A Pilot Trial to Assess Low-Intensity Ultrasound in Osteoarthritis

Study Overview
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Brief Summary
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The purpose of this exploratory trial is to investigate whether PLIUS is potentially effective as a disease and symptom modifying intervention in patients with early knee OA.

Detailed Description
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Osteoarthritis (OA), the most common form of arthritis, is a prevalent and debilitating disease without therapies that alter disease progress and is currently managed with symptom-modifying therapies that are only modestly effective. In spite of substantial progress in understanding the pathogenesis of OA, no effective disease modifying interventions have been established. Degenerative joint cartilage is a central feature of OA, yet joint cartilage has a limited capacity for repair. Results from animal research demonstrate that pulsed low intensity ultrasound (PLIUS) mechanically stimulates, and may promote, cartilage repair. This exploratory trial will investigate whether PLIUS is potentially effective as a disease and symptom modifying intervention in patients with early knee OA.

Official Title
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A Pilot Trial to Assess Low-Intensity Ultrasound in Osteoarthritis

Conditions
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Osteoarthritis, Degenerative

Intervention / Treatment
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* Device: Pulsed Low Intensity Ultrasound
* Device: Sham Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 40 years of age or older, and a US Military Veteran Clinical symptoms of osteoarthritis for at least 6 months Pain in the index knee on motion or weight bearing for the majority of days during the month before screening Clinical diagnosis of primary osteoarthritis of the knee based on clinical and radiographic criteria American Rheumatism Association Functional Class I, II, or III Females of childbearing potential must be willing to use a reliable form of medically acceptable contraception Exclusion Criteria: Concurrent medical/arthritis condition(s), or any other illness per the opinion of the investigator, that could interfere with the evaluation of pain or efficacy Spine or hip pain of significant magnitude History of significant ligament or meniscal injury of the index joint requiring surgical repair Arthroscopy of the index knee within 6 months of study entry Unable to undergo MRI of the knee Pregnancy or lactation Corticosteroid treatment within 1 to 3 months prior to study entry Intra-articular injection of hyaluronic acid or congeners to the index knee within 6 months of study entry Use of excluded therapy(ies) prior to study entry Use of disease modifying anti-rheumatic medications and chronic tetracycline or its derivatives Exposure to glucosamine, chondroitin sulfate, or any other investigational treatment, within 1 month of study entry Use of any medical therapy, complementary or alternative regimens for the treatment of osteoarthritis within 7 days prior to study entry Initiation of physical therapy or muscle conditioning program to the lower extremities within 2 months within 2 months prior to study entry Unlikely to comply with study requirements

