AutoInflammatory Disease Alliance Registry (AIDA)

Recruiting

• Conditions: Hereditary Autoinflammatory Diseases; Schnitzler Syndrome; Behcet Syndrome; PFAPA Syndrome; Still Disease; Autoinflammatory Syndrome, Unspecified; Uveitis; Scleritis; Vexas Syndrome; Spondyloarthritis (SpA)
• Interventions: Other: No intervention is foreseen by the protocol.

• Registration Number: NCT05200715
• Lead Sponsor: University of Siena

Brief Summary

Autoinflammatory diseases (AID) are clinical entities characterized by recurrent inflammatory attacks in absence of infection, neoplasm or deregulation of the adaptive immune system. Among them, hereditary periodic syndromes, also known as monogenic AID, represent the prototype of this disease group, caused by mutations in genes involved in the regulation of innate immunity, inflammation and cell death. Based on recent experimental acquisitions in the field of monogenic AID, several immunologic disorders have been reclassified as polygenic/multifactorial AID, sharing pathogenetic and clinical features with hereditary periodic fevers. This has paved the way to new treatment targets for patients suffering from rare diseases of unknown origin, including Behçet's disease, Still disease, Schnitzler's disease, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) syndrome, chronic recurrent multifocal osteomyelitis (CRMO), non-infectious uveitis and scleritis. Gathering information on such rare conditions is made difficult by the small number of patients, along with the difficulty of obtaining an accurate diagnosis in non-specialized clinical settings.

In this context, the AIDA project promotes international collaboration among clinical centres to develop a permanent registry aimed at collecting demographic, genetic, clinical and therapeutic data of patients affected by monogenic and polygenic AID, in order to expand the current knowledge of these rare conditions.

Detailed Description

The AIDA registry service is based on REDCap (Research Electronic Data Capture, project-redcap.org), a secure web application for building and managing online surveys and databases, designed to support data capture for research studies. The platform is directly accessible through the AIDA website, after inserting a personal username and password. Currently, 11 registries are available, each one dedicated to the collection of data about:

* monogenic AID

* PFAPA syndrome

* undifferentiated systemic AID (USAID)

* Behçet's disease

* Schnitzler's disease

* VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome

* Still disease

* noninfectious uveitis

* noninfectious scleritis

* spondyloarthritis

* Castleman disease

The registry will pursue the following aims within the first 36 months from the start of the enrollment:

1. to identify any association between clinical manifestations and gender, disease duration, body mass index and tabagism;

2. to detect differences in the clinical phenotype between pediatric-onset and adult-onset patients;

3. to identify the impact of different treatment approaches on clinical and laboratory disease manifestations.

Additional aims of the AIDA project, to be reached over the next 10 years, are the following:

1. to overcome fragmentation in the clinical experience on these rare conditions by sharing the knowledge at the international level;

2. to improve knowledge about the clinical presentation, genotype-phenotype correlations, response to treatment, long-term complications and social impact when monogenic and polygenic AID manifest during either childhood or adulthood;

3. to identify the long-term clinical course of patients diagnosed with monogenic or polygenic AID;

4. to promote awareness among physicians and enhance early recognition of these diseases;

5. to describe the impact of AID on quality of life;

6. to identify any impact of monogenic and polygenic AID on fertility;

7. to study the course of AID during pregnancy;

8. to assess the socioeconomic impact of AID;

9. to promote future multicentric studies.

Data collection is both retrospective and prospective. It includes demographic, clinical, diagnostic, genetic, clinimetric, laboratory, radiologic, therapeutic and socio-economic data. Instruments are designed to be filled out during routine clinical visits, usually scheduled every 3-6 months. Separation of personally identifiable information and medical data by using only pseudonyms for storing medical data ensures compliance with data protection regulations. The description of symptoms, diseases, procedures and injuries is based on the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 coding system. Data management is both central and decentral. Data are extracted and statistically analyzed on a regular basis according to individual study protocols. A policy for authorship and dissemination of research findings is in place among the AIDA partners contributing to the registry.

The AIDA registry will support data collection for the conduction of clinical trials, observational studies, comparative effectiveness research, and other research on patients with monogenic and polygenic AID.

