Artery Embolization vs Nerve Ablation for Knee Osteoarthritis

Overseen By David Clinkard, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: David Clinkard

Must not be taking: Immunosuppressants

Disqualifiers: Infection, Autoimmune diseases, Vascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 1 day

150 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the study involves patients with knee osteoarthritis resistant to non-surgical treatment, it might be possible to continue some medications. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of this treatment for knee osteoarthritis?

Research shows that genicular nerve ablation and genicular artery embolization are promising treatments for knee osteoarthritis pain, especially in patients who do not respond to other treatments. Studies indicate that these methods can help reduce pain by targeting specific nerves or blood vessels in the knee. ^{1 2 3 4 5}

Is genicular artery embolization or nerve ablation safe for humans?

Genicular artery embolization (GAE) is generally safe for treating knee pain from osteoarthritis, with adverse events being uncommon when the procedure is done carefully. The safety of chemical ablation of the genicular nerve with phenol has not been thoroughly examined, but it is being studied for its potential use in pain relief for knee osteoarthritis. ^{1 3 6 7 8}

How is the treatment for knee osteoarthritis using artery embolization and nerve ablation different from other treatments?

This treatment is unique because it combines genicular artery embolization (GAE), which blocks blood flow to reduce inflammation and pain, with genicular nerve ablation, which targets and disrupts pain signals from the nerves around the knee. Unlike traditional treatments that may focus on medication or surgery, this approach directly addresses both blood supply and nerve pathways to provide potentially long-lasting pain relief. ^{1 3 7 9 10}

What is the purpose of this trial?

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.

Research Team

Steve Mann, MD

Principal Investigator

Queen's University

David Clinkard, MD

Principal Investigator

Queen's University

Alexandre Menard, MD

Principal Investigator

Queen's University

Eligibility Criteria

This trial is for people over 40 with knee pain from osteoarthritis, who haven't improved after at least 3 months of non-surgical treatments and are considering knee replacement surgery. They must be able to follow the study plan and attend all check-ups.

Inclusion Criteria

I am over 40 years old.

I have had knee pain from arthritis for over 6 months.

Able to provide informed consent

Exclusion Criteria

My kidney function is low, with a GFR less than 30 in the last 60 days.

I have a condition like rheumatoid arthritis, Lupus, or MS.

I am currently on medication that weakens my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline assessment including WOMAC and NRS scores, MRI, and synovial fluid analysis

1 week

1 visit (in-person)

Treatment

Participants receive either genicular artery embolization, genicular nerve phenol nerve ablation, or a sham procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with WOMAC and NRS scores, MRI, and synovial fluid analysis

24 months

Phone follow-ups every 6 months, in-person visits at 3 months

Treatment Details

Interventions

• Genicular nerve phenol nerve ablation
• Geniculate artery embolization

Trial Overview The GENI study tests if genicular artery embolization (GAE) or genicular nerve phenol ablation (PNA) can relieve osteoarthritis symptoms better than a sham procedure. Patients will be randomly assigned to one of these three options.

Participant Groups

Group I: Genicular artery embolization Active Control 1 Intervention

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 II: Genicular nerve phenol nerve ablation Active Control 1 Intervention

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 III: Sham procedure Placebo Group 1 Intervention

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.

Genicular nerve phenol nerve ablation is already approved in United States, European Union for the following indications:

Approved in United States as Genicular nerve ablation for:

• Investigational for knee osteoarthritis pain relief

Approved in European Union as Genicular nerve ablation for:

• Not approved for routine use; considered investigational for knee osteoarthritis pain relief

Who Is Running the Clinical Trial?

David Clinkard

Lead Sponsor

Trials

1

Recruited

150+

David Clinkard

Lead Sponsor

Trials

1

Recruited

150+

Queen's University

Collaborator

Trials

382

Recruited

122,000+

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Queen's University

Collaborator

Findings from Research

A new 3-needle technique for genicular nerve ablation in patients with chronic knee osteoarthritis showed significantly better pain relief and improved knee function compared to the traditional single-needle method, based on a study of 50 patients.

The 3-needle approach resulted in higher patient satisfaction at all follow-up points (2 weeks, 1, 3, and 6 months) without any reported adverse events, indicating it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three Needles Approach-A New Technique of Genicular Nerves Radiofrequency Ablation for Pain Relief in Advanced Chronic Knee Osteoarthritis: A Randomized Trial. Mohamed, OS., Omar, SM., Gaber, AF., et al.[2021]

Genicular artery embolization (GAE) is an effective minimally invasive treatment for knee pain due to osteoarthritis, showing significant reductions in pain scores at 1, 3, 6, and 12 months after the procedure, based on a systematic review of 10 studies involving 351 treated knees.

Patients experienced substantial declines in pain, with a Hedge's g effect size indicating strong pain relief, particularly at 6 months with a score decrease of 41 points on the Visual Analog Scale, demonstrating GAE's potential as a durable pain management option for osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genicular Artery Embolization as a Treatment for Osteoarthritis Related Knee Pain: A Systematic Review and Meta-analysis. Epelboym, Y., Mandell, JC., Collins, JE., et al.[2023]

In a study of 21 patients with mild to moderate knee osteoarthritis, genicular artery embolization (GAE) significantly reduced pain and disability compared to a sham procedure, with notable improvements observed at 1 month.

