(P)Rehabilitation in Older People With Osteoarthritis Undergoing Total Hip Replacement : From Physicological Mechanism to Clinical Benefits
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 70
- 试验地点
- 2
- 主要终点
- Change in Cross-Sectional Area of Quadriceps measured via MRI - Scanning after resistance exercise training
研究概览
简要总结
The goal of this clinical trial is to determine the effect of Resistance Exercise Training (RET)-based (p)rehabilitation versus usual care on skeletal muscle mass and function, as well as on underlying biological processes, in older adults undergoing elective Total Hip Replacement (THR) due to severe Osteoarthritis (OA). The main questions it aims to answer are:
- What is the effects of RET-based (p)rehabilitation versus usual care to improve muscle mass and function in patients undergoing elective unilateral THR surgery for end-stage OA?
- What is the potential of certain circulating biomarkers to predict the efficacy of the musculoskeletal system response to RET in patients with severe OA? Researchers will compare RET-based (p)rehabilitation versus usual care to see if RET works to increase skeletal muscle mass and function.
Participants in the usual care group will undergo standard rehabilitation (12 weeks post-surgery), and participants in the (p)rehabilitation group will undergo RET-based full-body (p)rehabilitation (3x/week) for 2 weeks pre-surgery and 12 weeks post-surgery.
详细描述
Introduction: Due to age, patients suffering from osteoarthritis (OA) experience a loss of skeletal muscle mass, strength, and functional capacity both before and after total hip arthroplasty (THA). Progressive resistance exercise training (RET) is a safe and feasible intervention before and after THA. However, the physiological and clinical effects have not been investigated on a larger scale.
Objectives: To determine the effect of RET-based (p)rehabilitation versus usual care on skeletal muscle mass and function, as well as on underlying biological processes, in older adults undergoing elective THA due to severe OA.
Materials and Methods: Seventy older adults scheduled for elective unilateral THA due to severe primary OA (usual care group: n=35, ≥60 years; (p)rehabilitation group: n=35, ≥60 years) will be included in this single-blind randomized controlled trial. Participants in the usual care group will undergo standard rehabilitation (12 weeks post-surgery), and participants in the (p)rehabilitation group will undergo RET-based full-body (p)rehabilitation (3x/week) for 2 weeks pre-surgery and 12 weeks post-surgery. MRI scans of the thigh will be taken at baseline, 24 hours before, and 12 weeks after surgery to assess the cross-sectional area of the quadriceps. On the same days, blood and muscle samples will be collected, and dual-energy X-ray absorptiometry (DEXA) will be performed. Maximum strength, muscle function/morphology, physical capacity, quality of life, performance in activities of daily living, physical activity level, hip function, nutritional status, and cognitive status will also be assessed. The occurrence of serious adverse events, hospital readmissions, infections, and complications will be considered.
In a sub-study, 20 participants (n=10 from the usual care group and n=10 from the (p)rehabilitation group) will be included to investigate the effects of 2 weeks of (p)rehabilitation on tissue protein synthesis rates. A 2-week deuterium oxide (²H₂O or "heavy water") loading protocol will be implemented in both groups during the two weeks prior to THA to assess musculoskeletal tissue protein synthesis rates. This method allows for the evaluation of the protein synthesis rate in muscle, cartilage, and bone tissue when samples are collected two weeks after the (p)rehabilitation or usual care interventions. These tissues will be collected during surgery, so no additional procedures are required from participants. In addition to determining the effects of RET on protein synthesis rates in tissues relevant to musculoskeletal health, the association between protein synthesis rates and long-term clinical outcomes will also be explored.
Expected Results: It is hypothesized that 14 weeks (2 weeks pre- and 12 weeks post-surgery) of progressive RET-based (p)rehabilitation will increase muscle mass and function to a greater extent than usual care, which is based on mobility and strength exercises without progressive machine-based RET. Additionally, RET will induce an increase in protein synthesis rates in muscle, cartilage, and bone tissues through the activation/inhibition of established signaling pathway markers (Akt, mTOR, S6(K), 4E-BP1, MAFbx, MuRF1). Furthermore, it is hypothesized that the increase in protein synthesis rate in these tissues will be associated with specific circulating biomarkers of musculoskeletal health (including CTX-II, COMP, CTX-I, OC, PIIINP, S1) and will indicate gains in muscle mass and functional improvements in the progressive RET group compared to the usual care group.
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
- Double (Care Provider, Outcomes Assessor)
盲法说明
The physiotherapist performing the assessments will be blind to the intervention. The blinding will extend to the data analysis team.
