Efficacy of Bifidobacterium Bifidum on Symptoms of Infant Colic and Atopic Dermatitis: a Randomized Controlled Trial.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Treatment Response Rate Based on Daily Crying Duration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 1 Week 至 5 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Active Probiotic Group (Bifipral®)
Non-breastfed infants receiving oral drops containing a probiotic blend of Bifidobacterium bifidum BFP19® and Bifidobacterium bifidum BFP29® (Bifipral®) daily for 8 weeks.
干预措施: Bifidobacterium bifidum BFP19® and BFP29® (Bifipral®) (Dietary Supplement)
Placebo Control Group
Non-breastfed infants receiving oral drops of an indistinguishable placebo daily for 8 weeks.
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Treatment Response Rate Based on Daily Crying Duration
时间窗: 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.
次要结局
- 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))
- Change from Baseline in Stool Consistency Score(Baseline (3-day run-in average) to Week 8 (end of treatment))
- Change from Baseline in Fecal Microbiota Composition (Alpha Diversity)(Baseline (Visit 1) to Week 8 (Visit 2))
- Change from Baseline in Fecal Short-Chain Fatty Acid (SCFA) Concentrations(Baseline (Visit 1) to Week 8 (Visit 2))
- Change from Baseline in SCORing Atopic Dermatitis (SCORAD) Index Total Score(Baseline (Visit 1) to Week 8 (Visit 2))
研究者
Prof. Giovanni Di Nardo
Professor
University of Roma La Sapienza