The Effect of Probiotics on Symptoms of Infantile Colic

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effects of a probiotic formulation on the daily crying patterns of infants. It is hypothesized that participants given the probiotic formulation will show a significant reduction in daily crying duration compared to participants receiving the placebo.

Detailed Description
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Participants diagnosed with symptoms of infantile colic will be recruited to participate in this randomized, double-blind, placebo-controlled, two-arm parallel study. Eligible participants will be enrolled in this study for 6 weeks, and will undergo a 1-week run-in baseline period followed by a 4-week interventional period, then a 1-week follow-up period. The study will consist of 7 visits (V0 to V6): 4 in-person visits that alternate with 3 phone calls.

Official Title
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The Effect of a Probiotic on Symptoms of Infantile Colic: a Randomized, Double-blind, Placebo-controlled Study (PROCOLIN)

Conditions
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Colic

Intervention / Treatment
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* Dietary Supplement: Probiotic Formulation
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female. Age ≤ 8 weeks old. Diagnosis of infantile colic according to the Rome IV criteria. Infants must show cry or fuss behaviour for 3 or more hours per day, during 3 or more days in 7 days. Exclusively breastfeeding and planning to breastfeed for duration of study. With a written informed consent signed by the father, mother, or legal guardian, and with expressed or implied consent of the other parent. With parents willing to complete questionnaires, records, and diaries associated to the study and to complete all clinical visits and telephone calls. Exclusion Criteria: Birthweight < 2500 g. Gestational age < 37 weeks. Apgar score at 5 minutes < 7. Partially or fully formula fed infants, with the exception of the first 4 days after birth. Stunted growth/weight loss (< 100 g/week from birth to last reported). Gastroesophageal reflux disease, short bowel syndrome, chronic intestinal diseases or gastrointestinal malformations. Fever and/or infectious diseases, or current systemic infections, or history of congenital infections. Genetic diseases and chromosomal abnormalities. Metabolic diseases or pancreatic insufficiency. Immunodeficiency. Neurological diseases. Suspected or confirmed food allergies and intolerances. Use of probiotics, prebiotics, antibiotics, or gastric acid inhibitors by the infant at any time from birth to the moment of screening. Use of anti-colic medication at any time from birth to the moment of screening. Use of probiotic supplements by the mother between the birth of their infant and the moment of screening. Currently enrolled in another clinical study or having participated in another clinical trial from birth to the moment of screening.

Ages Eligible for Study
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Maximum Age: 8 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>Participants in this group will be randomized to receive the probiotic formulation for 4 weeks. | Dietary Supplement: Probiotic Formulation<br>* Participants will be asked to take one sachet daily, containing 1 billion CFU of the probiotic formula. Sachets must be dissolved in warm water or mother's milk before consumption.<br>|
| Placebo Comparator: Control Group<br>Participants in this group will be randomized to receive the placebo for 4 weeks. | Dietary Supplement: Placebo<br>* Participants will be asked to take one sachet containing the placebo daily. Sachets must be dissolved in warm water or mother's milk before consumption.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms of infantile colic | Comparison of the difference in the proportion of infants with reductions in mean daily crying duration by over 50 percent from baseline between the probiotic and placebo groups, as assessed by the baby's Daily Diary. | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms of infantile colic: Daily crying duration | Comparison of the average change from baseline in the mean daily crying duration between the probiotic and placebo groups, as assessed by the baby's Daily Diary. | 5 weeks | 
| Symptoms of infantile colic: Number of crying episodes | Comparison of the change in the number of crying episodes from baseline between the probiotic and placebo groups, as assessed by the baby's Daily Diary. | 5 weeks | 
| Symptoms of infantile colic: Sleep duration | Comparison of the difference in sleep duration from baseline between the probiotic and placebo groups, as assessed by the baby's Daily Diary. | 5 weeks | 
| Symptoms of infantile colic: Time to a 25 and 50 percent reduction in cry/fuss time | Comparison of the difference in time to reach a 25 percent and 50 percent improvement in cry/fuss time from baseline between the probiotic and placebo groups, as assessed by the baby's Daily Diary. | 5 weeks | 
| Symptoms of infantile colic: Parental perception | Comparison of the difference in the perceived evolution of colic symptoms by parents of participants in the probiotic and placebo groups, as assessed by questions about the evolution of colic symptoms at visits 2 and 4. | 5 weeks | 
| Change in the mother's quality of life | Comparison of the changes in the overall score of the SF-36 from baseline (0 to 100; a higher score corresponds to a better quality of life), between mothers of participants in the probiotic and placebo groups. | 5 weeks | 
| Bowel movement frequency | Comparison of the changes in bowel movement frequency and consistency from baseline between the probiotic and placebo groups, as assessed by the Amsterdam Infant Stool Scale. | 5 weeks | 
| Fecal strain recovery of the probiotic | Presence of the probiotic strain in participants in the probiotic group, as determined by qPCR analysis of stool samples collected at baseline and at week 4. | 5 weeks | 
| Fecal microbiome composition | Comparison of the differences in the composition of fecal microbiota and mycobiota between the probiotic and placebo groups, as determined by 16S sequencing of stool samples collected at baseline and at week 4. | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infantile colic, Crying time, Probiotics, Sleep duration