Overcoming TWEAK Signaling to Restore Muscle and Mobility After Joint Replacement (TWEAK)
2021年7月3日 更新者:Marcas M. Bamman, PhD、University of Alabama at Birmingham
This single-blind, randomized, controlled trial is designed to test the effect of an intensive, 16 week exercise rehabilitation program (progressive resistance training + functional mobility training) vs. usual care on restoration of muscle mass and mobility after total hip (THA) or knee (TKA) arthroplasty in men and women with end-stage osteoarthritis.
The molecular basis underlying the trial is the presence of significant muscle inflammation susceptibility in many of these individuals, and the expectation that the more intensive intervention will overcome this inflammatory burden to facilitate recovery.
研究概览
详细说明
While elective total hip (THA) and knee (TKA) arthroplasty relieve pain and improve mobility function for thousands with end-stage osteoarthritis (OA), up to 35% endure persistent muscle atrophy and mobility limitations for several years that impact life quality, increase morbidity, and burden the healthcare system.
Given that THA/TKA volumes are increasing exponentially with >1.1 million in the US annually, refractory mobility impairment is a major public health problem.
Together, the available data raise two important knowledge gaps in THA/TKA rehabilitation: (i) poorly understood factors that limit responsiveness of a large number of patients to current usual care; and (ii) the absence of rehabilitation programs proven to overcome these limitations.
The proposed project is designed to fill these gaps.
The investigators' fundamental tenet is that restoration of mobility function following THA/TKA requires: (i) regeneration of surgically damaged muscle; and (ii) regrowth of muscles that have atrophied over years of OA and limited usage.
The investigators suggest a major cause of muscle regeneration impairment in some individuals is what the investigators identified as muscle inflammation susceptibility (MuIS) - hyperactive inflammatory signaling in muscle of MuIS(+) individuals despite no systemic inflammation - which also manifests in isolated primary satellite cells and inhibits myogenesis in vitro, indicative of a true cellular phenotype beyond the niche.
The investigators' preliminary findings in THA/TKA patients strongly suggest the tumor necrosis factor-like weak inducer of apoptosis (TWEAK) signaling pathway may be central to MuIS and impaired THA/TKA recovery, as high perioperative muscle TWEAK signaling in the ipsilateral thigh was the most sensitive indicator of impaired muscle protein synthesis and failed strength recovery after 8 wk of usual care.
Progressive resistance exercise training (PRT) is a putative anabolic intervention that the investigators find consistently increases muscle mass to meet healthy standards in atrophied and mobility-impaired adults, by activating muscle protein synthesis and the myogenic activity of muscle satellite cells.
Together, these findings raise the central hypothesis that PRT plus adjunctive functional mobility training (PRT+FM) after THA/TKA will more effectively restore muscle mass and mobility function to healthy standards than usual care and, because MuIS(+) are predicted to suffer failed muscle recovery and persistent dismobility under usual care, the impact of PRT+FM will be greatest in MuIS(+).
The investigators will thoroughly test this hypothesis in a randomized controlled trial of 88 THA/TKA patients with the following aims.
Aim 1: To determine the effects of 16 wk of PRT+FM vs. usual care after elective THA/TKA on muscle mass, performance, and mobility function.
Aim 2: To determine whether MuIS status modifies the effects of PRT+FM or usual care after THA/TKA.
Cellular and molecular mechanisms of muscle mass regulation will be studied in detail.
Aim 3. To determine the long-term impact of 16 wk PRT+FM by re-assessing outcomes at 6 mo and 1 y.
The investigators fully expect the novel findings to lead a paradigm shift in THA/TKA rehabilitation that will have a profound impact on a growing segment of the population.
研究类型
介入性
注册 (实际的)
80
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
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Alabama
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Birmingham、Alabama、美国、35205
- UAB Center for Exercise Medicine
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
40年 至 80年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
Between the ages 40 and 80 y.
- Scheduled to undergo elective total hip or knee replacement specifically for the surgical indication of end-stage osteoarthritis.
- First-time hip or knee replacement.
- Capable of providing informed consent (cognitively intact if consenting to surgery).
Exclusion Criteria:
Any surgical indication other than first-time total joint replacement specifically for end-stage osteoarthritis.
- Bilateral knee/ hip replacement
- History of alcoholism or liver disease.
- Any history of hypo- or hyper-coagulation disorders including subjects taking Coumadin.
- Any individual with end-stage disease and/or a life expectancy less than one year.
- Pregnancy.
- Lactating Women.
- Neurological, musculoskeletal, or other disorder that would preclude them from completing the exercise training intervention and all performance tests.
- Uncontrolled hypertension, unstable or exercise-induced angina pectoris or myocardial ischemia, congestive heart failure.
- Uncontrolled diabetes mellitus.
- Any other condition or events considered exclusionary by the PIs and/or physician Co-Is.
- Lidocaine allergy (1% lidocaine is the local anesthetic used during the muscle biopsy procedure).
