RAre, But Not aLone: a Large Italian Network to Empower the Impervious diaGNostic Pathway of Rare cerEbrovascular Diseases (ALIGNED)

NCT ID: NCT06935578

Last Updated: 2025-04-20

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-05-01
• Study Completion Date: 2025-11-30

Brief Summary

Cerebrovascular diseases (CVDs) are one leading cause of morbidity and mortality worldwide. Despite intensive investigations, more than 30% of strokes remain of undetermined origin. Rare Cerebrovascular Diseases (rCVDs), including heritable (i.e., CADASIL, COL4A1 syndrome, Fabry disease) and acquired conditions (i.e., Sneddon syndrome, Moyamoya arteriopathy) account for a proportion of these strokes. However, rCVDs are often misdiagnosed since clinicians are not able to recognize them. Although rare, the identification of these stroke causes is important to establish appropriate management measures, including genetic counselling, and, if available, therapy. The lack of data on phenotype and clinical course of rCVDs, given the paucity of published series, makes the diagnosis and the development of therapies challenging. Furthermore, the molecular characterization of rCVDs is still lacking, despite progresses achieved in common stroke by applying high throughput approaches as multi-omics. Since the diagnosis and care of rCVDs require adequate expertise and instrumental tools, clinical and research activities are usually reserved to few specialized centers, mostly located in the North of Italy, leading patients to expensive trips for consultations. Therefore, the creation of a clinical and research network aimed at improving the diagnostic pathways of rCVDs is highly needed to improve the number of patients with rCVDs to better define the clinical phenotype and to transfer the knowledge on rCVDs in other centers overall Italy filling the geographical gap affecting Southern Italy.

Conditions

CADASIL; CADASIL (Diagnosis); Moya Moya Disease; Moyamoya; Moyamoya Syndrome; Sneddon Syndrome; Fabry Disease; COL4A1\2

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• patients with a clinical, genetic and/or neuroradiological diagnosis of rCVD (CADASIL, Fabry's disease, COL4A1, Sneddon's syndrome or Moyamoya arteriopathy), who have had at least one brain MRI study;

Exclusion Criteria

• na

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Ospedale Regionale Generale "F. Miulli", Acquaviva delle Fonti

Acquaviva delle Fonti, BA, Italy

Site Status: RECRUITING

ASST Melegnano Martesana

Melegnano, MI, Italy

Site Status: RECRUITING

Neurologia Stroke Unit dell'Asst Rhodense

Rho, Mi, Italy

Site Status: RECRUITING

Fondazione Istituto G. Giglio, Cefalù

Cefalù, PA, Italy

Site Status: RECRUITING

UO Neurologia degli Ospedali di Cesena e Forlì, Ospedale Bufalini Cesena ed Ospedale Morgagni-Pierantoni (Ausl della Romagna)

Cesena, , Italy

Site Status: RECRUITING

ASST di Cremona

Cremona, , Italy

Site Status: RECRUITING

Ospedale "Spaziani" di Frosinone

Frosinone, , Italy

Site Status: RECRUITING

U.O. Neurologia, Ospedale Sant'Andrea, La Spezia

La Spezia, , Italy

Site Status: RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status: RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, , Italy

