Sex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 37
- 试验地点
- 2
- 主要终点
- Quantitative RNA-sequencing
研究概览
简要总结
This project is a 2-phase, randomized clinical trial that includes 7 days of unilateral leg disuse (Phase 1), immediately followed by 1 week of bilateral leg rehabilitation (Phase 2). The investigators will recruit cohorts of healthy middle-aged men and women to address their aims:
- Demonstrate the sex-specific effects of skeletal muscle disuse (Phase 1)
- Identify key molecular determinates of susceptibility of skeletal muscle atrophy (Phase 1)
- Map the early, sex-specific molecular time-course of rehabilitation (Phase 2)
- Determine if disused and healthy muscle respond similarly to exercise (Phase 2)
Healthy, middle-age men and post-menopausal women (50-65 years) will be recruited from the greater Houston/Galveston area. This under-represented research demographic demonstrate few negative metabolic or phenotypic signs of advanced age, but are at increased risk of being hospitalized and experiencing accelerated loss of lean mass and muscle function that parallels a much older population.
The goal of this study is to characterize phenotypic and molecular skeletal muscle changes in middle-aged men and women during critical periods of disuse and rehabilitation and ultimately direct the development of targeted and effective prevention and treatment strategies.
详细描述
The negative health consequences of muscular disuse in aging populations are unequivocal. While descriptive, outcome data on disuse and recovery are abundant, key knowledge gaps limit researcher's ability to implement evidence-based, rehabilitation strategies. Limiters include: i) an inability to identify individuals most susceptible to disuse, ii) insufficient information to differentiate between, and respond to, disuse atrophy in men and women, iii) limited insight into the mechanisms driving adaptation to early rehabilitative exercise, and iv) the assumption that disused and healthy skeletal muscle will have a similar, positive response to resistance exercise. The investigators will complete a 2-phase, randomized clinical trial. The protocol includes 7-days of unilateral leg disuse (ULD; Phase 1), immediately followed by 1 week of bilateral leg rehabilitation (Phase 2). Healthy, middle-aged men (n=40) and (post-menopausal) women (n=40), (50-65 y) will be recruited; a neglected research demographic who present with a largely youthful phenotype, but are at risk of accelerated disuse atrophy.
This project will provide a highly powered, detailed phenotypic characterization of the continuum of adults most and least susceptible to muscular disuse. Clinical outcomes will be supported by RNA deep sequencing and pathway analysis to establish a platform that: i) improves scientists' ability to identify higher-risk individuals and ii) provides insight into time-sensitive, sex-specific and effective rehabilitation strategies. Findings and reposed molecular data from this study, may help identify future therapeutic targets and serve as an uncomplicated/comorbidity-free baseline for clinical trials in populations experiencing disuse atrophy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Other
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 50 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All races and ethnic backgrounds
- •Men and women, age 50-65 years
- •Generally healthy (see
排除标准
- •Able and willing to provide informed consent
- •Ability to speak and read English
- •Post-menopausal women (no menses within the last 12 months)
- •Body mass index: 18.5-35 kg/m2 or BMI>35 if thigh adiposity does not impair muscle biopsy
- •Exclusion Criteria:
- •Compromised musculoskeletal function that precludes safe participation or use of crutches
- •Pre-menopausal women
- •Hypogonadal men (testosterone <300 ng/dL)
- •Women taking hormone replacement therapy (HRT)
- •Sarcopenia (European Working Group on Sarcopenia in Older People, EWGSOP102)
- •Clinically significant heart disease (e.g. New York Heart Classification greater than grade II; ischemia)
- •Peripheral vascular disease
- •History of claudication
- •Pulmonary disease
- •History of systemic or pulmonary embolus
- •Uncontrolled blood pressure (systolic BP>170, diastolic BP>95 mmHg)
- •Impaired renal function (creatinine >1.5 mg/dl)
- •Anemia (hematocrit <33)
- •Untreated thyroid disease (abnormal TSH)
- •A recent history (<12 months) of GI bleed
- •Diabetes mellitus or other untreated endocrine or metabolic disease
- •Electrolyte abnormalities
- •Any history of stroke, hypo- or hyper-coagulation disorders
- •Employment requiring long (>1 h) uninterrupted period of standing
- •Inability to meet study travel requirements (e.g. manual geared car)
- •Recent history of balance issues or falls.
