Microgravity Research Analogue (MRA): Understanding the Health Impact of Inactivity for the Benefit of Older Adults and Astronauts Initiative
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Changes in brain structure with HDBR with and without exercise countermeasure.
研究概览
简要总结
Physical activity appears to be an important lifestyle habit to achieve healthy aging by promoting autonomy and quality of life. Interestingly, the dramatic changes that the human body undergoes due to bedrest for illnesses and hospitalization are similar to those seen over decades of normal aging. Bedrest in otherwise healthy older individuals can lead to a reduction of muscle size and strength, changes in bone strength and function of the heart and blood vessels. Bedrest can also lead to changes in keeping proper balance as well as changes in processing and understanding information. All of these factors negatively affect activities of daily living leading to physical function impairment and development of frailty, a clinical condition associated with an increased risk for disease and death.
The purpose of this study is to investigate whether exercise can counteract the negative effects of 2-week head tilt down bed rest on muscle function and metabolism, postural control, bone structure, orthostatic tolerance and cognitive function in adults.
For this study the investigators will recruit 24 healthy men and women between 55 - 65 years of age. All subjects will spend a total of 26 days (5 days of adaption period, 14 days of bed rest with 6 degrees of downward inclination, and 7 days of recovery period) at the McGill University Health Centre (MUHC). During this study, 12 subjects will randomly undergo an exercise intervention as countermeasure during the 14 days of bed rest period and 12 will serve as control.
Each subjects participation in this study will involve 1 telephone call (pre-screening) and 4 visits at the MUHC: 1 screening visit (Visit 1) followed by a 26-day long visit (Visit 2) and 2 follow-up visits (Visit 3 and Visit 4). During Visits 2 - 4 various measurements will be performed to assess sensorimotor control, muscle function and metabolism, bone structure, cardiovascular function, cognitive performance and function, and specimen collection (blood, urine, saliva, feces and muscle tissue).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A minimum of 20 and a maximum of 24 non-smoking participants in the age group of 55 to 65 years old, half male and half female.
- •Female participants must be menopausal (no menses for at least 1 year (or documented ovariectomy) and a serum FSH above 30 IU/L).
- •Height between 158 to 190 cm with a body mass index between 20 to 30 kg/m
- •Physically and mentally healthy subjects that will have successfully passed the psychological and medical screening appropriate for the age group.
- •Participation in at least 2.5 hours of exercise at a moderate to vigorous-intensity aerobic activity per week.
- •Willing to be assigned randomly either to the exercise or the control group.
排除标准
- •Participants must be dementia-free, drug- or alcohol-addiction free, with no history of heart attacks, no thrombosis risk, no severe allergies, no hypocalcaemia, no uric acidemia, no orthostatic intolerance, no vestibular disorders, no considerable musculoskeletal issues, no chronic back pain, no head trauma, no seizures, no ulcers, no renal stones, no gastro-esophageal reflux disease or renal function disorder, no hiatus hernia, no migraines, and no mental illness.
- •Electrocardiogram abnormalities
- •Low bone mineral density
- •Medication requirements that may interfere with the interpretation of the results
- •Recent substandard nutritional status
- •Claustrophobia
- •Special dietary requests (e.g. vegetarian, vegan or some other diet)
- •Sedentary people and people that are addicted to exercise
- •Metallic implants (pacemakers, ICDs, CRT devices, infusion pumps, cerebral artery aneurysm clips, dental implants, tissue expander etc.), osteosynthesis material
- •Given blood in the past 3 months before the onset of the experiment
- •Smoked (tobacco and/or marijuana (THC)) within 6 months prior to the start of the study
- •Abused drugs, medicine or alcohol within up to 30 days prior to the start of the study
- •Participated in another study within 2 months before study onset
结局指标
主要结局
Changes in brain structure with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline and Recovery periods
Assessment of brain anatomy using a MRI.
Changes in brain function with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline and Recovery periods
Measurement of neuronal, cerebrovascular, and connectivity integrity with functional MRI.
Changes in muscle muscle mass with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Body MRI
Changes in muscle fat infiltration with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Body MRI
Changes in adiposity with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Body MRI
Changes in ventricular volume of the heart with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Using a heart MRI left and right ventricular volumes will be assessed.
Changes in ventricular mass with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Using a heart MRI left and right ventricular mass will be assessed.
