Trial of Remote Ischemic Pre-Conditioning in Vascular Cognitive Impairment
试验速览
- 阶段
- 2 期
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Adherence
研究概览
简要总结
Cerebral small vessel disease is a common cause of cognitive impairment. Remote ischemic pre-conditioning (RIC) is a technique to induce brief periods of limb ischemia-reperfusion that is hypothesized to increase tolerance of the brain to hypoperfusion and increase cerebral blood flow. Patients with cognitive impairment, preserved basic activities of daily living, and brain computed tomography (CT) or magnetic resonance imaging (MRI) evidence of confluent white matter hyperintensities or multiple brain infarcts will be randomized to either RIC performed once a day on one arm, or twice per day on one arm, for 30 days, to test tolerability and effects on MRI markers of blood flow.
详细描述
Cerebral small vessel disease (cSVD) accounts for 20-25% of all strokes and is the most common cause of vascular cognitive impairment (VCI) as well as a major contributor to mixed dementia, potentially interacting with Alzheimer's disease. Remote ischemic pre-conditioning (RIC) is a technique to induce brief periods of limb ischemia-reperfusion that is hypothesized to increase tolerance of the brain to hypoperfusion. This is a prospective, open-label randomized controlled clinical trial with blinded endpoint assessment (PROBE). Participants that complete a 14-day run-in period will be randomized to 30 days of either: a) RIC performed once per day on one arm, or b) RIC performed twice per day on one arm. Each RIC session will consist of 4 cycles of unilateral upper arm ischemia for 5 minutes followed by reperfusion for another 5 minutes, administered by modified blood pressure monitor (under an Investigational Trail Authorization from Health Canada). The primary outcome is tolerability, defined as the proportion in each trial arm that complete 80% or more of the assigned RIC sessions. Secondary outcomes will include pain scores, cognition, and MRI markers of cerebral blood flow and white matter integrity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Outcomes will be assessed masked to treatment assignment. Participants will be aware of treatment assignment.
入排标准
- 年龄范围
- 60 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Evidence of cerebral small vessel disease on CT or MRI, defined as either beginning confluent white matter hypodensities/hyperintensities (ARWMC scale) or two or more supratentorial infarcts
- •Montreal Cognitive Assessment <25
- •Concern on the part of the patient, caregiver, or clinician that there has been a decline from previous level of cognitive functioning
- •Independent with basic activities of daily living (response (a) to questions 2, 4, 5, 6, 7, 8, 9, and 14 on the Bristol Activities of Daily Living scale).
排除标准
- •Cortical infarcts larger than 10 mm axial diameter
- •Neuroimaging evidence of mass lesion, intracerebral hemorrhage, vascular malformation, or evidence of non-vascular disease such as hydrocephalus.
- •Residence in long-term care facility.
- •Other significant neurological or psychiatric disease (e.g. multiple sclerosis).
- •Does not have a study partner who can provide corroborative information.
- •English or French is not sufficiently proficient for clinical assessment and neuropsychological testing
- •Montreal Cognitive Assessment score <13
- •Unable to undergo MRI due to medical contraindications or inability to tolerate the procedure.
- •Co-morbid medical illness that in the judgment of the study investigator makes it unlikely that the participant will be able to complete three months of study follow-up.
- •On therapeutic anticoagulation with doses used for treatment of deep venous thrombosis, pulmonary embolism, or for stroke prevention in atrial fibrillation.
- •Significant bleeding diathesis.
- •Any symptomatic or previously known arm soft-tissue disease, vascular injury, or peripheral vascular disease
- •Hypertension with systolic blood pressure >=180 mmHg despite medical treatment at the time of enrolment.
- •Planned revascularization (any angioplasty or vascular surgery) within the next 3 months.
- •Planned surgical procedure within the next 3 months.
- •Currently receiving an investigational drug or device by other studies
- •Blood pressure cuff cannot be sized properly (arm circumference is <23 cm or >42 cm)
研究组 & 干预措施
RIC once per day
RIC performed once a day on one arm. Each RIC session will consist of 4 cycles of unilateral or simultaneous bilateral upper arm ischemia for 5 minutes followed by reperfusion for another 5 minutes. The procedure will be performed by using an electric auto-control device with cuffs that inflate to a pressure of 200 mmHg during the ischemic period.
干预措施: Remote ischemic conditioning (Device)
RIC twice per day
RIC performed twice a day on one arm, approximately 12 hours apart. Each RIC session will consist of 4 cycles of unilateral or simultaneous bilateral upper arm ischemia for 5 minutes followed by reperfusion for another 5 minutes. The procedure will be performed by using an electric auto-control device with cuffs that inflate to a pressure of 200 mmHg during the ischemic period.
干预措施: Remote ischemic conditioning (Device)
结局指标
主要结局
Adherence
时间窗: 30 days
Proportion completing 80% or more sessions.
次要结局
- Neuropsychiatric symptoms(30 days and 90 days)
- Arm deep venous thrombosis(30 days)
- Discontinuation(30 days)
- Physical examination(30 days)
- Pain(30 days)
- Randomization(14 days)
- MRI white matter hyperintensity volume(30 days and 90 days)
- MRI cerebral blood flow(30 days and 90 days)
- MRI diffusion tensor imaging(30 days and 90 days)
- Global cognition(30 days and 90 days)
- Neuropsychological tests(30 days and 90 days)