The Effect of Probiotics on Symptoms of Infantile Colic (PROCOLIN)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Colic
• Intervention / Treatment: Dietary supplement: Probiotic Formulation; Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Susana Manzano Jiménez, Ph.D.; Phone Number: 918035179; Email: susana.manzano@probisearch.com

Study Locations

• Spain
  • Madrid, Spain, 28009
    • Centro de Salud Ibiza
  • Madrid, Spain, 28010
    • Hospital Vithas La Milagrosa
  • Madrid, Spain, 28018
    • Centro de Salud Campo de la Paloma
  • Madrid, Spain, 28023
    • Hospital Vithas Aravaca
  • Madrid
    • Majadahonda, Madrid, Spain, 28220
      • Centro de Salud Cerro del Aire

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 month (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Healthy male or female.
2. Age ≤ 8 weeks old.
3. 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.
4. Exclusively breastfeeding and planning to breastfeed for duration of study.
5. With a written informed consent signed by the father, mother, or legal guardian, and with expressed or implied consent of the other parent.
6. With parents willing to complete questionnaires, records, and diaries associated to the study and to complete all clinical visits and telephone calls.

Exclusion Criteria:

1. Birthweight < 2500 g.
2. Gestational age < 37 weeks.
3. Apgar score at 5 minutes < 7.
4. Partially or fully formula fed infants, with the exception of the first 4 days after birth.
5. Stunted growth/weight loss (< 100 g/week from birth to last reported).
6. Gastroesophageal reflux disease, short bowel syndrome, chronic intestinal diseases or gastrointestinal malformations.
7. Fever and/or infectious diseases, or current systemic infections, or history of congenital infections.
8. Genetic diseases and chromosomal abnormalities.
9. Metabolic diseases or pancreatic insufficiency.
10. Immunodeficiency.
11. Neurological diseases.
12. Suspected or confirmed food allergies and intolerances.
13. Use of probiotics, prebiotics, antibiotics, or gastric acid inhibitors by the infant at any time from birth to the moment of screening.
14. Use of anti-colic medication at any time from birth to the moment of screening.
15. Use of probiotic supplements by the mother between the birth of their infant and the moment of screening.
16. Currently enrolled in another clinical study or having participated in another clinical trial from birth to the moment of screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; Participants in this group will be randomized to receive the probiotic formulation for 4 weeks.	Dietary supplement: Probiotic Formulation; 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.
Placebo Comparator: Control Group; Participants in this group will be randomized to receive the placebo for 4 weeks.	Dietary supplement: Placebo; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal protein markers	Comparison of the differences in the concentration of fecal protein markers between probiotic and placebo groups in stool samples collected at baseline and at week 4. Proteins will be quantified using immunoassay methods.	5 weeks
Incidence of Adverse Events	Comparison of the number of adverse events (AEs) and serious adverse events (SAEs) recorded in the probiotic and placebo groups.	6 weeks

Collaborators and Investigators

• Sponsor: Lallemand Health Solutions
• Collaborators: ProbiSearch SL
• Investigators: Study Director: Esther Jiménez Quintana, Ph.D., ProbiSearch SL

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2022
• Primary Completion (Estimated): September 1, 2023
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: January 6, 2022
• First Posted (Actual): January 20, 2022

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Probiotics; Sleep duration; Crying time; Infantile colic
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Colic
• Other Study ID Numbers: L-022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: After publications of the results, de-identified data will be shared with qualified researchers and scientists upon reasonable request to the sponsor including a detailed proposal of the intended use of the data, as per the Lallemand Health Solutions Inc. Policy on Clinical Trial Transparency and Data Sharing (available upon request).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No