Infant ColicNCT07754968
Use of Bifidobacterium Bifidum in Formula-Fed Infants With Colic, With or Without Atopic Dermatitis
A study testing Bifidobacterium bifidum BFP19® and BFP29® (Bifipral®) in people with Infant Colic and Atopic Dermatitis, run by University of Roma La Sapienza at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 week to 5 monthsHealthy volunteers can take part
- Conditions the study is for
- Infant Colic, Atopic Dermatitis
- What is being tested?
- Bifidobacterium bifidum BFP19® and BFP29® (Bifipral®)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jul 2026to 1 Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 week to 5 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
AOU Sant'Andrea
Roma, RM, 00189
Maurizio Mennini, Doctor, 0633775870, dott.mauriziomennini@gmail.com
About this study
Official title: Efficacy of Bifidobacterium Bifidum on Symptoms of Infant Colic and Atopic Dermatitis: a Randomized Controlled Trial.
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:
Read more
- 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.
Read the detailed description
BACKGROUND AND SCIENTIFIC RATIONALE:
Bifidobacterium bifidum is a primary commensal of the human intestinal microbiota, exhibiting a pronounced tropism for the early stages of life. It is highly adapted to the neonatal ecosystem due to its ability to efficiently utilize both host glycans-specifically human milk oligosaccharides (HMOs)-and intestinal mucin. This capability is enabled by a rich repertoire of extracellular glycosidases and the presence of structures such as sortase-dependent pili, which promote adhesion to the epithelium, mucosal colonization, and interaction with the immune system.
The degradation of HMOs present in breast milk by B. bifidum confers a crucial role in modulating the gut microbiota: the released degradation products, such as fucose, sialic acid, and LNB (Lacto-N-Biose), serve as substrates for other beneficial species, promoting cross-feeding mechanisms and ensuring the establishment of a healthy microbial community.
While in breastfed infants the growth of B. bifidum is sustained by HMOs, non-breastfed infants exhibit a dramatic deficiency of this key species. However, the ability of B. bifidum to stably adhere to the mucosa via pili and metabolize endogenous mucin suggests that it can successfully colonize the intestine even in the absence of breastfeeding, acting as a functional surrogate to restore cross-feeding mechanisms and immune tolerance typical of healthy neonates. This positions B. bifidum among the primary intestinal colonizers capable of significantly modulating the infant's immunological trajectory.
A reduction in bifidobacteria has been associated with both infant colic, defined according to Rome IV criteria, and atopic manifestations, including atopic dermatitis. Both conditions share a background of immuno-enteric immaturity and a higher prevalence of dysbiosis characterized by a decrease in Bifidobacterium and an increase in gas-producing species. In light of this evidence, B. bifidum emerges as a key species whose decline is associated with adverse outcomes along a continuum that includes colic and atopic dermatitis.
STUDY HYPOTHESIS AND OBJECTIVES:
Despite the strong biological rationale, to date there are no randomized controlled trials specifically evaluating the efficacy of B. bifidum in non-breastfed infants with infant colic, nor are structured data available on its potential impact on symptoms associated with atopy.
The primary goal of this study is to evaluate whether daily administration of a probiotic blend consisting of Bifidobacterium bifidum BFP19® and Bifidobacterium bifidum BFP29® (Bifipral® drops) reduces crying duration in non-breastfed infants diagnosed with infant colic according to Rome IV criteria. Additionally, the study explores the impact of this intervention on sleep parameters, bowel habits, fecal microbiota composition (via shotgun metagenomics), short-chain fatty acids (SCFAs) levels, and, in subjects with concomitant atopic dermatitis, changes in the SCORAD score.
PROCEDURAL SUMMARY:
Following a 7-day observational run-in period to confirm diagnosis and collect baseline data, eligible infants are randomized (1:1 ratio, block randomization stratified by age) to receive either Bifipral® drops (5 drops/day, supplying 4 x 10^9 CFU/day total) or an indistinguishable placebo for 8 weeks. Daily diaries are maintained by parents to record behavioral and gastrointestinal outcomes. Clinical assessments and biological sampling occur at baseline (Visit 1), end of treatment at Week 8 (Visit 2), and a final safety follow-up visit scheduled 2 to 4 weeks post-treatment. Fecal samples are processed for metagenomic profiling and SCFA analysis.
- Conditions
- Infant Colic, Atopic Dermatitis
- Being tested
- Bifidobacterium bifidum BFP19® and BFP29® (Bifipral®), Placebo
- Keywords
- Bifidobacterium bifidum, Infant colic, Atopic dermatitis, Probiotics, Gut microbiota, Randomized Controlled Trial
- Medical subject headings
- Colic, Dermatitis, Atopic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
PlaceboDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (3-day run-in average) to Week 8 (end of treatment)
Secondary outcomes (9)
Change from Baseline in Daily Crying Episode Frequency
Change in the average number of crying episodes per 24-hour period, as recorded by parents in the structured daily behavioral diary.
