Genicular Artery Embolization vs Nerve Ablation Intervention (GENI) for Knee Osteoarthritis

NCT ID: NCT06166628

Last Updated: 2023-12-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-01
• Study Completion Date: 2026-12-31

Brief Summary

The genicular artery embolization vs nerve ablation intervention (GENI) knee OA study is a three-arm randomized controlled trial to evaluate symptoms of knee osteoarthritis (OA) in patients after receiving one of three interventions: sham procedure, geniculate artery embolization (GAE) or genicular nerve phenol nerve ablation (PNA).

The main question[s] the study aims to answer are:

• Does GAE or genicular nerve PNA result in OA symptom alleviation compared to sham procedure?
• Are there molecular or imaging biomarkers that aid in predicting treatment response for GAE or genicular nerve PNA?

Subjects (N=150) patients with knee OA, resistant to non-surgical treatment for at least 3 months will be randomized 1:1:1 to either after GAE, genicular nerve PNA or sham procedure. Clinical outcomes will be measured using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and 11-point numerical rating scale (NRS) for pain completed at baseline, 1 month, 3 months, and 6 months and then every 6 months for either two years or until the time of total knee arthroplasty (TKA) surgery.

Detailed Description

Osteoarthritis (OA) of the knee is a common and debilitating disease. Advanced disease can be treated with total knee arthroplasty (TKA), however knee OA that is either resistant to non-surgical options, or where surgical options are not available, represents a specific management challenge. Genicular artery embolization (GAE) and genicular nerve phenol nerve ablation (PNA) have emerged as potentially successful treatments to reduce knee OA symptoms, however, to date no randomized controlled trials have been completed comparing the two procedures.

The purpose of this study is to compare the clinical outcomes of GAE to genicular nerve PNA for chronic knee pain in patients with knee OA. Further, molecular biomarkers and imaging will be taken pre- and post-procedure to evaluate if immune-mediated neuroinflammation and angiogenesis can be helpful in predicting treatment response.

This single center randomized controlled trial will be conducted to determine if GAE, genicular nerve PNA, or sham procedure is associated with a clinically significant alleviation of knee OA symptoms. The investigators aim to include 150 participants in this study over the course of 24 months randomized 1:1:1 to receive either GAE, genicular nerve PNA, or sham procedure.

After eligibility is confirmed and consent is obtained, a baseline assessment will be conducted including baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and 11-point numerical rating scale (NRS) for pain scores. Participants will receive a knee 3T MRI with gadolinium contrast and 0.5 - 5 mL of synovial fluid will be aspirated for baseline analysis. Participants will receive Fitbit motion trackers to quantify activity levels throughout the study.

Study procedures will be performed by either a qualified Interventional Radiologist or fellowship-trained Anesthesiologist, depending on which study arm subjects randomized to.

Approximately 3 months after the procedure, repeat WOMAC and NRS scores will be obtained, in addition to repeat 3T MRI with gadolinium contrast and knee aspirate of 0.5 - 5 mL of synovial fluid. Additional questions pertaining to knee-specific analgesia use, adverse events from the procedure, or any concerns will be addressed and noted at this time.

Participants will be followed up by phone by a blinded member of the research team 6 months after the procedure and every 6 months thereafter for 2 years or until the time of TKA surgery (if applicable). During phone calls, questions relating to knee-specific analgesia use will be asked and repeat WOMAC and NRS scores will be acquired.

Data for this study includes: demographic information, knee-specific analgesia use, which procedure was performed, knee 3T MRI with gadolinium contrast, WOMAC scores, NRS pain scores, knee synovial fluid cytokine/chemokine biomarker analysis, and procedure-specific adverse events.

Conditions

Knee Osteoarthritis

Keywords

Artery embolization; Nerve ablation; Genicular Artery Embolization

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Genicular artery embolization

Genicular artery embolization will be performed by board certified Interventional Radiologists in the interventional radiology angiography suite at Kingston General Hospital. Patients will be blinded to which procedure they have been randomized too, careful language will be used by the clinical and research team throughout the procedure to not compromise the blinding. Patients will be positioned supine on the procedure table. The affected knee will be prepped and draped using standard sterile technique and 1-2cc of 1% lidocaine will be administered to the area for local anesthetic. A drape will be placed such that the patient is unable to see the affected knee during the procedure. Geniculate artery embolization will be performed via an intraarterial access and use of embolization microspheres injected into the hypervascular arteries feeding the knee joint.

Group Type: ACTIVE_COMPARATOR

Geniculate artery embolization

Intervention Type: PROCEDURE

Femoral arterial access will be obtained under ultrasound guidance. An angiographic catheter will then be advanced to the distal superficial femoral artery. Angiography will be performed to identify the appropriate genicular branches supplying the regions of hyperemia. A microcatheter (1.7-2.4-French) will then be advanced super-selectively into the genicular arteries and 100-300 um EmboSpheres (Merit Medical) will be injected under fluoroscopic guidance. Multiple geniculate arteries may be embolized until neovascularity is no longer seen and pathologic hyperemia is resolved. A repeat lower extremity angiogram will be performed to evaluate for success of embolization and to exclude complication. The catheter and sheath will then be removed, and hemostasis will be achieved using an AngioSeal (Terumo Vascular Interventions) vascular closure device.

Genicular nerve phenol nerve ablation

Genicular nerve phenol nerve ablation All procedures will be performed by a fellowship trained interventional pain physician in a fluoroscopy suite in Hotel Dieu Hospital using sterile precautions. Patients will be blinded to which procedure they have been randomized too, careful language will be used by the clinical and research team throughout the procedure to not compromise the blinding. IV access and saline lock obtained per our usual clinic protocol. Patients will be positioned supine on the procedure table. The affected knee will be prepped and draped using standard sterile technique and 1-2cc of 1% lidocaine will be administered to the area for local anesthetic. Phenol nerve ablation will be performed via ultrasound guidance.

