PRIORITY (Enpowering Progression Risk of Cerebral Amyloid Angiopathy)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Clinical Progression of CAA
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Clinical Progression of CAA
时间窗: 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.
Radiological Progression of CAA
时间窗: 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.
Identification of Protein and Lipid Biomarkers
时间窗: 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.
次要结局
- Cognitive Decline Assessment(Baseline (T0), 12 months (T1), 24 months (T2).)
- Development of a Predictive Model for Disease Progression(24 months (T2).)
- Hemorrhagic and Non-Hemorrhagic Event Incidence(24 months (T2))
- Therapeutic Target Identification(24 months (T2))
- Functional assessment(Baseline (T0), 12 months (T1), 24 months (T2))