Clinical Trial to Evaluate the Efficacy of Bifidobacterium BB-12® in the Treatment of Infantile Colic

Study Overview
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Brief Summary
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This is a single-center, randomized, double blind controlled study to investigate the effects of Bifidobacterium, BB-12® versus placebo in a study group of pediatric patients with infantile colic.

Official Title
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Studio Clinico Randomizzato Per Valutare l'Efficacia Del Bifidobacterium BB-12® Nel Trattamento Delle Coliche Infantili

Conditions
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Infantile Colic, Colic, Infantile

Intervention / Treatment
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* Dietary Supplement: Bifidobacterium, BB-12® (Bifidolactis Infant)
* Dietary Supplement: Bifidolactis Infant Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients are included in the study if they meet all the following criteria: Exclusively breastfed healthy infants of both sexes, aged ≤ 7 weeks. Diagnosis of IC according to Rome III criteria. Written informed consent of the parent/tutor. Exclusion Criteria: Patients are excluded from this study if they meet any of the following criteria: Birth weight < 2500 g. Gestational age < 37 weeks. APGAR 5 minutes < 7. Formula feeding. Stunting/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 (probiotics, prebiotics, antibiotics, gastric acidity inhibitors) in the last 2 weeks prior the enrollment. History of fever and/or infectious diseases in the last 2 weeks prior to enrollment. Ongoing systemic infections. History of congenital infections. Chronic intestinal diseases (cystic fibrosis or other forms of primitive pancreatic insufficiency) Primitive or secondary malformations of the gastrointestinal tract (such as esophageal atresia, intestinal atresia, short bowel syndrome, malrotation). 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
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Maximum Age: 7 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a prospective randomized double blind placebo controlled clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I<br>patients who take Bifidobacterium BB-12® (Bifidolactis Infant), 6 drops a day (guaranteeing a billion of living cells) for 28 consecutive days; | Dietary Supplement: Bifidobacterium, BB-12® (Bifidolactis Infant)<br> <br> |
| Placebo Comparator: Group II<br>patients who take Bifidolactis Infant Placebo 6 drops a day for 28 consecutive days. | Dietary Supplement: Bifidolactis Infant Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With >=50% Reduction in Mean Weekly Crying Duration | Treatment success rate was evaluated in terms of reduction of crying duration, comparing mean weekly duration of the last Week (from T4 to T5) and mean weekly duration of Week 1 (from T0 to T1). The daily number and duration of crying episodes has been collected in the 'Evaluation of crying' section of the patient diary. Weekly mean is defined as the mean of the calculated average daily durations during the selected week and is described by means of descriptive statistics for continuous data. Mean changes from baseline (i.e. mean of the first Week) to the mean of the selected week will be computed as well. The following categories of patients has been defined: Success = patients who meet the criteria for the treatment success rate No Success = patients who do not meet the criteria for the treatment success rate Missing = patients who did not do the last visit (Visit T5 - at 28 days from baseline) | at 28 days from the baseline (Visit T5) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Crying Episodes | Weekly mean of cries will be defined as the mean number of cries reported in the Evaluation of behavior section during the week (i.e. number of episodes/number of days with episodes) and will be described by means of descriptive statistics for continuous data. Mean changes from baseline (i.e. mean of the first Week) to the mean of the selected week will be analyzed too. | at 7 days (Visit T1 - baseline) and 28 days from the baseline (Visit T5) | 
| Infectious Diseases Incidence | Number of infections in respiratory system, gastrointestinal system, urinary tract and skin. An infection was defined as an Adverse Event with SOC equal to Infections and Infestations. | at each visit, for 5 weeks starting from the enrollment in the study (Visit T0, T1, T2, T3, T4 and T5) | 
| Bowel Evacuation - Stool Frequency | Daily frequency of bowel evacuation. The frequency of stools were collected daily in the diary. Stool frequency was evaluated as the mean of total daily stools reported per week. | at each weekly visit from baseline (Visit T1, T2, T3, T4 and T5) | 
| Bowel Evacuation - Stool Consistency | Stool consistency was evaluated as the number and the proportion of patients who reported at least one stool sample of each type per week, according to Bristol scale as follows: Type A = separate hard lumps, like nuts (hard to pass) Type B = sausage-shaped, but lumpy Type C = Like a sausage but with cracks on its surface Type D = like a sausage or snake, smooth and soft Only a descriptive statistics Type E = soft blobs with clear-cut edges (passed easily) Type F = fluffy pieces with ragged edges, a mushy stool Type G = watery, no solid pieces (entirely liquid). Patients could report more than one stool consistency per day then the sum of the Count of Participants for each group at each visit could be Greater then the Overall Number of Participants Analyzed | at each weekly visit from baseline (Visit T1, T2, T3, T4 and T5) | 
| Infant's Mood | The infant's mood (calm, asleep, agitated, irritable) was collected daily in the diary and was evaluated as the number and the proportion of infants who reported at least one mood of each type per week. Patients could report more than one mood per day then the sum of the Count of Participants for each group at each visit could be greater then the Overall Number of Participants Analyzed. | at each weekly visit from baseline (Visit T1, T2, T3, T4 and T5) | 
| Infant's Sleep | Duration of sleep (in minutes) was collected daily in the diary during the entire study period. Mean daily duration of sleep by week was defined as the mean of the daily durations during the selected week and was described by means of descriptive statistics for continuous data. | at each weekly visit from baseline (Visit T1, T2, T3, T4 and T5) | 
| Infant's Temper | Duration of temper episodes (in minutes) was collected daily in the diary during the entire study period. Mean daily duration of temper episodes by week was defined as the mean of the daily durations during the selected week and was described by means of descriptive statistics for continuous data. | at each weekly visit from baseline (Visit T1, T2, T3, T4 and T5) | 
| Infant's Feeding | Duration of feeding (in minutes) was collected daily in the diary during the entire study period. Mean daily feeding time by week was defined as the mean of the daily durations during the selected week and was described by means of descriptive statistics for continuous data. | at each weekly visit from baseline (Visit T1, T2, T3, T4 and T5) | 
| Calprotectin | Evaluation of calprotectin levels in fecal samples | at 7 days (Visit T1 - baseline) and 28 days from the baseline (Visit T5) | 
| Beta-defensin Type 2 | Evaluation of Beta-defensin type 2 levels in fecal samples | at 7 days (Visit T1 - baseline) and 28 days from the baseline (Visit T5) | 
| LL37 Peptide | Evaluation of LL37 peptide levels in fecal samples | at 7 days (Visit T1 - baseline) and 28 days from the baseline (Visit T5) | 
| Short Chain Fatty Acids - Butyrate | Evaluation of Butyrate levels in fecal samples | at 7 days (Visit T1 - baseline) and 28 days from the baseline (Visit T5) | 
| Secretory Immunoglobulin A (SIgA) | Secretory immunoglobulin A (SIgA) levels in fecal samples | at 7 days (Visit T1 - baseline) and 28 days from the baseline (Visit T5) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bifidobacterium