Clinical trial NCT05715970: ICT Tools for the Diagnosis of Autoimmune Diseases
Official title: ICT Tools for the Diagnosis of Autoimmune Diseases in the Mediterranean Area_CAPITALISATION PROJECT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Celiac Disease
Keywords: Celiac Disease
Point-of-Care-Test
Diagnosis
Lead sponsor: University of Palermo
Sponsor class: OTHER
First posted: 2023-02-08
Enrollment: 25000
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The ITAMA_CAP project, designed as a prospective, multicenter study \[U.O.C. of Geriatrics (21.01) of the University Hospital of Palermo and the "Mater Dei" Hospital of Malta), provides for the enrollment of about 25,000 subjects, divided between Sicily and Malta. Approximately 10,000 students aged between 12 and 18 will be enrolled in Malta and approximately 15,000 adults (\>18 years) will be enrolled in Sicily. These numbers are dictated by the need to obtain heterogeneous samples comparable with the subjects diagnosed in the previous ITAMA project (20,000). In Sicily, screening will be carried out in the GPs (Italian takers) clinics.
Primary purpose: SCREENING

Brief summary: The ITAMA project, which ended in 03/2022, came from the need to increase/anticipate the number of diagnosed cases of celiac disease (CD). The project involved the preliminary development of 'software tools' (Graphical User Interface (GUI), DATABASE, Decision Support System (DSS)) used to support the physicians to optimize CD diagnosis. Subsequently, through a screening of about 20,000 subjects of school age in Malta and about 1,000 subjects in Sicily, it was shown that, in compliance with international guidelines, it is possible to anticipate CD diagnosis and make it easy with the aid of a tool based on the search for specific antibodies in the blood, collecting a single drop of blood - with a test performed directly "in the points where care is provided" (eg schools, outpatient clinics) that is with a Point-of-Care-Test (PoCT). This system proved to be effective, and the method was minimally invasive (at least in some pediatric cases it was possible to avoid the endoscopic examination).

The ITAMA project has made it possible to bring out a submerged part of the "CD iceberg", a condition that in a large percentage of cases remains undiagnosed and transfer the know-how to commercial companies in the medical sector.

ITAMA project results allowed to verify and validate, on a large sample of subjects subjected to screening, that:

1. Diagnosis can be anticipated and facilitated by combined use of a rapid test (PoCT), medical history (supported by software) and traditional serological tests.
2. The diagnosis can be optimized by the support of Information Technology (IT) tools based on Artificial Intelligence (AI).
3. Non-invasive methods, if correctly applied, allow CD diagnosis avoiding invasive diagnostic techniques.
4. The reported procedures grant considerable savings for the National Health System (NHS).

Starting from the results of ITAMA, this capitalization project aims to extend the previous experience in a larger population with heterogeneous characteristics (both adults and children).

The goal of the new project is to use the combination of PoCT + tools software, to increase/anticipate CD diagnosis and, therefore, bring the number of diagnosed subjects closer to the number of expected cases, in Sicily and Malta. The inevitable implication of this would be the improvement in the quality of life of patients (reduction of symptoms, fewer medical visits and instrumental examinations performed, reduction of lost working days, improvement of social relations) and a significant reduction in costs for the NHS.

Detailed description: Background The diagnosis of celiac disease (CD), a known autoimmune disease, presupposes the recognition of symptoms/signs, the carrying out of serological tests and the diagnostic confirmation with histological examination of intestinal biopsies. The pediatric guidelines European Society for Pediatric Gastroenterology Hepatology and Nutrition report the possibility of avoiding biopsy in some classes of pediatric patients. It is estimated that about 1% of the world population is affected by CD, but only 0.37% of the Italian population and 0.40% in Malta, to date, has been diagnosed. In Sicily in particular, the cases not yet diagnosed are probably even more than in the rest of the Italian territory, because the prevalence was slightly lower than the national average (0.35%). It is clear from these data that CD is an underestimated pathology throughout the national territory and even more in Sicily. It is also known that CD is associated with various pathologies with an autoimmune component (including type 1 diabetes mellitus and Hashimoto's thyroiditis) and that, among its complications, more present in subjects who do not practice or are refractory to a gluten-free diet, neoplastic diseases are also included, such as intestinal T-cell lymphoma and small intestine adenocarcinoma.