- •Recent (3 years) treated cancer other than basal cell carcinoma
- •Systemic steroids, anabolic steroids, growth hormone or immunosuppressant use within 12 months
- •Recent (2 months) adherence to a weight-loss or weight-gain diet
- •Weight change of 5% or more in previous 6 months
- •Body mass index >30 or excess body fat that compromises muscle biopsy collection
- •Acute infectious disease or chronic infection
- •Alcohol or drug abuse
- •Any other condition or event considered exclusionary by study physician
研究组 & 干预措施
Male Rehabilitation (M-REHAB)
Disuse + resistance exercise rehabilitation
干预措施: Resistance Exercise Rehabilitation (Other)
Male Control (M-CON)
Disuse + ambulatory control rehabilitation
干预措施: Walking-based rehabilitation (Other)
Female Rehabilitation (F-REHAB)
Disuse + resistance exercise rehabilitation
干预措施: Resistance Exercise Rehabilitation (Other)
Female Control (F-CON)
Disuse + ambulatory control rehabilitation
干预措施: Walking-based rehabilitation (Other)
结局指标
主要结局
Quantitative RNA-sequencing
时间窗: Study day 1 (before starting leg disuse)
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Quantitative RNA-sequencing
时间窗: Study day 7 (after finishing leg disuse)
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Quantitative RNA-sequencing
时间窗: Study day 7 (after 1 bout of rehabilitation)
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Quantitative RNA-sequencing
时间窗: Study day 9 (after 2 bouts of rehabilitation)
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Quantitative RNA-sequencing
时间窗: Study Day 11 (after 3 bouts of rehabilitation)
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Muscle function
时间窗: Study day 1 (before starting leg disuse)
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Muscle function
时间窗: Study day 7 (after 1 bout of rehabilitation)
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Muscle function
时间窗: Study day 9 (after 2 bouts of rehabilitation)
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Muscle function
时间窗: Study Day 11 (after 3 bouts of rehabilitation)
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Body (leg) composition
时间窗: Study day 1 (before starting leg disuse)
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Body (leg) composition
时间窗: Study day 7 (after finishing leg disuse)
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Body (leg) composition
时间窗: Study day 9 (after 2 bouts of rehabilitation)
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Body (leg) composition
时间窗: Study Day 11 (after 3 bouts of rehabilitation)
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Quantitative RNA-sequencing
时间窗: Study Day 21 (after finishing 7 bouts of rehabilitation)
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Muscle function
时间窗: Study Day 21 (after finishing 7 bouts of rehabilitation)
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Body (leg) composition
时间窗: Study Day 21 (after finishing 7 bouts of rehabilitation)
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
次要结局
- Muscle fiber type(Study Day 21 (after finishing 7 bouts of rehabilitation))
- Diet recall(Study day 11 (after two bouts of rehabilitation))
- Physical activity(Study Days 7-21 (2 weeks of rehabilitation))
- Muscle fiber cross sectional area(Study day 1 (before starting leg disuse))
- Muscle fiber cross sectional area(Study day 7 (after finishing leg disuse))
- Muscle fiber cross sectional area(Study day 9 (after 2 bouts of rehabilitation))
- Muscle fiber cross sectional area(Study Day 11 (after 3 bouts of rehabilitation))
- Muscle fiber type(Study day 1 (before starting leg disuse))
- Muscle fiber type(Study day 7 (after finishing leg disuse))
- Muscle fiber type(Study day 9 (after 2 bouts of rehabilitation))
- Muscle fiber type(Study Day 11 (after 3 bouts of rehabilitation))
- Diet recall(Familiarization session (~1 week before starting leg disuse))
- Physical activity(Study Days -7 to Day 0 (1 week prior to starting leg disuse))
- Physical activity(Study Days 1-6 (1 week of disuse))
- Muscle fiber cross sectional area(Study Day 21 (after finishing 7 bouts of rehabilitation))