Wearable LITUS Device for Osteoarthritis of the Knee: a Randomized Double-Blind Placebo-Controlled Trial

Study Overview
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Brief Summary
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The purpose of this study is to measure the effectiveness of a wearable therapeutic ultrasound device in patients with stage I and stage II knee osteoarthritis. The ability of the device to reduce pain, increase mobility, increase range of motion and muscle strength of the affected leg, and improve quality of life in patients with knee osteoarthritis will be evaluated.

Detailed Description
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This is an eight week study to clinically evaluate the effect of the low intensity long duration ultrasound (LITUS) device on symptoms of patients suffering from knee osteoarthritis. The device, sam® has been FDA-cleared for use. For the first two weeks of the study, baseline data will be collected as patients report pain scores (NRS) three times per day. During the following 6 weeks, patients will self-apply the wearable LITUS device to their affected knee for 4 hours daily. Each day of the study, pain scores (NRS) will be recorded immediately before application of LITUS device as well as 30 minutes, 2-hours and 4-hours after applying the device. A quality of life assessment (WOMAC), muscle strength and range of motion assessment (JTech) will be performed prior to the patient beginning the protocol and at the conclusion of the protocol. Up to 93 subjects will be recruited from neighboring communities to the study site. The study is designed to reach a target patient population which includes rural citizens and socioeconomic disadvantaged individuals where non-pharmacotherapies do not exist to manage pain. Subjects will be randomly assigned to active (60%) and placebo groups (40%). The sponsor and investigators are blinded as to which type of device each patient is assigned. The study will be monitored by an external monitor and a data safety monitoring board (DSMB).

Official Title
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ZetrOZ Wearable Ultrasound Clinical Study

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Device: Sam Ultrasonic Diathermy Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Physician-diagnosed mild to moderate knee osteoarthritis (OARSI atlas grades 1-2) based on fixed-flexion x-ray radiological findings for osteophytes and joint space narrowing within the past 12 months Fulfill the American College of Rheumatology clinical and radiological diagnostic criteria for knee OA 35-80 years of age Report a frequent pain score between 3-7 (NRS range: 0-10) during the week preceding enrollment Report that knee pain negatively affects quality of life Willing not to use any cream, gel, or topical solution during the administration of treatment other than the approved ultrasound gel provided to the subject at the initiation of the study Deemed appropriate by their physician or by the study site physician to participate Exclusion Criteria: Cannot successfully demonstrate the ability to put on and take off the device Display any condition which, in the judgment of the investigator, would make participation in the study unacceptable, including, but not limited to, the subject's ability to understand and follow instructions. Have severe OA or have little to no cartilage in the knee Have knee replacement, other surgical intervention, or hyaluronidase injection in the affected knee in the past 6 months Are non-ambulatory Participated in a clinical trial for an investigational drug and/or agent within 30 days prior to screening Modify their medications during the course of the study (medications and doses must remain constant throughout the study) Currently taking steroids Have contraindication to radiograph Have a secondary cause of arthritis (metabolic or inflammatory)

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active ultrasound device<br>Patients receive treatment from the Sam Ultrasonic Diathermy Device for 4 hours every day for 6 weeks. The active device emits continuous ultrasound at 3 megahertz (MHz) frequency and 0.132 watts/cm2 intensity. | Device: Sam Ultrasonic Diathermy Device<br>* Patients apply the Sam Ultrasonic Diathermy Device daily for 4 hours of continuous therapeutic ultrasound at 3 megahertz (MHz) frequency and 0.132 Watts/cm2.<br>* Other names: long duration low intensity device;|
| Placebo Comparator: Placebo ultrasound device<br>Patients wear the Sam Ultrasonic Diathermy Device for 4 hours every day for 6 weeks. The placebo device appears and operates identically to the active device except that it does not emit ultrasound. | Device: Sam Ultrasonic Diathermy Device<br>* Patients apply the Sam Ultrasonic Diathermy Device daily for 4 hours of continuous therapeutic ultrasound at 3 megahertz (MHz) frequency and 0.132 Watts/cm2.<br>* Other names: long duration low intensity device;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain on the Numeric Rating Scale (NRS) Change From Baseline to Study Conclusion | The numeric rating scale (NRS) was used to assess change in pain from baseline to study conclusion. NRS range from 0-10 with 0 being no pain and 10 the worst pain possible. | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life (WOMAC) Change From Baseline | WOMAC questionnaire will be utilized (Western Ontario and McMaster Universities Arthritis Index). WOMAC was divided into 3 categories: pain, stiffness, function and total score. The pain category consists of five scores from 0-10, 0 is no pain 10 is worst pain possible for a range of 0 - 50 points. The stiffness category consists of two scores from 0-10, 0 is no stiffness 10 is worst stiffness possible for a range of 0 - 20 points. The function score consists of 17 scores from 0-10, 0 is normal function and 10 is severely limited function, for a range of 0 - 170 points. Categories were multiplied by 10 for analysis. Total score is the sum of pain, stiffness, and function scores (range of 0 - 2400). | Baseline, Week 6 | 
| Range of Motion Change From Baseline in Treated Knee | JTech equipment was used to evaluate range of motion range of motion using an inclinometer (www.jtechmedical.com) in flexion and extension of the treated knee. 0 degrees is fully extended and 150 degrees is normal flexion. Positive flexion change indicates improvement in flexion. Negative extension indicates improvement in extension. | Baseline, Week 6 | 
| Muscle Strength Change From Baseline in Treated Knee | Muscle strength in flexion, extension, and rotation were measured using JTECH muscle testing equipment. | Baseline to 6 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, osteoarthritis, arthritis, musculoskeletal, connective tissue disease, ultrasound, mobility, heat, strength, ZetrOZ, LITUS, Sam, grade 1, grade 2