Combined Probiotics is More Effective in the Treatment of Infantile Colic
Condition: Infantile Colic
MeSH terms: Colic
Study type: Interventional

Summary: 
      All participants are randomized into 1 of 3 treatment arms, the mixture L acidophilus, B
      longum and B. bifidum group, Lactobacillus reuteri or placebo group.

      Primary outcome is defined as a reduction in the duration of average crying and fussing
      times, from baseline (day 0) to age 6 months, to <3 hours per day. Secondary outcome are the
      number of participants who respond to treatment on days 7, 14, 21, 28 and each month till age
      6 months.
    

Detailed description: 
      Infantile colic or excessive infant crying with no medical cause is a burdensome condition.
      Although crying is often considered "normal behavior," 5%-40% of infants cry inconsolably and
      excessively, accompanied by bouts of fussiness and gas passing.

      The etiology of infantile colic remains unclear; various theories have been proposed,
      however, recent studies have implicated a potential role of the intestinal microbiome
      ,colicky infants presents lower amounts of Bifidobacteria and Lactobacilli. Several
      randomized clinical trials (RCT) have been conducted to examine the effectiveness of
      Lactobacillus reuteri DSM17938 vs placebo in the treatment of infantile colic. However, there
      is no trial adopt probiotics contained Bifidobacteria and Lactobacilli to treat infantile
      colic. In view of the above evidences, the investigators thus hypothesis that probiotics
      contained Bifidobacteria and Lactobacilli will more effect to increase the diversity of
      intestinal microbiome and alleviate infantile colic. The objective of this study is to
      evaluate the efficacy of combine probiotics (L. acidophilus, B. longus and B. bifidus)
      compare to Lactobacillus reuteri in the treatment infantile colic. Fecal calprotectin levels
      and microbial community in colic infants before and after probiotics will be evaluated to
      explore the mechanism of effectiveness of probiotics.

      This, double-blind RCT will be carried out from December 2016 to November 2018 at Children's
      hospital of China Medical university. Eligible infants are included in the study after
      written informed consent is obtained from a parent/guardian. Study participants will meet the
      following inclusion criteria: (1) diagnosis of infantile colic (ie, crying or fussy/gassy
      episodes ≥3 hours/day for ≥3 days/7 days, as defined by a modified definition of Wessel
      criteria) at study commencement; (2) age 3 weeks to 5 months at study commencement (although
      infantile colic typically manifests between age 2 weeks and 3-4 months, to capture infants
      with delayed onset of colic, infants with colic up to 6 months were eligible); (3)
      exclusively breastfed; (4) term delivery (≥37 weeks gestation); and (5) healthy infants with
      birth weight ≥2500 g. Exclusion criteria included: (1) a major medical problem or acute
      illness, including gastroesophageal reflux, as determined by a pediatrician; (2) history of
      antibiotic treatment before or during the study; (3) history of probiotic supplementation;
      (4) history of any allergies to any of the ingredients in the probiotic mixture of
      acidophilus, B longus and B. bifidus or placebo (sunflower oil, medium-chain triglyceride
      oil, and silicon dioxide); and (5) concurrent participation in another clinical trial.

      Primary outcome is defined as a reduction in the duration of average crying and fussing
      times, from baseline (day 0) to age 6 months, to <3 hours per day. Secondary outcome are the
      number of participants who respond to treatment on days 7, 14, 21, 28 and each month till age
      6months.

      All participants are randomized into 1 of 3 treatment arms, the mixture L acidophilus, B
      longus and B. bifidus group, Lactobacillus reuteri or placebo group. Independent Research
      Support Pharmacy personnel, not participating in the study at the pharmacy of the Children
      Hospital prepare a computer-generated 3-treatment randomization schedule with a random block
      of varying size to ensure balance in the allocation of participants between treatment arms.
      Stool bacterial microbiota will be accessed by next generation sequence and fecal
      calprotectin will be measured by ELISA.

      A minimum of 60 participants per study arm is needed to provide 80% power to detect an effect
      size of 0.5 and a detectable difference between groups in mean crying and fussing times of 50
      minutes. Statistical analyses are performed using SPSS version 20 (IBM, Armonk, New York)
      using an intention-to-treat approach. The Student t test is used to compare mean values of
      continuous variables approximating a normal distribution, and the Mann-Whitney U test is used
      for nonnormally distributed variables. Proportions are compared using the χ2 test or Fisher
      exact test, as appropriate. All reported statistical tests are 2-sided.
    

Intervention name(s): L. acidophilus TYCA06, B. longum BLI-02 and B. bifidum VDD088; L. reuteri GL-104; Placebo
Intervention type(s): Other; Other; Other
Intervention description(s): Taking 1 mix probiotics capsule at bed time everyday for three months.; Taking 1 probiotic capsule at bed time everyday for three months.; Taking 1 placebo capsule at bed time everyday for three months.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Infantile Colic; Bifidobacteria and Lactobacilli; Intestinal Microbiome; Probiotics