Use of a Home Test for Gluten Detection in Urine and Its Effect on Gluten-free Diet Adherence

Study Overview
=================
Brief Summary
-----------------
The use of a home rapid test for the detection of gluten immunogenic peptides (GIP) in urine of treated adolescent patients with celiac disease (CD) could facilitate the adherence to the gluten-free diet (GFD) and contribute to symptoms control and quality of life improvement. This single centre, randomized, unblinded, controlled study consists of 4 run-in weeks period followed by 8-weeks study period in which patients will be randomized to intervention group (home urine GIP testing) or the control group (no home urine GIP testing). The 12-week study will involve surveys, home stool and urine collection, home urine GIP test performance, and two study visits with the gastroenterologists. The main outcome is to determine whether the self-monitoring of the GFD with GIP testing in urine improves adherence to the GFD in treated adolescent patients with CD (measured by CDAT-Celiac Dietary Adherence Test, GFD adherence evaluation by gastroenterologist and rates of gluten exposure in urine and/or stool measured at a central laboratory) and subsequently improves quality of life (CDDUX-Coeliac Disease Dutch Questionnaire) and reduces symptoms (CSI-Celiac Symptoms Index questionnaire).

Detailed Description
-----------------
Hypothesis: the use of a home rapid test for the detection of gluten immunogenic peptides (GIP) in urine of treated adolescent patients with celiac disease (CD) could facilitate the adherence to the gluten-free diet (GFD) and contribute to symptoms control and quality of life improvement. Objectives: Primary objective: to determine in adolescent patients with CD whether the self-monitoring of the GFD with GIP testing in urine changes treatment adherence (intervention group) in comparison with patients that do not use the test (control group) measured by 1 - CDAT-Celiac Dietary Adherence Test; 2 - GFD adherence evaluation by gastroenterologist; 3- Detection rates of GIP in urine and/or stool (to be measured at a central laboratory); 4- Detection rates of GIP in urine (to be measured by home rapid tests). Secondary objectives: to determine whether the use of the home test for GIP detection in urine samples of treated patients with CD leads to 1 - change of quality of life (CDDUX-Coeliac Disease Dutch Questionnaire); 2- change of symptoms (CSI-Celiac Symptoms Index questionnaire). Study design: Single centre, randomized, unblinded, controlled, study. The study will consist of 4 run-in weeks period followed by 8-weeks study period in which patients will be randomized to intervention (home urine GIP testing) or the control group (no home urine GIP testing). Study participants: adolescent patients with CD, diagnosed by European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines, that have been following a strict GFD for at least 2 years. Study procedure: Patient enrolment. Run-in period (4 weeks): all participants will: A- complete quality of life questionnaire (CDDUX); B - complete GFD adherence questionnaire (CDAT); C - complete food diary for 4 consecutive days and GFD adherence will be evaluated by gastroenterologist; D - complete symptom questionnaire (CSI); E - be instructed in the use of the tests and sample collection; F - collect at the beginning and end of the period urine and stool samples. Study weeks (8): patients will be randomized to either the control or the study group by block randomization (size 4) using WINPEPI (Programs for epidemiologists for Windows) v11.65 (Abramson, J.H.). The study group will receive home use tests for GFD monitoring to be used at their discretion (but using at least 8 tests during the study period (1/week) so that they may receive immediate qualitative feedback regarding the presence of biomarkers of gluten exposure in their urine and they will have to register the results obtained. The control group will not receive the tests. Additionally, all patients will collect a urine and a stool sample every 4 weeks with the purpose of evaluating their adherence to the GFD. All collected samples will be kept frozen until their analysis and will be brought to the centre by the patients at the end of the study. All samples will be sent to a central laboratory for their analysis (Biomedal S.L., Seville, Spain). At the end of the study, patients will be evaluated as in the run-in period (post-intervention). Number of participants: with an alpha risk of 5%, a beta risk of 20% (80% of statistical power) and an estimated rate reduction of 0.33 the sample size needed was 66 subjects (33 subjects per group). The calculation was made using the tool Calculadora de Grandària Mostral (GRANMO) v7.12 April 2012 (Municipal Institute of Medical Research, Barcelona, Spain). Measurements: 1- Home rapid test (GlutenDetect, Biomedal S.L., Seville, Spain) for GIP determination in urine samples, laboratory rapid test (iVYCHECK GIP Urine, Biomedal S.L., Seville, Spain) for GIP determination in urine samples and ELISA test (iVYLISA GIP Stool, Biomedal S.L., Seville, Spain) for GIP determination in stool samples; 2- CD related symptoms (CSI questionnaire); 3- quality of life questionnaire (CDDUX); 4- GFD adherence questionnaire (CDAT); 5- GFD adherence evaluation by specialist (questionnaire and food diary); 6 - test results for the study group. Samples will be analysed in a central laboratory (Biomedal S.L., Seville, Spain). Statistical analysis: Will be done with IBM SPSS Statistics 25.0 for Windows (IBM Corporation, Armonk, New York, United States). 1- Difference in all parameters between and within the control and the study groups. Results will be compared at baseline, week 4 and week 12. 2- Differences in all parameters between patients with positive GIP testing compared to those with negative GIP testing (both home and laboratory GIP measurements). 3 - number of additional tests used by the patients since they will receive 24 tests and they must perform only 8 tests. They can use the additional test at their discretion.

