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Completed

NCT Number: NCT06960538

Enpowering Progression Risk of Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA) is a microangiopathy characterized by the progressive deposition of β-amyloid in cerebral vessel walls, contributing to intracerebral hemorrhages, cognitive decline, and other clinical manifestations. Despite recent advances in diagnosis and understanding, many pathogenic, prognostic, and therapeutic aspects remain unclear.

Study Objective:

PRIORITY is a prospective observational study aimed at identifying clinical, neuroradiological, and biochemical biomarkers that could improve early diagnosis, risk stratification, and the identification of personalized therapeutic targets for CAA.

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Key information

Conditions

Cerebral Amyloid Angiopathy Amyloidosis Amyloidosis, Familial Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn CAA - Cerebral Amyloid Angiopathy Cardiovascular Diseases Central Nervous System Diseases Cerebral Amyloid Angiopathy, Familial Cerebral Arterial Diseases Cerebral Small Vessel Diseases Cerebrovascular Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Intracranial Arterial Diseases Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Nutritional and Metabolic Diseases Proteostasis Deficiencies Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Italy

About this study

PRIORITY is a prospective, single-center observational study conducted at the Fondazione IRCCS Istituto Neurologico Carlo Besta in Milan. It will consecutively enroll patients over 18 years of age with possible or probable cerebral amyloid angiopathy (CAA), symptomatic or asymptomatic, with or without histological confirmation. Diagnosis will follow the updated Boston criteria 2.0, and a brain MRI is mandatory for inclusion.

The study duration is 36 months, with clinical and neuroimaging assessments at baseline (T0), 12 months (T1), and 24 months (T2). CSF analysis will be performed at T0; plasma biomarkers (via ELISA and SIMOA) will be assessed at all time points. Lipid profiles will be analyzed using mass spectrometry with both untargeted and targeted lipidomic approaches (e.g., sphingolipidomics).

The comprehensive clinical and biological dataset will be used to develop a machine learning-based predictive model to support diagnostic, prognostic, and therapeutic decision-making in CAAThe study duration is 36 months, with clinical and neuroimaging assessments at baseline (T0), 12 months (T1), and 24 months (T2). CSF analysis will be performed at T0; plasma biomarkers (via ELISA and SIMOA) will be assessed at all time points. Lipid profiles will be analyzed using mass spectrometry with both untargeted and targeted lipidomic approaches (e.g., sphingolipidomics).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • patients of either sex over 18 years of age;
  • patients with possible and probable symptomatic or asymptomatic CAA with or without histological demonstration (modified Boston criteria);
  • patients who have had at least one brain MRI.

Exclusion criteria

  • patients who have contraindications to undergoing brain MRI (e.g., pacemaker, incompatible mechanical valves, claustrophobia);
  • patients who have contraindications to or refuse to undergo lumbar puncture;
  • patients who are unable to provide informed consent for the study due to aphasic or cognitive impairment;
  • patients who are pregnant or breastfeeding.

Treatment and study plan

Primary outcomes

  1. Clinical Progression of CAA

    Time frame: Baseline (T0), 12 months (T1), 24 months (T2).

    Evaluation of the natural progression of cerebral amyloid angiopathy (CAA) through clinical assessments.

    At baseline, clinical data (e.g., history of stroke, a diagnosis of dementia, presence of seizures, gait disturbances, vascular risk factors, prior brain injury/surgery, family history, medications…) recorded in a binary (yes/no) scale, indicating the presence or absence of each condition or risk factor, will be collected for each patient.

    During follow-up, new clinical events (e.g., number of new ICH-intracerebral hemorrhages, number of new ischemic stroke, presence of seizures, presence of TFNEs, cognitive status, death) will be recorded and compared with T0.

  2. Radiological Progression of CAA

    Time frame: Baseline (T0), 12 months (T1), 24 months (T2).

    Evaluation of the natural progression of cerebral amyloid angiopathy (CAA) through neuroimaging markers (MRI).

    MRI assessment at baseline will include T1, T2, FLAIR, T2*, GRE, SWI, and DWI sequences. Imaging will be assessed using STRIVE (Standards for Reporting Vascular Changes on Neuroimaging) criteria, with standardized rating scales for: number of Microbleeds (Microbleed Anatomical Rating Scale - MARS); presence of Lobar ICH- intracerebral hemorrhages; presence of Superficial siderosis; presence of White matter lesions (Fazekas scale: o to 3 scores, where 0 means absence of white matter lesions and 3 large presence of them); presence of Perivascular spaces (CSO-PVS); presence of Cortical microinfarcts; presence of Global cortical atrophy; presence of Subarachnoid haemorrhage.

    Follow-up includes repeated MRI with the same sequences. MRI changes will be evaluated with the same standardized rating scales for progression or appearance of the same parameters evaluated in T0.

  3. Identification of Protein and Lipid Biomarkers

    Time frame: Baseline (T0), 12 months (T1), 24 months (T2).

    Analysis of cerebrospinal fluid and plasma to identify protein (e.g., concentrations in pg/mL of total Tau, p-Tau, Aβ42/Aβ40, NfL, GFAP) and lipid (qTOF-MS) signatures associated with CAA progression.

Secondary outcomes

  1. Cognitive Decline Assessment

    Time frame: Baseline (T0), 12 months (T1), 24 months (T2).

    Longitudinal evaluation of cognitive functions and disability to correlate with disease progression. A neuropsychological evaluation will be performed using the Montreal Cognitive Assessment (MoCA) test, scores range from 0 to 30, with lower scores indicating greater cognitive impairment.

  2. Development of a Predictive Model for Disease Progression

    Time frame: 24 months (T2).

    Development and validation of machine learning models (e.g., Random Forest, Decision Trees) to predict disease progression. Performance metrics include accuracy, sensitivity, specificity, PPV, NPV, and AUC based on integrated clinical, imaging, and biomolecular data.

  3. Hemorrhagic and Non-Hemorrhagic Event Incidence

    Time frame: 24 months (T2)

    Monitoring of symptomatic and asymptomatic cerebral hemorrhages, as well as other vascular events, to determine risk factors.

  4. Therapeutic Target Identification

    Time frame: 24 months (T2)

    Identification of potential molecular targets for future therapeutic interventions based on CSF and plasma biomarker analysis.

  5. Functional assessment

    Time frame: Baseline (T0), 12 months (T1), 24 months (T2)

    Disability will be assessed with the modified Rankin Scale (mRS, scores ranges from 0 - no symptoms - to 6 - death).

Sponsors and collaborators

Lead sponsor

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

Other

Registry information

Official study title

PRIORITY (Enpowering Progression Risk of Cerebral Amyloid Angiopathy)

Acronym: PRIORITY

Important dates

Study start
2021
Primary completion
2025
Study completion
2025
First posted
May 7, 2025
Registry last updated
Mar 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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