The ITAMA project, which ended in March 2022, was born from the need to increase/anticipate the number of diagnosed cases of CD by optimizing its diagnosis. The project has developed 'software tools' (Graphical User Interface (GUI), DATABASE, Decision Support System (DSS)) to support the physicians in optimizing CD diagnosis. Through a screening, conducted on 20,000 school-age subjects in Malta and about 1,000 subjects in Sicily, it was demonstrated that, in compliance with the European Society Paediatric Gastroenterology, Hepatology and Nutrition guidelines, it was possible to anticipate the diagnosis of CD and make it easy with the aid of a test performed directly "at the points where treatment is provided" (e.g. schools, medical clinics), i.e. with a Point-of-Care-Test (PoCT, Celiac Disease Quick TestBIOHIT HealthCare Srl, Milan, Italy), conducted on capillary blood obtained through simple and low cost finger prick. This system has proved to be an effective, and the method to be minimally invasive and inexpensive making it possible, at least in certain pediatric cases, to bring out a submerged part of the "CD iceberg", avoiding further investigations, even invasive, in patients with negative PoCT. With ITAMA it was therefore possible to transfer the "know-how" to commercial companies in the medical sector, activating a network between research and production areas in the healthcare sector through the development of information and communication technologies (ICT) for the diagnosis of the CD. The results made it possible to verify/validate, on a large sample of subjects, that:

* the diagnosis can be anticipated/facilitated through the combined use of a rapid test (PoCT), medical history and traditional serological tests
* the diagnosis can be optimized thanks to the support of computer tools based on artificial intelligence (AI).

The capitalization of the aforementioned results is probably possible through the National Health System (NHS) and schools and could be strategic because:

* non-invasive methods, if correctly applied, allow an early and effective diagnosis of CD (currently underdiagnosed) and, in some cases, can also allow patients not to be subjected to invasive diagnostic methods
* the aforementioned procedures allow a considerable saving for the NHS.

Objectives The present project aims to capitalize and extend the previous experience of ITAMA in a larger population with heterogeneous characteristics (young people and adults), through the Sicilian network of General Practitioners (GPs) and the involvement of numerous schools in Malta .

The goal is to use ITAMA outputs/results to increase/anticipate the diagnosis of CD and, therefore, bring the number of diagnosed subjects closer to the expected number of CD cases in Sicily and Malta. The consequence could be the improvement of the quality of life of the diagnosed patients (anticipation of diagnosis and therapy, with consequent reduction of symptoms/signs, reduction of medical visits/instrumental tests performed, reduction of lost working days, improvement of social relationships) and a significant reduction in costs for the NHS, as well as a reduction in the number of conventional tests (laboratory and instrumental investigations) not recommended in patients with negative PoCT and the further consequent costs caused by these.

Expected results The expected results from this "extension" of the ITAMA project would essentially consist in the capitalization of the previously observed results, through: A) the involvement of the Sicilian network of GPs and Maltese schools and their greater knowledge and awareness of the need to bring out the diagnoses miss you today; B) the confirmation of a possible and extensive outpatient use of the PoCT method to facilitate diagnosis.

From a clinical point of view, we also expect: 1) an increase in CD diagnoses, bridging the gap between diagnosed cases and estimated cases, also showing any differences in prevalence between adults and children; 2) a reduction in diagnostic delays, with a consequent improvement in the quality of life of patients and a reduction in costs for the NHS; 3) a reduction in the number of conventional tests (laboratory and instrumental investigations) not recommended in patients with negative PoCT and in the further consequent costs caused by these.