Several healthcare providers contributing to the AIDA Network are members of the European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA).

Study Timeline

• Study Start: 2020-08-06
• Study First Submitted: 2021-12-18
• Study First Submitted QC: 2022-01-06
• Study First Posted: 2022-01-21
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-29
• Primary Completion: 2026-08-06
• Study Completion: 2030-08-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 3500

Inclusion Criteria

• to be diagnosed with a monogenic AID according to the clinical phenotype and the detection of a confirmative genotype;
• to be diagnosed with clinical familial Mediterranean fever or Behçet's disease or Still disease or PFAPA syndrome or Schnitzler's disease or CRMO according to the corresponding clinical diagnostic and/or classification criteria;
• to be diagnosed with undifferentiated systemic AID;
• to be diagnosed with non-infectious uveitis according to the standardization for uveitis nomenclature (SUN) criteria;
• to be diagnosed with anterior or posterior non-infectious scleritis;
• to be diagnosed with spondyloarthritis according to ASAS and/or New York criteria;
• to be diagnosed with Castleman disease;

Exclusion Criteria

• informed consent/assent not provided by the patient and/or his/her legal representative.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients affected by autoinflammatory diseases	No intervention is foreseen by the protocol.	-

Primary Outcome Measures

Name	Time	Method
Change of the number of enrolled subjects	0-36-60-120 months	This is an observational registry. The primary outcome is the increase of the number of subjects enrolled within each nosologic group.

Secondary Outcome Measures

Name	Time	Method
Change in the overall damage score	0-36-60-120 months	Change in the overall damage score specific for the nosologic entity (ADDI score, BODI score, JADI score)
Change in the % of patients with new organ involvement	0-36-60-120 months
Incidence of death or adverse events	0-36-60-120 months
Change in visual acuity expressed as Best Corrected Visual Acuity (BCVA)	0-36-60-120 months
Change in the disease activity score	0-36-60-120 months	Change in the disease activity score specific for the nosologic entity (BDCAF score, Pouchot score, modified Pouchot score, JADAS27/JADAS27(CRP), DAS28) or according to composite indexes that will be defined in each study based on the registry.
Changes in height and weight percentile values for age and sex	0-36-60-120 months
Change in the inflammatory markers values (ESR)	0-36-60-120 months	ESR measured in mm/h
Change in the overall function score	0-36-60-120 months	Change in the overall function score according to HAQ (adults) or CHAQ (children)
Change in articular pain measured as Visual Analogue Scale for articular Pain (VAS Pain)	0-36-60-120 months
Change in the inflammatory markers values (CRP and SAA)	0-36-60-120	CRP and SAA measured in mg/dl
Change in the % of patients experiencing fatigue	0-36-60-120 months
Change in the socioeconomic indicators	0-36-60-120 months	Number of days lost at work/school during the last 3 months, Number of visits/ phone calls to the general practitioner during the last 3 months, Number of accesses to the Emergency Room during the last 6 months, Days of hospitalization during the last 3 months, Overall number of days lost at work by relatives during the last 3 months
Change in the % of patients with fertility reduction or pregnancy complications	0-36-60-120

Trial Locations

Locations (100)

