Inclusion criteria:
Adult patients (18-65 years old) referred to the "Outpatient Clinic for Celiac Disease
and Functional Disorders" who met the Rome III-IV criteria for IBS-D and were referred by
their local General Practitioner.
Exclusion criteria:
Presence of severe heart, liver, neurological or psychiatric disease or GI disease other
than IBS (e.g., inflammatory bowel disease, celiac disease) that could explain the
current symptoms.
Patients who have previously followed a diet low in particular substances (e.g., low
fermentable oligosaccharides, disaccharides, monosaccharides, and polyols - FODMAP -)
diet, vegan diet, a gluten-free diet).
Antidepressant use All patients will receive detailed verbal and written information
about the study before giving their written consent.
Methodology: V1. (Screening). Patients will be informed about the objective of the study;
V2. (Day 0). Seven days after the screening visit, patients will return for the
outpatient visit. At this time, patients will complete the symptom questionnaires. During
this visit, blood and biological samples (urine, feces) will be taken; anthropometrical
measurements and bioimpedance analysis (BIA) will be carried out. Additionally, ECG will
be performed at the Cardiology Unit. V3. (pre-treatment). Seven days before the start of
the exercise intervention, the enrolled subjects, only after submitting the certificate
of physical fitness issued by their doctor or general practitioner (GP), will undergo
three field physical tests for the initial assessment of their fitness. V4. (treatment).
Treatment begins after assessing the baseline level of physical activity through analysis
of the results of the three field tests. V5. (post-treatment). In the seven days
following the end of the Physical Exercise intervention, the subjects are assessed again
using the three field tests. V6. (Day 90).
End of treatment visit. During this visit, completed questionnaires will be collected,
including the symptom diary and daily exercise diary; in addition, patients will complete
the symptom questionnaires (IBS-SSS and GSRS). An anthropometric and bioimpedance
analysis will also be performed, and potential adverse events during the intervention
period will be assessed. Blood and biological samples necessary for the instrumental
evaluations in the study will be taken.
Physical Exercise Intervention: The exercise intervention tool will be Fitwalking, which
is structured, organized, supervised, and administered through a "Walking Group".
Fitwalking is a motor-sport activity that has innumerable potential for health and
physical well-being. Fitwalking is a type of training based on walking, carried out with
a precise technique, which allows you to walk well and be faster, thus producing positive
metabolic effects and improving physical efficiency. Fitwalking is an aerobic activity of
moderate intensity in which the workload produces progressive adaptations and allows for
improved recovery and load increase over time. An effective prescription includes a
systematically designed and individualized exercise program in terms of Frequency,
Intensity, Time, Type, Volume, and Progression (FITT-VP). These parameters are briefly
described below:
Frequency. Exercise (walking) will be carried out outdoors on an urban route 3 times a
week, on non-consecutive days, for 12 weeks.
Intensity. The intensity of the exercise (50/75% of HRmax) will be monitored through the
use of the heart rate monitor and will be personalized through the Tanaka formula. In
addition, to measure pace we will use the TALK TEST (a standardized and validated survey
tool based on the ability of the exercising subject to holding a conversation), and to
measure the perception of fatigue we will use the modified BORG scale (on a scale of
0-10, a perception of 5-6 is needed).
Type. The type of exercise is moderate aerobic with a speed ranging from 5 to 10 km/h.
The single outing lasting 60' will be structured as follows:
Volume. Participants in the project will perform 180' minutes per week of aerobic
exercise of moderate intensity, through walking in groups as per the ACSM (The American
College of Sports Medicine) guidance on preventive health. However, participants may also
increase their exercise volume through other activities outside the project. All exercise
data, both within and outside the project, will be recorded in a daily diary for the
assessment of energy expenditure (see appendix).
Progression. The FITT components (Frequency, Intensity, Type, and Time) can be modified
and increased according to the subjects' abilities and improvements, to achieve the
recommended volume of exercise as per the ACSM (The American College of Sports Medicine)
guidance on preventive health.
Statistical analysis. This study aims to evaluate the effectiveness of exercise in
symptom management of patients with IBS compared to standard dietary advice. The
collected data will be grouped and summarized concerning demographic variables, baseline
characteristics, and efficacy and safety assessments. Exploratory analyses will be
performed using descriptive statistics. Data will be presented (as mean - standard
deviation - SD, unless otherwise stated) for both the intention-to-treat population
(i.e., all patients who exercised) and the per-protocol population (i.e., all patients
who completed the study without major protocol violations). Patients who discontinued the
study will also be listed, and their reasons described analytically. Categorical
variables will be compared with the X2 test. Two-tailed p-values <0.05 will be considered
statistically significant.
Statistical analysis will be performed using the Generalized Estimating Equation
procedure to estimate the effect of interventions on the outcome (IBS-SSS). These models
are instrumental in biomedical studies to evaluate the change in outcome in the presence
of covariates. To overcome the non-normal distribution, a gamma distribution of the
outcome will be assumed, and the identity link will be used. The structure of the
covariance between the different measurements will be explored with special programs. The
results will be expressed in the natural scale of the outcome measurement as the mean and
the corresponding 95% confidence intervals. Marginal effects of interventions will also
be estimated for different covariates or combinations of covariates. All statistical
analyses will be performed using the statistical software Stata 17 (StataCorp, 4905
Lakeway Drive, College Station, Texas 77845 USA). In particular, the -xtgee- command will
be used, and the statistical structure of the covariance will be explored with the -qic-
command.