Fluoroscopic Versus Ultrasound Guidance for Cooled Radiofrequency Ablation of Geniculate Nerves in Knee Osteoarthritis: A Randomized Control Trial

Sponsor

University of Florida (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04472702

Collaborator

American Medical Society for Sports Medicine Collaborative Research Network (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

3.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Cooled radiofrequency ablation (cRFA) of the knee geniculate nerves is a promising treatment option for knee osteoarthritis, but has variable efficacy. Fluoroscopy is the typical guidance of choice, but uses bony landmarks to target these nerves which have variable positions around the knee. Alternatively, ultrasound allows for targeting based on visualization of bony landmarks, the nerves, and their accompanying vascular structures, and thus may offer greater accuracy. However, there are few studies which directly compare the clinical efficacy of these two guidance options. This study will compare these two options.

Condition or Disease	Intervention/Treatment	Phase
Knee Osteoarthritis	Procedure: cRFA	N/A

Detailed Description

Background: Cooled radiofrequency ablation (cRFA) of the knee geniculate nerves is a promising treatment option for knee osteoarthritis, but has variable efficacy. Fluoroscopy is the typical guidance of choice, but uses bony landmarks to target these nerves which have variable positions around the knee. Alternatively, ultrasound allows for targeting based on visualization of bony landmarks, the nerves, and their accompanying vascular structures, and thus may offer greater accuracy. However, there are few studies which directly compare the clinical efficacy of these two guidance options. Objective: To compare the effectiveness of geniculate nerve cRFA on knee osteoarthritis outcomes when using either ultrasound or fluoroscopic guidance. The primary outcome measures will be patient pain levels and patient-reported function. The secondary outcome measures will be objective performance-based functional outcomes. The exploratory outcome measures will be blood biomarkers of inflammation, extracellular matrix turnover, and cartilage degradation. Methods: Knee osteoarthritis patients (Kellegren-Lawrence Scale 2-4) that have been refractory to conservative treatments and report at least 80% pain relief with diagnostic geniculate nerve blocks will be enrolled and randomized to fluoroscopic (N=45) or ultrasound (N=45) cRFA treatment arms. Baseline assessments will include 1) Numeric Pain Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, and PROMIS depression and pain interference measures; 2) the Osteoarthritis Research Society International recommended physical performance assessments including the 30-Second Chair Stand Test, Stair Climb Test, 40m Fast Paced Walk Test, Timed Up and Go Test, and Six Minute Walk Test; and 3) in a subset of patients (N=24), blood biomarkers including MMP-3, IL-1β, TNF-α, COMP, and CTX-II. These measures will be re-assessed at one month (pain and patient-reported function only, via phone contact), three months, and 6 months after the cRFA procedure. Study endpoints will be assessed using a mixed model repeated measures analysis of variance using an alpha level of 0.05. Statement of Relevance: Knee osteoarthritis patients are commonly treated by sports medicine providers, who are typically well-trained in the use of ultrasound. Should ultrasound be demonstrated as effective for cRFA, sports medicine providers would be well-positioned to use relatively low-cost and accessible imaging technology to significantly improve patient pain and function using cRFA.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants (N=90; 45 at each site) will be randomized with equal probability to either treatment group, restricted by equal enrollment and equal distribution at each site. Patients will be enrolled for the exploratory aim separately at the University of Florida site only. After enrollment into the main study (primary and secondary aims), subjects at the UF site will be offered enrollment into the exploratory aim (N=24) on a consecutive basis restricted by equal enrollment into each treatment arm. A random number table will be used for group allocation and the values recorded separately into opaque, sealed envelopes. This will be performed by a clinical coordinator who is not involved in study to ensure allocation concealment. Outcomes for the primary, secondary, and exploratory aims will be completed by research staff who are blinded to the subject treatment allocation. Data analyses will also be completed in a blinded fashion by the study statistical consultant.Participants (N=90; 45 at each site) will be randomized with equal probability to either treatment group, restricted by equal enrollment and equal distribution at each site. Patients will be enrolled for the exploratory aim separately at the University of Florida site only. After enrollment into the main study (primary and secondary aims), subjects at the UF site will be offered enrollment into the exploratory aim (N=24) on a consecutive basis restricted by equal enrollment into each treatment arm. A random number table will be used for group allocation and the values recorded separately into opaque, sealed envelopes. This will be performed by a clinical coordinator who is not involved in study to ensure allocation concealment. Outcomes for the primary, secondary, and exploratory aims will be completed by research staff who are blinded to the subject treatment allocation. Data analyses will also be completed in a blinded fashion by the study statistical consultant.