ASST Fatebenefratelli Sacco - UOC Reumatologia; 🇮🇹 Milano, Italy

AOU Luigi Vanvitelli - UOC Pediatria 2; 🇮🇹 Napoli, Italy

Azienda Ospedaliera San Carlo; 🇮🇹 Potenza, Italy

Medical University of Lodz; 🇵🇱 Łódź, Poland

Ankara University; 🇹🇷 Ankara, Turkey

Antalya Education and Research Hospital; 🇹🇷 Antalya, Turkey

Sivas Cumhuriyet University; 🇹🇷 Sivas, Turkey

Gazi University; 🇹🇷 Ankara, Turkey

Manisa Celal Bayar University; 🇹🇷 Manisa, Turkey

Eskişehir Osmangazi University; 🇹🇷 Eskişehir, Turkey

Çukurova University; 🇹🇷 Adana, Turkey

Ankara Yıldırım Beyazıt University; 🇹🇷 Ankara, Turkey

Erzurum Education and Research Hospital; 🇹🇷 Erzurum, Turkey

Cerrahpasa Medical School Istanbul University; 🇹🇷 Istanbul, Turkey

Dokuz Eylul University School of Medicine; 🇹🇷 İzmir, Turkey

Università degli Studi di Palermo; 🇮🇹 Palermo, Italy

AOU di Parma - Ospedale dei Bambini P. Barilla; 🇮🇹 Parma, Italy

National Human Genome Research Institute; 🇺🇸 Bethesda, Maryland, United States

Antwerp University Hospital; 🇧🇪 Antwerp, Belgium

UZ Leuven Gasthuisberg Campus; 🇧🇪 Leuven, Belgium

Université M'Hamed Bougara de Boumerdas; 🇩🇿 Boumerdas, Algeria

Hospital das Clinicas da Faculdade de Medicina HCFMUSP; 🇧🇷 São Paulo, Brazil

Shariati Hospital - Tehran University of Medical Sciences; 🇮🇷 Tehran, Iran, Islamic Republic of

Cairo University; 🇪🇬 Cairo, Egypt

Universitätsklinikum Schleswig-Holstein; 🇩🇪 Lübeck, Germany

Korle Bu Teaching Hospital; 🇬🇭 Accra, Ghana

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

National and Kapodistrian University of Athens; 🇬🇷 Athens, Greece

Ospedale San Donato; 🇮🇹 Arezzo, Italy

AOUC Policlinico di Bari; 🇮🇹 Bari, Italy

University-Hospital of Bari - UOC Reumatologia; 🇮🇹 Bari, Italy

Azienda Ospedaliero-Universitaria Senese; 🇮🇹 Siena, Tuscany, Italy

University-Hospital of Bari - UOC Medicina Interna; 🇮🇹 Bari, Italy

Central Hospital of Bolzano; 🇮🇹 Bolzano, Italy

University-Hospital of Bari - UOC Pediatria; 🇮🇹 Bari, Italy

Azienda Ospedaliera Universitaria di Cagliari; 🇮🇹 Cagliari, Italy

IRCCS Istituto Ortopedico Rizzoli; 🇮🇹 Bologna, Italy

ASST degli Spedali Civili - P.O. Ospedale dei Bambini; 🇮🇹 Brescia, Italy

AOU Policlinico Vittorio Emanuele - Dip. Materno-Infantile; 🇮🇹 Catania, Italy

Azienda Ospedaliera per l'Emergenza Cannizzaro; 🇮🇹 Catania, Italy

ASST degli Spedali Civili; 🇮🇹 Brescia, Italy

Azienda Ospedaliera di Catanzaro Pugliese Ciaccio; 🇮🇹 Catanzaro, Italy

Arcispedale Sant'Anna; 🇮🇹 Ferrara, Italy

Ospedale SS Annunziata; 🇮🇹 Chieti, Italy

Ospedale San Giovanni di Dio; 🇮🇹 Firenze, Italy

Azienda Ospedaliera Universitaria Careggi - SOD Medicina Interna Interdisciplinare; 🇮🇹 Firenze, Italy

Azienza Ospedaliero-Universitaria Careggi - SOD Reumatologia; 🇮🇹 Firenze, Italy

Azienda Ospedaliero-Universitaria Careggi - SOD Immunologia e Terapie Cellulari; 🇮🇹 Firenze, Italy

Azienda Ospedaliero-Universitaria Meyer; 🇮🇹 Firenze, Italy

Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza; 🇮🇹 Foggia, Italy

IRCCS Ospedale Pediatrico Giannina Gaslini; 🇮🇹 Genova, Italy

ASL1 Avezzano, Sulmona, L'Aquila; 🇮🇹 L'Aquila, Italy

Università degli Studi di L'Aquila - UOC Medicina Interna e Nefrologia; 🇮🇹 L'Aquila, Italy

