An interventional study of Bifidobacterium bifidum BFP19® and BFP29® (Bifipral®) and Placebo in Infant Colic and Atopic Dermatitis, sponsored by University of Roma La Sapienza. Recruiting at 1 site in Italy. Open to participants aged 1 Week to 5 Months, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-10.
Sponsored by University of Roma La Sapienza · Not applicable, Interventional, and Prevention
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:
Participants will be asked to:
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.
127 studies on the registry are indexed under Colic; 18 are open to participants now.
This study's planned enrollment of 64 is below the median of 76 across 110 interventional studies indexed under Colic.
Browse Colic studies →University of Roma La Sapienza is the lead sponsor of 398 studies on the registry; 56 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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®)
Non-breastfed infants receiving oral drops of an indistinguishable placebo daily for 8 weeks.
Dietary Supplement: Placebo
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.
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.
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.
Time frame: Baseline (3-day run-in average) to Week 8 (end of treatment)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: Baseline (Visit 1) to Week 8 (Visit 2)
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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
Started Jul 2026 (actual). Primary completion is estimated for Sep 2028, 26 months after the start.
Of 32 non-industry interventional studies with no phase under Colic, half reached primary completion within 17 months of starting (the median), counting those still running; a quarter within 8 and three quarters within 40. This study's planned 26 months is above that.
Counting every sponsor, half of 44 studies reached it within 21 months; a quarter within 10 and three quarters within 40.
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