Evaluation of a Probiotic (Bifidobacterium in the Treatment of Infantile Colic (IC)

Study Overview
=================
Brief Summary
-----------------
Infantile colic (IC) criteria includes all of the following in subjects aged ≤ 4 months: paroxysms of irritability, fussing, or crying that start and stop without obvious cause; episodes lasting 3 or more hours per day and occurring at least 3 days per week for at least 1 week; and no failure to thrive. The condition is very common in the first 4 months of life (10-30 % of infants) with a peak prevalence at 6-8 weeks and is characterized by excessive and inconsolable crying without an identifiable cause. Infantile colic cause considerable stress for the baby and the family, huge medical expenses (the IC cause 10-20 % of all pediatric visits in the first 4 months of life) and frequent formula changes. The pathophysiology of IC is still poorly defined, but differences in gut microbiota composition seem to be involved. In particular, differences in the number and species of Lactobacilli spp, Klebsiella spp and Escherichia coli spp have been demonstrated in subjects with IC, and it has been postulated that these alterations could be responsible for an abnormal gas production within gut lumen resulting in distension and abdominal pain. These findings suggest the potential role of probiotics as preventive and therapeutic strategy for the IC.

Official Title
-----------------
Randomized Clinical Trial to Evaluate the Efficacy of Bifidobacterium in the Treatment of Infantile Colic (IC)

Conditions
-----------------
Infantile Colic

Intervention / Treatment
-----------------
* Dietary Supplement: probiotic (BIfidobacterium, BB-12®)
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: exclusively breastfed healthy infants of both sex, aged ≤ 7 weeks; Diagnosis of IC according to Rome III criteria Written informed consent of the parent/tutor Exclusion Criteria: Birth weight<2500 g Gestational age<37 weeks APGAR 5 minutes <7 Formula feeding Abnormal body growth/loss of weight (<100 g/weeks from birth to the last reported weight) Neurological diseases Known or suspected food allergy Gastroesophageal reflux disease Use of substances that alter gut microbiota (pre/pro/synbiotic, antibiotics, gastric acidity inhibitors) or any anti-colic drug in the last 2 weeks prior the enrollment History of fever and/or infectious diseases in the last 2 weeks prior the enrollment Ongoing systemic infections History of congenital infections Chronic intestinal diseases (cystic fibrosis or other forms of pancreatic insufficiency primitive) Malformation of the gastrointestinal (such as esophageal atresia, intestinal atresia, short bowel syndrome, malrotation), urinary or respiratory tract Metabolic diseases Genetic diseases and chromosomal abnormalities Primary or secondary immunodeficiencies Not sufficient reliability or presence of conditions that may result in non-compliance/adherence of the patient to the Protocol Previous participation in this study

Ages Eligible for Study
-----------------
Minimum Age: 1 Week
Maximum Age: 7 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic (Bifidobacterium)<br>Active, Bifidobacterium BB12 | Dietary Supplement: probiotic (BIfidobacterium, BB-12®)<br>* probiotic (Bifidobacterium, BB-12®)<br>|
| Placebo Comparator: Placebo<br>Placebo | Dietary Supplement: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean daily crying duration | reduction of ≥50% of mean daily crying duration | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of regurgitation |  | up to 28 days | 
| Evaluation of the gut microbiota modifications | Stool sample | up to 28 days | 
| fecal production of peptides from innate immune system | Stool sample | up to 28 days | 
| fecal short chain fatty acids production | Stool sample | 28 days | 
| evacuative frequency |  | up to 28 days | 
| consistency of the fecal mass | assessed by means of Bristol score | up to 28 days | 
| number of crying episode |  | up to 28 days | 
| sleep | duration of sleep | up to 28 days |