Ultrasound-Guided Pulsed Radiofrequency In The Treatment Of Patients With Osteoarthritis Knee (USPRFGENOAK)

Study Overview
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Brief Summary
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The purpose of this study is to determine if patients with chronic painful knee osteoarthritis experience meaningful and long-term improvement in pain, function, and analgesic use after ultrasound-guided pulsed radiofrequency of the genicular nerves following a double diagnostic genicular nerve blocks.

Detailed Description
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Osteoarthritis of the knee (kOA) is one of the main causes of disability. Population-based studies revealed that symptomatic kOA is present in 20-30% of the elderly population aged >65 years, and its prevalence is increasing due in part to the aging of the population. The goals of management of patients with kOA are to control pain and to minimize disability. Evidence-based guidelines from National Institute of Health and Clinical Excellence (NICE) and Osteoarthritis Research International (OARSI) suggest that the treatment should be multidisciplinary. Optimal management requires a combination of non-pharmacological (changes in lifestyle, pacing of activities, weight reduction, regular aerobic, acupuncture, muscle strengthening and range of motion exercises) and pharmacological modalities (paracetamol) when additional treatment is required. Total knee arthroplasty (TKA) should be considered for patients with significant symptoms, and/or functional limitations associated with a reduced health-related quality of life, despite conservative therapy. However, there are some fragile patients who are at high risk during surgery and other patients who are not willing to undergo surgery. Because the number of patients will increase as the population ages, alternative approaches to alleviate their joint pain other than conventional treatments are necessary. Ultrasound-guided pulsed radiofrequency of the genicular has recently become a promising treatment option in the management of osteoarthritis related knee pain. This study is a randomized, double-blind, placebo-controlled trial, parallel design. 142 out-patients with kOA will be recruited from Mallorca, Spain. Participants will be randomly allocated into two groups: Ultrasound-Guided Sham Genicular Nerve Pulsed Radiofrequency without active treatment (Sham GENPRF) and Ultrasound-Guided Real Genicular Nerve Pulsed Radiofrequency (Real GENPRF). All patients will be examined before and 1, 3, 6 and 12 months after the treatment (sham or active).

Official Title
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Ultrasound-Guided Pulsed Radiofrequency Of The Genicular Nerves In The Treatment Of Patients With Osteoarthritis Knee Pain: Randomized, Double-Blind, Placebo Controled Trial

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Procedure: Real Pulsed Radiofrequency
* Procedure: Sham Pulsed Radiofrequency


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic knee pain with pain intensity of at least 4 out 10 on the VAS on most or all days for more than 3 months Patients of either sex with primary osteoarthritis of one or both knees fulfilling diagnostic criteria for osteoarthritis knee laid down by American College of Rheumatology. Patients also had to have a Kellgren-Lawrence (radiologic criterion) score of at least 2 Pain resistant to conventional therapy including NSAIDs, opioids, muscle relaxants, oral steroids, physical therapy, and intra-articular injection therapy. Exclusion Criteria: The patients with secondary osteoarthritis of knees Associated systemic arthropathies, e.g. rheumatoid arthritis and gout Previous radiofrequency ablation treatment for similar symptoms. Intra-articular knee corticosteroid or hyaluronic acid injection in the past 3 months. Active systemic or local infections at the site of proposed needle and electrode placement. Coagulopathy or other bleeding disorder Cognitive deficit. Unstable medical or psychiatric illness. Previous knee joint replacement surgery Patients missing two or more appointments consecutively were excluded from the study