Ages Eligible for Study
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Minimum Age: 40 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 in this double-blind, randomized, sham-controlled trial will be randomly assigned to receive either sham or PLIUS device for 48 weeks.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham<br>Treatment to index knee with sham device for 48 weeks | Device: Sham Comparator<br>* 20 minutes daily for 48 weeks<br>|
| Experimental: PLIUS<br>Treatment to index knee with PLIUS device for 48 weeks | Device: Pulsed Low Intensity Ultrasound<br>* 20 minutes daily for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Co-Primary Measure: a) Symptom Reduction: OMERACT-OARSI Treatment Responsiveness | Outcome Measures in Rheumatology Clinical Trials- Osteoarthritis Research Society International (OMERACT-OARSI) Response incorporates changes in pain and global assessment to define response in OA clinical trials. A response is classified as: 1) An improvement in either pain or function of at least 50 percent accompanied by an absolute decrease of at least 20 mm on the visual-analogue scale for pain or function, OR 2) The occurrence of at least two of the following: a) a decrease in pain of at least 20 percent accompanied by a decrease of at least 10 mm on the visual-analogue scale; b) an improvement in function of at least 20 percent and a decrease of at least 10 mm on the visual-analogue scale; c) an increase in the patient's global assessment score by at least 20 percent accompanied by a decrease of at least 10 mm on the visual-analogue scale | 48 weeks | 
| Co-Primary Measure: b) Disease Modification as Measured by Change From Baseline in Cartilage Thickness of the Central Medial Femoral Condyle Disease | The study has been designed to determine if PLIUS potentially diminishes articular cartilage thinning by measuring cartilage thickness in the tibial femoral joint. The measure selected to best evaluate this is cartilage thickness of the central medial femoral condyle because studies of the OAI (Osteoarthritis Initiative) data have shown this region to be among those most sensitive to change and, due to the anatomical positioning of the device, the most likely to be affected by treatment. | Baseline, 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in WOMAC Stiffness Subscale Score | The WOMAC® Index questionnaire is a tri-dimensional, disease-specific, self-administered, health status measure. It probes clinically important, patient-relevant symptoms in the areas of pain, stiffness and physical function in patients with osteoarthritis of the hip and/or knee. The WOMAC has been linguistically validated and is a reliable and responsive measure of outcome, and has been used in diverse clinical and interventional environments. Range is from 0 - 200. The higher the score, the worse the symptoms. | Baseline, week 24, week 48 | 
| Change From Baseline in WOMAC Pain Subscale Score | The WOMAC® Index questionnaire [33] is a tri-dimensional, disease-specific, self-administered, health status measure. It probes clinically important, patient-relevant symptoms in the areas of pain, stiffness and physical function in patients with osteoarthritis of the hip and/or knee. The WOMAC has been linguistically validated and is a reliable and responsive measure of outcome, and has been used in diverse clinical and interventional environments. WOMAC pain scores from 0-500 mm. The higher the score, the worse the symptoms. | Baseline, week 24, week 48 | 
| Change From Baseline in WOMAC Functional Limits Subscale Score | The WOMAC® Index questionnaire [33] is a tri-dimensional, disease-specific, self-administered, health status measure. It probes clinically important, patient-relevant symptoms in the areas of pain, stiffness and physical function in patients with osteoarthritis of the hip and/or knee. The WOMAC has been linguistically validated and is a reliable and responsive measure of outcome, and has been used in diverse clinical and interventional environments. Range is from 0 - 1700. The higher the score, the worse the symptoms. | Baseline, week 24, week 48 | 
| Change From Baseline in Total WOMAC Score | The WOMAC® Index questionnaire is a tri-dimensional, disease-specific, self-administered, health status measure. It probes clinically important, patient-relevant symptoms in the areas of pain, stiffness and physical function in patients with osteoarthritis of the hip and/or knee. The WOMAC has been linguistically validated and is a reliable and responsive measure of outcome, and has been used in diverse clinical and interventional environments. Range is from 0 - 2400. The higher the score, the worse the symptoms. | Baseline, week 24, week 48 | 
| Change From Baseline in Patient Global Assessment of Disease Status | A patient global assessment of disease status on a Visual Analog Scale (VAS) will be measured at each clinic visit. Patients will be asked to quantify their disease status on a 100 mm VAS as follows: Considering all the ways your arthritis of the knee affects you, mark 'X' on the scale for how well you are doing. The scale shows the left hand marker Very Well, and the right hand marker Very Poor. Range 0 to 100 mm. The higher the score, the worse the symptoms. | Baseline, week 24, week 48 | 
| Change From Baseline in Investigator Global Assessment of Disease Status | An investigator global assessment of disease status on a 100 mm VAS was measured at each clinic visit as follows: Make a global assessment of the patient's disease status, with regard to the index knee, by marking an 'X' on the scale below., with left hand marker Very Well and right hand marker Very Poor. Range 0 to 100 mm. The higher the score, the worse the symptoms. | Baseline, week 24, week 48 | 
| Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Constant Pain Subscale | This 11-item tool is designed to assess pain in individuals with knee osteoarthritis taking into account both constant and intermittent pain experiences. This tool is designed to be interviewer-administered. Study participants are asked to respond to the questionnaire items based on index knee in the past week (i.e., past 7-day period). Study participants responded to all questions for the same joint. This tool is intended to be responsive to change in OA pain over time or with treatment. Range 0 to 100 mm. The higher the score, the worse the symptoms. | Baseline, week 24, week 48 | 
| Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Intermittent Pain Subscale | This 11-item tool is designed to assess pain in individuals with knee osteoarthritis taking into account both constant and intermittent pain experiences. This tool is designed to be interviewer-administered and takes less than 10 minutes to complete. Study participants will be asked to respond to the questionnaire items based on index knee in the past week (i.e., past 7-day period). Study participants will respond to all questions for the same joint. This tool is intended to be responsive to change in OA pain over time or with treatment. Range 0 to 100 mm. The higher the score, the worse the symptoms. | Baseline, week 24, week 48 | 
| Change From Baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) Total Pain Score | This 11-item tool is designed to assess pain in individuals with knee osteoarthritis taking into account both constant and intermittent pain experiences. This tool is designed to be interviewer-administered and takes less than 10 minutes to complete. Study participants will be asked to respond to the questionnaire items based on index knee in the past week (i.e., past 7-day period). Study participants will respond to all questions for the same joint. This tool is intended to be responsive to change in OA pain over time or with treatment. Range 0 to 100 mm. The higher the score, the worse the symptoms. | Baseline, week 24, week 48 | 
| Number of Participants Discontinuing the Study Device Due to an Adverse Device Event | Difference between study groups in number of participants who discontinued usage of the study device due to adverse device events at 4, 8, 12, 24, 36, and 48-week visits. | Baseline, 4, 8, 12, 24, 36, and 48-week visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Knee Osteoarthritis, Pulsed Low Intensity Ultrasound