Masking:

Single (Investigator)

Masking Description:

A random number table will be used for group allocation and the values recorded separately into opaque, sealed envelopes. This will be performed by a clinical coordinator who is not involved in study to ensure allocation concealment. Outcomes for the primary, secondary, and exploratory aims will be completed by research staff who are blinded to the subject treatment allocation. Data analyses will also be completed in a blinded fashion by the study statistical consultant.

Primary Purpose:

Treatment

Official Title:

Fluoroscopic Versus Ultrasound Guidance for Cooled Radiofrequency Ablation of Geniculate Nerves in Knee Osteoarthritis: A Randomized Control Trial

Actual Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subjects with knee OA using ultrasound for cRFA intervention Knee osteoarthritis patients (Kellegren-Lawrence Scale 2-4) that have been refractory to conservative treatments and report at least 80% pain relief with diagnostic geniculate nerve blocks will be enrolled and randomized to ultrasound (N=45) cRFA treatment arm.	Procedure: cRFA cRFA intervention will occur under sterile conditions, the patient will be placed in a supine position on a table and a bolster to provide flexion in the treated knee joint. Skin and soft tissues will be anaesthetized with 2 mL 1% lidocaine at each of the three anatomic sites for cRFA, and a introducer needle will then be placed under ultrasound or fluoroscopic guidance to the SLG, SMG, and IMG nerves. Adjustments at these positions will be made when using ultrasound guidance in order to capture the geniculate nerve if the nerve and/or its accompanying vasculature can be directly visualized using greyscale or Doppler modes. When using ultrasound, the physician will note and record whether their positioning of the needle is based on bony landmarks, direct visualization of the nerve, and/or vascularity accompanying the nerve. Once the introducer needle is placed, the cRFA will be placed into the introducer needle.
Experimental: Subjects with knee OA using fluoroscopy for cRFA intervention Knee osteoarthritis patients (Kellegren-Lawrence Scale 2-4) that have been refractory to conservative treatments and report at least 80% pain relief with diagnostic geniculate nerve blocks will be enrolled and randomized to fluoroscopic (N=45) cRFA treatment arm.	Procedure: cRFA cRFA intervention will occur under sterile conditions, the patient will be placed in a supine position on a table and a bolster to provide flexion in the treated knee joint. Skin and soft tissues will be anaesthetized with 2 mL 1% lidocaine at each of the three anatomic sites for cRFA, and a introducer needle will then be placed under ultrasound or fluoroscopic guidance to the SLG, SMG, and IMG nerves. Adjustments at these positions will be made when using ultrasound guidance in order to capture the geniculate nerve if the nerve and/or its accompanying vasculature can be directly visualized using greyscale or Doppler modes. When using ultrasound, the physician will note and record whether their positioning of the needle is based on bony landmarks, direct visualization of the nerve, and/or vascularity accompanying the nerve. Once the introducer needle is placed, the cRFA will be placed into the introducer needle.

Arm

Intervention/Treatment

Experimental: Subjects with knee OA using ultrasound for cRFA intervention

Knee osteoarthritis patients (Kellegren-Lawrence Scale 2-4) that have been refractory to conservative treatments and report at least 80% pain relief with diagnostic geniculate nerve blocks will be enrolled and randomized to ultrasound (N=45) cRFA treatment arm.

Procedure: cRFA

cRFA intervention will occur under sterile conditions, the patient will be placed in a supine position on a table and a bolster to provide flexion in the treated knee joint. Skin and soft tissues will be anaesthetized with 2 mL 1% lidocaine at each of the three anatomic sites for cRFA, and a introducer needle will then be placed under ultrasound or fluoroscopic guidance to the SLG, SMG, and IMG nerves. Adjustments at these positions will be made when using ultrasound guidance in order to capture the geniculate nerve if the nerve and/or its accompanying vasculature can be directly visualized using greyscale or Doppler modes. When using ultrasound, the physician will note and record whether their positioning of the needle is based on bony landmarks, direct visualization of the nerve, and/or vascularity accompanying the nerve. Once the introducer needle is placed, the cRFA will be placed into the introducer needle.

