The primary objective of this study is to determine the effect of mebeverine on abdominal pain intensity and frequency in children with irritable bowel syndrome or functional abdominal pain - not otherwise specified.
ID
Source
Brief title
Condition
- Gastrointestinal motility and defaecation conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the proportion of patients with at least 50% reduction
of their abdominal pain intensity and frequency at the end of treatment (12
weeks). The main goal in the treatment of patients with IBS or FAP-NOS is
reduction of abdominal pain and therefore pain is our primary outcome. Severity
of abdominal pain will be assessed using a diary card, on which patients record
daily intensity on a 6 point Likert scale and frequency of abdominal pain
episodes during a period of 7 consecutive days. Recording of pain during 7 days
is elaborate, but has the benefit that the problem of individual variability in
symptoms over time will be reduced. This 7-day diary recording will be done (I)
at the start of the baseline period, (II) in the fourth week of the study
(start of treatment), (III) in the eight week, (IV) at the twelfth week (end of
treatment) and (V) four weeks after the end of treatment.
Secondary outcome
Secondary outcomes of this study are to investigate the effect of mebeverine on
other outcome parameters such as adequate relief, quality of life, depression
and anxiety scores, and school absenteeism in children, to investigate the
effect of reassurance, explanation and simple dietary and behavioural advice,
to study the influence of labelling on the effect of both mebeverine and
placebo on pain scores, to study the effect of mebeverine on the faecal gut
microbiota composition and to determine the safety of mebeverine in children
with irritable bowel syndrome or functional abdominal pain - not otherwise
specified. These secondary outcomes will be measured at the start of the
baseline period and at the end of treatment.
Background summary
Chronic abdominal pain due to irritable bowel syndrome (IBS) or functional
abdominal pain - not otherwise specified (FAP-NOS) is common in children,
resulting in a reduced quality of life and associated with a higher risk of
depression and anxiety. The first line of standard medical care for chronic
abdominal pain consists of explanation, reassurance, dietary advice and
painkillers if needed. The effect of this therapy has not been investigated
thoroughly. Apart from the painkillers, mebeverine is also often prescribed by
general practitioners and paediatric gastroenterologists for children with IBS
or FAP-NOS. Mebeverine is a spasmolytic agent. In adults studies have been done
to assess the efficacy of this agent, but in children these studies are
lacking, even though mebeverine is already registered for the use in children
above 10 years.
The setting of an RCT is not comparable to daily practice in which patients
know that they are given an active drug. Information provided to patients is
thought to influence placebo and drug effects. To date, the influence of
labelling hasn*t been tested in children.
Study objective
The primary objective of this study is to determine the effect of mebeverine on
abdominal pain intensity and frequency in children with irritable bowel
syndrome or functional abdominal pain - not otherwise specified.
Study design
In this multicenter trial 284 children, aged between 12 and 18 years, with IBS
or FAP-NOS according to the Rome IV criteria will be included.
This multicentre study starts with a baseline observation period of four weeks
in which patients are treated according to the first line of treatment for IBS
or FAP-NOS. This standard medical therapy consists of reassurance, explanation
and simple dietary and behavioural advice. During the baseline observation
period no mebeverine or placebo and not any other drug influencing gut motility
is given. After this 4-week period the patients who achieve adequate relief
according to their parents with the standard medical treatment will be
excluded. The remaining patients will start an 8-week randomised double-blind
treatment period with either placebo or mebeverine. Half of the patients
randomised to either placebo or mebeverine, will be told that they will receive
the active drug. This results in a labelled drug. With this design of the
study, the therapeutic effect of positive labelling on abdominal pain will be
measured. The primary outcome is the proportion of patients with at least 50%
reduction of their abdominal pain intensity and frequency at the end of
treatment (12 weeks). The expected percentage of success after 8 weeks of
medication therapy in the unlabelled mebeverine group is 65% and the expected
percentage is 40% in the unlabelled placebo group. Equal group sizes of 62
achieve 80% power to detect a significant difference between groups using a
two-sided Chi-square test without continuity correction and with a significance
level of 0.05. Since we expect 10% to 15% dropout, a minimum of 71 per
unlabelled treatment group will be included. To investigate the influence of
labelling on outcome, we need two additional groups who will receive *open
label* mebeverine or *open label* (labelled as mebeverine) placebo. As far as
we know there is only one study assessing this two conditions, but this study
has been conducted in adults. We believe we cannot use their results with
respect to the difference in suggestibility between children and adults.
Therefore we must make reasonable estimates, resulting in a difference of 25%
on outcome between the unlabelled- and the labelled-group in both treatment
arms which we consider as clinically relevant. Using the exact calculation as
described above, we likewise have to include a minimum of 71 per labelled
treatment group. Consequently we will need 284 patients for this trial.
