Clinical trial NCT05119322: Use of a Home Test for Gluten Detection in Urine and Its Effect on Gluten-free Diet Adherence
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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Celiac Disease
Treatment Adherence
Adolescent
Keywords: Celiac disease
Gluten-free diet adherence
Adolescent
Gluten immunogenic peptides
Urine tests
Lead sponsor: Biomedal S.L.
Sponsor class: OTHER
Collaborators: name: FUNDACION IHP
First posted: 2021-11-15
Enrollment: 66
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intervention and control groups
Primary purpose: TREATMENT

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:

1. Patient enrolment.
2. 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.
3. 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).
4. 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.

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.

Primary outcomes:
measure: Gluten-free adherence change
timeFrame: 8 weeks
measure: Gluten-free adherence change
timeFrame: 8 weeks
measure: Gluten-free adherence change
timeFrame: 8 weeks
measure: Gluten-free adherence change
timeFrame: 8 weeks
Secondary outcomes:
measure: Quality of life change
timeFrame: 8 weeks
measure: Symptoms change
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Seville
country: Spain
facility: Grupo IHP
Study officials:
affiliation: Biomedal S.L.
name: Laura Coto Alonso
role: PRINCIPAL_INVESTIGATOR
affiliation: Biomedal S.L.
name: Ángel Cebolla Ramírez
role: STUDY_DIRECTOR
affiliation: Fundación IHP
name: Joaquín Reyes Andrade
role: PRINCIPAL_INVESTIGATOR
References:
citation: Comino I, Real A, Vivas S, Siglez MA, Caminero A, Nistal E, Casqueiro J, Rodriguez-Herrera A, Cebolla A, Sousa C. Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces. Am J Clin Nutr. 2012 Mar;95(3):670-7. doi: 10.3945/ajcn.111.026708. Epub 2012 Jan 18.
citation: Moreno ML, Cebolla A, Munoz-Suano A, Carrillo-Carrion C, Comino I, Pizarro A, Leon F, Rodriguez-Herrera A, Sousa C. Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing. Gut. 2017 Feb;66(2):250-257. doi: 10.1136/gutjnl-2015-310148. Epub 2015 Nov 25.
citation: Gerasimidis K, Zafeiropoulou K, Mackinder M, Ijaz UZ, Duncan H, Buchanan E, Cardigan T, Edwards CA, McGrogan P, Russell RK. Comparison of Clinical Methods With the Faecal Gluten Immunogenic Peptide to Assess Gluten Intake in Coeliac Disease. J Pediatr Gastroenterol Nutr. 2018 Sep;67(3):356-360. doi: 10.1097/MPG.0000000000002062.
citation: Comino I, Fernandez-Banares F, Esteve M, Ortigosa L, Castillejo G, Fambuena B, Ribes-Koninckx C, Sierra C, Rodriguez-Herrera A, Salazar JC, Caunedo A, Marugan-Miguelsanz JM, Garrote JA, Vivas S, Lo Iacono O, Nunez A, Vaquero L, Vegas AM, Crespo L, Fernandez-Salazar L, Arranz E, Jimenez-Garcia VA, Antonio Montes-Cano M, Espin B, Galera A, Valverde J, Giron FJ, Bolonio M, Millan A, Cerezo FM, Guajardo C, Alberto JR, Rosinach M, Segura V, Leon F, Marinich J, Munoz-Suano A, Romero-Gomez M, Cebolla A, Sousa C. Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients. Am J Gastroenterol. 2016 Oct;111(10):1456-1465. doi: 10.1038/ajg.2016.439. Epub 2016 Sep 20.
citation: Costa AF, Sugai E, Temprano MP, Niveloni SI, Vazquez H, Moreno ML, Dominguez-Flores MR, Munoz-Suano A, Smecuol E, Stefanolo JP, Gonzalez AF, Cebolla-Ramirez A, Maurino E, Verdu EF, Bai JC. Gluten immunogenic peptide excretion detects dietary transgressions in treated celiac disease patients. World J Gastroenterol. 2019 Mar 21;25(11):1409-1420. doi: 10.3748/wjg.v25.i11.1409.
citation: Comino I, Segura V, Ortigosa L, Espin B, Castillejo G, Garrote JA, Sierra C, Millan A, Ribes-Koninckx C, Roman E, Rodriguez-Herrera A, Diaz J, Silvester JA, Cebolla A, Sousa C. Prospective longitudinal study: use of faecal gluten immunogenic peptides to monitor children diagnosed with coeliac disease during transition to a gluten-free diet. Aliment Pharmacol Ther. 2019 Jun;49(12):1484-1492. doi: 10.1111/apt.15277. Epub 2019 May 10.