Dorsal Root Ganglion Stimulation for the Treatment of Arthritic Knee Pain

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

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.

Study Overview

• Status: Recruiting
• Conditions: Knee Osteoarthritis; Knee Arthritis; Knee Arthropathy; Knee Pain Chronic
• Intervention / Treatment: Device: Dorsal Root Ganglion Stimulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kenneth B Chapman, MD; Phone Number: 7186673577; Email: chapmanken@spinepainny.com
• Study Contact Backup: Name: Tariq a Yousef, MD; Phone Number: 7186673577; Email: tyousef@spinepainny.com

Study Locations

• United States
  • New York
    • New York, New York, United States, 10305
      • Recruiting
      • The Spine and Pain Institute of New York
      • Contact: Ahmad Amireh, BS; Phone Number: 718-667-3577; Email: tyousef@spinepainny.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	All complications of DRG-S trial, implant, and stimulation therapy will be reported	Up to 12 months post-implant

Collaborators and Investigators

• Sponsor: Kenneth B Chapman
• Collaborators: Abbott

Publications and helpful links

General Publications

• Yu G, Segel I, Zhang Z, Hogan QH, Pan B. Dorsal Root Ganglion Stimulation Alleviates Pain-related Behaviors in Rats with Nerve Injury and Osteoarthritis. Anesthesiology. 2020 Aug;133(2):408-425. doi: 10.1097/ALN.0000000000003348.
• Bjerre-Bastos JJ, Bay-Jensen A-C, Karsdal MA, Byrjalsen I, Andersen JR, Riis BJ, et al. Biomarkers of bone and cartilage turnover CTX-I and CTX-II predict total joint replacements in osteoarthritis. Osteoarthr Cartil [Internet]. 2019;27(2019):S31-2. Available from: https://doi.org/10.1016/j.joca.2019.02.046
• Convill JG, Tawy GF, Freemont AJ, Biant LC. Clinically Relevant Molecular Biomarkers for Use in Human Knee Osteoarthritis: A Systematic Review. Cartilage. 2021 Dec;13(1_suppl):1511S-1531S. doi: 10.1177/1947603520941239. Epub 2020 Jul 17.
• Adhikary SD, Liu WM, Memtsoudis SG, Davis CM 3rd, Liu J. Body Mass Index More Than 45 kg/m(2) as a Cutoff Point Is Associated With Dramatically Increased Postoperative Complications in Total Knee Arthroplasty and Total Hip Arthroplasty. J Arthroplasty. 2016 Apr;31(4):749-53. doi: 10.1016/j.arth.2015.10.042. Epub 2015 Nov 10.
• van Bussel CM, Stronks DL, Huygen FJPM. Dorsal Column Stimulation vs. Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome Confined to the Knee: Patients' Preference Following the Trial Period. Pain Pract. 2018 Jan;18(1):87-93. doi: 10.1111/papr.12573. Epub 2017 May 4.
• Kallewaard JW, Edelbroek C, Terheggen M, Raza A, Geurts JW. A Prospective Study of Dorsal Root Ganglion Stimulation for Non-Operated Discogenic Low Back Pain. Neuromodulation. 2020 Feb;23(2):196-202. doi: 10.1111/ner.12937. Epub 2019 Mar 1.
• Huygen F, Liem L, Cusack W, Kramer J. Stimulation of the L2-L3 Dorsal Root Ganglia Induces Effective Pain Relief in the Low Back. Pain Pract. 2018 Feb;18(2):205-213. doi: 10.1111/papr.12591. Epub 2017 Dec 6.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): May 31, 2024
• Study Completion (Anticipated): May 31, 2024

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: November 1, 2021
• First Posted (Actual): November 2, 2021

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: osteoarthritis; knee pain; knee arthritis; Dorsal Root Ganglion Stimulation
• Additional Relevant MeSH Terms: Neoplasms; Cysts; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Mucinoses; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Ganglion Cysts
• Other Study ID Numbers: DRG-S for Knee OA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes