Bifidobacteria In Children With Abdominal Pain-Associated Functional Gastrointestinal Disorders
Condition: Irritable Bowel Syndrome; Dyspepsia Chronic
MeSH terms: Irritable Bowel Syndrome; Gastrointestinal Diseases; Digestive System Diseases; Dyspepsia; Abdominal Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      Abdominal pain (AP)-associated functional gastrointestinal disorders (FGIDs), particularly
      Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD), are common in pediatrics, and
      no safe and effective treatment is available. Although probiotics have shown promising
      results in adults, few studies have been published in children. The Bifidobacterium Infantis,
      Bifidobacterium Breve and Bifidobacterium Longum are the most important beneficial bacteria
      in children and represent 95% of the total bacterial population in the intestine of breastfed
      infant.

      Objectives: 1) To evaluate the effect of oral administration of a mixture of Bifidobacteria
      on the improvement of frequency and intensity of AP in children with FD and IBS. 2) To
      evaluate the effect of oral administration of a mixture of Bifidobacteria on quality of life
      in children with FD and IBS.
    

Detailed description: 
      The study was a randomized, double blind, placebo-controlled, crossover trial conducted at
      two pediatric tertiary care centers in Naples and Foggia. All children aged 8-17 years
      referred for IBS or FD to the Pediatric Clinics of the two participating centers between
      January and December 2014 were eligible for the study. IBS and FD were diagnosed using the
      Rome III criteria for pediatric FGIDs. The main exclusion criterion was the presence of
      chronic organic gastrointestinal diseases, assessed by full clinical history and examination,
      and initial laboratory investigation including complete blood cell count, erythrocyte
      sedimentation rate, C-reactive protein, serum amylase and lipase, tissue transglutaminase
      antibodies, total serum immunoglubulins A, and fecal calprotectin. Abnormalities in any of
      these tests resulted in the patient's exclusion from the study. Further exclusion criteria
      were previous abdominal surgery, diseases affecting bowel motility, or concomitant
      psychiatric, neurological, metabolic, renal, hepatic, infectious, hematological,
      cardiovascular or pulmonary disorders. Finally, patients who had been using any commercial
      preparation of probiotics during the previous 3 months were also excluded.

      The study was articulated in 16 weeks. After recruitment, patients entered a 2 week-run-in
      phase during which evacuative frequency, stool features and gastrointestinal symptoms were
      recorded on a daily basis using a questionnaire/diary provided at the study entry by the
      physician. At the end of the baseline period, patients returned to the center where
      information regarding AP characteristics, bowel habits and associated symptoms were recorded
      using a previously validated interviewer-administered questionnaire for pediatric FGIDs. The
      "Functional Disability Inventory" (FDI), a second interviewer-administered validated
      questionnaire was used to assess physical and psychosocial functions and investigate
      patients' QoL. The instrument consists of 15 items concerning perceptions of activity
      limitations during the past 2 weeks; total scores are computed by summing the ratings for
      each item. Total available score ranges from 0 to 60 and higher scores indicate greater
      disability. After completing these questionnaires, patients were assigned in a double-blinded
      fashion to the placebo or intervention group according to a computer-generated randomization
      allocation table. Participants were randomized to receive either 1 sachet per day of a
      mixture of three Bifidobacteria (namely, 3 billions of Bifidobacterium longum BB536®, 1
      billion of Bifidobacterium infantis M-63®, and 1 billion of Bifidobacterium breve M-16V®), or
      an identical looking and tasting placebo for six weeks. No further medication other than
      analgesics was allowed for the whole duration of the study.

      After completing the six weeks of treatment, no preparation was administered for a
      2-week-''washout'' period. Afterwards, each patient was switched to the other group and
      treated with placebo or probiotics for a period of six further weeks.

      At each follow-up visit subjects underwent a complete physical examination, data recorded on
      the daily diaries were collected and compliance to treatment was verified. Furthermore, the
      FGIDs symptoms questionnaire and the FDI were administered by the physician and answers were
      recorded.

      The main outcome parameters considered for the assessment of the efficacy of the administered
      treatment were abdominal pain and QoL. The investigators considered a decrease in FDI score
      of at least 75% of the baseline score to define a relevant improvement in QoL. Secondary
      outcome parameters were changes in bowel habit for IBS patients, and the effect of the tested
      treatment on nausea for FD subjects.

      The investigators involved in the recruitment and follow-up of patients, those coordinating
      the study and analyzing the data, patients themselves and their caregivers were all unaware
      of the randomization group at each phase of the study.

      The institutional ethical review boards of both participating centers approved the study
      protocol. Written informed consent was obtained from the parents or legal guardians before
      enrollment.
    

Intervention name(s): Mixture of three Bifidobacteria
Intervention type(s): Drug
Intervention description(s): This investigation will be a randomized, double-blind, placebo-controlled, cross-over trial. The study will include 70 children with FD or IBS and will be articulated in 16 weeks as follows. Fifty-nine children (median age 11.2 years, range 5.2-17.9) with IBS and FD were randomized to receive either a mixture of three Bifidobacteria or a placebo for 6 weeks. At the end, after a 2-week-''washout'' period, each patient was switched to the other group and followed for 6 further weeks. At baseline and at follow-up, patients and/or their parents completed a dairy for bowel habit and gastrointestinal symptoms, and a quality of life (QoL) questionnaire.
Other intervention name(s): Bifidobacterium infantis M-63® breve M-16V® longum BB536®
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Children; Abdominal Pain; Functional Dyspepsia; Irritable Bowel Syndrome; Quality of Life