Prospective Study to Determine the Factors Influencing Infant Colic

Study Overview
=================
Brief Summary
-----------------
Randomized study to determine the effect of a commercialized combination of 2 probiotic strains (Bifidobacterium Longum and Pediococcus pentosaceus) and the impact of feeding type in babies diagnosed with colic under Roma IV criteria when administered for 21 days.

Detailed Description
-----------------
Randomized, single-blind, interventional study with two parallel groups to determine the effect of two different commercialized probiotic products (Lactobacillus reuteri or a combination of two different strains (Bifidobacterium longum and Pediococcus pentosaceus)) and the impact of feeding type in babies diagnosed with colic under Roma IV criteria. Infants meeting selection criteria are randomized 1:1 and stratified according to the type of feeding (breastfed or formula). Probiotics are administered once a day (5 drops) for 21 days. Parents must document clinical parameters during this 21 days. This parameters include colic-related symptoms, other functional gastrointestinal disorders symptoms, parental anxiety and adverse events. Moreoever, stool samples are collected to determine intestinal microbiota and calprotectin levels.

Official Title
-----------------
Prospective Study to Determine the Factors Influencing Infant Colic Course in Infants Taking Probiotics

Conditions
-----------------
Infant Colic

Intervention / Treatment
-----------------
* Dietary Supplement: Lactoflora colicare
* Dietary Supplement: Reuteri gotas


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy infants from 2 to 12 weeks of age Infants diagnosed with infant colic following Roma IV criteria for clinical research Gestational age greater or equal to 37 weeks Birth weight greater than 2100 g Exclusively breastfed or formula fed with a maximum of one daily intake of breast milk. Exclusion Criteria: Infants that are fed with solid food. Infants whose parents can not appropriately follow the requirements of the study. Antibiotics or probiotics administration to the infant (including infant formula with probiotics) 2 weeks prior the inclusion in the study. Breastfed infants whose mothers have taken antibiotics and/or probiotics 2 weeks prior the inclusion in the study. Specific medication use for the treatment of functional digestive disorder: antacids (IBP type or H2 blockers), laxative Polyethylene glycol (8PEG), lactulose, magnesia), lactase or simeticone. Infants going through therapies related with acupuncture, homeopathy, medicinal herbs, or taking anti-inflammatory or antispasmodic drugs.

Ages Eligible for Study
-----------------
Minimum Age: 2 Weeks
Maximum Age: 12 Weeks

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, multicentric, single-blind trial in infants between 2 and 12 weeks of age diagnosed with infant colic, who will be allocated to receive one of the two comercialized probiotic products B. Longum and P. Pentosaceus (branch one) or L. Reuteri (branch two) for 21 days
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lactoflora colicare<br>Probiotic multi-strain formulation comprising Bifidobacterium longum CECT7894 and Pediococcus pentosaceus CECT8830 in sunflower oil and medium-chain triglyceride oil. Probiotic strains have Qualified Presumption of Safety (QPS) status by European Food Safety Authority | Dietary Supplement: Lactoflora colicare<br>* Probiotic multi-strain formulation containing Bifidobacterium longum CECT7894 and Pediococcus pentosaceus CECT8830 for 21 days, 5 drops/day preferably during the first intake of milk<br>|
| Active Comparator: Reuteri gotas<br>Probiotic single-strain formulation comprising Lactobacillus reuteri DSM17938 in sunflower oil and medium-chain triglyceride oil. Probiotic strains have Qualified Presumption of Safety (QPS) status by European Food Safety Authority | Dietary Supplement: Reuteri gotas<br>* Probiotic single-strain formulation containing Lactobacillus reuteri DSM17938 for 21 days, 5 drops/day before or after any daily meal.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of crying and fussing | Change on daily crying and fussing minutes measured through Barr ( Barr et al., 1988).validated crying and fussing scale. The Barr scale consists of a 24 hours dairy where parents paint number of hours crying and fussing every day. Results show the number of hours of crying and fussing per day. | 21 days | 
| Percent of responders | Percent of subjects whose change in crying time is equal or larger than 50% from baseline | 7, 14, 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of regurgitations | Change in daily number of regurgitations | 21 days | 
| Bowel movements | Change in daily number of bowel movements | 21 days | 
| Food intake | Frequency of food intake | 21 days | 
| Parent's anxiety and depression | Change in parent's anxiety and depression score measured through Hospital Anxiety and Depression Scale (HADS). The HADS questionnaire has 7 items each for depression and anxiety subscales. Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. A total subscale score of >8 points out of a possible 21 denotes considerable symptoms of anxiety or depression. | baseline, day 21 | 
| Fecal microbiome | Changes on fecal microbiome evaluated by RNA ribosomal 16S genes analysis | baseline, day 21 | 
| Fecal calprotectin | Change on calprotectin in feces | baseline, day 21 | 
| Adverse events | Frequency of adverse events reported on dairy report form after randomization and until day 21 | 21 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Infant colic, probiotic