The Effects of Pulsed Electromagnetic Field Therapy on Patients With End-stage of Knee Osteoarthritis With Sarcopenia

Study Overview
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Brief Summary
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A double-blinded, randomizepd controlled trial to investigate the treatment effects of pulsed electromagnetic field (PEMF) on end stage of knee osteoarthritis patients with sarcopenia will be carried out. Subjects will be recruited from the Prince of Wales Hospital. Sixty participants age ≥ 60 will be invited to join this trial after informed consent. They will be randomised to any of the 2 groups: intervention group (n=30; PEMF (Quantum Tx) treatment), and control group (n=30; sham treatment with dummy exposure to PEMF). Baseline measurements include appendicular muscle mass by DXA, bone microarchitecture (XtremeCT II), knee flexion and extension strength by handheld dynamometer, knee flexion and extension range of motion by goniometer, self-reported knee pain (VAS) and function by The Knee Injury and Osteoarthritis Outcome Score (KOOS), International Physical Activity Questionnaire (IPAQ) for assessment of physical activity level, quality of life by SF-36, hand grip test, bioelectrical impedance analysis （BIA）of body composition, postural stability, chair stand test, 30s arm curl test and 6-meter walking test. These measurements will be performed again at middle and end of treatment, 3, 6, and 12 months after commencement of treatment, except DXA, which will not be performed at the midpoint. In addition, blood samples will be taken at baseline, middle, and end of treatment, 3, 6, and 12 months after commencement of treatment, for determing of serum myokines which are reported to be sensitive to PEMF treatment and contribute to myogenesis. The aim of this study is to conduct a double-blinded, randomized controlled trial to investigate the effects of PEMF treatment on muscle gain and pain relief in knee osteoarthritis with sarcopenia elderly in Hong Kong. We hypothesize that PEMF treatment is effective to promote a gain in muscle mass and function and pain relief in knee osteoarthritis with sarcopenia elderlies.

Detailed Description
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PEMF therapy is the use of electromagnetic fields in a pulsating pattern directed towards the body. Diagnosis of sarcopenia Based on the European Working Group of Sarcopenia in Older People (EWGSOP) and the adapted diagnostic criteria for Asians by AWGS, sarcopenia will be diagnosed with reduced muscle mass (screening by bioelectrical impedance analysis (BIA) and confirmed at recruitment stage by DXA) accompanied by low hand grip strength (in Handgrip strength test) and/or poor 6-meter gait speed (in 6 meter-gait speed test) or poor 5-time chair stand test (in 5-time chair stand test) .

Official Title
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The Effects of Pulsed Electromagnetic Field Therapy on Patients With End-stage of Knee Osteoarthritis With Sarcopenia: A Double-blinded Randomized Control Trial

Conditions
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Knee Osteoarthritis, Sarcopenia