Group Type: ACTIVE_COMPARATOR

Genicular nerve phenol nerve ablation

Intervention Type: PROCEDURE

A high frequency ultrasound probe and anatomic landmarks will be used to identify the location of the genicular nerves as well as the nerves to the vastus lateralis, vastus intermedius and vastus medialis. Utilizing an in or out of plane approach as necessary, a 25 g spinal needle will be advanced to the appropriate location after skin anesthesia with 1cc of 1% lidocaine. After negative aspiration, 2 cc of 6% phenol will be injected at each location with an end target of fascial expansion under the relevant fascial plane.

Sham procedure

The sham procedure will be performed by a fellowship trained interventional pain physician in a fluoroscopy suite in Hotel Dieu Hospital using sterile precautions. Patients will be blinded to which procedure they have been randomized too, careful language will be used by the clinical and research team throughout the procedure to not compromise the blinding. IV access and saline lock obtained per our usual clinic protocol. The patient will be placed supine, and the appropriate knee prepped and draped using appropriate sterile technique . A drape will be placed such that the patient is unable to see the affected knee during the procedure.

Group Type: SHAM_COMPARATOR

Skin infiltration of 2cc of 0.25% bupivacaine at the knee

Intervention Type: PROCEDURE

A high frequency ultrasound probe and anatomic landmarks will be used to identify the location of the genicular nerves as well as the nerves to the vastus lateralis, vastus intermedius and vastus medialis will be identified. Utilizing an in or out of plane approach as necessary, a 25 g spinal needle will be advanced to the appropriate location after skin anesthesia with 1cc of 1% lidocaine. After negative aspiration, 1.5 cc of sterile saline will then be injected at each location.

Interventions

Geniculate artery embolization

Femoral arterial access will be obtained under ultrasound guidance. An angiographic catheter will then be advanced to the distal superficial femoral artery. Angiography will be performed to identify the appropriate genicular branches supplying the regions of hyperemia. A microcatheter (1.7-2.4-French) will then be advanced super-selectively into the genicular arteries and 100-300 um EmboSpheres (Merit Medical) will be injected under fluoroscopic guidance. Multiple geniculate arteries may be embolized until neovascularity is no longer seen and pathologic hyperemia is resolved. A repeat lower extremity angiogram will be performed to evaluate for success of embolization and to exclude complication. The catheter and sheath will then be removed, and hemostasis will be achieved using an AngioSeal (Terumo Vascular Interventions) vascular closure device.

Intervention Type: PROCEDURE

Genicular nerve phenol nerve ablation

A high frequency ultrasound probe and anatomic landmarks will be used to identify the location of the genicular nerves as well as the nerves to the vastus lateralis, vastus intermedius and vastus medialis. Utilizing an in or out of plane approach as necessary, a 25 g spinal needle will be advanced to the appropriate location after skin anesthesia with 1cc of 1% lidocaine. After negative aspiration, 2 cc of 6% phenol will be injected at each location with an end target of fascial expansion under the relevant fascial plane.

Intervention Type: PROCEDURE

Skin infiltration of 2cc of 0.25% bupivacaine at the knee

A high frequency ultrasound probe and anatomic landmarks will be used to identify the location of the genicular nerves as well as the nerves to the vastus lateralis, vastus intermedius and vastus medialis will be identified. Utilizing an in or out of plane approach as necessary, a 25 g spinal needle will be advanced to the appropriate location after skin anesthesia with 1cc of 1% lidocaine. After negative aspiration, 1.5 cc of sterile saline will then be injected at each location.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age > 40 years
• Able to provide informed consent
• Knee pain due to osteoarthritis for at least 6 months
• Pain refractory to conservative therapies (oral medication, or physical therapy, or activity modification) for at least 3 months with a desire for TKA
• Candidate for TKA at Hotel Dieu Hospital Site
• Able to comply with all treatments and protocol follow-up visits

Exclusion Criteria

• Current local infection
• Systemic or joint centered inflammatory disease (ie rheumatoid arthritis, Lupus, multiple sclerosis or other autoimmune diseases)
• Current use of systemic immunosuppression therapy
• Known lower extremity vascular disease or lower extremity symptoms thought to be secondary to arterial vascular disease (eg claudication, ischemic rest pain)
• Irreversible coagulopathy
• Renal dysfunction as defined by GFR (eGFR) of <30 obtained within the past 60 days
• Contraindication for MR Imaging (such as claustrophobia, metallic fragment or foreign bones, implants or prosthesis)
• IV CT and/or MRI contrast allergy characterized by anaphylaxis or anaphylactoid reactions
• Pregnancy or women of childbearing potential not currently on a medically acceptable method of birth control

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Queen's University

OTHER

Sponsor Role: collaborator

David Clinkard

OTHER

Sponsor Role: lead

Responsible Party

David Clinkard

Anesthesiologist, Department of Anesthesiology and Perioperative Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David Clinkard, MD

Role: PRINCIPAL_INVESTIGATOR

Queen's University

Alexandre Menard, MD

Role: PRINCIPAL_INVESTIGATOR

Queen's University

Steve Mann, MD

Role: PRINCIPAL_INVESTIGATOR

Queen's University

Locations

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

David Clinkard, MD

Role: CONTACT

Phone: 613-549-6666

Email: david.clinkard@kingstonhsc.ca

Facility Contacts

David Clinkard, MD

Role: primary

Other Identifiers

6038931

Identifier Type: -

Identifier Source: org_study_id