The protocol will be submitted for review by the Research Committee and the Ethics
Committee of the Regional University Hospital of Colima. Upon receiving approval, a
double-blind, placebo-controlled, randomized clinical trial will be carried out, based on
CONSORT guidelines. This trial involves the participation of pediatric patients aged 4 to
18.
Patients will be selected from those attending private practice and satisfying Rome IV
criteria for any of the Functional Abdominal Pain Disorders (FAPD). Before any
intervention takes place, the purpose and procedures of the study will be explained to
both the patients and their legal guardians. If they decide to participate, they will be
asked to sign an informed consent letter and assent form for minors. Patients will be
selected through stratified probabilistic sampling in 4 categories (Irritable Bowel
Syndrome, Functional Dyspepsia, Abdominal Migraine, and Functional Abdominal Pain not
otherwise specified (FAP-NOS)) until the desired sample size of 82 participants is
reached. Once participants are selected, they will be randomly assigned to one of the
three groups: trimebutine/probiotic, probiotic/placebo, or trimebutine/placebo, with each
group consisting of at least 20 participants. The initial diagnosis will be carried out
using the Rome IV Criteria Questionnaires for pediatric patients, and the intensity of
pain will be evaluated using the Visual Analog Scale (VAS) and quality of life with
PedsQL 4.0. Patients will be administered the treatment corresponding to their assigned
group and will be clinically followed up at 4 and 8 weeks. During these follow-up
consultations, the Rome IV Criteria Questionnaires and scales will be reapplied to assess
the evolution of the patients' symptoms and their response to treatment. Any patient who
requests voluntary withdrawal, those with treatment adherence less than 80%, and those
participating in another study or being treated by another physician simultaneously will
be removed from the study.
Statistical analysis will be carried out using international Business Machine (IBM®)
Statistical Package for the Social Sciences (SPSS®) Statistics 26. Descriptive statistics
with measures of central tendency will be used, presenting the results in tables and
graphs. To determine whether the data follow a normal distribution, the
Kolmogorov-Smirnov and Shapiro-Wilk tests will be applied. Measurements in 3 groups
(trimebutine, probiotics, and control) and at 3 times (0, 4, and 8 weeks) will be
analyzed. For intervening categorical variables like gender and education, the chi-square
test (X2) will be used. For continuous variables like age and BMI, the Mann-Whitney U
test will be applied, expecting statistically significant differences with p < 0.05.
If the data follow a normal distribution, repeated measures ANOVA will be used to compare
the means of the 3 groups (trimebutine, probiotics, and placebo). McNemar's test or the
sign test will be considered as secondary analyses to evaluate changes within each group
over time (0, 4, and 8 weeks). If the data do not follow a normal distribution,
non-parametric tests like the Friedman test will be employed.
In case of finding a statistically significant difference in repeated measures ANOVA or
the Friedman test, post hoc tests will be performed to identify specific differences
between groups and times. If necessary, correlation tests like Pearson or Spearman will
be used to evaluate relationships between different variables within the study.