Use of Bifidobacterium Bifidum in Formula-Fed Infants With Colic, With or Without Atopic Dermatitis

NCT07754968 | Recruiting

• 2 other identifiers: AORN-SP-1/26A126C997677-LB
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate whether daily probiotic supplementation with Bifidobacterium bifidum (Bifipral® drops) can reduce crying time in formula-fed infants aged 5 months or younger diagnosed with infant colic (according to Rome IV criteria), with or without concomitant atopic dermatitis. The main questions it aims to answer are:

• Does daily administration of B. bifidum for 8 weeks achieve at least a 50% reduction in average daily crying duration compared to placebo?
• Does B. bifidum supplementation improve secondary outcomes, including crying frequency, sleep quality, bowel movement frequency, stool consistency, fecal microbiota composition, short-chain fatty acid (SCFA) levels, and SCORAD score in infants with atopic dermatitis? Researchers will compare formula-fed infants receiving Bifipral® drops (containing B. bifidum strains BFP19® and BFP29®) to a comparison group receiving an indistinguishable placebo to see if the probiotic safely improves colic symptoms and gut microbiota balance. Participants will be asked to:
• Complete a 7-day observational run-in period to confirm eligibility and record baseline symptoms in a daily diary.
• Administer 5 drops daily of the study product (probiotic or placebo) for 8 weeks.
• Complete daily diaries tracking crying duration/frequency, sleep parameters, and bowel habits.
• Attend 3 clinical visits (Baseline, Week 8, and a Safety Follow-up 2-4 weeks post-treatment).
• Provide fecal samples at Baseline (Visit 1) and Week 8 (Visit 2) for microbiota profiling and SCFA analysis.

Conditions

Infant Colic; Atopic Dermatitis

Keywords

Bifidobacterium bifidum; Infant colic; Atopic dermatitis; Probiotics; Gut microbiota; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Treatment Response Rate Based on Daily Crying Duration

  Proportion of infants achieving a clinical response, defined as a \>/=50% reduction in the mean daily crying duration compared to baseline. Crying duration is recorded by parents in a structured daily diary. Baseline crying duration is calculated as the average of the values recorded during the 3 consecutive days preceding the baseline visit., in accordance with methodological standards of probiotic studies and Rome IV recommendations.

  Baseline (3-day run-in average) to Week 8 (end of treatment)

Secondary Outcomes (9)

• Change from Baseline in Daily Crying Episode Frequency

  Baseline (3-day run-in average) to Week 8 (end of treatment)

• Change from Baseline in Total 24-Hour Sleep Duration

  Baseline (3-day run-in average) to Week 8 (end of treatment)

• Change from Baseline in Number of Nocturnal Awakenings

  Baseline (3-day run-in average) to Week 8 (end of treatment)

• Change from Baseline in Longest Uninterrupted Nighttime Sleep Episode

  Baseline (3-day run-in average) to Week 8 (end of treatment)

• Change from Baseline in Daily Bowel Movement Frequency

  Baseline (3-day run-in average) to Week 8 (end of treatment)

Study Arms (2)

Active Probiotic Group (Bifipral®)

EXPERIMENTAL

Non-breastfed infants receiving oral drops containing a probiotic blend of Bifidobacterium bifidum BFP19® and Bifidobacterium bifidum BFP29® (Bifipral®) daily for 8 weeks.

Dietary Supplement: Bifidobacterium bifidum BFP19® and BFP29® (Bifipral®)

Placebo Control Group

PLACEBO COMPARATOR

Non-breastfed infants receiving oral drops of an indistinguishable placebo daily for 8 weeks.

Dietary Supplement: Placebo

Interventions

Bifidobacterium bifidum BFP19® and BFP29® (Bifipral®) DIETARY_SUPPLEMENT

Oral drops containing a combination of Bifidobacterium bifidum BFP19® and Bifidobacterium bifidum BFP29®. Administered at a dose of 5 drops once daily (providing a total of 4 x 10⁹ CFU/day, 2 x 10⁹ CFU per strain), preferably in the morning before feeding, for 8 weeks.

Active Probiotic Group (Bifipral®)

Placebo DIETARY_SUPPLEMENT

Matching placebo oral drops, indistinguishable from the active intervention in packaging, color, odor, taste, consistency, and labeling. Administered at a dose of 5 drops once daily, preferably in the morning before feeding, for 8 weeks.

Placebo Control Group

Eligibility Criteria

• Age: 1 Week - 5 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Non-breastfed infants aged ≤ 5 months diagnosed with infant colic according to Rome IV criteria, with or without atopic dermatitis.
• Written informed consent from parents or legal guardians.

You may not qualify if:

• Age \> 5 months.
• Exclusive breastfeeding or mixed feeding.
• Absence of infant colic diagnosis.
• Presence of chronic diseases, neoplasms, immunodeficiencies, chronic infections, autoimmune diseases, IBD, celiac disease, genetic-metabolic disorders, cystic fibrosis or other chronic pulmonary diseases, cardiovascular/respiratory/GI malformations, neuropsychiatric disorders, neurological conditions, or vegetarian/vegan diet.

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

AOU Sant'Andrea

Roma, RM, 00189, Italy

RECRUITING

Related Publications (11)

• Nocerino R, De Filippis F, Cecere G, Marino A, Micillo M, Di Scala C, de Caro C, Calignano A, Bruno C, Paparo L, Iannicelli AM, Cosenza L, Maddalena Y, Della Gatta G, Coppola S, Carucci L, Ercolini D, Berni Canani R. The therapeutic efficacy of Bifidobacterium animalis subsp. lactis BB-12(R) in infant colic: A randomised, double blind, placebo-controlled trial. Aliment Pharmacol Ther. 2020 Jan;51(1):110-120. doi: 10.1111/apt.15561. Epub 2019 Dec 3.