- Phenylketonuria (phenylalanine tracer for metabolic studies).
- Currently receiving androgen (e.g., testosterone) or anabolic (e.g., growth hormone (GH), insulin-like growth factor-I (IGF-I)) therapy.
- Body mass index ≥ 35.
- History of lower body progressive resistance training within the past year.
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:单身的
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:PRT + FM
Progressive resistance training + functional mobility training 3 d/wk x 16 wk
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Supervised progressive resistance training + functional mobility training (PRT+FM) 3 days per week for 16 weeks post-surgery.
Post-surgical usual care activities including any prescribed physical therapy
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有源比较器:Usual Care
Post-surgical usual care including physical therapy
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Post-surgical usual care activities including any prescribed physical therapy
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Change in unilateral (surgical) thigh muscle mass (unit of measure = grams)
大体时间:Pre-surgery to 16 weeks post-surgery
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Primary muscle mass outcome of Aim 1
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Pre-surgery to 16 weeks post-surgery
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Change in unilateral (surgical) knee extension power (unit of measure = watts)
大体时间:Pre-surgery to 16 weeks post-surgery
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Primary functional outcome of Aim 1
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Pre-surgery to 16 weeks post-surgery
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Change in short physical performance battery (SPPB) (unit of measure = score)
大体时间:From 16 weeks post-surgery to 26 and 52 weeks post-surgery
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Primary outcome of Aim 3
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From 16 weeks post-surgery to 26 and 52 weeks post-surgery
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Muscle inflammation susceptibility (MuIS) status (unit of measure = relative value)
大体时间:At the time of surgery
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Primary outcome of Aim 2: Muscle inflammation susceptibility (MuIS) defined by TWEAK receptor gene expression
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At the time of surgery
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次要结果测量
结果测量 |
大体时间 |
---|---|
Change in muscle fiber size (unit of measure = micrometers squared)
大体时间:From the time of surgery to 16 weeks post-surgery
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From the time of surgery to 16 weeks post-surgery
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Change in unilateral (surgical) knee extension isometric strength (unit of measure = Newton-meters)
大体时间:Pre-surgery to 16 weeks post-surgery
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Pre-surgery to 16 weeks post-surgery
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Change in maximum 10-meter gait speed (unit of measure = meters per second)
大体时间:Pre-surgery to 16 weeks post-surgery
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Pre-surgery to 16 weeks post-surgery
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Change in free-living physical activity (unit of measure = steps per day)
大体时间:Pre-surgery to 8, 16, 26, and 52 weeks post-surgery
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Via wearable technology (i.e.
step counter)
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Pre-surgery to 8, 16, 26, and 52 weeks post-surgery
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Change in self-reported health status (unit of measure = score)
大体时间:Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
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Via Short Form-36v2 Health Survey (SF-36v2)
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Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
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Change in cellular and molecular markers (unit of measure = arbitrary units)
大体时间:From the time of surgery to 16 weeks post-surgery
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Experiments using muscle tissue and primary muscle satellite cells collected from surgical and contralateral limbs.
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From the time of surgery to 16 weeks post-surgery
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Change in fatigue (unit of measure = score)
大体时间:Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
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Via Patient Reported Outcomes Measurement Information System (PROMIS)
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Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
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Change in pain (unit of measure = score)
大体时间:Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
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Via Patient Reported Outcomes Measurement Information System (PROMIS)
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Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
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Change in depression (unit of measure = score)
大体时间:Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
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Beck Depression Inventory (BDI II)
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Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
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Change in fatigue severity (unit of measure = score)
大体时间:Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
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Fatigue Severity Scale (FSS)
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Pre-surgery to 1, 8, 16, 26, and 52 weeks post-surgery
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
合作者
调查人员
- 首席研究员:Marcas M Bamman, PhD、University of Alabama at Birmingham
- 首席研究员:S Louis Bridges, MD, PhD、University of Alabama at Birmingham
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2015年10月1日
初级完成 (实际的)
2020年9月1日
研究完成 (实际的)
2021年2月28日
研究注册日期
首次提交
2015年8月5日
首先提交符合 QC 标准的
2015年12月10日
首次发布 (估计)
2015年12月11日
研究记录更新
最后更新发布 (实际的)
2021年7月7日
上次提交的符合 QC 标准的更新
2021年7月3日
最后验证
2021年7月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
PRT + FM的临床试验
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Oulu University HospitalLoisto Terveys, Oulu; Fysios Kastelli, Oulu; Faskia-Markus, Oulu邀请报名
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Stanford UniversityAnonymous Donor招聘中
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Indiana UniversityRichard L. Roudebush VA Medical Center完全的
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Proteon TherapeuticsUniversity of California, San Francisco完全的
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Massachusetts General HospitalNational Center for Complementary and Integrative Health (NCCIH)完全的
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Hugo W. Moser Research Institute at Kennedy Krieger...U.S. Department of Education主动,不招人