Efficacy and Safety of an Active Pulsed Electromagnetic Field for the Treatment of Osteoarthritis of the Knee

The hypothesis of this study is that exposure to PEMF alters the cytokine environment of OA joints associated with a reduction of inflammation and improved homeostasis of the extracellular matrix (ECM), both potentially effecting symptomatic relief of OA pain, reducing cartilage breakdown, stimulate new cartilage formation therefore preserving joint structure.

The hypothesis of this study is that exposure to PEMF alters the cytokine environment of OA joints associated with a reduction of inflammation and improved homeostasis of the extracellular matrix (ECM), both potentially effecting symptomatic relief of OA pain, reducing cartilage breakdown, stimulate new cartilage formation therefore preserving joint structure. The primary objective of this study is to prospectively determine, at 12 months post treatment, the safety and efficacy of treating OA of the knee with PEMF. Safety will be assessed through adverse event collection. Study subjects will be randomized in a 2:1 ratio (active: placebo control) to either an active or placebo control (inactive) Physio-Stim device. The study is powered to detect a significant difference between groups when 120 subjects (80 active: 40 placebo control) have completed the study. Planned enrollment for the study is 150 subjects, to allow for an attrition rate of 20%.

Eligibility Criteria:
Inclusion Criteria:

1. Subject must be able to wear the investigational device so that there is adequate PEMF exposure to the knee.
2. Subject must have a body mass index ≤ 45 at the time of consent.
3. Subject must be at least forty (≥ 40) years of age of age at the time of consent.
4. Subject must have an established diagnosis of primary femorotibial OA in the target knee by modified American College of Rheumatology criteria for at least 6 months and at least one of the following:

   i. Stiffness less than 30 min ii. Crepitus (noise or cracking on knee motion)
5. Subject must have symptomatic Kellgren-Lawrence (K-L) Grades 1-3 OA by radiograph (PA flexion) within 90 days of screening, where the K-L grades are defined as:

   Grade 1: doubtful narrowing of joint space and possible osteophytic lipping; Grade 2: definite osteophytes and definite narrowing of joint space; Grade 3: moderate multiple osteophytes and definite narrowing of joint space and some sclerosis and possible deformity of bone contour
6. Subject must have a visual analog pain score between 4 cm and 8 cm on a 10 cm scale in the target knee at the time of screening.
7. Subject must have a normal tibiofemoral angle (0-8°) and a joint space width of ≥ 3mm confirmed by radiograph.
8. Subject must be ambulatory.
9. Subject must NOT have had arthroscopy within 8 weeks of randomization.
10. Subject must NOT have had viscosupplementation within 8 weeks of randomization.
11. Subject must NOT have had NSAIDs within 1 week of randomization (low-dose aspirin as cardioprotective prophylaxis is permitted).
12. Subject must be willing to discontinue corticosteroids administered by any route except intranasal spray, steroid- containing ophthalmic solutions and anti-asthmatics.
13. Subject must be willing to take acetaminophen (up to 3000 mg/day) as pain medication for the duration of the study. Other pain medications may be allowed during the course of the study if the subject meets specific criteria.
14. Subject must be willing to STOP taking any pain medications 24 hours prior any scheduled study visit.
15. Subject must NOT have participated in a clinical study within the past 12 weeks that required the use of an investigational device, drug or biologic.
16. Subjects must be proficient in English.
17. Subject must be willing and able to sign an informed consent document.
18. Subjects must be willing and able to comply with all study procedures for the duration of the clinical study.

Exclusion criteria:

1. Subjects who have a body mass index \> 45 at the time of consent.
2. Subjects with a diagnosis of inflammatory arthritis (rheumatoid arthritis, gout, joint infection, Lyme disease, SLE, etc.).
3. Subjects with a diagnosis of secondary arthritis (acromegaly, Charcot's arthropathy, hemochromatosis, Wilson's disease, ochronosis, etc.).
4. Subjects with confounding factors such as ipsilateral hip OA or chronic pain syndromes (fibromyalgia, Crohn's disease, ulcerative colitis, interstitial cystitis).
5. Subjects who have had an injury or an acute traumatic injury to the index knee within 6 months of screening will be excluded.
6. Subjects who have had treatment of the target knee with intra-articular injections of steroids within 8 weeks of screening.
7. Subjects who have had intra-articular injections of hyaluronic acid within 8 weeks of screening.
8. Subjects who plan to have surgery on the target knee within the study period.
9. Subjects who have used electrotherapy or acupuncture for OA of the target knee within 4 weeks of screening.
10. Subjects with significant and clinically evident mal-alignment of the target knee (\> 10 degrees varus or valgus in the target knee).
11. Subjects with surgical metallic hardware in the target knee.
12. Subjects with pain in any other area of the lower extremities or back that is equal to or greater than the pain in the target knee.
13. Subjects who have contraindications to MRI and X-rays, for example, implanted electrical devices (cardiac pacemakers, deep brain stimulators).
14. Subjects with a current malignancy or who have received treatment for malignancy with the last 5 years, with the exception of resected basal cell carcinoma and squamous cell carcinoma of the skin.
15. Subjects who have an active substance abuse problem (drugs or alcohol) or a history of chronic substance abuse (\> 5 years).
16. Subjects with skin breakdown or infection in the area where the study device will be placed.
17. Subjects with any chronic conditions (e.g., diabetes, hypertension, congestive heart failure, etc.) that have not been well-controlled for at least 3 months prior to screening.
18. Subjects who have any ongoing litigation for worker's compensation.
19. Subjects with any condition, in the opinion of the Investigator that might interfere with the evaluation of the study objectives.
20. Subjects who are unwilling or unable to adhere to the follow up schedule and procedures.
21. Subjects who are pregnant.
22. Subjects who are prisoners.