To Investigate the Effect of PEMF for Knee OA Patients

Study Overview
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Brief Summary
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Health care costs are increasing alarmingly, which will impose an overwhelming economic burden to an aging society like that of Hong Kong. For example, degenerative musculoskeletal disorders such as osteoarthritis (OA) present a grand challenge with its high prevalence (>40% in the elderly suffered from knee OA). Knee osteoarthritis (OA) is the most common form of arthritis, and around 2 million population worldwide suffer from this disorder. OA is a debilitating progressive disease with typical pathological progress such as cartilage degeneration, inflammation, joint width narrowing and developing osteophytes. The main system of knee OA is acute pain leading to loss of mobility. There is no effective treatment to cure or stop the progression of OA. For now, the main method is to alleviate the pain and symptoms, including control weight, exercise, physical treatment and intake of NSAIDs/ paracetamol. Pulsed electromagnetic field (PEMF) treatment has shown to enhance cell activity related to tissue healing, delay bone and cartilage degeneration and give beneficial effects such as relief in pain, anti-inflammation and reduce swelling. In clinic, PEMF treatment has been reported to be safe, and has been proved to reduce the usage of NSAIDs and pain in patients with knee OA. This study aims to investigate the effectiveness of PEMF therapy on for patients with knee OA, including delay the degeneration of articular cartilage, restore the subchondral bone, reduce knee pain and symptoms as well as improve the muscle strength and functions, and even improving the quality of life. Based on the aim of this study, older adult patients (aged 50 or above) with a unilateral knee OA with Kellgren-Lawrence (KL) grade 2-3 by X-ray, visual analogue scale (VAS) >4, no acute knee injuries and muscle strain in past 3 months, and no alleviation of symptoms after ≥ 3 months of nonsurgical treatment. To estimate the improvement of patients the following assessments will be performed, including patient-reported outcomes, muscle strength and physical function assessments, serum evaluation, and imaging examination.

Official Title
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Pulsed Electromagnetic Fields (PEMF) in Knee Osteoarthritis: a Double-blind, Placebo-controlled, Randomised Clinical Trial

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Device: PEMF treatment
* Device: Placebo treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary osteoarthritis of knee VAS score ≥ 4 Grade 2 and 3 osteoarthritis (Kellgren-Lawrence criteria) No alleviation of symptoms after ≥ 3 months of nonsurgical treatment No acute knee injuries in both limbs in the past 3 months No muscle strain in both limbs in the past 3 months Voluntarily agreed to participate and signed the informed consent form Exclusion Criteria: Skin diseases around the target knee joint Severe pain in other areas affects the diagnosis of function and symptoms of knee joints Injection in target knee within 3 months of enrolment Inflammatory joint disease (e.g., rheumatic inflammation) Infectious joint disease (e.g., septic arthritis) Pregnant or breastfeeding Patient with a pacemaker, an implantable defibrillator, neurosurgical clips, a neurostimulator, cochlear implant, a stent, an insulin pump Physical inability to undertake testing procedures Inability to give informed consent

