Acoustic Emission Biomarkers for the Detection and Monitoring of Early Knee Osteoarthritis
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- PROMS
研究概览
简要总结
The aim of this exploratory study is to further investigate the potential of acoustic emission biomarkers, assessed by the inmodi knee brace, to diagnose osteoarthritis (OA) at earlier stages. Therefore, 20 healthy participants and 100 patients with increased risk of knee OA will be recruited from the Schulthess Klinik in Zurich and examined twice with 9 ± 3 months' time interval. Anthropometric data, EOS radiographs and MR images of both knees, PROMs and acoustic emission data will be collected and evaluated. Artificial Intelligence algorithm will then be used to identify and validate the most promising acoustic emission biomarkers with a prognosis value in the prediction of knee osteoarthritis progress.
详细描述
Disease background Osteoarthritis (OA) is a highly prevalent and disabling condition that affects over 7% of people globally (528 million people). It is significantly limiting their mobility and independent lifestyle. OA is mainly described by loss of cartilage, structural changes in bone, and inflammation of the synovium and joint capsule. Common risk factors include aging, obesity, prior joint injury and overuse. OA takes several years to develop, before the patient sees the doctor when pain intensifies. In early stages patients are asymptomatic or only experience activity related pain. The pain becomes constant over time with intermittent intense pain episodes. In regions around the world, the average annual cost of OA for an individual is estimated between USD $700-$15,600 (2019). Consequently, OA has a large socioeconomic impact due to its high medical costs, early retirements, and high absenteeism from work.
OA typically affects the hips, knees, hands, feet, and spine, with a high prevalence of polyarticular involvement. This study focuses on OA of the knee.
Current standard of assessment The current gold-standard assessment of the severity of knee OA is based on plain radiography, using the Kellgren-Lawrence (KL) grading system, which was accepted as a standard by the World Health Organization in 1961. This system does not evaluate the primary affected tissue - cartilage - but only the overall aspect of the joint. It is therefore unable to detect early stages of OA and the diagnosis is often established at a late stage, with few treatment options besides knee arthroplasty.
Alternative assessment methods Earlier diagnostic and improved patient stratification is required to deploy preventive OA treatments. Possible early diagnostic options include Magnetic Resonance Imaging (MRI) and biochemical markers. MRI can be used to assess changes in cartilage volume, thickness or even quality, however, widespread use of MRI is limited by its high cost, availability, and the absence of a validated international score. Many biochemical markers are currently under investigation, but so far they lack specificity to joint tissues and to particular joints, and sensitivity and specificity are still not high enough for widespread clinical use.
Recently, there has been a growing interest in acoustic analysis as an alternative to conventional biomarkers, particularly for the knee joint where poorly lubricated moving joint surfaces generate abnormal sounds that acoustic analysis could reveal.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Group A: persons judging themselves to be of good subjective health without any knee problems, aged 35-65 years
- •Groups B&C: participant in MAC registry, completed patient reported-outcome measurements (PROM) questionnaires at 2y or 5y within the last 6 months, aged 35-65 years, unilateral knee surgery (another side as internal control), B1/C1: the normal group is defined as patients closely around the median COMI scores of their respective group (determined medians are: 2yr females: 0.9 / 2yr males: 0.7 / 5yr females: 0.5 / 5yr males: 0.5), B2/C2: the poor outcomes group consists of patients with scores ≥
- •Group D: patient booked for TKA due to severe OA, aged 35-75 years
排除标准
- •inability to give consent or follow procedures
- •no understanding of German language
- •open wounds or tissue injuries
- •irritated or infected sections on the limbs
- •Class II obesity defined by Body Mass Index (BMI) ≥ 35 kg/m2 (comorbidities associated with obesity should be investigated in future studies)
- •uncooperative patients who disregard or cannot follow instructions, including those who abuse drugs and/or alcohol
- •Pregnant or with intention to get pregnant (x-rays)
- •Current address outside of Switzerland
- •Groups B&C: revision surgeries at the operated knee, death, known pathologies or former injuries of the comparator knee
结局指标
主要结局
PROMS
时间窗: 1 year and 2 years
Five different patient reported outcome measures are used: * Oxford Knee Score: contains 12 questions about individual's activities of daily living and how they have been affected by pain over the last 4 weeks. * Core Outcome Measures Index Knee: assesses the main outcomes of importance to patients with knee problems (pain, function, symptom-specific well-being, quality of life, disability). * University of California at Los Angeles: an activity rating scale, which rates the activity level of joint replacement patients globally in one out of 10. * Knee injury and osteoarthritis outcome score: an instrument to assess the patient's opinion about their knee and associated problems. * Forgotten Joint Score 12 is a concise 12-item PROM that evaluates patients' ability to forget their joint in daily life.
EOS / leg alignment
时间窗: 1 year and 2 years
Bilateral long-leg radiographic images will be acquired in a standing position as stereoradiography using the EOS Edge (EOS X-Ray Imaging Acquisition System, Paris, France). Images will be analyzed for OA grading (Kellgren-Lawrence grade 0 - 4) and leg alignment parameters (hip-knee-ankle angle, mechanical axis length and deviation, proximal tibia width and compartmental joint space width).
acoustic emissions
时间窗: 1 year and 2 years
Acoustic sensors are embedded in the hardware of the inmodi knee brace, allowing the non-invasively collection of acoustic data at frequencies between 100Hz and 20 kHz. During data analysis, signals will be segmented and frequency components of low interest will be removed. Specific sound features, such as spectral, fractality, peak amplitude or click patters will be extracted. Data of both knees will be assessed at the same time with the inmodi knee brace (v2) during four different tests, based on recommendations by the Osteoarthritis Research Society International (OARSI) for people with knee OA: - unloaded flexion-extension (F/E) of the knee in a seated position, - Sit-to-Stand test (STS), - One-step test (OST), - Walk test. Associations between the extracted sound parameters and kinematic data, MOAKS grading, KL grading, leg alignment angles and PROMS will be studied to identify biomarkers with a prognosis value in the prediction of OA progress.
kinematic data
时间窗: 1 year and 2 years
Inertial sensors, also embedded in the hardware, do collect movement trajectories at the same time during the four different tests. This kinematic data will be combined with the acoustic emissions to analyze which sound features appear at specific ranges of motion (knee flexion/extension).
MRI / MOAKS
时间窗: 1 year and 2 years
Patients will be scanned using a 3T MRI scanner (Magnetom Prisma, Siemens). MRI allow to visualize and assess structural changes in joint tissues, such as cartilage, meniscus and subchondral bone. Semi-quantitative scoring of these degenerative structures in OA will be done using the MRI Osteoarthritis Knee Score (MOAKS) system by a radiologist.
次要结局
未报告次要终点