Changes in bone structure with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline and Recovery periods
High resolution peripheral quantitative computed tomography (HR-pQCT)
Changes in muscle-pump baroreflex with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Supine-to-stand test
Changes in orthostatic tolerance with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline and Recovery periods
Tilt test
Changes in sleep architecture with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Using 3-electrode electroencephalogram (EEG) Sleep Profiler electrical patterns of brain activity will be measured in order to assess sleep cycles and sleep stages.
Changes in frailty status with HDBR with and without exercise countermeasure.
时间窗: Throughput the 26-day study period: at Baseline, HDBR and Recovery periods
CLSA-FI questionnaire
Changes in balance control with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline and Recovery periods
Postural equilibrium control test
Changes in Fractional Synthesis Rate (FSR) with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: during HDBR period
Measurement of protein turnover.
Changes in sleep quality with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Sleep quality will be assessed using a 3-electrode electroencephalogram (EEG) Sleep Profiler and a wrist worn actigraphy.
Changes in the constitution of the oral microbiome with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
To assess oral microbiome, saliva samples will be collected and targeted sequencing of the variable regions 4 and 5 (V4-V5) of the 16S ribosomal RNA gene will be performed on an Illumina MiSeq.
Changes in the gut microbiome with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
To assess gut microbiome, stool samples will be collected and targeted sequencing of the variable regions 4 and 5 (V4-V5) of the 16S ribosomal RNA gene will be performed on an Illumina MiSeq.
Changes in dynamic balance with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline and Recovery periods
Four-square step test
Changes in bone markers with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline and Recovery periods
The following bone markers will be assessed using ELISA kits: * Total osteocalcin * Undercarboxylated osteocalcin * Sclerostin * NTX (N-terminal Telopeptide) * CTX (C-terminal telopeptide) * Bone Specific Alkaline Phosphatase (BSAP) * Procollagen type 1 amino-terminal propeptide (P1NP)
Changes in growth factors with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline and Recovery periods
The following growth factors will be measured with Multiplex: * Basic fibroblast growth factor * Granulocyte colony-stimulating factor (G-CSF) * Granulocyte-macrophage colony-stimulating factor (GM-CSF) * Platelet-derived growth factor BB (PDGF-BB) * Transforming growth factor β (TGF-β) * Vascular endothelial growth factor (VEGF)
Changes in cytokines with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline and Recovery periods
The following cytokines will be measured with Multiplex: * Eotaxin * Interferon gamma (IFN-γ) * IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17 * Tumour necrosis factor (TNF-α) * Interferon gamma- induced protein 10 (IP-10) * Monocyte chemoattractant protein 1 (MCP-1) * Macrophage inflammatory protein-1α (MIP-1α) * Macrophage inflammatory protein-1β (MIP-1β)
Changes in cognition status of participants with head down bed rest (HDBR) with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
NIH Toolbox Cognition Battery (computerized)
Changes in emotional status of participants with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Positive and Negative Affect Scale - For both scales scores can range from 10-50, with higher scores representing higher levels of positive or negative affect.
Changes in muscle strength with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline and Recovery periods
Quantitative Muscle Dynamometry (Biodex)
Cardiac and vascular changes with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline, HDBR and Recovery periods
Using high frame rate ultrasound (HiFRUS) arterial wall shear stress will be assessed.
Changes in physical performance with HDBR with and without exercise countermeasure.
时间窗: Throughout the 26-day study period: at Baseline and Recovery periods
Short Physical Performance Battery test
次要结局
- Changes in neuromotor function with HDBR with and without exercise countermeasure.(Throughout the 26-day study period: at Baseline and Recovery periods)
- Changes in body composition with HDBR with and without exercise countermeasure.(Throughout the 26-day study period: at Baseline and Recovery periods)
- Changes in aerobic capacity with HDBR with and without exercise countermeasure.(Throughout the 26-day study period: at Baseline and Recovery periods)
- Changes in insulin sensitivity with HDBR with and without exercise countermeasure.(Throughout the 26-day study period: at Baseline, HDBR and Recovery periods)
- Changes in neuronal factors with HDBR with and without exercise countermeasure.(Throughout the 26-day study period: at Baseline, HDBR and Recovery periods)
研究者
Jose Morais
Professor and Director, Division of Geriatric Medicine, McGill University
McGill University Health Centre/Research Institute of the McGill University Health Centre