LEukoaraiosis and blOod Pressure Reduction in OLD People
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 820
- 试验地点
- 4
- 主要终点
- The main criterion is based on the quantitative assessment of White Matter Lesions (WML) volumes at the beginning and at the end of the study for each patient and each arm of the trial. The WML volume from the final MRI is compared to that of the initial
研究概览
简要总结
The purpose of the study is to test the hypothesis of slowing the progression of White Matter Lesions (WML) by lowering blood pressure (BP) in patients with cognitive complaints and a moderate to high grade of WML on brain MRI.
详细描述
SCIENTIFIC BACKGROUND: White Matter Lesions (WML) are cerebrovascular abnormalities discovered on MRI that are associated with an increased risk of dementia. High blood pressure (BP) is a major risk factor for WML. WML are therefore key lesions in the causal chain linking vascular factors and dementia, particularly Alzheimer's disease.
However, it has not been shown that lowering BP could limit the progression of the WML in people with cognitive impairment.
OBJECTIVES: To test the hypothesis of slowing progression of WML by lowering BP in patients with memory complaints with a moderate to high grade of WML on brain MRI.
STUDY DESIGN: PROBE (Prospective randomized open blinded end-point) trial. Blind reading of both MRI for every patient in each group. After stratified randomization on age, sex and center, patients will be assigned to two strategies:
- Reinforced Group (RG): enhanced strategy aiming at a systolic BP <135 mmHg;
- Usual Group (UG): usual strategy based on the usual routine care.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 88 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •60 to 88 years old patients;
- •Patient with cognitive complaint with MMSE ≥ 20performed within 6 months prior to enrollment (with or without dementia)
- •Patient with a socio-educational level ≥ 3
- •Presence of hyperintensities of moderate to high grade on the last MRI or old scan (grades C and D on the modified Scheltens scale, grades 2/3 Fazekas).
- •Hypertension defined by a Systolic Blood Pressure (SBP) and / or a Diastolic Blood Pressure (DBP) ≥ 140/90 mmHg, treated or not
- •Affiliation to a social security system
- •Informed consent given, signed consent
排除标准
- •Presence of severe orthostatic hypotension defined as a decrease of 30 mmHg in SBP standing within 3 minutes
- •Contraindication to MRI (presence of ferromagnetic foreign body (especially some intracranial clips, some heart valves, intraocular foreign bodies, metal prosthesis), subject carrying pacemaker, claustrophobic participants)
- •Severe diseases associated with a life expectancy of less than 3 months;
- •Major physical impairments that can interfere with the feasibility of the tests (sight, hearing ...)
- •Presence of another dementia different than Alzheimer's disease vascular dementia or mixed dementia,
- •Persons under guardianship;
- •Secondary hypertension: renovascular hypertension, primary aldosteronism, pheochromocytoma ...;
- •Patient already receiving 4 or more antihypertensive drugs at maximum dosage
- •Patient participating in another clinical research study on drug requiring exclusion period
- •severe renal impairment
结局指标
主要结局
The main criterion is based on the quantitative assessment of White Matter Lesions (WML) volumes at the beginning and at the end of the study for each patient and each arm of the trial. The WML volume from the final MRI is compared to that of the initial
时间窗: 36 months + 6 months max
次要结局
- Clinical criteria: number of incident cases of dementia(36 months)
- Number of incident cases of vascular events validated by an expert committee(36 months)
- Clinical criteria: total mortality by cause(36 months+ 6 months max)
- Imaging criteria : changes in the number of large or confluent WML(36 months+ 6 months max)
- Imaging criteria : changes in the number of microbleeds(36 months+ 6 months max)
- Imaging criteria : changes in the volume of WML depending on their location (periventricular and deep white matter)(36 months+ 6 months max)
- Imaging criteria : evolution of brain volumes (gray matter, white matter, CSF, and regional volumes including hippocampus)(36 months+ 6 months max)
- Imaging criteria : changes in the number of silent infarctus(36 months+ 6 months max)
- Clinical criteria: clinical criteria (changes in neuropsychological tests(36 months)
- Clinical criteria: changes inwalking speed(36 months)