MRgFUS in the Treatment of Osteoarthritic Knee Pain

Study Overview
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Brief Summary
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A double-blind placebo-controlled randomized clinical trial to evaluate the efficacy of magnetic resonance-guided focused ultrasound surgery (MRgFUS) in the treatment of pain caused by knee osteoarthritis (OA)

Detailed Description
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Osteoarthritis (OA) is a common, disabling, and costly disease, and the knee is one of the most affected joints. The predominant symptom is pain. Effective and lasting non-invasive treatment approaches are missing. MR-guided focused ultrasound surgery (MRgFUS) is a new minimally invasive technique which may represent a valid solution providing several advantages. The primary aim of this work will be to assess the efficacy of MRgFUS in the treatment of pain caused by knee OA in 80 patients candidate for arthroplasty in a prospective, randomized, double-blinded, placebo-controlled clinical trial. Different parameters related to pain, quality of life, function, and imaging will be collected and analyzed in a 12-month follow-up. The secondary aims will be focused on a) the evaluation of the effects on the joint organ and changes of biological features in response to MRgFUS, and b) the impact of selective ablation of nociceptors on OA pain, based on the analysis of resected joint tissues.

Official Title
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Pain in Knee Osteoarthritis, a Placebo-controlled Randomized Clinical Trial for a New Potential Therapeutic Approach: Magnetic Resonance Guided Focused Ultrasound Surgery (MRgFUS)

Conditions
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Osteo Arthritis Knee, Osteoarthritis, Osteoarthritis, Knee

Intervention / Treatment
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* Device: MRgFUS Treatment
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female aged 50-80 years Activity-related joint pain Patients who have not responded to previous treatments and patients candidate for surgery Kellgren-Lawrence score 2-4 on X-rays Patients able to give their informed consent Exclusion Criteria: Prior surgery in the past 12 months or previous local treatment in the past 3 months Changes in medications used during the previous 2 months Corticosteroid use for more than 3 months within the preceding year Rheumatologic and neurological disorders Fibromyalgia Trauma, fracture or osteomyelitis of the investigated joints within the preceding year Pregnancy Patients with large scars potentially included in the ultrasound beam path General contraindications to MRI and/or to anaesthesiological procedures Presence of internal hardware or device potentially affecting MR thermometry Patients involved in other clinical studies

Ages Eligible for Study
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Minimum Age: 50 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
Interventional Model Description: Double-blind placebo-controlled randomized clinical trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>MRgFUS treatment of pain caused by knee osteoarthritis | Device: MRgFUS Treatment<br>* Treatment of pain caused by knee osteoarthritis with high-intensity focused ultrasound<br>|
| Placebo Comparator: Placebo<br>Procedures in the placebo group will be identical to procedures in the active group, except no sonications (ultrasound emission) will be used. | Other: Placebo<br>* Procedures in the placebo group will be identical to procedures in the active group, except no sonications (ultrasound emission) will be used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of MRgFUS in the treatment of pain caused by knee OA | The efficacy of MRgFUS will be demonstrated if the treatment group has a mean reduction of Visual Analog Pain Scale (VAS) of at least 1.5 points greater than the control group. | Baseline (Day 1), 24 hours post MRgFUS, Week 1, 2, 3, Month 1, 3, 6,12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of MRgFUS on the joint organ: inflammation | Enzyme linked immuno assays kits will be used to test inflammatory markers in serum. The reference standard values of the standardized markers will be considered for the evaluations. | Baseline (Day 1), 24 hours post MRgFUS, Month 1, 3, 6,12 | 
| Effects of MRgFUS on the joint organ: bone turnover | Enzyme linked immuno assays kits will be used to test bone turnover markers in serum. The reference standard values of the standardized markers will be considered for the evaluations. | Baseline (Day 1), 24 hours post MRgFUS, Month 1, 3, 6,12 | 
| Effects of MRgFUS on the joint organ: pain | Enzyme linked immuno assays kits will be used to test pain markers in serum. The reference standard values of the standardized markers will be considered for the evaluations. | Baseline (Day 1), 24 hours post MRgFUS, Month 1, 3, 6,12 | 
| Effects of MRgFUS on the joint organ: cartilage turnover | Enzyme linked immuno assays kits will be used to test cartilage turnover markers in urine. The reference standard values of the standardized markers will be considered for the evaluations. | Baseline (Day 1), 24 hours post MRgFUS, Month 1, 3, 6,12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Knee, MRgFUS, ExAblate, Pain, High-Intensity Focused Ultrasound Ablation