Midlife Hypertension and Structural and Functional Brain MRI: Catching the First Signs of Cerebral Small Vessel Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Standard neuroimaging markers of SVD, assessed using STRIVE criteria
研究概览
简要总结
Cerebral small vessel disease (SVD) describes a set of pathologies affecting the smallest blood vessels in the brain. SVD contributes to up to a fifth of ischemic and hemorrhagic strokes en is the main vascular cause of dementia. On MRI, SVD is marked by different types of lesions, including white matter abnormalities, and small infarcts and hemorrhages. Recent studies indicate that SVD develops slowly over the years, starting presumably decades before the typical MRI lesions become apparent. High blood pressure plays an important role in the development of SVD MRI lesions. However, it remains unclear exactly how hypertension leads to vascular pathology. To gain more insight into how hypertension leads to SVD it is important to study mechanisms in individuals (largely) free of SVD, that is before midlife.
Therefore, the investigators aim to examine abnormalities in brain (micro) structure and vascular function in young patients with hypertension. Furthermore, the investigators aim to determine the effects of blood pressure increase and subsequent blood pressure reduction during a period of withdrawal and restart of blood pressure lowering drugs on brain (micro)structure and vascular function.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-40 years
- •Blood pressure above 140/90 mmHg, measured within three months prior to study participation
排除标准
- •Pre-existing cerebrovascular disease
- •Pregnancy
- •Contraindications for 3 T MRI
- •Renal function eGFR below 30 ml/min (for Dynamic Contrast Enhanced [DCE]-MRI
- •Major risk factors for acute ischemic stroke other than SVD according to the TOAST criteria, including, but not limited to, large-artery atherosclerosis, cardioembolism and vasculitis based on medical history and ultrasound of the carotids collected at baseline or any chronic disease that could lead to brain lesions mimicking SVD
- •Major (neurological/psychiatric) disease (e.g. multiple sclerosis)
- •Not able to give informed consent
- •Study 2: longitudinal study
- •Inclusion criteria:
- •Age 18-55 years
- •Undergoing diagnostic routine of temporary antihypertensive withdrawal for biochemical analysis as part of clinical work-up
- •Exclusion criteria:
- •Pre-existing cerebrovascular disease
- •Pregnancy
- •Contraindications for 3 T MRI
- •Renal function eGFR below 30 ml/min (for Dynamic Contrast Enhanced [DCE]-MRI
- •Major risk factors for acute ischemic stroke other than SVD according to the TOAST criteria,22 including, but not limited to, large-artery atherosclerosis, cardioembolism and vasculitis based on medical history and ultrasound of the carotids collected at baseline or any chronic disease that could lead to brain lesions mimicking SVD
- •Major (neurological/psychiatric) disease (e.g. multiple sclerosis)
- •Not able to give informed consent
研究组 & 干预措施
Longitudinal study
In a cohort study, we will examine the effects of an increase and decrease in blood pressure on the brain. For this analysis, we will include hypertensive patients that are referred to the Radboudumc Department of Internal Medicine for a diagnostic work up on the cause(s) of their hypertension. The diagnostic procedure entails withdrawal of antihypertensives for approximately four weeks, as per the routine diagnostic protocol to allow for diagnosis of the cause of hypertension, and subsequent restart of treatment until the target blood pressure is reached (normotension). Measurements are performed just before antihypertensive medication is withdrawn (baseline), approximately four weeks after withdrawal (T=1), once patients have reached their target blood pressure and blood pressure is stable, estimated to occur within 2-4 months (T=2) and approximately 1 year after T=2 (T=3).
干预措施: Antihypertensive medication withdrawal (Drug)
结局指标
主要结局
Standard neuroimaging markers of SVD, assessed using STRIVE criteria
时间窗: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
This includes white matter hyperintensity volumes, lacunes, microbleeds, DWI+ positive lesions.
DCE-MRI outcomes
时间窗: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Volume fraction (Vl)
Intravoxel Incoherent Motion outcomes
时间窗: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Microvascular perfusion (fD\*)
Resting state fMRI
时间窗: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Functional connectivity
DTI outcomes
时间窗: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Peak Skeleton ofMean diffusivity (PSMD)
次要结局
- Motor functioning(Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.)
- Blood markers(Four weeks after antihypertensive drug withdrawal and after 1-4 months when blood pressure is stable.)
- Cognition(Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.)