1. Title: To check the effect of Biophysically stimulated knee orthosis on pain, functionality and articular cartilage in persons with knee osteoarthritis. 

1. Background: Articular cartilage is a complex tissue that lines the joint articular surface to promote frictionless movements. It allows the joints to withstand action reaction forces generated during activities of daily living. But, when these forces fall abruptly on joint during various activities, it stimulates cartilage degeneration process. Unlike other tissues, articular cartilage is avascular in nature and lacks self -healing capability. If the cartilage degeneration process is not medically intervened at its early stages, it may lead to complete damage of the cartilage and its associated joint. Several studies have reported that the primary and secondary stages of cartilage degeneration process show symptoms of severe pain and reduced functionality of the associated joint. In many cases, the affected patients need to go for complete joint replacement surgeries at an early stage itself. This puts them under lots of burden owing to the surgery’s pain, its associated side effects, expenses and restricted functionality. If this problem remains unsolved it will further create a lot of social and financial burden to the individual and to a nation as whole. 

As far as the current treatment regimens of the cartilage degenerations are concerned, they only focus on controlling inflammations in soft tissues and its associated symptoms. None of the existing medical interventions could regenerate the cartilage. Additionally, there are no techniques available for real time monitoring of the cartilage degeneration at earlier stages. Hence, now it’s a high time to come up with a technology that can address some of the issues mentioned above. 

Biophysics is the study of biological systems and biological processes using physics-based methods or based on physical principles. In biophysical stimulation (for example using PEMF) a physical stimulus triggers a biological response by regulating specific intracellular pathways, thus acting as a drug. The device which provides this electric stimulation is known as a biophysically stimulating device. The efficacy of such an electrical stimulus, however, depends on the specific features of its physical wave, i.e. frequency and amplitude- and on the exposure time. In joint biophysics, the use of such biophysical stimulation (i.e PEMF-therapy) plays a central role since several preclinical and clinical studies have reported positive effects of PEMFs on pain, functionality, articular cartilage, subchondral bone and synovium. A biophysically stimulated PEMF device acts by producing a magnetic field that, in turn, induces currents to flow in nearby tissues. These induced currents mimic the natural electrical activities created within bones during movements, thus triggering a cascade of activities, from the cell membrane to the nucleus and on to the gene level, where specific changes take place. It is seen that the application of suitable PEMF parameters results in increased cytosolic calcium concentration and regulates the calcium-calmodulin pathway. In human chondrocytes (T/C-28a cells), PEMFs also acts by activating and upregulating the adenosine receptors, mainly the A2A and A3 subtypes, thus leading to an anti-inflammatory effect. This is an interesting biologic effect that could explicate the efficacy of PEMFs in reducing articular inflammation.

Therefore, in this proposal, we are proposing a non- invasive and an extremely portable biophysically stimulated electronic device having both therapeutic and monitoring features to slow down and to track down the cartilage health from early to advance stages. 

1. Aims & Objective:  i. Primary: To check the effect of Biophysically stimulated orthosis on pain and functionality in persons with knee osteoarthritis.  ii. Secondary: To check the effect of Biophysically stimulated orthosis on articular cartilage in persons with knee osteoarthritis 
2. 3. Research questions and Hypothesis: 

Research Questions: 

1. i. Is there any significant reduction in pain after application of biophysically stimulated knee orthosis in persons with knee osteoarthritis? 

1. ii. Is there any significant improvement in functionality after application of biophysically stimulated knee orthosis in persons with knee osteoarthritis? 
2. iii. Is there any significant effect on the articular cartilage after application of biophysically stimulated knee orthosis in persons with knee osteoarthritis? 

Experimental Hypothesis: 

1. i. Biophysically stimulated orthosis will reduce the pain in persons with knee osteoarthritis. 
2. ii. Biophysically stimulated orthosis will improve the functionality in persons with knee osteoarthritis. 
3. iii. Biophysically stimulated orthosis will impart positive effect on articular cartilage in persons with knee osteoarthritis. 

4. Materials and Methods 

i. Only humans are involved in this research, animals are not included for this study. 

ii. Randomized controlled trials will be used in the study. 

Inclusion criteria: 

1. i. Primary OA Kellgren Lawrence Grade 1 -3 osteoarthritic patients. 
2. ii. Both male and female 
3. iii. Age 40-70 years 
4. iv. symptomatic disease for at least 6 months prior to enrolment 
5. v. persistent pain despite receiving the maximal tolerated doses of conventional medical therapy 

Exclusion criteria: 

1. i. Persons fitted with pacemaker. 
2. ii. Any prior knee surgery. 
3. iii. Persons fitted with any metallic implants. 
4. iv. Osteoarthritic patients having Kellgren Lawrence grade as 4. 

1. v. Persons who do not provide consent for participation. 
2. vi. Presence of any medical condition that can impart effect on proposed intervention. 

Sample Size calculations: 

Sample size in each group and sample size determination methods: Total sample size of 42 where 21 in experimental group and 21 in control group: - 

Sample size calculation is based on research entitled “Pulsed Electromagnetic fields 1h knee osteoarthritis a double blind, placebo controlled, randomized clinical trial” by Gian Luca Bagnato et.al. The pain (VAS) was taken as reference variable at end point. Assuming a pooled SD of 15.51 units, the new would require a sample size of 21 for each group. (i.e total sample size of 42 assuming each group size) to achieve a power of 80%and level of significance of 5% (two sided) for detecting a true difference in mean between the test cases and the reference group (control) of 13.6 units. 

Formula used: 

The sample size, 

N= ((Zα/2 + Zβ)2 x 2 x σ2)/ d2 ≈ 21 

Zα/2 = 1.96 (α = 0.05, confidence level) 

Zβ = 0.84 (β = 0.20, power in 80%) 

σ2 = population variance = [15.5 unit = σ] 

d = difference in mean (d = 13.6) 

5. Procedure: 

i. Subjects’ will be recruited based on inclusion and exclusion criteria. 

ii. Recruited subjects will be introduced to the study 

iii. Consent form from each and individual patient will be collected. 

iv. Randomization of the recruited subjects into control and experimental group will be done

v. Both pre and post data related to pain and functionality from each and individual subjects on 1st, 5th, 15th, 30th, 45th and 60th day will be recorded using following methodologies in the experimental group (i.e., various data before and after the application of proposed medical device will be monitored): (a). Pain Monitoring using Visual Analogue Scale (VAS) and Pain Pressure Threshold (PPT) device (b). Functionality Monitoring using Knee Injury and Osteoarthritis Outcome Score (KOOS) and joint Angular movement measurement using Goniometers. (c). Patient lifestyle measurement using KOOS. (d). Effect of proposed device on articular (if any) using MRI 

vi. The same data will also be recorded from the control group without the application of the proposed medical device. 

vii. 90 days follow-up will be taken from the recruited patients. 

viii. The third party data analysis will be done