Dorsal Root Ganglion Stimulation for the Treatment of Arthritic Knee Pain

Study Overview
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Brief Summary
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Dorsal root ganglion stimulation (DRG-S) may be able to treat mechanical pain caused by tissue injury or damage such as trauma or arthritis in addition to pain caused by nerve dysfunction or injury. The purpose of this study is to determine if dorsal root ganglion stimulation (DRG-S) can effectively treat arthritic pain of the knee.

Detailed Description
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Dorsal root ganglion stimulation (DRG-S) is a novel form of neuromodulation used to treat chronic neuropathic pain of the groin and lower extremities related to complex regional pain syndrome type I or II (causalgia). DRG-S has shown promise in treating traditionally mixed neuropathic and mechanical pain syndromes such as axial low back pain, suggesting DRG-S may be able to treat mechanical pain in addition to neuropathic pain. Additionally, in a rodent model of osteoarthritis of the knee, DRG-S alleviated pain related behavior in rats. This open label feasibility study seeks to evaluate if dorsal root ganglion stimulation with Abbott's Proclaim Dorsal Root Ganglion Neurostimulator System can effectively treat osteoarthritis of the knee. Patients with either osteoarthritis of the non-operated knee or osteoarthritis of the surgically repaired knee will be trialed for one week with dorsal root ganglion stimulation to determine if they positively respond with 50% or greater pain relief. For those patients that have a successful trial, they will be implanted with a permanent stimulation device system and followed for one year post implant to measure knee pain, function and disability, and other related outcomes with sustained DRG-S therapy. Patients will be seen and evaluated prior to DRG-S trial, and for those that receive permanent implants, re-evaluated at 1, 3, 6, 9 and 12 months after implant.

Official Title
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Dorsal Root Ganglion Stimulation Outcomes for the Treatment of Mechanical Knee Pain Among Patients With Osteoarthritis of the Surgical and Non-surgical Knee

Conditions
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Knee Osteoarthritis, Knee Pain Chronic, Knee Arthritis, Knee Arthropathy

Intervention / Treatment
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* Device: Dorsal Root Ganglion Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 21 years old Able to provide informed consent Primary complaint of chronic knee pain for at least 1 year that interferes with functional activities Current pain score on visual analog scale (VAS) intensity ≥60 mm One of two groups: 1) Non-operated knee pain patients who want to pursue alternative therapies and delay surgery or are not candidates for knee arthroplasty based on age, frailty, non-operable condition, or poor outcome with other side arthroplasty, or 2) Post traumatic knee pain patients with history of surgical repair (such as meniscal or ligament repair). Radiologic confirmation (x-ray/MRI/CT) of Kellgren-Lawrence OA grade of 2 (mild) or 3 (moderate) or 4 (severe) noted within 6 months for the index knee Continued pain in the target knee despite at least 3 months of conservative treatments with documented failure of physical therapy and standard conservative therapy, including trials of at least two different classes of analgesic medication Failure of one or more prior interventional pain procedures such intraarticular corticosteroid or hyaluronidase knee injections, cooled radiofrequency ablation therapy, or regenerative medicine or prior surgery of the knee Exclusion Criteria: Non-English speaking Douleur neuropathique 4 (DN4) score ≥4 Receiving opioid analgesic medication at a dose of ≥90 mg oral morphine equivalents Workers' compensation or no-fault insurance Signs or symptoms of active infection in the index knee joint Pregnancy BMI >45 Presence of any contraindication for DRG stimulation, including neurological, medical, psychiatric, or social conditions. Widespread pain conditions like fibromyalgia Autoimmune/Inflammatory arthritic conditions such as Rheumatoid and psoriatic arthritis and other allied disorders (sjogren, felty, inflammatory bowl disease etc) Collagen diseases (systemic lupus erythematosus, Scleroderma, etc) Infectious arthritis Evidence of prespecified joint safety conditions (eg, rapidly progressive OA, subchondral insufficiency fracture, osteonecrosis, pathologic fracture) in the index knee on screening radiographs Scheduled for or anticipating any surgery during the trial period

Ages Eligible for Study
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Minimum Age: 21 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will undergo one week DRG-S trial, and for those that respond as defined by 50% or greater pain relief, proceed to DRG-S permanent device system implant
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-operated Knee Osteoarthritis<br>DRG-S for knee osteoarthritis patients with no history of knee surgery | Device: Dorsal Root Ganglion Stimulation<br>* Stimulation at L2, L3, L4 and S1 spinal levels<br>|
| Experimental: Surgically Repaired Knee Osteoarthritis<br>DRG-S for knee osteoarthritis patients with history of surgical repair of the knee | Device: Dorsal Root Ganglion Stimulation<br>* Stimulation at L2, L3, L4 and S1 spinal levels<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment success rate at 3 months | Percent of DRG-S implanted patients that successfully respond to stimulation therapy as defined by >=50% reduction in reported pain score from baseline | 3 months post-implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VAS pain scores | Patient's pain score using standard 10cm pain scale that represents a continuum between no pain and worst pain. | 1-, 3-, 6-, 9-, and 12 months post-implant | 
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) for knee pain patients | At each study visit, subjects will complete WOMAC survey which assesses pain, stiffness, and function in patients with OA of the knee. | 1-, 3-, 6-, 9-, and 12 months post-implant | 
| European Quality of Life 5 Dimension (EQ-5D) | At each study visit, subjects will complete EQ-5D survey which assesses health-related quality of life | 1-, 3-, 6-, 9-, and 12 months post-implant | 
| Short Form 36 Mental Component Summary (SF-36 MCS) | At each study visit, subjects will complete SF-36 MCS survey which assesses mental health | 1-, 3-, 6-, 9-, and 12 months post-implant | 
| Pain Disability Index (PDI) | At each study visit, subjects will complete PDI survey which assesses pain-related disability | 1-, 3-, 6-, 9-, and 12 months post-implant | 
| Patient Global Impression of Change (PGIC) | At each study visit, subjects will complete PDI survey which assesses patient's belief about the efficacy of treatment | 1-, 3-, 6-, 9-, and 12 months post-implant | 
| Medication Dosage | Patient's dose of narcotic analgesics measured in morphine milligram equivalents (MME) and non-narcotic analgesics and dosages | 1-, 3-, 6-, 9-, and 12 months post-implant | 
| Timed Up and Go (TUG) | Video recordings of motor task exams will be used to measure TUG, a performance-based measure of functional mobility which measures the time for subject to rise from a chair, walk three meters, turn around, return to the chair, and sit down. | 1-, 3-, 6-, 9-, and 12 months post-implant | 
| Knee Range of Motion (ROM) | Video recordings of motor task exams will be used to measure ROM of the index knee | 1-, 3-, 6-, 9-, and 12 months post-implant | 
| Serum concentrations of molecular biomarkers | Serum concentrations of molecular biomarkers related to knee OA including but not limited to C-telopeptide of crosslinked collagen type I and type II (CTX-I and CTX-II) | 3-, 6-, and 12-months post-implant | 
| Kellgren-Lawrence System for Classification of Osteoarthritis | Radiologic classification of subject's knee x-ray to grade progression/severity of osteoarthritis | 6- and 12-months post-implant | 
| Treatment success rate at other post-implant timepoints | Percent of DRG-S implanted patients that successfully respond to stimulation therapy as defined by >=50% reduction in reported pain score from baseline | 1-, 6-, 9-, and 12-months post-implant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dorsal Root Ganglion Stimulation, knee pain, knee arthritis, osteoarthritis