Effectiveness of probiotics in the treatment of children with chronic abdominal pain and small intestinal bacterial overgrowth. A randomized placebo-controlled trial.

Chronic abdominal pain is present in 0.3-19% of school-going children in the US
and Europe and is one of the most frequent reasons to visit a pediatrician1. In
29.1% of patients with chronic abdominal pain, pain persists for more than 5
years, despite frequent medical attention.
The pathogenesis of chronic abdominal pain remains unclear, although several
mechanisms have been proposed to explain the symptoms of this condition. Recent
studies have also pointed to an underlying gut microbial mechanism for chronic
abdominal pain. When the microbial population native to the large intestine
migrates proximally into the small intestine, a shift in the host-gut microbial
relationship occurs, known as small intestinal bacterial overgrowth (SIBO).
Similar to children with chronic abdominal pain, children with SIBO complain of
nausea, abdominal pain, flatulence, diarrhoea and constipation.
In a recent study, small intestinal bacterial overgrowth has been reported in
91% of children with chronic abdominal pain compared to 35% in healthy
children. They also found an association between small intestine bacterial
overgrowth and irritable bowel syndrome in children.
There are no published data on the effect of probiotic treatment in children
with chronic abdominal pain, but recent unpublished study results showed that
70% of children with chronic abdominal pain and small intestinal bacterial
overgrowth have an improvement of symptoms after treatment with probiotics.

The aim of this study is to find a succesful treatment for chronic abdominal
pain and small intestinal bacterial overgrowth in children and at the same time
improve the quality of life of these children. A second aim is to reduce the
hospital visits and with that the costs.

70 children age 8-18 years will be randomized and receive probiotics or
placebo.
Children in the probiotics group will be given daily probiotics for 8 weeks (8
grams of powder 4 x 10E9 cfu / g Bifidobacterium and Lactobacillus (Ecologic
junior)). Children in the placebo group will be given daily placebo for 8 weeks.

Outcomes are assessed at several time points: a t=0 (at baseline; before
randomisation), at t=1 (directly after finishing the treatment period), at t=2
(four months after finishing the treatment period) and at t=3 (ten months after
finishing the treatment period).

We will use the following instruments:

•Abdominal pain diary (APD): Patients will be instructed to score pain
intensity and pain frequency in an abdominal pain diary during the baseline
period (a month prior to t=0), for a month prior to t = 1 and for a month prior
to t = 2. Pain intensity will be scored using the validated six-face Faces Pain
Scale-Revised 12: ranging from 1 (=no pain) to 6 (very much pain) (Fig. 1).
Pain frequency will be scored as 0 = no pain, 1 = 0*20 min of pain, 2 = 20 40
min of pain, 3 = 40*90 min of pain and 4 = more than 90 min of daily pain.
The daily scores will be added up to obtain a pain intensity score (minimum
score of 31 and a maximum score of 186) and a pain frequency score (with a
minimal score of 0 and a maximum score of 124) for these different time points.

•Hydrogen breath test: Patients will take this hydrogen breath test three
times, at t=0, t=1 and t=2. In this test, hydrogen exhaled in the breath is
estimated using a gas chromatograph. Bacteria, especially anaerobic, colonizing
the large bowel in health and small bowel in diseased conditions produce
hydrogen by fermentation of unabsorbed carbohydrates. Though small amount of
hydrogen is produced from limited amounts of unabsorbed carbohydrate reaching
the colon, large amounts of hydrogen may be produced if there is malabsorption
of carbohydrate in the small intestine allowing larger amount to reach the
colon or if there is excess of bacteria in the small bowel. The hydrogen
produced by the bacteria is absorbed through the wall of the small or large
intestine or both. The hydrogen-containing blood travels to the lungs where the
hydrogen is released and exhaled in the breath where it can be measured. Breath
test will be performed after overnight fast. Before the test, subjects will be
asked to brush their teeth and rinse mouth with antiseptic mouth wash and tap
water, to eliminate an early hydrogen peak due to action of oral bacteria on
test sugars. End-expiratory breath samples will be collected either in bag or
syringes. At the start of the test, fasting breath hydrogen will be measured. A
fasting breath hydrogen concentration above 20 ppm will be interpreted as small
intestinal bacterial overgrowth.

•Microbiota analyze: faeces samples are collected at t=0 and t=1, before and
after the intervention. In case of a positive effect of the probiotics we would
like to gain insight in the possible mechanisms of probiotic intake on
abdominal pain in children. Therefore, we would like to study the composition
and functionality of the microbiota. DNA based techniques will be used for
microbiota analyses.

The probiotics consist of a mixture of Bifidobacterium and Lactobacillus (8
grams of powder 4 x 10E9 cfu Bifidobacterium and Lactobacillus (Ecologic
junior)). This has te be used once a day for 8 weeks.

The dosage of Winclove 349 (4x10^9 daily dosage ) is in accordance with most
probiotic dosages used in studies and many commercially available products,
ranging from 10^9-10^10 cfu/daily dose. It is not possible to state a general
dose for probiotics; some have shown to be efficacious at lower levels, while
other require substantially more. The dosage of Winclove 349 is based on prior
human studies with similar probiotic products showing a health benefit and no
adverse reactions. In addition, the strains in the product are commercially
available in other similar probiotic powder product sold thought out Europe in
daily dosages varying from 1x109 - 1x1010.