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals aged from 60 y and over.
- •18.5 < BMI < 40 kg/m
- •Individuals on waiting list to undergo a unilateral elective surgery for Total Hip Replacement due to primary severe Osteoarthritis.
排除标准
- •Individuals with severe OA in the contralateral hip.
- •Individuals who has been performing regular RET (2 or more times per week) in the previous 6 months.
- •Individuals who smoke.
- •Significant psychiatric or neurological disorders, with the use of acetylcholinesterase inhibitors, and untreated mood disorders or depressive pathology.
- •Neuromuscular or mobility disorders that prevent safe resistance training (debilitating arthritis, spasticity/rigidity, and paralysis), along with untreated metabolic disorders (such as uncontrolled systemic hypertension).
研究组 & 干预措施
Usual Care Group
Participants assigned to the control group will receive the usual therapy, medical monitoring, and educational lectures after surgery. No intervention is planned before total hip replacement surgery. In a sub-study, the first 10 participants of Usual Care group will be included to study the effects of 2 weeks prehabilitation on tissue protein synthesis rates. A two-week deuterium oxide (2H2O or 'heavy water') loading protocol will be conducted during the two week before THR surgery to assess diurnal rates of musculoskeletal protein synthesis.
干预措施: Usual Care (Other)
(P)rehabilitation Group
Participants assigned to the (p)rehabilitation group will perform a supervised Progressive Resistance Exercise Training 2 week program for the whole body three times per week before total hip replacement surgery and for 12 weeks after. In a sub-study, the first 10 participants of (P)rehabilitation group will be included to study the effects of 2 weeks prehabilitation on tissue protein synthesis rates. A two-week deuterium oxide (2H2O or 'heavy water') loading protocol will be conducted during the two week before THR surgery to assess diurnal rates of musculoskeletal protein synthesis.
干预措施: (P)rehabilitation Progresive Resistance Exercise Training (Behavioral)
(P)rehabilitation Group
Participants assigned to the (p)rehabilitation group will perform a supervised Progressive Resistance Exercise Training 2 week program for the whole body three times per week before total hip replacement surgery and for 12 weeks after. In a sub-study, the first 10 participants of (P)rehabilitation group will be included to study the effects of 2 weeks prehabilitation on tissue protein synthesis rates. A two-week deuterium oxide (2H2O or 'heavy water') loading protocol will be conducted during the two week before THR surgery to assess diurnal rates of musculoskeletal protein synthesis.
干预措施: Prehabilitation Group Deuterated Water (Biological)
Usual Care Group
Participants assigned to the control group will receive the usual therapy, medical monitoring, and educational lectures after surgery. No intervention is planned before total hip replacement surgery. In a sub-study, the first 10 participants of Usual Care group will be included to study the effects of 2 weeks prehabilitation on tissue protein synthesis rates. A two-week deuterium oxide (2H2O or 'heavy water') loading protocol will be conducted during the two week before THR surgery to assess diurnal rates of musculoskeletal protein synthesis.
干预措施: Usual Care Group Deuterated Water (Biological)
结局指标
主要结局
Change in Cross-Sectional Area of Quadriceps measured via MRI - Scanning after resistance exercise training
时间窗: The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention in both groups
Anatomic CSA of the quadriceps muscle will be assessed in the study by MRI scanning at baseline, after 2 weeks of prehabilitation and after 12 weeks of rehabilitation for all participants. On the obtained MRI images, muscle tissue will be defined by threshold values of 0-100 Hounsfield Units, and the quadriceps muscle will be selected by manual tracing using ImageJ software (version 1.45d, National Institute of Health, Maryland, USA). All analyses will be performed by one investigator blinded to participant coding.
Change in Protein Synthesis Rates (MPS) on Muscle, Bone and Cartilage measured via tissue samples after resistance exercise training.
时间窗: The assessment will be conducted 2 weeks before surgery and during the surgery.
All tissue samples (muscle, cartilage and bone) will be collected through surgical excision in the sub-study, except for the vastus lateralis muscle which will be collected from the middle region of the vastus lateralis during the surgical procedure. Conventional muscle biopsy samples of the vastus lateralis will be collected to assess MPS rates and compare this between the intervention and usual care group, as well as to provide a reference to the synthesis rates of the various musculoskeletal tissues obtained during surgery. Hereafter, samples will be freed from any visible blood, immediately frozen in liquid nitrogen, and will be stored at -80°C until subsequent analysis (38). Intramuscular free and bound 2H-Alanine enrichment will be analyzed by gas-chromatography mass spectrometer (GC-MS; Agilent 5975C MSD \& 7890A GC, Wilmington, DE).