  PMID: 31797399 BACKGROUND

• Samarra A, Renwick S, Arzamasov AA, Rodionov DA, Spann K, Cabrera-Rubio R, Acuna-Gonzalez A, Martinez-Costa C, Hall L, Segata N, Osterman AL, Bode L, Collado M. Human milk oligosaccharide metabolism and antibiotic resistance in early gut colonizers: insights from bifidobacteria and lactobacilli in the maternal-infant microbiome. Gut Microbes. 2025 Dec;17(1):2501192. doi: 10.1080/19490976.2025.2501192. Epub 2025 May 9.

  PMID: 40340669 BACKGROUND

• Hoskinson C, Medeleanu MV, Reyna ME, Dai DLY, Chowdhury B, Moraes TJ, Mandhane PJ, Simons E, Kozyrskyj AL, Azad MB, Petersen C, Turvey SE, Subbarao P. Antibiotics taken within the first year of life are linked to infant gut microbiome disruption and elevated atopic dermatitis risk. J Allergy Clin Immunol. 2024 Jul;154(1):131-142. doi: 10.1016/j.jaci.2024.03.025. Epub 2024 Apr 24.

  PMID: 38670232 BACKGROUND

• Rahman T, Sarwar PF, Potter C, Comstock SS, Klepac-Ceraj V. Role of human milk oligosaccharide metabolizing bacteria in the development of atopic dermatitis/eczema. Front Pediatr. 2023 Mar 20;11:1090048. doi: 10.3389/fped.2023.1090048. eCollection 2023.

  PMID: 37020647 BACKGROUND

• Ouwehand AC, Isolauri E, He F, Hashimoto H, Benno Y, Salminen S. Differences in Bifidobacterium flora composition in allergic and healthy infants. J Allergy Clin Immunol. 2001 Jul;108(1):144-5. doi: 10.1067/mai.2001.115754. No abstract available.

  PMID: 11447399 BACKGROUND

• Partty A, Kalliomaki M, Endo A, Salminen S, Isolauri E. Compositional development of Bifidobacterium and Lactobacillus microbiota is linked with crying and fussing in early infancy. PLoS One. 2012;7(3):e32495. doi: 10.1371/journal.pone.0032495. Epub 2012 Mar 5.

  PMID: 22403665 BACKGROUND

• Lordan C, Roche AK, Delsing D, Nauta A, Groeneveld A, MacSharry J, Cotter PD, van Sinderen D. Linking human milk oligosaccharide metabolism and early life gut microbiota: bifidobacteria and beyond. Microbiol Mol Biol Rev. 2024 Mar 27;88(1):e0009423. doi: 10.1128/mmbr.00094-23. Epub 2024 Jan 11.

  PMID: 38206006 BACKGROUND

• Verma R, Lee C, Jeun EJ, Yi J, Kim KS, Ghosh A, Byun S, Lee CG, Kang HJ, Kim GC, Jun CD, Jan G, Suh CH, Jung JY, Sprent J, Rudra D, De Castro C, Molinaro A, Surh CD, Im SH. Cell surface polysaccharides of Bifidobacterium bifidum induce the generation of Foxp3+ regulatory T cells. Sci Immunol. 2018 Oct 19;3(28):eaat6975. doi: 10.1126/sciimmunol.aat6975.

  PMID: 30341145 BACKGROUND

• Egan M, Motherway MO, Kilcoyne M, Kane M, Joshi L, Ventura M, van Sinderen D. Cross-feeding by Bifidobacterium breve UCC2003 during co-cultivation with Bifidobacterium bifidum PRL2010 in a mucin-based medium. BMC Microbiol. 2014 Nov 25;14:282. doi: 10.1186/s12866-014-0282-7.

  PMID: 25420416 BACKGROUND

• Turroni F, Duranti S, Bottacini F, Guglielmetti S, Van Sinderen D, Ventura M. Bifidobacterium bifidum as an example of a specialized human gut commensal. Front Microbiol. 2014 Aug 21;5:437. doi: 10.3389/fmicb.2014.00437. eCollection 2014.

  PMID: 25191315 BACKGROUND

• Turroni F, Duranti S, Milani C, Lugli GA, van Sinderen D, Ventura M. Bifidobacterium bifidum: A Key Member of the Early Human Gut Microbiota. Microorganisms. 2019 Nov 9;7(11):544. doi: 10.3390/microorganisms7110544.

  PMID: 31717486 BACKGROUND

MeSH Terms

Conditions

Colic; Dermatitis, Atopic

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Giovanni Di Nardo, Professor

  UOC Pediatrics, AOU Sant'Andrea, Rome / Sapienza University of Rome

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giovanni Di Nardo, Professor

CONTACT

0633775870; giovanni.dinardo@uniroma1.it

Maurizio Mennini, MD

CONTACT

+39 0633775780; dott.mauriziomennini@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The study is a randomized, double-blind, placebo-controlled, parallel-group (1:1) trial. Block randomization will be stratified by age (\<3 months / 3 to 5 months) to control for variability related to the physiological maturation of the microbiota and crying patterns.

Study Record Dates

• First Submitted: July 28, 2026
• First Posted: August 10, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: August 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)