Experimental: Subjects with knee OA using fluoroscopy for cRFA intervention

Procedure: cRFA

Outcome Measures

Primary Outcome Measures

Numeric Pain Rating Scale [Baseline up to 24 months]
The objective is to rate patient's reported pain. The NPRS asks for a number between zero and ten that fits best to the subject's pain intensity, with zero as "no pain at all" and ten representing "the worst pain ever possible". It has a similar minimal clinically significant difference (20%) as the visual analog scale and can be administered via a phone interview.
Western Ontario and McMaster Universities Arthritis Index (WOMAC) [Baseline up to 24 months]
The objective is to measure the patient's reported functional status.The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. Usually a sum of the scores for all three subscales gives a total WOMAC score, however there are other methods that have been used to combine scores
PROMIS - Depression [Baseline up to 24 months]
The objective is to measure items relevant to the subject's mood, views of self, and engagement. The test version 8b has good responsiveness with a minimally important difference range of 3-3.1 in adults with knee OA.
PROMIS - Pain Interference [Baseline up to 24 months]
The objective is to measure the consequences of pain on the subject's life with a minimally important difference range of 2.35 to 2.4

Secondary Outcome Measures

30-Second Chair Stand Test [The subjects will perform the OARSI-recommended performance-based functional tests at the baseline, three month, and six month time periods.]
The objective is to determine the maximum number of chair stand repetitions possible in a 30 second period.
Stair Climb Test [The subjects will perform the OARSI-recommended performance-based functional tests at the baseline, three month, and six month time periods.]
The objective is to determine the time (seconds) it takes to ascend and descend a flight of stairs.
40m Fast Paced Walk Test [The subjects will perform the OARSI-recommended performance-based functional tests at the baseline, three month, and six month time periods.]
The objective is to determine the time (seconds) it takes to complete a fast-paced walking task over 4x10m (total 40m).
Timed Up and Go Test48 [The subjects will perform the OARSI-recommended performance-based functional tests at the baseline, three month, and six month time periods.]
The objective is to determine the time (seconds) to rise from a chair, walk 3m, turn, walk back to the chair, and then sit down.
Six Minute Walk Test [The subjects will perform the OARSI-recommended performance-based functional tests at the baseline, three month, and six month time periods.]
The objective is to determine the maximal distance covered in a 6min period.

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. patients of either gender with primary knee OA of one or both knees fulfilling the diagnostic criteria for knee OA by the American College of Rheumatology,
1. Kellgren-Lawrence score of two to four,
1. reported NPRS pain intensity of at least four on most or all days of the past week
1. pain resistant to conventional treatments which may include but is not limited to medications (e.g. acetaminophen, oral or topical non-steroidal anti-inflammatory drugs, opioids), physical therapy, and intra-articular injections (e.g. corticosteroids, hyaluronic acid, platelet-rich-plasma) for at least 3 months. In the case of bilateral knee OA, the most symptomatic knee will be treated and studied.

Exclusion Criteria:

1. age <35 years,
1. non-English speaking patients,
1. body mass index greater than 40,
1. previous radiofrequency ablation procedure for the knee,
1. active systemic or local infections at the site of needle/cRFA probe placement,
1. previous knee joint replacement surgery,
1. autoimmune or inflammatory cause of knee arthritis such as rheumatoid or psoriatic arthritis,
1. non-ambulatory patients,
1. patients who are unable to provide their own consent (e.g. dementia),
1. unstable medical or psychiatric illness,
1. patients with pacemakers, spinal cord stimulators, deep brain stimulators, or similar devices,
1. patients seeking care as a part of workman's compensation or have litigation pending
1. a negative response to diagnostic geniculate nerve lidocaine injections.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UF and Shands Orthopaedics and Sports Medicine Institute	Gainesville	Florida	United States	32611

Sponsors and Collaborators

University of Florida
American Medical Society for Sports Medicine Collaborative Research Network

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Florida

ClinicalTrials.gov Identifier:

NCT04472702

Other Study ID Numbers:

IRB202001574
OCR36642

First Posted:

Jul 15, 2020

Last Update Posted:

Dec 3, 2021

Last Verified:

Dec 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Osteoarthritis

Osteoarthritis, Knee

Study Results

No Results Posted as of Dec 3, 2021