The Effect of PEMF for Patients With Quadriceps Muscle Weakness After ACLR

Study Overview
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Brief Summary
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In Hong Kong, over 3000 Anterior Cruciate Ligament Reconstructions (ACLR) are performed each year in order to restore knee function after an ACL injury. The ultimate goal of ACLR is to fulfil the return-to-play (RTP) criteria. Despite successful surgery and a demanding rehabilitation process, some athletes still fail to comply to RTP. For those who achieve RTP, 23% of those who return to their sports would suffer a second ACL injury. Quadriceps muscle strength is one of the key determinants for a patient's successful return- to-play after ACLR. Quadriceps muscle atrophy can persist beyond the completion of the rehabilitation program in almost half the patients and the reason behind this is still unknown. Therefore, there is need to find a more effective way to increase quadriceps strength. There are emerging evidences showing that pulsed electromagnetic field (PEMF) can modulate mitochondrial activities for muscle gain. PEMF exposure on top of regular exercise training may promote muscle regeneration and tissue healing. This study aims to conduct a double-blinded, randomized controlled trial to investigate the effects of PEMF treatment during the late postoperative period on quadriceps muscle strength in ACL injured patient. Muscle endurance could only be investigated in late postoperative period. The investigators hypothesize that PEMF treatment is effective to reduce muscle weakness and promote gain in quadriceps muscle strength in ACLR patients. Based on the aim of this study, adult patients (aged 18-30) with a unilateral ACL injury, total quadriceps muscle volume is equal or morn than 7% deficit on involved leg compared with uninvolved leg, sporting injury with a Tegner score of 7+, both knees without a history of injury/prior surgery will be recruited. To estimate the improvement of patients, Isokinetic muscle assessment, ultrasound imaging and MRI for quadriceps muscle thickness, self-reported outcomes with questionnaires, KT-1000 for knee laxity and biomechanical analysis, Xtreme CT for Bone mineral density will be performed. To investigate the mechanism of PEMF therapy on increasing quadriceps strength, samples of blood serum will be draw before and after intervention.

Official Title
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A Double-Blinded, Randomized-Controlled-Trial to Investigate the Effect of Pulsed Electromagnetic Field (PEMF) for Patients With Quadriceps Weakness After Anterior Cruciate Ligament Reconstruction (ACLR)

