ForceLoss: Part II - Osteoarthritic Patients. Development and Validation of Methods to Generate Personalised Models for the Differential Diagnosis of the Loss of Muscle Force
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Muscle Inhibition level
研究概览
简要总结
The ForceLoss study aims to develop personalised modeling and simulation procedures to enable the differential diagnosis for the loss of muscle force, namely dynapenia. The primary causes of dynapenia can be identified in a diffuse or selective sarcopenia, a lack of activation (inhibition), or suboptimal motor control. Each of these causes requires different interventions, but a reliable differential diagnosis is currently impossible. While biomedical instruments and tools can provide valuable information, it is often left to the experience of the single clinican to integrate such information into a complete diagnostic picture. An accurate diagnosis for dynapenia is important for a number of pathologies, including neurological diseases, age-related frailty, diabetes, and orthopaedic conditions.
The hypothesis is that the use of mechanistic, subject-specific models (digital twins) to simulate a maximal isometric knee extension task, informed by experimental measures may be employed to conduct a robust differential diagnosis for dynapenia.
In this study, on patients candidate for knee arthroplasty, the investigators will expand (i) the experimental protocol previously developed and tested on healthy volunteers with a measure of involuntary muscle contraction (superimposed neuromuscular electrical stimulation, SNMES), a hand-grip test, measures of bio-impedance and clinical questionnaires, and (ii) the modeling and simulation framework to include one additional step (to check for muscle inhibition).
Medical imaging, electromyography (EMG) and dynamometry data will be collected and combined to inform a digital twin of each participant. Biomechanical computer simulations of a Maximal Voluntary Isometric Contraction (MVIC) task will then be performed. Comparing the models' estimates to in vivo dynamometry measurements and EMG data, the investigators will test one by one the three possible causes of dynapenia, and, through a process of hypothesis falsification will exclude those that do not explain the observed loss of muscle force.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
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
- 否
入选标准
- •Diagnosis of Primary Arthrosis at the knee (according to the American College of Rheumatology criteria), subjects elected for tota knee arthroplasty
- •Body Mass Index between 18.5 and 30 kg/m2
- •Health status (according to the American Society of Anesthesiology classification) equal to 1 or 2
- •Suspected systemic sarcopenia due to aging or localized sarcopenia due to disuse
排除标准
- •Neurological, rheumatic or tumoral diseases
- •Inguinal or abdominal hernia
- •Severe Hypertension (Level 3)
- •Severe Cardio-pulmonary insufficiency
- •Diagnosis of Osteonecrosis in the lower limb joints
- •Pathologies or physical conditions incompatible with the use of magnetic resonance imaging and electrostimulation (i.e., active and passive implanted biomedical devices, epilepsy, severe venous insufficiency in the lower limbs)
- •Previous interventions or traumas to the joints of the lower limb
结局指标
主要结局
Muscle Inhibition level
时间窗: at baseline (Day 0)
The difference between the maximal force exerted during the MVIC test (voluntary contraction) and that achieved when the muscles are electrically stimulated (involuntary contraction) will be computed.
MVIC Torque
时间窗: at baseline (Day 0)
Dynamometry data will be acquired while participants perform a MVIC leg extension test. The maximum torque values (Nm) measured over three repetitions will be recorded. These correspond to the values observed in correspondence of the plateaux of force, developed over a sustained contraction.
Muscle volume
时间窗: at baseline (Day 0)
Full lower limb MRI data will be acquired with subjects in supine position. Individual muscle volumes (in cm3) will be segmented using commercial software and stored in anonymized form.
Co-contraction index (CCI)
时间窗: at baseline (Day 0)
Experimental EMG data will be recorded from the major lower limb muscles involved in the knee extension, while participants perform a maximal voluntary isometric contraction on a dynamometer (i.e., MVIC test to quantify muscle strength). The co-contraction index, defined as the relative activation of agonist and antagonist muscles (for this task: quadriceps and hamstrings) in the act of kicking (MVIC test), will be computed according to Li et al (2020).
次要结局
未报告次要终点