Intervention / Treatment
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* Device: Pulse Electromagnetic Field device
* Device: Sham Pulse Electromagnetic Field device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - subjects with knee osteoarthritis who meet the AWGSOP criteria will be included: radiographic Kellgren/Lawrence scale knee OA grade ≥3 Appendicular muscle mass by DXA (< 7 kg/m2 in men, < 5.4kg/m2 in women), with either hand grip strength<28 kg in men, <18 kg in women or 6-meter gait speed ≤1 m/seconds or 5-time chair stand test ≥12 seconds. Exclusion Criteria: 1. With medical or musculoskeletal problems that could affect the ability to complete assessments (i.e. with walking aids or wheel-chaired). 2. Severe cognitive impairments and neurological disorders that will affect data collection by questionnaires. 3. Any medical conditions which are contraindicated to do exercise by PARQ restricting any physical activity. 4. Age less than 60 years old.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 90 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
Interventional Model Description: Participants will be assigned into either treatment group or sham group.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Participants in the intervention group will be exposed to PEMF treatment by a PEMF device (Quantum Tx, Singapore). Alternate legs will be exposed to PEMF treatment for 10 minutes per session, and the treatment regime will run biweekly for 8 weeks, summing up 16 sessions of PEMF exposure in total. | Device: Pulse Electromagnetic Field device<br>* Subjects will receive PEMF treatment with the duration of 8 weeks, twice a week with total 16 treatment sessions.<br>|
| Sham Comparator: Sham group<br>Participants in the intervention group will be exposed to PEMF treatment by a PEMF device (Quantum Tx, Singapore). Alternate legs will be exposed to PEMF treatment for 10 minutes per session, and the treatment regime will run biweekly for 8 weeks, summing up 16 sessions of sham exposure in total. | Device: Sham Pulse Electromagnetic Field device<br>* Sham Pulse Electromagnetic Field Subjects will receive sham PEMF treatment with the duration of 8 weeks, twice a week with a total of 16 treatment sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the change of knee extensor and flexor strength | The peak torque in KG will be recorded in 2 trials in the 5 seconds isometric muscle strength test. | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the change of Muscle mass | Skeletal muscle mass will be measured by a Dual-energy X ray absorptiometry (DXA) scan according to standardized procedure The muscle mass in kg m^2 will be recorded in different time points. | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of knee range of motion | The knee flexion/extension range of motion will be measured with a standard goniometer. Measurement of knee flexion will be performed in the supine position by simultaneously flexing the hip and knee, with the foot on the measured side resting on the table as far as possible. The opposite leg will be kept extended on the table. Knee extension will be also measured with patients lying supine on an examination couch with the leg kept straight, and the examiner supported the weight of the leg as the patient moves. The fully extended knee will be considered zero position, and the degrees of maximum flexion, maximum extension, and extension deficit, when present, will be recorded. A negative ROM score for extension indicated that the patient will be unable to reach the zero position. The angle between maximum flexion and the maximum extension will be described as the excursion range. The range of motion in ° will be recorded. | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of self-report knee pain and function | Self-reported pain and physical function will be measured using the the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire. This 42-item questionnaire is divided into five sub-scales, which address pain, other disease symptoms, function in activities of daily living, function in sport and recreation, and quality of life. | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of Time -Up -and-Go | The ''Timed Up and Go''（TUG） test is an internationally accepted functional, dynamic test of postural control with known reliability and validity, as well as being low cost and easy to apply. The TUG test measures the time in seconds that takes a subject to stand up from a chair, walk three meters at a comfortable and safe pace, turn around, walk back to the chair, and sit down. In this study, participants will be asked to perform TUG three times; and the final TUG score will be the average of three times. | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of 30s Arm curl | The participants receive a weight on the dominant hand. The weight is 2.27 kg [5 lb] for women and 3.63 kg [8 lb] for men. The task is to perform a 30s Arm Curl test. The number of the arm curl will be recorded. | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of muscle image | Aixplorer (Supersonic Imagine, Aix-en-Provence, France) will be used to obtain ultrasound image of knee extensor group (quadriceps femoris). Muscle thickness (MT) will be measured from the superior border of the deep aponeurosis to the inferior border of the superficial aponeurosis of the muscle of interest (rectus femoris, vastus lateralis) and sub- cutaneous fat thickness (SCFT) will be measured from the superior border of the superficial aponeurosis to the inferior border of the dermis layer. | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of bone image | High-Resolution Peripheral Quantitative Computed Tomography Scans (HR-pQCT) High-resolution peripheral quantitative computed tomography scans (HR-pQCT) using XtremeCT II (Scanco Medical AG️, Brüttisellen, Switzerland) provides an analysis of bone microarchitecture at human peripheral sites with high spatial resolution and low exposure to radiation. Bone mineral density (BMD, calibrated with hydroxyapatite standards) and finite element analysis of subchondral bone over the knee joint will be performed using the Scanco software. Scans will be performed on both legs before the start of the PEMF treatment, in the middle of 8weeks, and after the completion of the PEMF treatment (3, 6- and 12-months). | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of chair stand test | The rate of force development will be determined as the mean slope of the rising force of the first force peak of each of the 2nd to the 6th repetition in the interval of 30-70% exerted peak force. Results are reported as the mean of the two fastest approved trials in body weight per second (BW/s). | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of postural stability | A force platform (Tekscan, U.S.) will be utilized to evaluate static postural control using the COP measures in static and dynamic postural control conditions. Sway path length (cm) of center of pressure (COP), velocity of COP (cm/s), ellipse area (cm^2)of COP (will be recorded.These static postural conditions include stand on double leg with open (DO) and close eyes (DC) for 30s, tandem stance for 30s, squat for 15s and stand on one leg with open eyes (SO) for 10s.Dynamic postural control will be evaluated using the task of transitioning from double-leg to single-leg standing. | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of Serum myokine evaluation | Blood taking (5 ml) will be performed before PEMF treatment, and at 3, 6, and 12 months after the commencement of treatment. Serum will be prepared by centrifugation and kept in -80º freezer until use. Quantitative analysis for myokines and proteins related to muscle metabolism will be performed by Human Myokine Magnetic Bead Panel (Millipore) with Bioplex-200 bead-based suspension assay system (LKSIHS core facilities), or enzyme linked immunosorbent assay (ELISA). These include Brain-derived neurotrophic factor (BDNF), Fibroblast growth factor-21 (FGF-21), Interleukin-6 (IL-6), IL-15, Irisin, Myostatin (MSTN)/GDF8, Insulin-like growth factor 1 (IGF-1), FGF-2, IL-8, Follistatin, Musclin, Myonectin, Decorin, Meteorinlike, Osteopontin, Secreted protein acidic and rich in cysteine (SPARC), Klotho, Procollagen type III N-terminal peptide (P3NP), and C-terminal of troponin T1 (TNNT1) | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of self-report pain | The Visual Analogue Scale (VAS) requires participants to rate participants' pain on a defined scale from 0-10 after each ending session of the PEMF therapy. | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of self-report quality of life | Short Form-36 questionnaires (SF-36) will be used to evaluate Health-Related Quality of Life. | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 
| the change of physical activity | Physical Activity Readiness Questionnaire (PAR-Q) and International Physical Activity Questionnaire (IPAQ) will be used to determine whether participants should complete medical evaluation before participating in the exercise program in this study. | pre, mid, end of PEMF treatment , 2-months, 3-months, 6-months, and 12-months after the commencement of PEMF] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulse electromagnetic field, PEMF, Knee Osteoarthritis, Knee OA, sarcopenia