Ages Eligible for Study
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Minimum Age: 40 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Real Pulsed Radiofrequency<br>Before needle insertion, the patient's inferomedial (IM), superomedial (SM), and superolateral (SL) GN branches will be identified under ultrasound guidance. RF needles and probes will be advanced to each of the target nerves under ultrasound guidance. A 50 Hz-frequency sensorial stimulation will be applied with a threshold of < 0.5 mA to identify the nerve position, the current intensity (mA) will be reduced at < 0,2 mA. During the sensorial stimulation, the patients will be asked if they feel tingling, pain, or discomfort inside the knee. The RF probe will be maintained in place until one of those feelings is elicited. In order to avoid inactivating motor nerves, the nerve will be tested for the absence of fasciculation in the the lower extremity on stimulation of 0,5 mA at 2 Hz. | Procedure: Real Pulsed Radiofrequency<br>* Pulsed Radiofrequency uses radiofrequency current in short (20 ms), high-voltage bursts; the silent phase (480 ms) allows time for heat elimination, generally keeping the target tissue below 42° C. The Radiofrequency (RF) electrode will be inserted through the canula, and RF lesions will be generated by applying pulsed RF treatment to the inferomedial (IM), superomedial (SM), and superolateral (SL) GN branches for 8 minutes at 42°C.<br>|
| Sham Comparator: Sham Pulsed Radiofrequency<br>Control patients will undergo the same procedure. The sensorial and motor stimulations will be applied too. The RF electrode will be then inserted through the cannula, and RF lesions will be simulated without applying pulsed RF treatment to the IM, SM and SL, GN branches for 8 minutes each GN branch and the temperature of the electrode tip was not raised. | Procedure: Sham Pulsed Radiofrequency<br>* Control patients will undergo the same procedure. The sensorial and motor stimulations will be applied too. The RF electrode will be then inserted through the cannula, and RF lesions will be simulated without applying pulsed RF treatment to the IM, SM and SL, GN branches for 8 minutes each GN branch and the temperature of the electrode tip was not raised.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in visual analogue scale (VAS) | The VAS is a continuous scale made up of a 100-mm, unmarked, horizontal line, upon which the subject makes a hash mark depending on the amount of pain felt; a mark on the far left of the line indicates no pain (score of 0), and a mark to the far right qualifies as pain as bad as it could be or unbearable pain (score of 100). | baseline and the completion of treatment at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Goldberg Depression and Anxiety scales | This consists of two subscales (of nine questions for each scale): an anxiety scale (1-9) and a depression scale (10-18). The first questions for each scale (1-4 and 10-13) are preconditioned questions to determine whether the patient should attempt to answer the rest of the questions of the two subscales. Effectively, at least two questions must be answered affirmatively in the first scale (1-4) for the patient to continue; in the second scale, one answer is sufficient for questions 10-13 for the patient to continue with the rest of the questions. This study will use the Spanish version validated by Montón et al. | at 1 month | 
| Change from Baseline in Goldberg Depression and Anxiety scales | This consists of two subscales (of nine questions for each scale): an anxiety scale (1-9) and a depression scale (10-18). The first questions for each scale (1-4 and 10-13) are preconditioned questions to determine whether the patient should attempt to answer the rest of the questions of the two subscales. Effectively, at least two questions must be answered affirmatively in the first scale (1-4) for the patient to continue; in the second scale, one answer is sufficient for questions 10-13 for the patient to continue with the rest of the questions. This study will use the Spanish version validated by Montón et al. | at 3 months | 
| Change from Baseline in Goldberg Depression and Anxiety scales | This consists of two subscales (of nine questions for each scale): an anxiety scale (1-9) and a depression scale (10-18). The first questions for each scale (1-4 and 10-13) are preconditioned questions to determine whether the patient should attempt to answer the rest of the questions of the two subscales. Effectively, at least two questions must be answered affirmatively in the first scale (1-4) for the patient to continue; in the second scale, one answer is sufficient for questions 10-13 for the patient to continue with the rest of the questions. This study will use the Spanish version validated by Montón et al. | at 6 months | 
| Change from Baseline in Goldberg Depression and Anxiety scales | This consists of two subscales (of nine questions for each scale): an anxiety scale (1-9) and a depression scale (10-18). The first questions for each scale (1-4 and 10-13) are preconditioned questions to determine whether the patient should attempt to answer the rest of the questions of the two subscales. Effectively, at least two questions must be answered affirmatively in the first scale (1-4) for the patient to continue; in the second scale, one answer is sufficient for questions 10-13 for the patient to continue with the rest of the questions. This study will use the Spanish version validated by Montón et al. | up to 1 year | 
| Change from baseline in WOMAC index | The WOMAC scale is used to evaluate the condition of patients with OA of the knee and the hip and includes pain, stiffness, and physical functioning of the joints. This scale measures five items for pain (with a score range of 0-20), two for stiffness (score range of 0-8), and 17 for functional limitation (score range of 0-68). The physical functioning questions cover everyday activities. These scales will be used separately and will not be summed. Patients will respond orally to the five levels with the following criteria: none = 0, a bit = 1, quite a bit = 2, a lot = 3, and very much = 4. If two or more questions are left unanswered, the scale will be declared invalid. If the patient does not respond to one question, a mean will be taken from the results of the other questions. The range will be 0-98. | at 1 month | 