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Knee OA KL Grade2 PEMF Treatment<br>Patients with knee OA grade 2 will accept PEMF treatment | Device: PEMF treatment<br>* Patient will receive a PEMF treatment. The involved leg will be exposed to PEMF for 30 minutes per session, and the treatment regime will run three times a week for eight weeks, summing up 24 sessions of PEMF exposure in total.<br>|
| Placebo Comparator: Knee OA KL Grade2 Placebo Treatment<br>Patients with knee OA grade 2 will accept placebo treatment | Device: Placebo treatment<br>* Patient will receive a placebo treatment. The involved leg will be exposed to placebo treatment for 30 minutes per session, and the treatment regime will run three times a week for eight weeks, summing up 24 sessions of placebo exposure in total.<br>|
| Experimental: Knee OA KL Grade3 PEMF treatment<br>Patients with knee OA grade 3 will accept PEMF treatment | Device: PEMF treatment<br>* Patient will receive a PEMF treatment. The involved leg will be exposed to PEMF for 30 minutes per session, and the treatment regime will run three times a week for eight weeks, summing up 24 sessions of PEMF exposure in total.<br>|
| Placebo Comparator: Knee OA KL Grade3 Placebo Treatment<br>Patients with knee OA grade 3 will accept placebo treatment | Device: Placebo treatment<br>* Patient will receive a placebo treatment. The involved leg will be exposed to placebo treatment for 30 minutes per session, and the treatment regime will run three times a week for eight weeks, summing up 24 sessions of placebo exposure in total.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type II collagen-specific biomarker change | The serum will be prepared by centrifugation of blood (10ml), aliquoted and kept in a -80° freezer until use. Biomarkers of cartilage breakdown, type II collagen-specific biomarker, will be measured by enzyme-linked immunosorbent assays (ELISA). | Change from baseline cartilage turnover at 8 weeks | 
| Type II collagen-specific biomarker change | The serum will be prepared by centrifugation of blood (10ml), aliquoted and kept in a -80° freezer until use. Biomarkers of cartilage breakdown, type II collagen-specific biomarker, will be measured by enzyme-linked immunosorbent assays (ELISA). | Change from baseline cartilage turnover at 6 months | 
| Type II collagen-specific biomarker change | The serum will be prepared by centrifugation of blood (10ml), aliquoted and kept in a -80° freezer until use. Biomarkers of cartilage breakdown, type II collagen-specific biomarker, will be measured by enzyme-linked immunosorbent assays (ELISA). | Change from baseline cartilage turnover at 12 months | 
| Type VI collagen-specific biomarker change | The serum will be prepared by centrifugation of blood (10ml), aliquoted and kept in a -80° freezer until use. Biomarkers of cartilage breakdown, type VI collagen-specific biomarker, will be measured by enzyme-linked immunosorbent assays (ELISA). | Change from baseline cartilage turnover at 8 weeks | 
| Type VI collagen-specific biomarker change | The serum will be prepared by centrifugation of blood (10ml), aliquoted and kept in a -80° freezer until use. Biomarkers of cartilage breakdown, type VI collagen-specific biomarker, will be measured by enzyme-linked immunosorbent assays (ELISA). | Change from baseline cartilage turnover at 6 months | 
| Type VI collagen-specific biomarker change | The serum will be prepared by centrifugation of blood (10ml), aliquoted and kept in a -80° freezer until use. Biomarkers of cartilage breakdown, type VI collagen-specific biomarker, will be measured by enzyme-linked immunosorbent assays (ELISA). | Change from baseline cartilage turnover at 12 months | 
| Cartilage oligomeric matrix protein change | The serum will be prepared by centrifugation of blood (10ml), aliquoted and kept in a -80° freezer until use. Biomarkers of cartilage breakdown, cartilage oligomeric matrix protein, will be measured by enzyme-linked immunosorbent assays (ELISA). | Change from baseline cartilage turnover at 8 weeks | 
| Cartilage oligomeric matrix protein change | The serum will be prepared by centrifugation of blood (10ml), aliquoted and kept in a -80° freezer until use. Biomarkers of cartilage breakdown, cartilage oligomeric matrix protein, will be measured by enzyme-linked immunosorbent assays (ELISA). | Change from baseline cartilage turnover at 6 months | 
| Cartilage oligomeric matrix protein change | The serum will be prepared by centrifugation of blood (10ml), aliquoted and kept in a -80° freezer until use. Biomarkers of cartilage breakdown, cartilage oligomeric matrix protein, will be measured by enzyme-linked immunosorbent assays (ELISA). | Change from baseline cartilage turnover at 12 months | 
| Cartilage thickness change-US | Ultrasound (US) offers an alternative quantitative measurement of cartilage thickness which is more available and more cost-effective compared to MRI. The US will be performed on both knees, the L18-5 MHz linear transducer will be positioned in the axial plane on the suprapatellar region. In order to image the femoral cartilage, all subjects will be placed in the supine position with maximum knee flexion. In this study, the US will be used to assess cartilage thickness of the tibiofemoral joint. | Change from baseline cartilage thickness at 8 weeks | 
| Cartilage thickness change-US | Ultrasound (US) offers an alternative quantitative measurement of cartilage thickness which is more available and more cost-effective compared to MRI. The US will be performed on both knees, the L18-5 MHz linear transducer will be positioned in the axial plane on the suprapatellar region. In order to image the femoral cartilage, all subjects will be placed in the supine position with maximum knee flexion. In this study, the US will be used to assess cartilage thickness of the tibiofemoral joint. | Change from baseline cartilage thickness at 6 months | 
| Cartilage thickness change-US | Ultrasound (US) offers an alternative quantitative measurement of cartilage thickness which is more available and more cost-effective compared to MRI. The US will be performed on both knees, the L18-5 MHz linear transducer will be positioned in the axial plane on the suprapatellar region. In order to image the femoral cartilage, all subjects will be placed in the supine position with maximum knee flexion. In this study, the US will be used to assess cartilage thickness of the tibiofemoral joint. | Change from baseline cartilage thickness at 12 months |