Measured: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Total 24-Hour Sleep Duration
Change in total sleep duration over a 24-hour period (expressed in hours per day), calculated as the average of 3 consecutive days recorded by parents in the daily diary.
Measured: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Number of Nocturnal Awakenings
Change in the mean number of nocturnal awakenings per night, calculated as the average of 3 consecutive nights recorded by parents in the daily diary.
Measured: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Longest Uninterrupted Nighttime Sleep Episode
Change in the duration (expressed in hours) of the longest continuous nighttime sleep episode per night, calculated as the average of 3 consecutive nights recorded by parents in the daily diary.
Measured: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Daily Bowel Movement Frequency
Change in the mean number of bowel movements per day, as recorded by parents in the daily diary.
Measured: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Stool Consistency Score
Change in stool consistency assessed using the modified Bristol Stool Form Scale for infants. The scale ranges from Type 1 (hard lumps) to Type 7 (watery/liquid). Minimum score is 1, maximum score is 7; lower scores indicate harder stool consistency and higher scores indicate looser/more liquid stool consistency.
Measured: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Fecal Microbiota Composition (Alpha Diversity)
Change in gut microbial community alpha diversity (Shannon Diversity Index) determined by shotgun metagenomic sequencing of collected fecal samples.
Measured: Baseline (Visit 1) to Week 8 (Visit 2)
Change from Baseline in Fecal Short-Chain Fatty Acid (SCFA) Concentrations
Change in absolute concentrations (expressed in micromoles per gram of dry stool) of key fecal short-chain fatty acids (acetate, propionate, and butyrate) measured via gas chromatography/mass spectrometry.
Measured: Baseline (Visit 1) to Week 8 (Visit 2)
Change from Baseline in SCORing Atopic Dermatitis (SCORAD) Index Total Score
Change in the SCORing Atopic Dermatitis (SCORAD) index total score evaluated in the subgroup of participants with concomitant atopic dermatitis. The SCORAD total score evaluates disease extent, clinical severity of 6 parameters, and subjective symptoms (pruritus and sleep loss). The total score ranges from 0 to 103, where 0 indicates absence of disease and higher scores represent greater disease severity (worse outcome).
Measured: Baseline (Visit 1) to Week 8 (Visit 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2026
- Study start1 Jul 2026
- Primary completion1 Sep 2028 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Infant ColicStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Giovanni Di Nardo, University of Roma La Sapienza
- Investigators
- Giovanni Di Nardo, Professor, Principal investigator, UOC Pediatrics, AOU Sant'Andrea, Rome / Sapienza University of Rome
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07754968
- Sponsor's protocol ID
- AORN-SP-1/26
- Other IDs
- A126C997677-LB
- Status last verified
- Jul 2026
- First submitted
- 28 Jul 2026
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The study involves the prospective collection of new clinical data and biological samples within the framework of a randomized controlled experimental intervention. Data will be stored in a pseudonymized form using unique identification codes and processed in compliance with current privacy regulations. Informed consent will be obtained by the investigators or designated staff
Publications
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.
PubMed 31797399Samarra 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.
PubMed 40340669Hoskinson 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.
PubMed 38670232Rahman 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.
PubMed 37020647Ouwehand 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.
PubMed 11447399Partty 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.
PubMed 22403665Lordan 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.
PubMed 38206006Verma 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.
PubMed 30341145Egan 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.
PubMed 25420416Turroni 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.
PubMed 25191315Turroni 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.
PubMed 31717486
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Bifidobacterium Bifidum on Symptoms of Infant Colic and Atopic Dermatitis: a Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT07754968
- Acronym / sponsor ID
- AORN-SP-1/26
- Conditions
- Infant Colic, Atopic Dermatitis
- Keywords
- Bifidobacterium bifidum, Infant colic, Atopic dermatitis, Probiotics, Gut microbiota, Randomized Controlled Trial
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- 1 Jul 2026 (actual)
- Primary completion
- 1 Sep 2028 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 10 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
BACKGROUND AND SCIENTIFIC RATIONALE:
Bifidobacterium bifidum is a primary commensal of the human intestinal microbiota, exhibiting a pronounced tropism for the early stages of life. It is highly adapted to the neonatal ecosystem due to its ability to efficiently utilize both host glycans-specifically human milk oligosaccharides (HMOs)-and intestinal mucin. This capability is enabled by a rich repertoire of extracellular glycosidases and the presence of structures such as sortase-dependent pili, which promote adhesion to the epithelium, mucosal colonization, and interaction with the immune system.
The degradation of HMOs present in breast milk by B. bifidum confers a crucial role in modulating the gut microbiota: the released degradation products, such as fucose, sialic acid, and LNB (Lacto-N-Biose), serve as substrates for other beneficial species, promoting cross-feeding mechanisms and ensuring the establishment of a healthy microbial community.
While in breastfed infants the growth of B. bifidum is sustained by HMOs, non-breastfed infants exhibit a dramatic deficiency of this key species. However, the ability of B. bifidum to stably adhere to the mucosa via pili and metabolize endogenous mucin suggests that it can successfully colonize the intestine even in the absence of breastfeeding, acting as a functional surrogate to restore cross-feeding mechanisms and immune tolerance typical of healthy neonates. This positions B. bifidum among the primary intestinal colonizers capable of significantly modulating the infant's immunological trajectory.
