The Mito-Frail Trial: Effects of MitoQ on Vasodilation, Mobility and Cognitive Performance in Frail Older Adults
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in Vascular Endothelial Function
研究概览
简要总结
The goal of this clinical trial is to test the effects of MitoQ supplementation in older adults and frail older adults with physical dysfunction and/or cognitive dysfunction. The main question[s] it aims to answer are:
- To compare vascular function, oxidative stress levels, and physical and cognitive function among older adults and frail older adults with physical and cognitive dysfunction
- To determine whether MitoQ supplementation has the potential to improve vascular function in central and cerebral vessels
- To determine whether MitoQ supplementation can enhance physical and cognitive capabilities.
详细描述
Chronic diseases and associated declines in physical and cognitive performance contribute greatly to lost independence with aging. In addition to a lack of effective interventions other than exercise to address either problem, few studies have examined strategies for targeting both conditions in frail individuals who may experience difficulties with both walking and memory. Use of geroscience-guided therapies permits us to target mechanisms shared by aging with chronic conditions for which aging represents a major risk factor. Thus, instead of focusing on one single disease at a time, it may be possible to delay the onset and progression of disability involving multiple functional domains.
Gait speed is predictive of mobility, morbidity, and mortality in older adults. Vasoreactivity is a critical cerebrovascular control mechanism used to maintain brain perfusion during metabolic demands such as walking. In contrast to healthy older adults, middle cerebral artery blood flow velocities fail to increase proportionally in response to walking speed in slow walkers. Thus, abnormalities in vasoreactivity and perfusion adaptation to metabolic demands may reflect and contribute to declines in gait speed.
Mild cognitive impairment (MCI), an intermediate condition between normal cognitive performance and dementia, significantly increases the risk of transitioning dementia caused by Alzheimer's disease (AD). Moreover, changes in physical and cognitive function frequently co-exist in the same individual and influence each other.
In the absence of other effective therapies, modifiable cardiovascular risk factors (e.g., hypertension, atherosclerosis, cerebral hypoperfusion) represent opportunities to prevent declines in physical and cognitive function by targeting the vascular endothelium and vasodilation.
Physiological reactive oxygen species (ROS) levels play critical roles in cerebral vasculature, which can contribute to the regulation of brain perfusion through their action in vascular tone control. Of the many potential cellular sources of ROS in the vasculature, mitochondria are the major source in endothelium regulation of vascular homeostasis and are associated with aging and cardiovascular disease. Specifically, mitochondrialtargeted antioxidant, MitoQ, improves vascular endothelial function by reducing mitochondrial ROS (mtROS) in older adults and animal models.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Double-blind, placebo-controlled
入排标准
- 年龄范围
- 65 Years 至 80 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •men and women aged 65-80 with a slow gait speed (0.4m/s based on a 4m walk) and/or mild cognitive impairment.
- •good cardiovascular health (not taking any blood pressure/flow/metabolism altering medications)
排除标准
- •A vaccination in past two weeks
- •Recent acute infection three weeks prior to enrollment
- •Known immunodeficiency (including HIV infection, primary immunodeficiency, any history of chemotherapy or radiotherapy
- •Use of medicines during past 6 months known to alter immune response such as high- dose corticosteroids
- •Severe autoimmune disease requiring biological therapy
- •Major severe illness and/or Hospitalization in past 3 months
- •On warfarin or other medications that are considered a blood thinner
- •Recent fall or other conditions that will impair ability to complete and/or interpret mobility performance test
- •Known bleeding disorder
- •Any conditions that would impair the function to perform grip strength test
- •include advanced neurological disease, severe co-morbid disease, terminal illness with reduced life expectancy, severe disability, unintentional weight loss in last 12 months and participation in another study.
- •Diabetes patients requiring insulin (For reducing the risk that participants will have hypoglycemic episodes when fasting for study visits)
- •Baseline ECG QTc >450 ms in men and QTc >460 ms in women
- •Prior diagnosis of ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
研究组 & 干预措施
Placebo capsule
Gelatin capsules
干预措施: Placebo capsule (Dietary Supplement)
MitoQ capsule
Capsules containing mitoquinone mesylate (MitoQ, 5 mg/capsule) totaling 20 mg taken every day for 12 weeks.
干预措施: Mitoquinone Mesylate (Drug)
结局指标
主要结局
Change in Vascular Endothelial Function
时间窗: 4 visits : Baseline, 12 weeks (MitoQ or Placebo), 8 weeks washout, 12 weeks (MitoQ or Placebo)
Assess Femoral artery through Passive Leg Movement and Brachial artery flow-mediated dilation (% \[relative\] and mm \[absolute\])
Change in Cerebrovascular Function
时间窗: 4 visits : Baseline, 12 weeks (MitoQ or Placebo), 8 weeks washout, 12 weeks (MitoQ or Placebo)
Utilize ultrasound to measure a change in blood flow velocity in response to a breathing test (cm/s)
Change in NIH Tool Box Composite
时间窗: 4 visits : Baseline, 12 weeks (MitoQ or Placebo), 8 weeks washout, 12 weeks (MitoQ or Placebo)
NIH Toolbox Cognitive Battery is a multidimensional set of brief measures assessing cognitive (as well as emotional, motor and sensory) function. There is no score range, but mean score is 100 with standard deviation 15. A score at or near 100 indicates average ability compared with others. Scores around 115 suggest above-average ability. Scores around 130 suggest superior ability (in the top 2 percent nationally). A score around 85 suggests below-average ability. A score in the range of 70 or below suggests significant impairment.
Change in walking speed
时间窗: 4 visits : Baseline, 12 weeks (MitoQ or Placebo), 8 weeks washout, 12 weeks (MitoQ or Placebo)
Gait speed calculated from 10 meter walk test. Only the 6 intermediate meters are recorded. Time is recorded by a manual chronometer. 3 records are done, mean time is calculated. Mean time is divided by 6 to obtain mean gait speed
Sensitivity of a Montreal Cognitive Assessment score
时间窗: 4 visits : Baseline, 12 weeks (MitoQ or Placebo), 8 weeks washout, 12 weeks (MitoQ or Placebo)
sensitivity of a Montreal Cognitive Assessment score \< 26 to detect cognitive impairment defined as an abnormal result in at least one of the following tests : Test of Attentional Performance of Zimmermann and and Fimm (\< 5th percentile in at least one of the subscales) ; Wechsler Adult Intelligence Scale 4th version digit span (standard score ≤ 5) ; Wechsler memory scale III, spatial span (standard score ≤ 5) ; Wisconsin Card Scoring Test, GREFEX version (number of categories ≤ 5th percentile or if the number of perseverations is ≥ 95th percentile) Wechsler Adult Intelligence Scale 4th version block design (standard score ≤ 5) ; Six elements test GREFEX version (rank score ≤ 5th percentile ); free and cued selective reminding test, 16 items, B version (Z-score ≤ -1,65 in at least one of the subscales)
次要结局
- Change in Mitochondrial Function measured in peripheral blood mononuclear cells (PBMCs)(4 visits : Baseline, 12 weeks (MitoQ or Placebo), 8 weeks washout, 12 weeks (MitoQ or Placebo))
- Change in Oxidative Stress measured in peripheral blood mononuclear cells (PBMCs) by O2flux in pmol/second/cell numbers(4 visits : Baseline, 12 weeks (MitoQ or Placebo), 8 weeks washout, 12 weeks (MitoQ or Placebo))
研究者
Oh Sung Kwon
Assistant Professor
University of Connecticut