Secondary outcomes of this study are to investigate the effect of mebeverine on
other outcome parameters such as adequate relief, quality of life, depression
and anxiety scores, and school absenteeism in children, to investigate the
effect of reassurance, explanation and simple dietary and behavioural advice,
to study the influence of labelling on the effect of both mebeverine and
placebo on pain scores, to study the effect of mebeverine on the faecal gut
microbiota composition and to determine the safety of mebeverine in children
with irritable bowel syndrome or functional abdominal pain - not otherwise
specified.
Intervention
This multicentre study starts with a baseline observation period of four weeks
in which patients are treated according to the first line of treatment for IBS
or FAP-NOS. This standard medical therapy consists of reassurance, explanation
and simple dietary and behavioural advice. During the baseline observation
period no mebeverine or placebo and not any other drug influencing gut motility
is given. After this 4-week period the patients who achieve adequate relief
according to their parents with the standard medical treatment will be
excluded. The remaining patients will start an 8-week randomised double-blind
treatment period with either twice a day a placebo or twice a day mebeverine.
Half of the patients randomised to either placebo or mebeverine, will be told
that they will receive the active drug. This results in 4 groups: the
unlabelled mebeverine group, the labelled mebeverine group, the unlabelled
placebo group and the labelled placebo group.
Study burden and risks
During the first consult a full patients history and a thorough physical
examination will be done. Blood and feces tests will be performed to exclude
organic causes for the abdominal pain, if this hasn*t been done recently by the
general practitioner. When patients fulfill the Rome IV criteria for either
functional abdominal pain - not otherwise specified or irritable bowel syndrome
they will be invited to participate in the study. At the start of the baseline
period, the children and parents will complete three questionnaires. In
addition, they will record the severity of their abdominal pain concerning the
preceding week on a pain diary card. All the participants will receive the
first part of standard medical care for IBS or FAP-NOS during the first four
weeks. After this 4-week period the patients who achieve adequate relief
according to their parents with the standard medical treatment will be
excluded. The remaining patients will start an 8-week randomised double-blind
treatment period with either a placebo or mebeverine. We will ask all the
randomised participants to record the severity of their abdominal pain on a
pain diary card again on week 8 (seen from baseline), week 12, week 16 and week
36. Furthermore we will ask the children and the parents to fulfill three
questionnaires at week 12 and week 36 and one last questionnaire at week 16.
Eventually, we will ask the children to bring some morning stool samples at
baseline (week 0), 4 weeks and 12 weeks.
There are hardly any risks for the participating children in this study.
Studies in adults assessing the efficacy and safety of mebeverine show it is
safe to use. Apart from that, the experience of prescribing mebeverine for
children for several years has learned us that there is a very small risk of
side effects.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
All children aged between 12 and 18 years diagnosed with irritable bowel
syndrome or functional abdominal pain - not otherwise specified according to
the Rome lV criteria and where informed consent, given by both parents and by
children aged 12 years and older, is available, will be invited to participate.
The Rome lV criteria form the internationally accepted standard for defining
functional gastrointestinal disorders like irritable bowel syndrome and
functional abdominal pain-not otherwise specified. Before inclusion, all
patients undergo routine laboratory testing to exclude underlying organic
disorders: complete blood cell count, C-reactive protein, celiac screening
(anti-transglutaminase antibodies and IgA), and fecal calprotectin.
Finally, according to a recently published guideline by the Rome Foundation for
the design of pharmacological clinical trials in children, patients are
required to have an average daily pain rate of >=2 on the Wong Baker Faces Pain
Scale
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
• Current treatment by another health care professional for abdominal symptoms
• Previous use of mebeverine
• Known hypersensitivity to the active substance or to any of the excipients
(magnesium stearate, polyacrylate dispersion, talc, hypromellose, methacrylic
acid - ethyl acrylate copolymer (1:1) dispersion, glycerol triacetate,
gelatine, titanium dioxide (E171), shellac (E904), propylene glycol, ammonia
solution (concentrated), potassium hydroxide, iron oxide black (E172)).
• Known diagnosis of cystic fibrosis
• Known diagnosis of porphyria
• Known concomitant organic gastrointestinal disease
• Current use of drugs which influence gastrointestinal motility, such as
erythromycin, azithromycin, domperidone, and Iberogast (current use of drugs
which influence gastrointestinal motility may be met as long as the subject is
on a stable dose and the dose will not be adjusted during the study.
• Insufficient knowledge of the Dutch language
• Known pregnancy or current lactation
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-003293-32-NL |
| CCMO | NL55301.018.15 |
| Other | Trial NL7508 |
| OMON | NL-OMON23931 |