Sapienza University - Polo Pontino; 🇮🇹 Latina, Italy

Ospedale Galateo - San Cesario; 🇮🇹 Lecce, Italy

ASST Fatebenefratelli Sacco - UO Medicina Generale; 🇮🇹 Milano, Italy

AOU Policlinico G. Martino; 🇮🇹 Messina, Italy

Ospedale Fatebenefratelli e Oftalmico; 🇮🇹 Milano, Italy

AOU Luigi Vanvitelli - UO Reumatologia; 🇮🇹 Napoli, Italy

Policlinico di Milano; 🇮🇹 Milan, Italy

IRCCS Ospedale San Raffaele; 🇮🇹 Milano, Italy

ASST Gaetano Pini/ CTO; 🇮🇹 Milan, Italy

Azienda Ospedaliera Universitaria di Padova; 🇮🇹 Padova, Italy

Policlinico Federico II; 🇮🇹 Napoli, Italy

Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello; 🇮🇹 Palermo, Italy

ARNAS Ospedale Civico di Cristina Benfratelli; 🇮🇹 Palermo, Italy

Fondazione IRCCS Policlinico San Matteo - Dip. Medicina Diagnostica e Servizi: L.S.R. Area Biotecnologie; 🇮🇹 Pavia, Italy

Azienda Ospedaliera di Perugia; 🇮🇹 Perugia, Italy

Fondazione IRRCS San Matteo - SC Reumatologia; 🇮🇹 Pavia, Italy

Azienda Ospedaliera Universitaria di Pisa; 🇮🇹 Pisa, Italy

Azienda USL di Piacenza; 🇮🇹 Piacenza, Italy

Grande Ospedale Metropolitano - Azienda Ospedaliera Bianchi-Melacrino-Morelli; 🇮🇹 Reggio Calabria, Italy

Arcispedale Santa Maria Nuova; 🇮🇹 Reggio Emilia, Italy

AOU Policlinico Umberto I; 🇮🇹 Roma, Italy

IRCCS Fondazione PU Agostino Gemelli - UOC Medicina Interna Columbus; 🇮🇹 Roma, Italy

Azienda Ospedaliera San Camillo Forlanini; 🇮🇹 Roma, Italy

IRCCS Fondazione PU Agostino Gemelli - UOC Pediatria; 🇮🇹 Roma, Italy

Ospedale Universitario Campus Bio-Medico; 🇮🇹 Roma, Italy

Ospedale Pediatrico Bambino Gesù; 🇮🇹 Roma, Italy

Azienda Ospedaliera Universitaria di Salerno; 🇮🇹 Salerno, Italy

Sapienza University - Polo Pontino - SCIAC; 🇮🇹 Roma, Italy

ATS Sardegna; 🇮🇹 Tempio Pausania, Italy

AO Ordine Mauriziano; 🇮🇹 Torino, Italy

Presidio Ospedaliero Molinette; 🇮🇹 Torino, Italy

Presidio Ospedaliero Santa Chiara; 🇮🇹 Trento, Italy

American University of Beirut; 🇱🇧 Beirut, Lebanon

Azienda Ospedaliera Universitaria Integrata; 🇮🇹 Verona, Italy

Mohammed V University; 🇲🇦 Rabat, Morocco

Central Clinical Hospital of the Ministry of National Defense - Military Institute of Medicine; 🇵🇱 Warsaw, Poland

Pomeranian Medical University; 🇵🇱 Szczecin, Poland

Sf. Maria Hospital - University of Medicine and Pharmacy "Carol Davila"; 🇷🇴 Bucharest, Romania

Centro Hospitalar e Universitário do Porto; 🇵🇹 Porto, Portugal

King Saud University; 🇸🇦 Riyadh, Saudi Arabia

King Faisal Specialist Hospital and Research Center; 🇸🇦 Riyadh, Saudi Arabia

Hospital Clinic of Barcelona; 🇪🇸 Barcelona, Spain

Vall d'Hbron University Hospital; 🇪🇸 Barcelona, Spain

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Spain

Hospital Álvaro Cunquiero-Complejo Hospitalario Universitario de Vigo; 🇪🇸 Vigo, Spain

China Medical University; 🇨🇳 Taichung, Taiwan

Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain