Natural History of Familial Cerebral Cavernous Malformations: the CCM_Italia Cohort Study

NCT06983132 | Recruiting

• 2 other identifiers: ID 5417PNRR-MR1- 2023-12378478
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 6

Brief Summary

Patients with symptomatic and asymptomatic familial cerebral cavernous malformation (fCCM) will be included. The goal of this observational study is to learn about the long-term evolution of this condition. The subjects enrolled will be followed for two years and will undergo an annual neurological examination with the recording of clinical events, a brain MRI according to a dedicated protocol, and a blood draw for the determination of circulating biomarkers. They will also be asked to complete questionnaires on quality of life. The data derived from the study will allow for a better understanding of the natural history of the disease and the identification of neuroradiological and/or circulating biomarkers capable of predicting the clinical evolution of the condition.

Conditions

CCM; Familial Cerebral Cavernous Malformation

Keywords

CCM; fCCM

Outcome Measures

Primary Outcomes (1)

• Occurrence of CCM-related clinical events

  New occurrence of intracerebral haemorrhage (ICH) or focal neurological deficits (FNDs)

  24 months

Secondary Outcomes (3)

• Other clinical manifestations

  24 months

• Neuroradiological markers of disease progression

  24 months

• Circulating biomarkers

  24 months

Other Outcomes (1)

• Patients reported outcome measures

  24 months

Study Arms (1)

Patients with symptomatic and asymptomatic familial cerebral angiomatosis will be included.

Patients with symptomatic and asymptomatic familial cerebral angiomatosis will be included. Subjects without genetic diagnosis will not be included. Other exclusion ctiteria will be current inclusion in a different clinical study, inability to cooperate with study procedures, contraindication to cerebral MRI.

Diagnostic Test: Cerebral imaging (MRI) according to a dedicated protocol with central MRI reading; Diagnostic Test: Determination of circulating biomarkers

Interventions

Cerebral imaging (MRI) according to a dedicated protocol with central MRI reading DIAGNOSTIC_TEST

Cerebral MRI according to dedicated protocol, central MRI reading.

Also known as: Circulating biomarkers, Cerebral MRI

Patients with symptomatic and asymptomatic familial cerebral angiomatosis will be included.

Determination of circulating biomarkers DIAGNOSTIC_TEST

High-throughput molecular analysis will be performed on plasma samples collected assessing a selected panel of biomarkers, associated with endothelial cell profiles using automated and high-throughput ELISA. The interactions between mutation profile, protein biomarkers, and clinical variables will be correlated with patients' outcomes.

Patients with symptomatic and asymptomatic familial cerebral angiomatosis will be included.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with familial cerebral cavernous malformations (FCCM), documented by mutations in the CCM1, CCM2, or CCM3 genes. Either symptomatic or asymptomatic subjects will be considered for inclusion

You may qualify if:

• Patients with familial cerebral cavernous malformations (FCCM), documented by mutations in the CCM1, CCM2, or CCM3 genes;
• Asymptomatic patients or those with a history of clinical symptoms or events, such as intracerebral hemorrhage, stroke, permanent or transient focal deficits, seizures, disability, or any other neurological symptom presumably related to CCM;
• Life expectancy at least equal to the duration of the study follow-up;
• Written informed consent from the patient (or guardian in the case of minors) to participate in the study.

You may not qualify if:

• Implanted pacemaker or any other condition that precludes magnetic resonance imaging;
• Participation in another ongoing interventional clinical study;
• Inability to cooperate with the study procedures.

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• Mario Negri Institute for Pharmacological Research: collaborator
• Istituto Giannina Gaslini: collaborator
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: collaborator
• Azienda Ospedaliero-Universitaria Careggi: collaborator
• University of Bari: collaborator
• Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona: collaborator

Study Sites (6)

Policlinico di Bari

Bari, 70124, Italy

NOT YET RECRUITING

Careggi Hospital, Firenze

Florence, Italy

RECRUITING

Istituto Giannina Gaslini, Genova

Genova, Italy

NOT YET RECRUITING

Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy

Milan, 20122, Italy

RECRUITING

Istituto di Ricerche Farmacologiche Mario Negri

Milan, 20256, Italy

ACTIVE NOT RECRUITING

San Giovanni di Dio e Ruggi d'Aragona", Salerno

Salerno, Italy

RECRUITING

Related Publications (6)

• Latouche A, Porcher R, Chevret S. Sample size formula for proportional hazards modelling of competing risks. Stat Med. 2004 Nov 15;23(21):3263-74. doi: 10.1002/sim.1915.

  PMID: 15490425 BACKGROUND

• Schoenfeld DA. Sample-size formula for the proportional-hazards regression model. Biometrics. 1983 Jun;39(2):499-503.

  PMID: 6354290 BACKGROUND

• Meessen JMTA, Abete-Fornara G, Zarino B, Castori M, Tassi L, Carriero MR, D'Alessandris QG, Al-Shahi Salman R, Blanda A, Nicolis EB, Novelli D, Caruana M, Vasami A, Lanfranconi S, Latini R. Patient-reported outcome measures in patients with familial cerebral cavernous malformations: results from the Treat_CCM trial. Front Neurol. 2024 Feb 14;15:1338941. doi: 10.3389/fneur.2024.1338941. eCollection 2024.

  PMID: 38419711 BACKGROUND

• Lazzaroni F, Meessen JMTA, Sun Y, Lanfranconi S, Scola E, D'Alessandris QG, Tassi L, Carriero MR, Castori M, Marino S, Blanda A, Nicolis EB, Novelli D, Calabrese R, Agnelli NM, Bottazzi B, Leone R, Mazzola S, Besana S, Catozzi C, Nezi L, Lampugnani MG, Malinverno M, Grdseloff N, Rodel CJ, Rezai Jahromi B, Bolli N, Passamonti F, Magnusson PU, Abdelilah-Seyfried S, Dejana E, Latini R. Circulating biomarkers in familial cerebral cavernous malformation. EBioMedicine. 2024 Jan;99:104914. doi: 10.1016/j.ebiom.2023.104914. Epub 2023 Dec 18.

  PMID: 38113759 BACKGROUND

• Lanfranconi S, Scola E, Meessen JMTA, Pallini R, Bertani GA, Al-Shahi Salman R, Dejana E, Latini R; Treat_CCM Investigators. Safety and efficacy of propranolol for treatment of familial cerebral cavernous malformations (Treat_CCM): a randomised, open-label, blinded-endpoint, phase 2 pilot trial. Lancet Neurol. 2023 Jan;22(1):35-44. doi: 10.1016/S1474-4422(22)00409-4. Epub 2022 Nov 17.

  PMID: 36403580 BACKGROUND

• Lanfranconi S, Scola E, Novelli D, Poggesi A, Pescini F, Pavanello M, Romano F, D'Alessandris QG, Marani W, Signorelli F, Iaconetta G, Torelli G, Fainardi E, Severino M, Remore LG, Bertani GA, Conte G, Capra V, Vasami A, Nicolis E, Contino G, Ronchi D, Palmieri MC, Previtali A, Mattogno PP, Sturiale CL, Solarino ME, Caliulo R, Bozzi MT, Fratini F, Zanier ER, Latini R, Meessen JMTA, Locatelli M; and the CCM_Italia investigators. Natural history of familial cerebral cavernous malformations: the CCM_Italia cohort study. Front Neurol. 2026 Jan 5;16:1668098. doi: 10.3389/fneur.2025.1668098. eCollection 2025.

  PMID: 41561324 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

15,5 ml of blood

MeSH Terms

Conditions

Familial cerebral cavernous malformation

Interventions

Magnetic Resonance Imaging

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Central Study Contacts

Silvia Lanfranconi, MD, Neurologist

CONTACT

+390255033802; silvia.lanfranconi@policlinico.mi.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2025
• First Posted: May 21, 2025
• Study Start: November 18, 2024
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: May 21, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6)