From a scientific point of view, this study will contribute to: 1) define more precisely the prevalence of CD in two populations of the Mediterranean area; 2) create a database usable by researchers for this and future research; 3) to demonstrate the utility of a minimally invasive and low-cost screening test for the early identification of patients with CD.

Eligibility criteria: Inclusion Criteria:

* age \>12 and \<18 years for subjects enrolled in Malta;
* age \>18 years for subjects enrolled in Sicily.

Exclusion Criteria:

* age \<12 and \>18 years for subjects enrolled in Malta;
* age \<18 years for subjects enrolled in Sicily;
* refusal to undergo the proposed diagnostic procedures;
* lack of informed consent.

Primary outcomes:
measure: Identification of subjects testing positive to PoCT.
timeFrame: 1 day
measure: Identification of subjects with probable CD by the use of software tools
timeFrame: 1 day
measure: Identification of patients positive to CD serological markers (IgA anti-tTg)
timeFrame: 2 weeks
measure: Identification of patients positive to CD serological markers (IgG anti-tTg)
timeFrame: 2 weeks
measure: Identification of patients positive to CD serological markers (EmA)
timeFrame: 2 weeks
measure: Identification of patients positive to CD histology
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Palermo
country: Italy
facility: University Hospital of Palermo
state: Sicily
city: La Valletta
country: Malta
facility: Mater Dei Hospital
Study officials:
References:
citation: Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, Elitsur Y, Green PH, Guandalini S, Hill ID, Pietzak M, Ventura A, Thorpe M, Kryszak D, Fornaroli F, Wasserman SS, Murray JA, Horvath K. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med. 2003 Feb 10;163(3):286-92. doi: 10.1001/archinte.163.3.286.
citation: Mansueto P, Spagnuolo G, Calderone S, D'Agate CC, Cosenza S, Leonardi G, Camilleri S, Pistone M, Seminara G, Alaimo C, Soresi M, Carroccio A, Garufi S. Improving the diagnostic approach to celiac disease: Experience from a regional network. Dig Liver Dis. 2022 Jun;54(6):771-775. doi: 10.1016/j.dld.2021.11.016. Epub 2021 Dec 21.
citation: Husby S, Koletzko S, Korponay-Szabo I, Kurppa K, Mearin ML, Ribes-Koninckx C, Shamir R, Troncone R, Auricchio R, Castillejo G, Christensen R, Dolinsek J, Gillett P, Hrobjartsson A, Koltai T, Maki M, Nielsen SM, Popp A, Stordal K, Werkstetter K, Wessels M. European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. J Pediatr Gastroenterol Nutr. 2020 Jan;70(1):141-156. doi: 10.1097/MPG.0000000000002497.
citation: Magazzu G, Aquilina S, Barbara C, Bondin R, Brusca I, Bugeja J, Camilleri M, Cascio D, Costa S, Cuzzupe C, Duca A, Fregapane M, Gentile V, Giuliano A, Grifo A, Grima AM, Ieni A, Li Calzi G, Maisano F, Melita G, Pallio S, Panasiti I, Pellegrino S, Romano C, Sorce S, Tabacchi ME, Taormina V, Tegolo D, Tortora A, Valenti C, Vella C, Raso G. Recognizing the Emergent and Submerged Iceberg of the Celiac Disease: ITAMA Project-Global Strategy Protocol. Pediatr Rep. 2022 Jun 10;14(2):293-311. doi: 10.3390/pediatric14020037.
citation: Catassi C, Fasano A. Celiac disease diagnosis: simple rules are better than complicated algorithms. Am J Med. 2010 Aug;123(8):691-3. doi: 10.1016/j.amjmed.2010.02.019.
citation: Caio G, Volta U, Sapone A, Leffler DA, De Giorgio R, Catassi C, Fasano A. Celiac disease: a comprehensive current review. BMC Med. 2019 Jul 23;17(1):142. doi: 10.1186/s12916-019-1380-z.