Change in Cross-Sectional Area of Quadriceps measured via MRI - Scanning after resistance exercise training
时间窗: The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention in both groups
Anatomic CSA of the quadriceps muscle will be assessed in the study by MRI scanning at baseline, after 2 weeks of prehabilitation and after 12 weeks of rehabilitation for all participants. On the obtained MRI images, muscle tissue will be defined by threshold values of 0-100 Hounsfield Units, and the quadriceps muscle will be selected by manual tracing using ImageJ software (version 1.45d, National Institute of Health, Maryland, USA). All analyses will be performed by one investigator blinded to participant coding.
Change in Protein Synthesis Rates (MPS) on Muscle, Bone and Cartilage measured via tissue samples after resistance exercise training.
时间窗: The assessment will be conducted 2 weeks before surgery and during the surgery.
All tissue samples (muscle, cartilage and bone) will be collected through surgical excision in the sub-study, except for the vastus lateralis muscle which will be collected from the middle region of the vastus lateralis during the surgical procedure. Conventional muscle biopsy samples of the vastus lateralis will be collected to assess MPS rates and compare this between the intervention and usual care group, as well as to provide a reference to the synthesis rates of the various musculoskeletal tissues obtained during surgery. Hereafter, samples will be freed from any visible blood, immediately frozen in liquid nitrogen, and will be stored at -80°C until subsequent analysis (38). Intramuscular free and bound 2H-Alanine enrichment will be analyzed by gas-chromatography mass spectrometer (GC-MS; Agilent 5975C MSD \& 7890A GC, Wilmington, DE).
次要结局
- Change in functional capacity measured via Short Physical Performance Battery (SPPB) after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Immunodetection of protein synthesis markers in tissue sample 2 weeks before surgery, during surgery and after resistance exercise training.(The assessments will be conducted with the samples obtained 2 weeks before surgery, during surgery and after 12-week intervention.)
- Change in biomarkers measured via blood samples after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Change in functional capacity measured via Timed Up and Go test (TUG) after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before and after the 12-week intervention)
- Change in muscle strength measured via 1RM strength tests after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention)
- Change in body composition measured via dual-energy X-ray absorptiometry scanning after resistance exercise training(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention)
- Change in quality of life measured via SF-36 scale after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Change in Independence in Activities of Daily Living via Lawton and Brody questionnaire after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Change in Cognitive Function measured via MoCA questionnaire after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Change in Nutritional Status measured via Mini Nutritional Assessment and Malnutrition Universal Screening Tool after resistance exercise training.(The assessments will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Change in Perceived Hip Functionality measured via Harris Hip Score Questionnaire.(The assessment will be conducted 2 weeks and 48 hours before surgery and after 12-week intervention.)
- Change in habitual physical activity measured via Physical Activity Scale for Elderly (PASE) after resistance exercise training(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Immunodetection of protein synthesis markers in tissue sample 2 weeks before surgery, during surgery and after resistance exercise training.(The assessments will be conducted with the samples obtained 2 weeks before surgery, during surgery and after 12-week intervention.)
- Change in quality of life measured via SF-36 scale after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Change in Cognitive Function measured via MoCA questionnaire after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Change in functional capacity measured via Short Physical Performance Battery (SPPB) after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Change in biomarkers measured via blood samples after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Change in functional capacity measured via Timed Up and Go test (TUG) after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before and after the 12-week intervention)
- Change in Nutritional Status measured via Mini Nutritional Assessment and Malnutrition Universal Screening Tool after resistance exercise training.(The assessments will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Change in Perceived Hip Functionality measured via Harris Hip Score Questionnaire.(The assessment will be conducted 2 weeks and 48 hours before surgery and after 12-week intervention.)
- Change in muscle strength measured via 1RM strength tests after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention)
- Change in body composition measured via dual-energy X-ray absorptiometry scanning after resistance exercise training(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention)
- Change in habitual physical activity measured via Physical Activity Scale for Elderly (PASE) after resistance exercise training(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
- Change in Independence in Activities of Daily Living via Lawton and Brody questionnaire after resistance exercise training.(The assessment will be conducted 2 weeks and 48 hours before surgery and after the 12-week intervention.)
研究者
Gabriel Nasri Marzuca-Nassr
Principal Investigator
Universidad de La Frontera