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

NCT06935578 | Recruiting

• 1 other identifier: ALIGNED
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 17

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; Sneddon Syndrome; Fabry Disease; COL4A1\2; Moyamoya Syndrome

Keywords

Rare Cerebrovascular Diseases; italian network; CADASIL; COL4A1 syndrome; Fabry Disease; Sneddon Syndrome; Moyamoya arteriopathy; COL4A1/2

Outcome Measures

Primary Outcomes (2)

• Describe the phenotypic characteristics of rCVD patients

  To describe the phenotypic characteristics of rCVD patients. All patients will complete a standardized neurological assessment consisting of anamnestic data collection (family history of neurological pathology, and in particular of rCVD, cardiovascular risk factors, medications taken, comorbidities, recent or previous head injuries) and a complete physical examination.

  0-12 months

• Assess the natural history of disease

  To develop a new, unique, and large registry on rCVDs recruiting a large number of patients (500) , patients will be recruited by all the participating clinical centers

  0-12 months

Secondary Outcomes (3)

• Identify the molecular mechanisms

  12-30 months

• Identify biomarkers

  12-30 months

• Provide the best clinical and therapeutic management

  12-30 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults, male and female patients affected by a Rare Cerebrovascular Disease (rCVD)

You may qualify if:

• 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;

Sponsors & Collaborators

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead

Study Sites (17)

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

Acquaviva delle Fonti, BA, Italy

RECRUITING

ASST Melegnano Martesana

Melegnano, MI, Italy

RECRUITING

Neurologia Stroke Unit dell'Asst Rhodense

Rho, Mi, Italy

RECRUITING

Fondazione Istituto G. Giglio, Cefalù

Cefalù, PA, Italy

RECRUITING

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

Cesena, Italy

RECRUITING

ASST di Cremona

Cremona, Italy

RECRUITING

Ospedale "Spaziani" di Frosinone

Frosinone, Italy

RECRUITING

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

La Spezia, Italy

RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Italy

RECRUITING

Ospedale Luigi Sacco, ASST Fatebenefratelli Sacco

Milan, Italy

RECRUITING

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

Milan, Italy

RECRUITING

IRCCS Policlinico San Matteo, Pavia

Pavia, Italy

RECRUITING

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

Pescara, Italy

RECRUITING

Neurologia dell'Ospedale Sandro Pertini - ASL Roma2

Roma, Italy

RECRUITING

Policlinico Tor Vergata, UOSD Stroke Unit

Roma, Italy

RECRUITING

Neurologia PO Levante Asl 2 Savonese

Savona, Italy

RECRUITING

Related Publications (10)

• 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.

  PMID: 34756108 BACKGROUND

• 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.

  PMID: 34548610 BACKGROUND

• 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.

  PMID: 28143922 BACKGROUND

• 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.

  PMID: 19038914 BACKGROUND

• 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.

  PMID: 34609660 BACKGROUND

• 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.

  PMID: 27245348 BACKGROUND

• 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.

  PMID: 30311053 BACKGROUND

• 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.

  PMID: 30604336 BACKGROUND

• 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.

  PMID: 27084221 BACKGROUND

• 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.

  PMID: 30519889 BACKGROUND

MeSH Terms

Conditions

CADASIL; Disease; Moyamoya Disease; Sneddon Syndrome; Fabry Disease

Condition Hierarchy (Ancestors)

Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Dementia, Vascular; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Stroke; Dementia; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Carotid Artery Diseases; Arterial Occlusive Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Central Study Contacts

Anna Bersano, MD

CONTACT

+ 39 02.2394; anna.bersano@istituto-besta.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: April 20, 2025
• Study Start: May 1, 2023
• Primary Completion (Estimated): May 19, 2026
• Study Completion (Estimated): May 19, 2026
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (17)