A reduction in bifidobacteria has been associated with both infant colic, defined according to Rome IV criteria, and atopic manifestations, including atopic dermatitis. Both conditions share a background of immuno-enteric immaturity and a higher prevalence of dysbiosis characterized by a decrease in Bifidobacterium and an increase in gas-producing species. In light of this evidence, B. bifidum emerges as a key species whose decline is associated with adverse outcomes along a continuum that includes colic and atopic dermatitis.
STUDY HYPOTHESIS AND OBJECTIVES:
Despite the strong biological rationale, to date there are no randomized controlled trials specifically evaluating the efficacy of B. bifidum in non-breastfed infants with infant colic, nor are structured data available on its potential impact on symptoms associated with atopy.
The primary goal of this study is to evaluate whether daily administration of a probiotic blend consisting of Bifidobacterium bifidum BFP19® and Bifidobacterium bifidum BFP29® (Bifipral® drops) reduces crying duration in non-breastfed infants diagnosed with infant colic according to Rome IV criteria. Additionally, the study explores the impact of this intervention on sleep parameters, bowel habits, fecal microbiota composition (via shotgun metagenomics), short-chain fatty acids (SCFAs) levels, and, in subjects with concomitant atopic dermatitis, changes in the SCORAD score.
PROCEDURAL SUMMARY:
Following a 7-day observational run-in period to confirm diagnosis and collect baseline data, eligible infants are randomized (1:1 ratio, block randomization stratified by age) to receive either Bifipral® drops (5 drops/day, supplying 4 x 10^9 CFU/day total) or an indistinguishable placebo for 8 weeks. Daily diaries are maintained by parents to record behavioral and gastrointestinal outcomes. Clinical assessments and biological sampling occur at baseline (Visit 1), end of treatment at Week 8 (Visit 2), and a final safety follow-up visit scheduled 2 to 4 weeks post-treatment. Fecal samples are processed for metagenomic profiling and SCFA analysis.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Active Probiotic Group (Bifipral®) | Experimental | Dietary Supplement: Bifidobacterium bifidum BFP19® and BFP29® (Bifipral®)Non-breastfed infants receiving oral drops containing a probiotic blend of Bifidobacterium bifidum BFP19® and Bifidobacterium bifidum BFP29® (Bifipral®) daily for 8 weeks. |
| Placebo Control Group | Placebo comparator | Dietary Supplement: PlaceboNon-breastfed infants receiving oral drops of an indistinguishable placebo daily for 8 weeks. |
Who may qualify
- Ages
- 1 week to 5 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bifidobacterium bifidum BFP19® and BFP29® (Bifipral®)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. | Dietary supplement | Active Probiotic Group (Bifipral®) |
| PlaceboMatching 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. | Dietary supplement | Placebo Control Group |
Primary outcome
Treatment Response Rate Based on Daily Crying Duration
Time frame: Baseline (3-day run-in average) to Week 8 (end of treatment)
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.
9 secondary outcomes
Change from Baseline in Daily Crying Episode Frequency
Time frame: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Total 24-Hour Sleep Duration
Time frame: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Number of Nocturnal Awakenings
Time frame: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Longest Uninterrupted Nighttime Sleep Episode
Time frame: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Daily Bowel Movement Frequency
Time frame: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Stool Consistency Score
Time frame: Baseline (3-day run-in average) to Week 8 (end of treatment)
Change from Baseline in Fecal Microbiota Composition (Alpha Diversity)
Time frame: Baseline (Visit 1) to Week 8 (Visit 2)
Change from Baseline in Fecal Short-Chain Fatty Acid (SCFA) Concentrations
Time frame: Baseline (Visit 1) to Week 8 (Visit 2)
Change from Baseline in SCORing Atopic Dermatitis (SCORAD) Index Total Score
Time frame: Baseline (Visit 1) to Week 8 (Visit 2)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- Background: PubMed 31797399Nocerino 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.
- Background: PubMed 40340669Samarra 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.
- Background: PubMed 38670232Hoskinson 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.
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- Individual participant dataSharing planned: No. The study involves the prospective collection of new clinical data and biological samples within the framework of a randomized controlled experimental intervention. Data will be stored in a pseudonymized form using unique identification codes and processed in compliance with current privacy regulations. Informed consent will be obtained by the investigators or designated staff
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giovanni Di Nardo, Professor principal investigator
UOC Pediatrics, AOU Sant'Andrea, Rome / Sapienza University of Rome
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bifidobacterium bifidum BFP19® and BFP29® (Bifipral®) in people with Infant Colic and Atopic Dermatitis, run by University of Roma La Sapienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giovanni Di Nardo, Professor (0633775870, giovanni.dinardo@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Response Rate Based on Daily Crying Duration (time frame: Baseline (3-day run-in average) to Week 8 (end of treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07754968, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.