Protecting the Brain From Post-Stroke Cognitive Impairment and Dementia With Multimodal Exercise Training: A Bayesian Adaptive Trial (PROTECT)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Cognition
研究概览
简要总结
The rates of cognitive decline and dementia after stroke are disproportionately high. Strategies that can protect the brain early after the stroke event could reduce the future risk of cognitive decline and dementia in these patients. Although physical exercise is usually recommended after stroke, there is very little information about the protective effect of exercise implemented in early stages of recovery as a potential protective measure against cognitive decline and dementia risk in these patients. This study will investigate the effect of a multimodal exercise intervention implemented early after the stroke event on cognition and on a selected group of markers that can predict cognitive decline and dementia risk.
详细描述
Rationale: Stroke triggers acute vascular and inflammatory mechanisms that predispose the brain to rapid neurodegeneration. Up to 52% of stroke survivors develop cognitive impairment within 6 months and 20% receive a clinical diagnosis of dementia within 5 years. The subacute phase (<6 months) represents a critical window in which the brain may be most responsive to neuroprotective interventions. Multimodal aerobic and resistance training improves cognition in chronic stroke, but whether it improves cognition, neuroimaging markers, and blood biomarkers of dementia risk when delivered during this early window remains unknown.
Aims: To compare the effects of 12 weeks of multimodal exercise (moderate-to-high-intensity resistance and aerobic training) versus a low-intensity community-based stroke exercise comparator on cognition, neuroimaging outcomes, blood biomarkers of cognitive decline and dementia risk in people with subacute stroke.
Sample size estimates: Sample size was estimated via 20,000 Monte Carlo simulations using an Alzheimer's Disease Assessment Scale-Cognitive assessment (ADAS-Cog) effect size of Cohen's d = 0.63 from a previous exercise RCT. The target was ≥80% power to detect this treatment effect at a one-sided Type I error rate of 2.5%, using a weakly informative prior centered at zero with a variance of 100. The minimum required was 45 completers per arm (N = 90) and accounting for 25% attrition, up to 120 participants (60 per arm) will be enrolled.
Methods and design: PROTECT is a 12-week, Phase 3, assessor-blinded, multisite Bayesian adaptive RCT following a two-arm parallel group sequential design with 6- and 12-month follow-up (NCT07445841). Participants will be randomized to multimodal training or the comparator using concealed allocation with permuted blocks of varying sizes. Pre-planned adaptive features include: (1) two interim analyses at 50% and 75% of completers; (2) early stopping for efficacy and futility; and (3) sample size re-estimation.
Study outcomes: The primary outcome is cognition, measured using the 13-item ADAS-Cog. Secondary outcomes include ADAS-Cog-Plus, structural and perfusion neuroimaging, and blood biomarkers of inflammation and neurodegeneration. Tertiary outcomes will include cardiorespiratory fitness, functional mobility, muscle strength, body composition, neuropsychological battery, patient-reported cognition, quality of life, fatigue, and healthcare utilization. Outcomes will be assessed at baseline, post-intervention (primary endpoint) and at 6- and 12-month follow-up.
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 (Investigator, Outcomes Assessor)
盲法说明
Statistician
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •medically stable
- •have had a first-ever ischemic/hemorrhagic stroke confirmed by MRI/CT 0-6 months prior to participation.
- •Able to independently walk at least 10 meters (assistive devices permitted) and capable of following instructions will be required.
排除标准
- •Diagnosed with dementia
- •Medications that impact cognition
- •Absolute contraindications to exercise or MRI scanning
- •Significant disability (modified Rankin score >3)
- •Participants will be excluded if they have been engaged in a structured exercise training program outside their regular in/out-patient hospital rehabilitation since suffering the stroke.
- •Co-morbidities that preclude exercise participation, pain worsened with exercise, and communication (e.g., severe aphasia) or behavioral issues limiting safe participation will also be reasons for exclusion.
研究组 & 干预措施
Multimodal Exercise
Twelve weeks of combined resistance and aerobic exercise training held three times per week.
干预措施: Multimodal Training (Other)
Balance, Toning and Stretching
Twelve weeks of low-intensity task-specific strengthening, balance, mobility, and stretching training held three times per week that is based off the Fitness and Mobility Exercise Program.
干预措施: Balance, Toning and Stretching (Other)
结局指标
主要结局
Cognition
时间窗: Baseline (T0), 12-week post-intervention (T1), follow-up at 6 months (T2) and 12 months (T3)
The primary outcome will be change in cognition immediately post-intervention (T1, primary endpoint) as measured by the ADAS-Cog-13, a 13-item cognitive assessment with scores ranging from 0 to 85, where lower scores indicate better cognition. The minimal clinical importance difference (MCID) on this scale is 2.
次要结局
- Cerebral Blood Velocity (Middle Cerebral Artery Velocity)(Baseline (T0), 12-week post-intervention (T1), follow-up at 6 months (T2) and follow-up at 12 months (T3))
- Neurodegeneration(Baseline (T0), 12-week post-intervention (T1), and follow-up at 6 (T2), and 12 months (T3))
- Cognition(Baseline (T0), 12-week post-intervention (T1), follow-up at 6 months (T2) and 12 months (T3))
- Gait Speed(Baseline (T0), 12-week post-intervention (T1), follow-up at 6 (T2) and 12 months (T3))
- Cerebral Blood Flow(Baseline (T0), 12-week post-intervention (T1), and follow-up at 12 months (T3))
- Body Composition and Anthropometrics(Baseline (T0), 12-week post-intervention (T1) and 12 months follow up)
- Blood Brain Barrier Permeability(Baseline (T0), 12-week post-intervention (T1), and follow-up at 12 months (T3))
- Inflammation(Baseline (T0), 12-week post-intervention (T1), and follow-up at 6 (T2), and 12 months (T3))
- Axonal Injury(Baseline (T0), 12-week post-intervention (T1), follow-up at 6 (T2) and 12 months (T3))
- Strength(Baseline (T0), 12-week post-intervention (T1), follow-up at 6 (T2) and 12 months (T3))
- Functional Mobility(Baseline (T0), 12-week post-intervention (T1), follow-up at 6 (T2) and 12 months (T3))
- Self-reported Cognitive Function(Baseline (T0), 12-week post-intervention (T1), and follow-up at 6 (T2) and 12 months (T3))
- Cardiorespiratory Fitness(Baseline (T0), 12-week post-intervention (T1), follow-up at 6 months (T2) and 12 months (T3))
- Health-related Quality of Life(Baseline (T0), 12-week post-intervention (T1), follow-up at 6 (T2) and 12 months (T3))
- Fatigue(Baseline (T0), 12-week post-intervention (T1), and follow-up at 6 (T2) and 12 months (T3))
- Health Care Utilization (cost-effectiveness, cost-utility, intervention costs, and health care costs)(Time Frame: Baseline (T0), 12-week post-intervention (T1), follow-up at 6 months (T2) and follow-up at 12 months (T3))