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

Infantile Colic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03434249
• Other study ID #: PSC-DS BIGI
• Status: Completed
• Phase: N/A
• Start date: November 11, 2016
• Est. completion date: November 6, 2017

Study information

• Verified date: January 2020
• Source: SOFAR S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: November 6, 2017
• Est. primary completion date: November 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 7 Weeks

Eligibility

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.

Related Conditions & MeSH terms

• Colic
• Colic, Infantile
• Infantile Colic

Intervention

Dietary Supplement:
• Bifidobacterium, BB-12® (Bifidolactis Infant)

• Bifidolactis Infant Placebo

Locations

Country	Name	City	State
Italy	Dipartimento di Scienze Mediche Traslazionali - Sezione Pediatria - Università degli Studi di napoli "Federico II"	Napoli

Sponsors (1)

Lead Sponsor	Collaborator
SOFAR S.p.A.

Country where clinical trial is conducted

Italy, 

References & Publications (13)

BRAZELTON TB. Crying in infancy. Pediatrics. 1962 Apr;29:579-88. — View Citation

Gupta SK. Is colic a gastrointestinal disorder? Curr Opin Pediatr. 2002 Oct;14(5):588-92. Review. — View Citation

Hall B, Chesters J, Robinson A. Infantile colic: a systematic review of medical and conventional therapies. J Paediatr Child Health. 2012 Feb;48(2):128-37. doi: 10.1111/j.1440-1754.2011.02061.x. Epub 2011 Apr 7. Review. — View Citation

Hyman PE, Milla PJ, Benninga MA, Davidson GP, Fleisher DF, Taminiau J. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology. 2006 Apr;130(5):1519-26. Review. — View Citation

Iacovou M, Ralston RA, Muir J, Walker KZ, Truby H. Dietary management of infantile colic: a systematic review. Matern Child Health J. 2012 Aug;16(6):1319-31. doi: 10.1007/s10995-011-0842-5. Review. — View Citation

Kabeerdoss J, Devi RS, Mary RR, Prabhavathi D, Vidya R, Mechenro J, Mahendri NV, Pugazhendhi S, Ramakrishna BS. Effect of yoghurt containing Bifidobacterium lactis Bb12® on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers. Nutr J. 2011 Dec 23;10:138. doi: 10.1186/1475-2891-10-138. — View Citation

Lucassen PL, Assendelft WJ, van Eijk JT, Gubbels JW, Douwes AC, van Geldrop WJ. Systematic review of the occurrence of infantile colic in the community. Arch Dis Child. 2001 May;84(5):398-403. Review. — View Citation

Mohan R, Koebnick C, Schildt J, Mueller M, Radke M, Blaut M. Effects of Bifidobacterium lactis Bb12 supplementation on body weight, fecal pH, acetate, lactate, calprotectin, and IgA in preterm infants. Pediatr Res. 2008 Oct;64(4):418-22. doi: 10.1203/PDR.0b013e318181b7fa. — View Citation

Mohan R, Koebnick C, Schildt J, Schmidt S, Mueller M, Possner M, Radke M, Blaut M. Effects of Bifidobacterium lactis Bb12 supplementation on intestinal microbiota of preterm infants: a double-blind, placebo-controlled, randomized study. J Clin Microbiol. 2006 Nov;44(11):4025-31. Epub 2006 Sep 13. — View Citation

Savino F, Bailo E, Oggero R, Tullio V, Roana J, Carlone N, Cuffini AM, Silvestro L. Bacterial counts of intestinal Lactobacillus species in infants with colic. Pediatr Allergy Immunol. 2005 Feb;16(1):72-5. — View Citation

Savino F, Cordisco L, Tarasco V, Calabrese R, Palumeri E, Matteuzzi D. Molecular identification of coliform bacteria from colicky breastfed infants. Acta Paediatr. 2009 Oct;98(10):1582-8. doi: 10.1111/j.1651-2227.2009.01419.x. Epub 2009 Jul 9. — View Citation

Savino F, Cresi F, Pautasso S, Palumeri E, Tullio V, Roana J, Silvestro L, Oggero R. Intestinal microflora in breastfed colicky and non-colicky infants. Acta Paediatr. 2004 Jun;93(6):825-9. — View Citation

Szajewska H, Gyrczuk E, Horvath A. Lactobacillus reuteri DSM 17938 for the management of infantile colic in breastfed infants: a randomized, double-blind, placebo-controlled trial. J Pediatr. 2013 Feb;162(2):257-62. doi: 10.1016/j.jpeds.2012.08.004. Epub 2012 Sep 14. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Calprotectin	Evaluation of calprotectin levels in fecal samples	at 7 days (Visit T1 - baseline) and 28 days from the baseline (Visit T5)
Secondary	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)
Secondary	LL37 Peptide	Evaluation of LL37 peptide levels in fecal samples	at 7 days (Visit T1 - baseline) and 28 days from the baseline (Visit T5)
Secondary	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)
Secondary	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)