ICT Tools for the Diagnosis of Autoimmune Diseases

NCT05715970 | Completed

• 1 other identifier: ACPM32
• Study Type: interventional
• Target: 25,000
• Locations: 2 countries
• Sites: 2

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. 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. 2.The diagnosis can be optimized by the support of Information Technology (IT) tools based on Artificial Intelligence (AI).
3. 3.Non-invasive methods, if correctly applied, allow CD diagnosis avoiding invasive diagnostic techniques.
4. 4.The reported procedures grant considerable savings for the National Health System (NHS).

Conditions

Celiac Disease

Keywords

Celiac Disease; Point-of-Care-Test; Diagnosis

Outcome Measures

Primary Outcomes (6)

• Identification of subjects testing positive to PoCT.

  Point-of-Care-Test (PoCt) will be performed on all subjects recruited at General Practitioner's clinics in Sicily and at schools in Malta. Whole blood sample will be collected by puncture of the index, middle or ring finger. The blood must be dispensed slowly onto the test cassette, where there is a special oval indicated by an arrow. After 30-60 seconds two drops of buffer diluent should be added in the same window. After 10 minutes, the healthcare professional will be able to read the test. Reading Test Results: NEGATIVE: Only one BLUE band appears in the Results Window near the letter "C" (control line) of the Test Cassette. This band must always appear. POSITIVE: In addition to the BLUE control band, a discernible PINK-RED band also appears in the result window near the letter "T" (test line) of the test cassette. The intensity of the line depends on the concentration of antibodies in the blood. INVALID: absence of BLUE band in the results window near the letter "C".

  1 day

• Identification of subjects with probable CD by the use of software tools

  A structured questionnaire to Celiac Disease (CD) symptoms, signs and predisposing factors (eg. familiarity, etc.) will be administered to all subjects recruited at General Practitioner's clinics in Sicily and at schools in Malta, by the use of the software tools developed in the ITAMA project. In particular, data entry into the Database, already implemented in the ITAMA project, can be managed through a GUI created in the Java language for greater product portability. The GUI allows the presentation of the outputs in a structured way and has, among its functions: a) the data acquisition mode (DAQ), b) the data search and consultation mode (QUERY) and c) the execution of the Decision Support System (DSS) for the diagnosis of CD. The DSS will provide an output according to the software elaboration as: 'Probable CD: further diagnostic testing is suggested' or 'Unlikely CD: no further diagnostic testing is suggested'.

  1 day

• Identification of patients positive to CD serological markers (IgA anti-tTg)

  All patients who tested positive to PoCT and/or who had the 'Probable Celiac Disease: further diagnostic testing is suggested' output after the software tools elaboration will be subjected to the search for specific antibodies for celiac disease. Immunoglobulin A class anti-transglutaminase will be analyzed by commercial kits, on blood samples collected by venipuncture.

  2 weeks

• Identification of patients positive to CD serological markers (IgG anti-tTg)

  All patients who tested positive to PoCT and/or who had the 'Probable Celiac Disease: further diagnostic testing is suggested' output after the software tools elaboration will be subjected to the search for specific antibodies for celiac disease. Immunoglobulin G class anti-transglutaminase will be analyzed by commercial kits, on blood samples collected by venipuncture.

  2 weeks

• Identification of patients positive to CD serological markers (EmA)

  All patients who tested positive to PoCT and/or who had the 'Probable Celiac Disease: further diagnostic testing is suggested' output after the software tools elaboration will be subjected to the search for specific antibodies for celiac disease. Anti-Endomysial Antibody will be analyzed by commercial kits, on blood samples collected by venipuncture.

  2 weeks

• Identification of patients positive to CD histology

  All patients who had serological tests compatible with Celiac Disease (immunoglobulin (Ig)A class anti-transglutaminase (tTg) and Anti-Endomysial Antibody (EmA) positivity in IgA-sufficient patients or IgG class anti-tTG and EmA in IgA-deficient subjects) will be subjected to esophago-gastro duodenoscopy and will be diagnosed as suffering from Celiac Disease according the results of histology examination (Marsh-Oberhuber classification).

  4 weeks

Study Arms (1)

General population

EXPERIMENTAL

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. In Malta the recruitment will be performed in the schools (Maltese takers). Furthermore, in Malta, a further extension of the results provides for the execution of the PoCT+questionnaire in the asymptomatic first-degree relatives of the pediatric subjects with an ascertained diagnosis of CD identified in the previous project.

Diagnostic Test: PoCT+questionnaire administration

Interventions

PoCT+questionnaire administration DIAGNOSTIC_TEST

In Sicily, screening will be carried out in the general practitioner's clinics (GPs). GPs will have to submit the patients attending their clinics to the PoCT + software tools questionnaire. Subjects who are PoCT positive and/or who reach the minimum score in the questionnaire will be considered 'patients at risk of CD' and must be subjected, with prior consent, to in-depth diagnostics using standard serological methods. The subjects resulting positive in the serological investigations will then undergo the appropriate endoscopic and biopsy investigations to ascertain the presence of CD. In Malta the recruitment will exactly repeat the modalities already carried out in the ITAMA project, through the schools of Malta (Maltese takers), while the laboratory and endoscopic examinations of the subjects who tested positive for the PoCT and/or who will reach the minimum score in the software tools questionnaire will be centralized at the "Mater Dei" hospital.

General population

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Palermo: lead

Study Sites (2)

University Hospital of Palermo

Palermo, Sicily, 90127, Italy

Location

Mater Dei Hospital

Valletta, 2090, Malta

Location

Related Publications (6)

• 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.

  PMID: 12578508 BACKGROUND

• 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.

  PMID: 34952810 BACKGROUND

• 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.

  PMID: 31568151 BACKGROUND

• 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.

  PMID: 35736659 BACKGROUND

• 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.

  PMID: 20670718 BACKGROUND

• 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.

  PMID: 31331324 BACKGROUND

MeSH Terms

Conditions

Celiac Disease; Disease

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: February 8, 2023
• Study Start: June 1, 2023
• Primary Completion: February 28, 2024
• Study Completion: December 31, 2024
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); MA (1)