Site Status: RECRUITING

Ospedale Luigi Sacco, ASST Fatebenefratelli Sacco

Milan, , Italy

Site Status: RECRUITING

Stroke Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, , Italy

Site Status: RECRUITING

IRCCS Policlinico San Matteo, Pavia

Pavia, , Italy

Site Status: RECRUITING

Neurologia d'Urgenza e Stroke Unit dell'Ospedale di Pescara

Pescara, , Italy

Site Status: RECRUITING

Neurologia dell'Ospedale Sandro Pertini - ASL Roma2

Roma, , Italy

Site Status: RECRUITING

Policlinico Tor Vergata, UOSD Stroke Unit

Roma, , Italy

Site Status: RECRUITING

Neurologia PO Levante Asl 2 Savonese

Savona, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Anna Bersano, MD

Role: CONTACT

anna.bersano@istituto-besta.it

+ 39 02.2394

Facility Contacts

Gaspare Scaglione, MD

Role: primary

g.scaglione@miulli.it

+ 39 02.2394

Carla Zanferrari, MD

Role: primary

carla.zanferrari@asst-melegnano.it

+ 39 02.2394

Maria Grazia Riggio, MD

Role: primary

griggio@asst-rhodense.it

+ 39 02.2394

Luigi Grimaldi, MD

Role: primary

luigi.grimaldi@hsrgiglio.it

+ 39 02.2394

Marco Longoni, MD

Role: primary

longonimarco@hotmail.com

+ 39 02.2394

Alessia Giossi, MD

Role: primary

alessia.giossi@asst-cremona.it

Roberto De Simone, MD

Role: primary

rdesimone09@gmail.com

+ 39 02.2394

Massimiliano Godani, MD

Role: primary

massimiliano.godani@asl5.liguria.it

+ 39 02.2394

Cristina Motto, MD

Role: primary

c.motto@tiscali.it

+ 39 02.2394

Anna Bersano, MD

Role: primary

anna.bersano@istituto-besta.it

+ 39 02.2394

Leonardo Pantoni, MD

Role: primary

leonardo.pantoni@unimi.it

+ 39 02.2394

Sara Bonato, MD

Role: primary

sara.bonato@policlinico.mi.it

+ 39 02.2394

Luisa Chiapparini, MD

Role: primary

l.chiapparini@smatteo.pv.it;

+ 39 02.2394

Maria Vittoria De Angelis, MD

Role: primary

mv.deangelis@asl.pe.it

+ 39 02.2394

Francesca Gragnani, MD

Role: primary

francesca.gragnani@aslroma2.it

+ 39 02.2394

Marina Diomedi, MD

Role: primary

marina.diomedi@uniroma2.it

+ 39 02.2394

Cinzia Finocchi, MD

Role: primary

c.finocchi@asl2.liguria.it

+ 39 02.2394

References

Caponnetto V, Ornello R, De Matteis E, Papavero SC, Fracasso A, Di Vito G, Lancia L, Ferrara FM, Sacco S. The COVID-19 Pandemic as an Opportunity to Improve Health Care Through a Nurse-Coordinated Multidisciplinary Model in a Headache Specialist Center: The Implementation of a Telemedicine Protocol. Telemed J E Health. 2022 Jul;28(7):1016-1022. doi: 10.1089/tmj.2021.0414. Epub 2021 Nov 9.

Reference Type: BACKGROUND

PMID: 34756108 (View on PubMed)

Banfi C, Baetta R, Barbieri SS, Brioschi M, Guarino A, Ghilardi S, Sandrini L, Eligini S, Polvani G, Bergman O, Eriksson P, Tremoli E. Prenylcysteine oxidase 1, an emerging player in atherosclerosis. Commun Biol. 2021 Sep 21;4(1):1109. doi: 10.1038/s42003-021-02630-z.

Reference Type: BACKGROUND

PMID: 34548610 (View on PubMed)

Degan D, Ornello R, Tiseo C, De Santis F, Pistoia F, Carolei A, Sacco S. Epidemiology of Transient Ischemic Attacks Using Time- or Tissue-Based Definitions: A Population-Based Study. Stroke. 2017 Mar;48(3):530-536. doi: 10.1161/STROKEAHA.116.015417. Epub 2017 Jan 31.

Reference Type: BACKGROUND

PMID: 28143922 (View on PubMed)

Sacco S, Marini C, Toni D, Olivieri L, Carolei A. Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry. Stroke. 2009 Feb;40(2):394-9. doi: 10.1161/STROKEAHA.108.523209. Epub 2008 Nov 26.

Reference Type: BACKGROUND

PMID: 19038914 (View on PubMed)

Romani I, Nencini P, Sarti C, Pracucci G, Zedde M, Nucera A, Cianci V, Moller J, Toni D, Orsucci D, Casella C, Pinto V, Palumbo P, Barbarini L, Bella R, Ragno M, Scoditti U, Mezzapesa DM, Tassi R, Diomedi M, Cavallini A, Volpi G, Chiti A, Bigliardi G, Sacco S, Linoli G, Ricci S, Giordano A, Bonetti B, Rasura M, Cecconi E, Princiotta Cariddi L, Curro Dossi R, Melis M, Consoli D, Guidetti D, Biagini S, Accavone D, Inzitari D. Fabry-Stroke Italian Registry (FSIR): a nationwide, prospective, observational study about incidence and characteristics of Fabry-related stroke in young-adults. Presentation of the study protocol. Neurol Sci. 2022 Apr;43(4):2433-2439. doi: 10.1007/s10072-021-05615-2. Epub 2021 Oct 5.

