A Multicentre, Randomised, Double-Blind, Placebo Controlled, Crossover Trial On The Efficacy Of A Mixture Of Three Bifidobacteria In Children With Abdominal Pain-Associated Functional Gastrointestinal Disorders
Bifidobacteria In Children With Abdominal Pain-Associated Functional Gastrointestinal Disorders
Sponsors
Source
Federico II University
Oversight Info
Has Dmc
Yes
Brief 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.
Overall Status
Completed
Start Date
2013-12-01
Completion Date
2015-09-01
Primary Completion Date
2015-07-01
Phase
Phase 4
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
Abdominal Pain Frequency |
16 weeks from the enrollment |
Secondary Outcome
Measure |
Time Frame |
Functional Disability |
16 weeks from the enrollment |
Enrollment
73
Conditions
Intervention
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
Mixture of three Bifidobacteria
Placebo
Other Name
Bifidobacterium infantis M-63® breve M-16V® longum BB536®
Eligibility
Criteria
Inclusion Criteria:
- Age 4-18years;
- Diagnosis of FD and IBS pain according to the Rome III criteria
- All parents or legal tutors must sign an informed consent document indicating their
awareness of the investigational nature of this study.
Exclusion Criteria:
- Taking any other type of probiotic in the 2 months prior to enrollment
- Presence of intestinal motility disorders
- Presence of any other significant medical condition
- Presence of previous abdominal surgery
- Inability or unwillingness to give informed consent
Gender
All
Minimum Age
4 Years
Maximum Age
18 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
Eleonora Giannetti, MD |
Principal Investigator |
Department of Translational Medical Sciences, Federico II University |
Location
Facility |
University of Naples "Federico II" Italy Naples 80131 Italy |
Location Countries
Country
Italy
Verification Date
2015-09-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Principal Investigator
Investigator Affiliation
Federico II University
Investigator Full Name
Erasmo Miele
Investigator Title
Assistant Professor
Keywords
Has Expanded Access
No
Condition Browse
Number Of Arms
2
Arm Group
Arm Group Label
Mixture of three Bifidobacteria
Arm Group Type
Active Comparator
Description
Patients were administered 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®) for six weeks. Subsequently, no preparation was administered for a 2-week-''washout'' period. 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.
Arm Group Label
Placebo
Arm Group Type
Placebo Comparator
Description
Patients were administered 1 sachet per day of placebo for six weeks. Subsequently, no preparation was administered for a 2-week-''washout'' period. 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.
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Crossover Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Study First Submitted
February 25, 2014
Study First Submitted Qc
October 1, 2015
Study First Posted
October 2, 2015
Last Update Submitted
October 1, 2015
Last Update Submitted Qc
October 1, 2015
Last Update Posted
October 2, 2015
ClinicalTrials.gov processed this data on December 05, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.