controlled empirical description. Pediatrics. 1992 Jul;90(1 Pt 1):14-21.
citation: Romanello S, Spiri D, Marcuzzi E, Zanin A, Boizeau P, Riviere S, Vizeneux A, Moretti R, Carbajal R, Mercier JC, Wood C, Zuccotti GV, Crichiutti G, Alberti C, Titomanlio L. Association between childhood migraine and history of infantile colic. JAMA. 2013 Apr 17;309(15):1607-12. doi: 10.1001/jama.2013.747.
citation: Savino F, Cordisco L, Tarasco V, Calabrese R, Palumeri E, Matteuzzi D. Molecular identification of coliform bacteria from colicky breastfed infants. Acta Paediatr. 2009 Oct;98(10):1582-8. doi: 10.1111/j.1651-2227.2009.01419.x. Epub 2009 Jul 9.
citation: de Weerth C, Fuentes S, Puylaert P, de Vos WM. Intestinal microbiota of infants with colic: development and specific signatures. Pediatrics. 2013 Feb;131(2):e550-8. doi: 10.1542/peds.2012-1449. Epub 2013 Jan 14.
citation: 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.
citation: Iacono G, Merolla R, D'Amico D, Bonci E, Cavataio F, Di Prima L, Scalici C, Indinnimeo L, Averna MR, Carroccio A; Paediatric Study Group on Gastrointestinal Symptoms in Infancy. Gastrointestinal symptoms in infancy: a population-based prospective study. Dig Liver Dis. 2005 Jun;37(6):432-8. doi: 10.1016/j.dld.2005.01.009. Epub 2005 Mar 2.
citation: Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006 Apr;130(5):1377-90. doi: 10.1053/j.gastro.2006.03.008. No abstract available.
citation: Charrois TL, Sandhu G, Vohra S. Probiotics. Pediatr Rev. 2006 Apr;27(4):137-9. doi: 10.1542/pir.27-4-137. No abstract available.
citation: http://www.biogaia.com/lactobacillus-reuter
citation: Talarico TL, Casas IA, Chung TC, Dobrogosz WJ. Production and isolation of reuterin, a growth inhibitor produced by Lactobacillus reuteri. Antimicrob Agents Chemother. 1988 Dec;32(12):1854-8. doi: 10.1128/AAC.32.12.1854.
citation: Morelli L, Capurso L. FAO/WHO guidelines on probiotics: 10 years later. J Clin Gastroenterol. 2012 Oct;46 Suppl:S1-2. doi: 10.1097/MCG.0b013e318269fdd5. No abstract available.
citation: Lifschitz C. Probiotics: Implications for Paediatric Health, Nestlé Nutrition Institute, South Asia Workshop Proceedings Vol. 1, Issue 1, 2013
citation: 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.
citation: Savino F, Cordisco L, Tarasco V, Palumeri E, Calabrese R, Oggero R, Roos S, Matteuzzi D. Lactobacillus reuteri DSM 17938 in infantile colic: a randomized, double-blind, placebo-controlled trial. Pediatrics. 2010 Sep;126(3):e526-33. doi: 10.1542/peds.2010-0433. Epub 2010 Aug 16.
citation: Chumpitazi BP, Shulman RJ. Five probiotic drops a day to keep infantile colic away? JAMA Pediatr. 2014 Mar;168(3):204-5. doi: 10.1001/jamapediatrics.2013.5002. No abstract available.
citation: Sung V, Collett S, de Gooyer T, Hiscock H, Tang M, Wake M. Probiotics to prevent or treat excessive infant crying: systematic review and meta-analysis. JAMA Pediatr. 2013 Dec;167(12):1150-7. doi: 10.1001/jamapediatrics.2013.2572.
citation: Indrio F, Di Mauro A, Riezzo G, Civardi E, Intini C, Corvaglia L, Ballardini E, Bisceglia M, Cinquetti M, Brazzoduro E, Del Vecchio A, Tafuri S, Francavilla R. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr. 2014 Mar;168(3):228-33. doi: 10.1001/jamapediatrics.2013.4367.