Official Title
-----------------
Study of the Use of a Home Test for the Detection of Gluten Immunogenic Peptides in Urine and Its Effect on Gluten-free Diet Adherence

Conditions
-----------------
Adolescent, Celiac Disease, Treatment Adherence

Intervention / Treatment
-----------------
* Diagnostic Test: GlutenDetect home urine test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willingness to take part in the study. Signed informed consent. Diagnosis of CD confirmed by biopsy and/or serology. Ability to: provide urine and stool samples, perform the home tests, and register results. Exclusion Criteria: Not precise diagnostic of CD. Comorbid condition that in the opinion of the investigator would interfere with the study. Lack of willingness to take part in the study. Inability to use the test or provide samples. Frequent voluntary GFD transgressions. To provide less than 70% of the required samples.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Intervention and control groups
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GlutenDetect home urine test<br>The GlutenDetect home urine test group will receive home use tests for GIP detection in urine to self-monitor the GFD. Tests will be used at their discretion, but using at least 8 tests during the study period (1/week), so that they may receive immediate qualitative feedback regarding the presence of biomarkers of gluten exposure in their urine and they will have to register the results obtained. Additionally, patients will collect a urine and a stool sample every 4 weeks to evaluate their adherence to the GFD in the laboratory. | Diagnostic Test: GlutenDetect home urine test<br>* GFD compliance self-asessment using a home rapid test for GIP detection in urine.<br>|
| No Intervention: Control group<br>The control group will not receive any home urine tests but will collect a urine and a stool sample every 4 weeks with the purpose of evaluating their adherence to the GFD in the laboratory. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gluten-free adherence change | Number of participants adherent to GFD in intervention and control arms as assessed by Celiac Dietary Adherence Test (CDAT), change from baseline in scores on the test after 8 weeks of intervention. The scores on the CDAT have a scale from 7 to 35. A score of <13 is considered as good diet adherence and a score >17 is considered as bad diet adherence. | 8 weeks | 
| Gluten-free adherence change | Number of participants adherent to GFD in intervention and control arms as assessed by GFD adherence evaluation questionnaire by gastroenterologist, change from baseline in level of diet adherence on the questionnaire after 8 weeks of intervention. The scores have a scale from 0 to 32 and social questions (5) have a yes/no answer. A score of 0-7 and no in all social questions is considered excellent diet adherence; a score of 8-15 and no in all social questions is considered good diet adherence; a score of 8-15 and yes in one social question is considered regular diet adherence; a score of 16-24 and yes in two social questions is considered regular diet adherence; a score of 16-24 and yes in three social questions is considered bad diet adherence; a score of 25-32 and yes in two social questions is considered bad diet adherence; a score of 25-32 and yes in three social questions is considered very bad diet adherence. | 8 weeks | 
| Gluten-free adherence change | Number of participants adherent to GFD in intervention and control arms as assessed by detection of GIP in urine and/or stool samples (measured at a central laboratory), change from baseline in GIP qualitative and quantitative results after 8 weeks of intervention. | 8 weeks | 
| Gluten-free adherence change | Number of participants adherent to GFD in intervention group as assessed by detection of GIP in urine samples (measured by home rapid tests), change from baseline in GIP qualitative results after 8 weeks of intervention. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life change | Number of participants with affected quality of life in intervention and control arms as assessed by Coeliac Disease Dutch Questionnaire (CDDUX), change from baseline in scores from after 8 weeks of intervention. The scores on the CDDUX are recoded into a scale from 1 to 100. A score of 1-20 is considered very bad, 21-40 is bad, 41-60 is neutral, 61-80 is good, and 81 to 100 is very good. | 8 weeks | 
| Symptoms change | Number of participants with CD symptoms in intervention and control arms as assessed by Celiac Symptoms Index questionnaire (CSI), change from baseline in symptom scores after 8 weeks of intervention. The scores on the CSI are recoded into a scale from 16 to 80. A score of ≥38 is considered as symptomatic. | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Celiac disease, Gluten-free diet adherence, Adolescent, Gluten immunogenic peptides, Urine tests