Participants:
In the present two-arm, parallel design randomized controlled clinical trial, the patients were selected randomly from the East-Azerbaijan celiac disease registry database based on the following criteria: age>18 years, being at least 6 months postdiagnosis, and use of a smartphone. Patients who had other chronic inflammatory GI diseases, diabetes, psychiatric, or neurological disease that could interfere with assessments were excluded. All patients were diagnosed based on positive serology markers (including anti-tissue transglutaminase (tTG) antibodies, endomysial antibodies (EMA) and deamidated gliadin peptide (DGP) antibodies) confirmed by compatible duodenal histological findings.
In the present study, 65 celiac patients were randomly selected out of 80 patients who had eligibility criteria. Five patients did not consent to participate in the study, and 60 patients were randomly assigned into two groups using the GraphPad randomization software tool. The randomization process was conducted by a third person not involved in the research protocol. All patients received GFD recommendations in the celiac clinic of Imam Reza Hospital with the help of leaflets before the study. An expert nutritionist designed the leaflets. The patients in the intervention group (n=30) received the “celiac” application, and they were asked to use it for three months to obtain the required information. The patients in the control group (n=30) continued their weekly routine education with the help of leaflets in the clinic. Both programs (application or leaflet) had identical topics and included information about disease, gluten-free food items, gluten-free drugs, gluten-free food labeling, and gluten-free cooking. The outcome assessor and statistition were blind to group allocation.
“celiac” is a Persian language application designed by our research team based on the Analysis, Design, Development, Implementation, Evaluation (ADDIE) model18.
In the first phase, we reviewed the published articles, various health and diet-related applications, and interviewed patients with celiac disease to gather the relevant information to define the education scopes and purposes of the application and create the main contents and sub-contents of application. Then, based on this information, a professional Web producer developed the first draft of an application. A team of gastroenterologists and expert nutritionists evaluated the first version. In addition, with the help of five patients with celiac disease, the usability of the application was checked. Based on the experts' and patients' comments, minor modifications were made, and the “celiac” was developed.
The “celiac” is the free anroid-based application that can be used both on smartphones and android tabs and provides different information regarding CD and GFD in seven sections, including “about disease”, “gluten-free diet”, “gluten-free drugs and supplements”, “gluten-free food labeling”, “gluten-free cooking”, “calculations” and “celiac centers in Iran”. In the “about disease” section, various information, such as disease causes, symptoms, diagnosis, and treatments, was provided. In the “gluten-free diet” section, more than 150 foods were marked by three colors: green for allowed foods, red for prohibited foods, and orange for suspicious foods. The generic name and factory name of the gluten-free drug list introduced by Iran's Food and Drug Organization were provided in the “gluten-free drugs and Supplements” section. In “gluten-free food labeling”, the names of different food ingredients that may contain gluten were provided. In “gluten-free cooking”, the cooking methods of different foods with gluten-free ingredients were provided. The calculation section allowed patients to calculate their body mass index (BMI) and to register their tissue transglutaminase antibodies for follow-up. Finally, the “Celiac Disease Centers” section listed the address of CD clinics and gluten-free food providers in different provinces of Iran for more access of patients to gluten-free foods when they are on the journey. The patients were asked to use it for obtaining the required information for three months and informed us about the probable difficulties.
Outcome measure:
The difference in the severity of gastrointestinal symptoms between the two groups was the outcome of interest that was assessed by the Gastrointestinal Symptom Rating Scale score (GSRS) questionnaire. This questionnaire is a seven-point Likert scale with 15 questions that has response options ranging from “no problem (0)” to “severe discomfort (6)”. The questionnaire is divided into 5 domains that cover the gastrointestinal system: diarrhea (3 questions; score range: 0-18), constipation (3 questions; score range: 0-18), abdominal pain (3 questions; score range: 0-18), reflux (2 questions; score range: 0-12), and indigestion (4 questions; score range: 0-24). The questionnaire was translated into the Persian language and validated in our population previously19. In a post hoc analysis, the three domains that are most relevant to celiac disease were evaluated separately using celiac disease-GSRS (CD-GSRS). This modified questionnaire contains 10 questions from the GSRS and includes the following domains: diarrhea (3 questions; score range: 0-18), abdominal pain (3 questions; score range: 0-18), and indigestion (4 questions; score range: 0-24)20. Higher scores represent worse symptoms.
This study adheres to CONSORT guidelines.
Statistical analysis:
Originally, the study was designed and powered to detect the effects of a smartphone application on patients' knowledge and adherence level, which were taken as the primary endpoints (data were presented in our previous publication). In this study, we presented the secondary outcome variables and the gastrointestinal effects of our intervention. Using the results of a previous study that assessed the effect of education on celiac patient adherence score (CDAT score)6, assuming a significance level of 0.05 and power of 80%, the minimum sample size needed to detect a significant between-group difference in adherence level was 24 participants in each group. Considering the probability of a 20% attrition rate, the desired sample size was 30 patients in each group.
SPSS 21.0 was used for statistical analysis. Skewness and kurtosis were used to test the assumption of normality. The continuous values were reported as the mean and standard deviation, and the nominal and categorical variables such as sex, educational status, occupation categories, family history, comorbidities presence, and March categories were reported in frequency and percentage. A paired t-test was used to compare the changes in each score before and after the interventions. The differences in baseline values between two groups were compared by independent sample t-test. One-way analysis of covariance (ANCOVA) with adjustment for age, sex, disease duration, educational level, and baseline values was used to compare the after intervention values between the two groups. For comparing the nominal and ordinal variables, the chi-square and Mann-Whitney U tests were used. Test results are reported as significant for P < 0.003, adjusted for multiplicity (Bonferroni's correction 0.05/14)21.