Reference Type: BACKGROUND

PMID: 34609660 (View on PubMed)

Bersano A, Markus HS, Quaglini S, Arbustini E, Lanfranconi S, Micieli G, Boncoraglio GB, Taroni F, Gellera C, Baratta S, Penco S, Mosca L, Grasso M, Carrera P, Ferrari M, Cereda C, Grieco G, Corti S, Ronchi D, Bassi MT, Obici L, Parati EA, Pezzini A, De Lodovici ML, Verrengia EP, Bono G, Mazucchelli F, Zarcone D, Calloni MV, Perrone P, Bordo BM, Colombo A, Padovani A, Cavallini A, Beretta S, Ferrarese C, Motto C, Agostoni E, Molini G, Sasanelli F, Corato M, Marcheselli S, Sessa M, Comi G, Checcarelli N, Guidotti M, Uccellini D, Capitani E, Tancredi L, Arnaboldi M, Incorvaia B, Tadeo CS, Fusi L, Grampa G, Merlini G, Trobia N, Comi GP, Braga M, Vitali P, Baron P, Grond-Ginsbach C, Candelise L; Lombardia GENS Group*. Clinical Pregenetic Screening for Stroke Monogenic Diseases: Results From Lombardia GENS Registry. Stroke. 2016 Jul;47(7):1702-9. doi: 10.1161/STROKEAHA.115.012281. Epub 2016 May 31.

Reference Type: BACKGROUND

PMID: 27245348 (View on PubMed)

Bersano A, Bedini G, Markus HS, Vitali P, Colli-Tibaldi E, Taroni F, Gellera C, Baratta S, Mosca L, Carrera P, Ferrari M, Cereda C, Grieco G, Lanfranconi S, Mazucchelli F, Zarcone D, De Lodovici ML, Bono G, Boncoraglio GB, Parati EA, Calloni MV, Perrone P, Bordo BM, Motto C, Agostoni E, Pezzini A, Padovani A, Micieli G, Cavallini A, Molini G, Sasanelli F, Sessa M, Comi G, Checcarelli N, Carmerlingo M, Corato M, Marcheselli S, Fusi L, Grampa G, Uccellini D, Beretta S, Ferrarese C, Incorvaia B, Tadeo CS, Adobbati L, Silani V, Farago G, Trobia N, Grond-Ginsbach C, Candelise L; Lombardia GENS-group. The role of clinical and neuroimaging features in the diagnosis of CADASIL. J Neurol. 2018 Dec;265(12):2934-2943. doi: 10.1007/s00415-018-9072-8. Epub 2018 Oct 11.

Reference Type: BACKGROUND

PMID: 30311053 (View on PubMed)

Bersano A, Bedini G, Nava S, Acerbi F, Sebastiano DR, Binelli S, Franceschetti S, Farago G, Grisoli M, Gioppo A, Ferroli P, Bruzzone MG, Riva D, Ciceri E, Pantaleoni C, Saletti V, Esposito S, Nardocci N, Zibordi F, Caputi L, Marzoli SB, Zedde ML, Pavanello M, Raso A, Capra V, Pantoni L, Sarti C, Pezzini A, Caria F, Dell' Acqua ML, Zini A, Baracchini C, Farina F, Sanguigni S, De Lodovici ML, Bono G, Capone F, Di Lazzaro V, Lanfranconi S, Toscano M, Di Piero V, Sacco S, Carolei A, Toni D, Paciaroni M, Caso V, Perrone P, Calloni MV, Romani A, Cenzato M, Fratianni A, Ciusani E, Prontera P, Lasserve ET, Blecharz K, Vajkoczy P, Parati EA; GEN-O-MA study group. GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease-study protocol and preliminary results. Neurol Sci. 2019 Mar;40(3):561-570. doi: 10.1007/s10072-018-3664-z. Epub 2019 Jan 3.

Reference Type: BACKGROUND

PMID: 30604336 (View on PubMed)

Bersano A, Morbin M, Ciceri E, Bedini G, Berlit P, Herold M, Saccucci S, Fugnanesi V, Nordmeyer H, Farago G, Savoiardo M, Taroni F, Carriero M, Boncoraglio Giorgio B, Perucca L, Caputi L, Parati Eugenio A, Kraemer M. The diagnostic challenge of Divry van Bogaert and Sneddon Syndrome: Report of three cases and literature review. J Neurol Sci. 2016 May 15;364:77-83. doi: 10.1016/j.jns.2016.03.011. Epub 2016 Mar 5.

Reference Type: BACKGROUND

PMID: 27084221 (View on PubMed)

Panara V, Navarra R, Mattei PA, Piccirilli E, Bartoletti V, Uncini A, Caulo M. Correlations between cervical spinal cord magnetic resonance diffusion tensor and diffusion kurtosis imaging metrics and motor performance in patients with chronic ischemic brain lesions of the corticospinal tract. Neuroradiology. 2019 Feb;61(2):175-182. doi: 10.1007/s00234-018-2139-5. Epub 2018 Dec 5.

Reference Type: BACKGROUND

PMID: 30519889 (View on PubMed)

Other Identifiers

ALIGNED

Identifier Type: -

Identifier Source: org_study_id