| Change from baseline in WOMAC index | The WOMAC scale is used to evaluate the condition of patients with OA of the knee and the hip and includes pain, stiffness, and physical functioning of the joints. This scale measures five items for pain (with a score range of 0-20), two for stiffness (score range of 0-8), and 17 for functional limitation (score range of 0-68). The physical functioning questions cover everyday activities. These scales will be used separately and will not be summed. Patients will respond orally to the five levels with the following criteria: none = 0, a bit = 1, quite a bit = 2, a lot = 3, and very much = 4. If two or more questions are left unanswered, the scale will be declared invalid. If the patient does not respond to one question, a mean will be taken from the results of the other questions. The range will be 0-98. | at 3 months | 
| Change from baseline in WOMAC index | The WOMAC scale is used to evaluate the condition of patients with OA of the knee and the hip and includes pain, stiffness, and physical functioning of the joints. This scale measures five items for pain (with a score range of 0-20), two for stiffness (score range of 0-8), and 17 for functional limitation (score range of 0-68). The physical functioning questions cover everyday activities. These scales will be used separately and will not be summed. Patients will respond orally to the five levels with the following criteria: none = 0, a bit = 1, quite a bit = 2, a lot = 3, and very much = 4. If two or more questions are left unanswered, the scale will be declared invalid. If the patient does not respond to one question, a mean will be taken from the results of the other questions. The range will be 0-98. | at 6 months | 
| Change from baseline in WOMAC index | The WOMAC scale is used to evaluate the condition of patients with OA of the knee and the hip and includes pain, stiffness, and physical functioning of the joints. This scale measures five items for pain (with a score range of 0-20), two for stiffness (score range of 0-8), and 17 for functional limitation (score range of 0-68). The physical functioning questions cover everyday activities. These scales will be used separately and will not be summed. Patients will respond orally to the five levels with the following criteria: none = 0, a bit = 1, quite a bit = 2, a lot = 3, and very much = 4. If two or more questions are left unanswered, the scale will be declared invalid. If the patient does not respond to one question, a mean will be taken from the results of the other questions. The range will be 0-98. | up to 1 year | 
| EUROHIS (European Health Survey System) theoretical recommendations and design of a questionnaire Changes in baseline use of medication | This questionnaire will have four questions developed according the EUROHIS (European Health Interview Survey) recommendations in order to harmonize the information regarding medicine use [31]. Subjects will be asked (1) about the prescription medicine their general practitioner may have prescribed for them (Have you taken any pain medicine prescribed by your general practitioner?) as well as any medication not prescribed by their general practitioner (Have you taken any pain medicine not prescribed by your general practitioner) and (2) whether or not their prescribed and non-prescribed pain medication use has increased or decreased. | at 1 month | 
| EUROHIS (European Health Survey System) theoretical recommendations and design of a questionnaire Changes in baseline use of medication | This questionnaire will have four questions developed according the EUROHIS (European Health Interview Survey) recommendations in order to harmonize the information regarding medicine use [31]. Subjects will be asked (1) about the prescription medicine their general practitioner may have prescribed for them (Have you taken any pain medicine prescribed by your general practitioner?) as well as any medication not prescribed by their general practitioner (Have you taken any pain medicine not prescribed by your general practitioner) and (2) whether or not their prescribed and non-prescribed pain medication use has increased or decreased. | at 3 months | 
| EUROHIS (European Health Survey System) theoretical recommendations and design of a questionnaire Changes in baseline use of medication | This questionnaire will have four questions developed according the EUROHIS (European Health Interview Survey) recommendations in order to harmonize the information regarding medicine use [31]. Subjects will be asked (1) about the prescription medicine their general practitioner may have prescribed for them (Have you taken any pain medicine prescribed by your general practitioner?) as well as any medication not prescribed by their general practitioner (Have you taken any pain medicine not prescribed by your general practitioner) and (2) whether or not their prescribed and non-prescribed pain medication use has increased or decreased. | at 6 months | 
| EUROHIS (European Health Survey System) theoretical recommendations and design of a questionnaire Changes in baseline use of medication | This questionnaire will have four questions developed according the EUROHIS (European Health Interview Survey) recommendations in order to harmonize the information regarding medicine use [31]. Subjects will be asked (1) about the prescription medicine their general practitioner may have prescribed for them (Have you taken any pain medicine prescribed by your general practitioner?) as well as any medication not prescribed by their general practitioner (Have you taken any pain medicine not prescribed by your general practitioner) and (2) whether or not their prescribed and non-prescribed pain medication use has increased or decreased. | up to 1 year | 
| Change from baseline in a visual analogue scale (VAS) | The VAS is a continuous scale made up of a 100-mm, unmarked, horizontal line, upon which the subject makes a hash mark depending on the amount of pain felt; a mark on the far left of the line indicates no pain (score of 0), and a mark to the far right qualifies as pain as bad as it could be or unbearable pain (score of 100). | at 1 month | 
| Change from baseline in a visual analogue scale (VAS) | The VAS is a continuous scale made up of a 100-mm, unmarked, horizontal line, upon which the subject makes a hash mark depending on the amount of pain felt; a mark on the far left of the line indicates no pain (score of 0), and a mark to the far right qualifies as pain as bad as it could be or unbearable pain (score of 100). | at 6 months | 
| Change from baseline in a visual analogue scale (VAS) | The VAS is a continuous scale made up of a 100-mm, unmarked, horizontal line, upon which the subject makes a hash mark depending on the amount of pain felt; a mark on the far left of the line indicates no pain (score of 0), and a mark to the far right qualifies as pain as bad as it could be or unbearable pain (score of 100). | up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Knee pain, osteoarthritis, genicular nerve, ultrasonography, pulsed radiofrequency