CAndesartan vs LIsinopril Effects on the BRain and Endothelial Function in eXecutive MCI (CALIBREX)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 176
- 试验地点
- 1
- 主要终点
- NINDS-initiated EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" Tool Box.
研究概览
简要总结
The aim of this study is to conduct a 1-year double blind randomized control trial comparing candesartan to lisinopril in 140 individuals with hypertension and executive mild cognitive impairment in their effects on executive function, neuroimaging markers, and vascular indicators.
详细描述
- Hypertension is associated with cognitive impairment even in the absence of clinical dementia. To date, no specific treatment is available for this pattern of mild cognitive impairment related to hypertension.
- Objectives or purpose: The aims of this study are to investigate the effects of candesartan on executive function decline and on changes in cerebral perfusion, cerebrovascular reserve and microvascular brain injury. The study also intends to identify potential underlying mechanisms related to vascular structure and function, including atherosclerosis, vascular inflammation, vascular stiffness, and endothelial progenitor cells, by which candesartan may affect the cognitive and cerebrovascular outcomes.
- Study methodology:This is a double blind randomized clinical trial that will be conducted in 140 individuals (70 in the candesartan group, 70 in the lisinopril group). Our target population is subjects: 55 years or older with hypertension and Executive Mild Cognitive Impairment.
- Endpoints to be measured:Our measures include cognitive function, cerebral perfusion and reserve, markers of vascular brain damage, atherosclerosis, stiffness, vascular inflammation and endothelial function.
- Description of intervention, follow-up, and duration of study: Eligible participants will undergo randomization into 2 groups and will be seen frequently until their blood pressure is controlled (<140/90 mmHg). Participants will be seen at 3, 6 and 12 months afterwards.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age: 55 years or older;
- •Hypertension: SBP≥140 mm Hg or DBP≥ 90 mm or receiving antihypertensive medications.
- •Executive MCI will be defined using these criteria:
- •The Montreal Cognitive Assessment (MoCA) score less than or equal to 26
- •Executive dysfunction: A performance at the 10th percentile or below on at least one of four screening tests for executive function: Trail Making Test, Part B (TMT-B), modified Stroop interference, Digit Span and Digit Sequencing, and Letter fluency.
- •Minimal Functional limitation as reflected by the Functional Assessment Questionnaire (FAQ)≤7
排除标准
- •Intolerance to study drugs;
- •SBP >200 or DBP >110 mm Hg;
- •Renal disease or hyperkalemia
- •Active medical or psychiatric problems
- •Uncontrolled congestive heart failure;
- •History of stroke in the past 3 years;
- •Inability to perform the study procedures
- •Women of childbearing potential
- •diagnosis of dementia
- •In those who lack decision capacity, a study surrogate who can sign on their behalf will be required. Since we are enrolling only those with MCI, we anticipate that most participants will have decision capacity
- •Current use of Lithium, as most antihypertensive classes may lead to increased lithium toxic levels.
研究组 & 干预措施
Candesartan
To achieve blood pressure control, we will use a stepwise protocol as follows: candesartan (blinded) 8mg→ 16mg→ 32mg. Both groups will also receive (unblinded) , if needed to achieve blood pressure control, HCTZ 12.5mg→ 25mg, Amlodipine 2.5mg→ 5mg →10mg and metoprolol succinate extended release 12.5mg→ 25mg→ 50mg. Antihypertensive medications will be increased every 2 weeks until control is achieved.
干预措施: Candesartan (Drug)
Lisinopril
To achieve blood pressure control we will use a stepwise protocol as follows: lisinopril (blinded) 10mg→ 20mg→ 40mg. Both groups will also receive (unblinded), if needed to achieve blood pressure control, HCTZ 12.5mg→ 25mg, Amlodipine 2.5mg→ 5mg→ 10mg and metoprolol succinate extended release 12.5mg→ 25mg→ 50mg. Antihypertensive medications will be increased every 2 weeks until control is achieved.
干预措施: Lisinopril (Drug)
结局指标
主要结局
NINDS-initiated EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" Tool Box.
时间窗: 12 months
EXecutive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research or "EXAMINER" tool box. This test batteryThe battery includes 11 tasks that generate 15 primary variables. Within this set, the EXAMINER includes: working memory, inhibition, set shifting, and fluency. The parts of EXAMINER that were used for this study include: Flanker task (inhibition) which involves responding to a central stimulus while ignoring flanking stimuli that are either compatible or incompatible with the central stimulus; Set-shifting, a measure of mental flexibility; Spatial 1-Back test assesses spatial working memory; Dot Counting test assesses verbal working memory; Verbal Fluency tested using a List Generation test which require the participant to generate words beginning with a specific letter, and category fluency in which the participant generates words from a specified category (e.g., animals, fruits). Higher are reflective of better executive function (-1 to +1)
Executive Function
时间窗: 12 months
Executive function will be assessed using Trail Making Test (part B-A). Part A was collected to correct for motor speed and visual-perceptual demands on TMT by subtracting completion time for TMT Part A from completion time for Part B (TMT B - A). TMT Part B-A provides a relatively purer measure of executive functioning. It has a timed scale from 0 sec (min) to 300 secs (max). Along this scale, a lower score is better.
次要结局
- Attention Measured Using Digit Span Backward(12 months)
- White Matter Lesion Volume(12 months)
- Language(12 months)
- Cerebral Perfusion(12 months)
- Attention Measured Using Digit Span Forward(12 months)
- Memory(12 months)
研究者
Ihab Hajjar
Principal Investigator
Emory University