Only minor adverse events were reported, indicating that GAE is a safe intervention for treating knee pain associated with osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Randomized Sham Controlled Study of Genicular Artery Embolization for Knee Pain Secondary to Osteoarthritis. Bagla, S., Piechowiak, R., Sajan, A., et al.[2022]

Genicular artery embolisation (GAE) is a promising treatment for knee osteoarthritis, and understanding the anatomy of the genicular arteries is crucial for ensuring the safety and effectiveness of the procedure, as demonstrated by a detailed dissection of 20 human lower limb specimens.

The study found that the descending genicular artery (DGA) is the primary vessel involved in medial osteoarthritis, with significant risks of non-target embolisation (NTE) due to anastomoses between key arteries, highlighting the need for careful planning during GAE to avoid damaging critical structures like the cruciate ligaments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cadaveric and Angiographic Anatomical Considerations in the Genicular Arterial System: Implications for Genicular Artery Embolisation in Patients with Knee Osteoarthritis. O'Grady, A., Welsh, L., Gibson, M., et al.[2021]

Genicular artery embolization (GAE) shows promise as a treatment for knee osteoarthritis, with pain being the most commonly reported outcome in 95.8% of the 24 studies reviewed.

However, the studies exhibit significant variability in design and methodology, which limits the ability to draw strong conclusions about the efficacy and safety of GAE, highlighting the need for more standardized research protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common Design, Data Elements and Core Outcome Measures Reported on Clinical Trials of Genicular Artery Embolization for Knee Osteoarthritis: An Interactive Systematic Review. Bolsegui, ML., Ghozy, S., Kobeissi, H., et al.[2023]

Both genicular nerve neurolysis with phenol and radiofrequency ablation (RFA) effectively reduce pain in patients with chronic knee osteoarthritis, with significant pain relief observed at 1 week, 1 month, and 3 months after treatment.

While both techniques showed similar efficacy in pain relief, phenol neurolysis resulted in a higher rate of transient paresthesia (34.4%) compared to RFA (6.3%), suggesting that RFA may have a better safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy of genicular nerve phenol neurolysis and radiofrequency ablation for pain management in patients with knee osteoarthritis. Yildiz, G., Perdecioglu, GRG., Yuruk, D., et al.[2023]

Genicular artery embolization (GAE) is a safe and effective treatment for knee pain caused by osteoarthritis, offering long-lasting pain relief for many patients.

Successful GAE requires careful attention to procedural techniques, including understanding arterial anatomy and avoiding complications, but when performed correctly, adverse events are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genicular Artery Embolization Technique. Sterbis, E., Casadaban, L.[2023]

In a study of 43 patients with chronic knee osteoarthritis pain, ultrasound-guided chemical neurolysis using phenol significantly reduced pain intensity from an average of 7.2 to 4.2 on the Numeric Rating Scale over 6 months.

The treatment also led to substantial functional improvement, as indicated by a decrease in the WOMAC score from 48.7 to 20.7, with only temporary mild adverse effects such as local pain and swelling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemical Ablation of Genicular Nerve with Phenol for Pain Relief in Patients with Knee Osteoarthritis: A Prospective Study. Risso, RC., Ferraro, LHC., Nouer Frederico, T., et al.[2021]

A study of 205 patients who underwent genicular artery embolization (GAE) revealed that the anatomy of the genicular arteries is complex, with various branching patterns identified, which is crucial for effective treatment of knee osteoarthritis.

Using cone-beam computed tomography (CBCT) during the procedure allows for better visualization of these arteries, helping to accurately target the right vessels for embolization and reducing the risk of affecting unintended areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classification of Genicular Artery Anatomic Variants Using Intraoperative Cone-Beam Computed Tomography. Callese, TE., Cusumano, L., Redwood, KD., et al.[2023]

Genicular artery embolization (GAE) is a safe and effective treatment for symptomatic knee osteoarthritis, with a 100% technical success rate and no major adverse events reported in a study of 16 patients.

At the 12-month follow-up, 83% of patients achieved a clinically meaningful reduction in pain, and there was a significant decrease in nerve growth factor levels, which may help explain the pain relief and potential slowing of cartilage degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genicular Artery Embolization for Treatment of Knee Osteoarthritis: Interim Analysis of a Prospective Pilot Trial Including Effect on Serum Osteoarthritis-Associated Biomarkers. Taslakian, B., Swilling, D., Attur, M., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Three Needles Approach-A New Technique of Genicular Nerves Radiofrequency Ablation for Pain Relief in Advanced Chronic Knee Osteoarthritis: A Randomized Trial. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Genicular Artery Embolization as a Treatment for Osteoarthritis Related Knee Pain: A Systematic Review and Meta-analysis. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Multicenter Randomized Sham Controlled Study of Genicular Artery Embolization for Knee Pain Secondary to Osteoarthritis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Cadaveric and Angiographic Anatomical Considerations in the Genicular Arterial System: Implications for Genicular Artery Embolisation in Patients with Knee Osteoarthritis. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Common Design, Data Elements and Core Outcome Measures Reported on Clinical Trials of Genicular Artery Embolization for Knee Osteoarthritis: An Interactive Systematic Review. [2023]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy of genicular nerve phenol neurolysis and radiofrequency ablation for pain management in patients with knee osteoarthritis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Genicular Artery Embolization Technique. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Chemical Ablation of Genicular Nerve with Phenol for Pain Relief in Patients with Knee Osteoarthritis: A Prospective Study. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Classification of Genicular Artery Anatomic Variants Using Intraoperative Cone-Beam Computed Tomography. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Genicular Artery Embolization for Treatment of Knee Osteoarthritis: Interim Analysis of a Prospective Pilot Trial Including Effect on Serum Osteoarthritis-Associated Biomarkers. [2023]