Conditions
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Anterior Cruciate Ligament Injuries, Quadriceps Muscle Atrophy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-50 with a unilateral ACL injury Sporting injury with a Tegner score of 7+ LSI for quadriceps strength <70% of the contralateral leg at 4 months post-up Both knees without a history of injury/prior surgery Exclusion Criteria: Ages smaller than 18 years old or greater than 50 years old Any concomitant bone fracture, major meniscus injury or full-thickness chondral injuries requiring altered rehabilitation program post-op Preoperative radiographic signs of arthritis Metal implants that would cause interference on MRI Non-HS graft for ACLR Patient non-compliance to the rehabilitation program Pregnancy or possibility of pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum 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
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> | Device: Pulse Electromagnetic Field<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> | Device: Sham Pulse Electromagnetic Field<br>* Subjects will receive sham PEMF treatment with the duration of 8 weeks, twice a week with total 16 treatment sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of peak torque of Isokinetic muscle strength | The peak torque in N will be the single highest repetition value within the 30 repetitions in the isokinetic muscle strength test. | pre intervention, 4weeks, 8 weeks and 8 months after the commencement of intervention | 
| Change of Fatigue index of isokinetic muscle strength | The Fatigue index (F.I) can be used to calculated the percent decrease for each variable which reflected the muscle endurance. | pre PEMF treatment , 4weeks, 8 weeks and 8 months after the commencement of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI Muscle thickness | Muscle volumes of quadriceps muscle are measured using a 1.5 or 3.0 Tesla MRI Scanner. Axial (3mm thick cut) T1W images are obtained from the anterior superior iliac spine (ASIS) to the patella. Quadriceps muscles were manually outlined in each axial slice. Muscle volume was calculated by summing all of the slice-multiplied by slice thickness. The quality of the muscle is assessed by analyzing the fat content of the muscle mass using a technique that has been reported by Reeder et al. Scans will be performed on both legs before the start of the PEMF treatment (4 months post-op) and only on the injured side repeated after the completion of the 8 weeks PEMF treatment (6 months post-op). The uninjured side will be used as a reference for 'normal volume'. | pre PEMF intervention and 8 weeks after the commencement of intervention | 
| Ultrasound imaging muscle thickness | The Aixplorer® ultrasound system and a linear transducer probe with a bandwidth of 2-10 MHz were used to measure the muscle thickness of Vastus Medialis (VM), Vastus Lateralis (VL), and Rectus Femoris (RF) on both the injured and uninjured leg. Participants laid supine on a treatment table for the assessment. A measuring tape was used to locate VM, VL, RF and the patella by palpation, consequently marked with a pen for reference. RF was marked at 1/2 of the distance from the anterior superior iliac spine (ASIS) to the superior pole of the patella, VM was located at 1/5 of the distance away from the midpoint of the medial patella border to the ASIS, and VL was noted at 1/3 of the distance from the midpoint of the lateral patella border to the ASIS. After locating the anatomical points, excess contact gel was applied on these points. The transducer probe was aligned in the transverse plane and moved along the entire muscle bundle to capture a view of the VM, VL and RF. | pre PEMF treatment , 4weeks, 8 weeks and 8 months after the commencement of intervention | 
| Serum myokine evaluation | Phlebotomy (5ml) will be performed on the day before PEMF treatment, at 4- and 8- weeks after commencement of treatment, and at 8 months after the commencement of intervention. The serum will be prepared by centrifugation and kept in a -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) and report with pg/ml. 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 PEMF treatment , 4weeks, 8 weeks and 8 months after the commencement of intervention | 
| Passive Knee laxity | To measure anterior-posterior knee laxity, the KT-1000 knee ligament arthrometer (MEDmetric Corp, San Diego, CA, USA) will be used. A manual force test will be applied until a 30lb sound signal is activated. Three trials will be performed. A side difference of 3 mm above is considered clinically relevant. | pre PEMF treatment , 4weeks, 8 weeks and 8 months after the commencement of intervention | 
| Reaming size of the bone | The reaming size of the bone in mm on the involved side will be scanned by XtremeCT II which provides an analysis of bone microarchitecture at human peripheral sites with high spatial resolution and low exposure to radiation. | pre PEMF treatment , 4weeks, 8 weeks and 8 months after the commencement of intervention | 
| Ground reaction force | The Kinetic variables including vertical and horizontal ground reaction force (GRF) will be evaluated by a synchronized force plate at the centre of the capture volume at 1000Hz. | pre PEMF treatment , 4weeks, 8 weeks and 8 months after the commencement of intervention | 
| Knee Joint moments | The kinematics will be assessed by the skin marker-based motion analysis system with the lower-body marker setup followed the OSTRC standard using 16-camera and 16 reflective skin marker during the single leg squat and single leg hop test. | pre PEMF treatment , 4weeks, 8 weeks and 8 months after the commencement of intervention | 
| Single leg hop distance | The average of single leg hop distance in cm with three attempts will be measured during the single leg hop test. | 4weeks, 8 weeks and 8 months after the commencement of intervention | 
| Visual Analogue Scale | The subjective measurement for chronic and acute pain will be recorded by the Visual Analogue Scale (VAS). VAS consists of a 10-cm line which represents the continuum between painless and worst pain from 0 cm to 10 cm. The subject will be asked to draw a mark of it before and after each PEMF treatment session. | Before and after 1st - 16th of PEMF treatment | 
| Tegner activity score | This is an activity level scaled from 1 (low activity) to 10 (high activity). | pre PEMF treatment , 4weeks, 8 weeks and 8 months after the commencement of intervention | 
| International Knee Documentation Committee | Consists of 10 questions on symptoms and activity ranging from 0 to 100 where 100 implies perfect knee function. | pre PEMF treatment , 4weeks, 8 weeks and 8 months after the commencement of intervention | 
| Lysholm knee scoring system | Consists of eight items, total score ranging from 0 to 100 where higher scores indicate a better outcome with fewer symptoms or disability. | pre PEMF treatment , 4weeks, 8 weeks and 8 months after the commencement of intervention | 
| International Physical Activity Questionnaire | Consists of four items recording the subject's time of spending on physical activities during the past 7 days with a validated Chinese version of the quantitative physical activity questionnaire, and the physical activity level will be evaluated by Metabolic Equivalent of task(MET) per minute and classified as physical level with Low, Moderate or High. | pre PEMF treatment , 4weeks, 8 weeks and 8 months after the commencement of intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACL, Pulsed electromagnetic field, PEMF, Quadricep Strength, ACLR