Cryoneurolysis for Improvements in Pain, ADL and QOL in Patients With Ankle Osteoarthritis

Study Overview
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Brief Summary
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This will be an open-label trial to describe the effects of cryoneurolysis with iovera° on symptom relief in patients with painful Kellgren-Lawrence (KL) grade 2-4 ankle osteoarthritis (OA). The Foot and Ankle Outcome Score (FAOS) subscales will be used to assess outcomes at 6, 12 and 24 weeks after treatment.

Detailed Description
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The aim of this study is to assess clinically significant long-term symptomatic relief with cryoneurolysis in people with unilateral ankle osteoarthritis (OA). The investigators will treat 1) the Superficial Fibular Nerve (SFN), Sural Nerve (SN) and Saphenous Nerve and/or 2) the Deep Fibular Nerve (DFN) with cryoneurolysis using the iovera° device. The primary study endpoint, clinically significant improvement in pain 12 weeks after each treatment, will be assessed using the FAOS pain subscale. If a participant is a non-responder (<20% improvement in pain within the 12 weeks following baseline), then the other treatment will be offered (e.g. if start with superficial group, then offer the DFN). The secondary outcomes will be improvement in quality of life (FAOS-QoL), activities of daily living (FAOS-ADL) and Numerical Rating Scale (NRS) for pain. The tertiary outcome will be improvement in physical performance measures (40m fast-paced walking test, standing balance test).

Official Title
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Cryoneurolysis for Improvements in Pain, Activities of Daily Living and Quality of Life in Patients With Ankle Osteoarthritis

Conditions
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Ankle Osteoarthritis

Intervention / Treatment
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* Device: iovera


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participation in an institutional review board-approved informed consent process, culminating in providing written consent. Willingness and ability to comply with the study procedures, visit schedules and ability to follow verbal and written instructions. Male or female over 18 years of age. Currently Kellgren-Lawrence (KL) Grade 2, 3 or 4 in the ankle based on X-ray (weight-bearing mortise views with 20° internal rotation) or weight-bearing CT scan of the ankles. Limited by unilateral ankle pain, rated on a Numerical Rating Scale for pain severity as ≥5 on most days over the last month. Foot and ankle outcome score (FAOS) of < 75 in at least 1 category. Body mass index (BMI) ≤ 50 kg/m2 Ambulatory Willingness to abstain from the use of protocol-restricted medications during the study and also willing to abstain from use of analgesics other than acetaminophen 1 week prior to beginning of the study. Has undergone at least one prior conservative osteoarthritis treatment (e.g. physical therapy, analgesics). Exclusion Criteria: Baseline knee, hip, spine or other limitations that affect walking ability to a greater extent than the ankle. Cryoglobulinemia, paroxysmal cold hemoglobinuria, Raynaud's disease, cold urticaria. Clinical signs or symptoms of active or recurrent infection in the index ankle joint or overlying skin. IA, IV or IM corticosteroid (investigational or marketed) within 3 months of screening Oral corticosteroids (investigational or marketed) within 2 weeks of screening (unless on a chronic stable dose for ≥3 months prior to enrollment). Women who are pregnant (due to potential for the change in body mass and distribution to alter ankle symptoms over the period of follow-up). Any condition other than OA of the ankle joint which, in the opinion of the investigators, affects their ability to ambulate to a sufficient degree to interfere with the assessment of the safety and treatment effects of the study injection. Arthroscopy or open surgery of the ankle joint within 6 months of screening. Planned/anticipated surgery of the index ankle joint during the 6-month study period. Any clinically significant degree of cognitive impairment or other condition, finding, or psychiatric illness at screening which, in the opinion of the investigator, could compromise patient safety or interfere with the assessment of the safety and treatment effects of the study injection. Skin breakdown at the ankle joint where the injection is planned to take place. Participated in any investigational drug or device trial within 30 days prior to screening or concurrent participation in another research study that could complicate interpretation of the findings of either study. Current consumption of more than 14 alcoholic drinks per week. Patients with diffuse pain conditions (Complex pain - diffuse or confounding pain, fibromyalgia, etc.). Known altered nerve anatomy or physiology (e.g. neuropathy) at the target, such as due to a congenital, traumatic or surgical cause.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iovera<br>The iovera° device consists of a reusable, portable hand-piece, along with a single-patient use sterile smart Tip (cryoprobe) and disposable nitrous oxide (N2O) cartridges (cryogen). The smart tip is composed of closed-tip stainless steel needles, thereby fully enclosing the cryogen. There are 2 types of smart tips that will be utilized during this study, depending on the depth of the nerves being treated. The shorter smart tip comes in 2 variants - three X 6.9 mm or 8.9 mm, 27-gauge needles, with an attached skin warmer to prevent damage to the underlying skin. The longer smart tip also comes in 2 variants - 55 mm 22-gauge needle or a 90 mm 20G needle. The effect is by initiation of a cooling cycle, by fully inserting the smart tip into the procedure site and activating the cryogen flow. As the gas travels through the length of the needle, an ice ball develops around the needle freezing the surrounding tissue. | Device: iovera<br>* The iovera° device is 510(k)-cleared (K133453 and K161835) and is used to form a precisely controlled, sub-dermal cold zone of -20 to -88.5 degrees Celsius to temporarily disrupt peripheral nerve function, ultimately blocking pain. It is not indicated for the treatment of central nervous system tissue.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FAOS - PAIN | FAOS-Pain is a subscale of the Foot and ankle outcome score (FAOS) which is a self-reported outcome score.The sub scale ranges from 0 to 100 where higher values represents a better outcome. | change between baseline/screening and 12-weeks following treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FAOS - ADL(Activity of daily living) | FAOS - ADL(Activity of daily living) is a subscale of the Foot and ankle outcome score (FAOS) which is a self-reported outcome score. It is similar to the KOOS - ADL components.The sub scale ranges from 0 to 100 where higher values represents a better outcome. | change between baseline/screening and 12-weeks following treatment | 
| FAOS - ADL(Activity of daily living) | FAOS - ADL(Activity of daily living) is a subscale of the Foot and ankle outcome score (FAOS) which is a self-reported outcome score. It is similar to the KOOS - ADL components.The sub scale ranges from 0 to 100 where higher values represents a better outcome. | change between baseline/screening and 6-weeks following treatment | 
| FAOS - ADL(Activity of daily living) | FAOS - ADL(Activity of daily living) is a subscale of the Foot and ankle outcome score (FAOS) which is a self-reported outcome score. It is similar to the KOOS - ADL components.The sub scale ranges from 0 to 100 where higher values represents a better outcome. | change between baseline/screening and 24-weeks following treatment | 
| FAOS-QoL(Quality of life) | FAOS-QoL(Quality of life) is a subscale of the Foot and ankle outcome score (FAOS) which is a self-reported outcome score. It is similar to the KOOS - QoL components.The sub scale ranges from 0 to 100 where higher values represents a better outcome. | change between baseline/screening and 12-weeks following treatment | 
| FAOS-QoL(Quality of life) | FAOS-QoL(Quality of life) is a subscale of the Foot and ankle outcome score (FAOS) which is a self-reported outcome score. It is similar to the KOOS - QoL components.The sub scale ranges from 0 to 100 where higher values represents a better outcome. | change between baseline/screening and 6-weeks following treatment | 
| FAOS-QoL(Quality of life) | FAOS-QoL(Quality of life) is a subscale of the Foot and ankle outcome score (FAOS) which is a self-reported outcome score. It is similar to the KOOS - QoL components.The sub scale ranges from 0 to 100 where higher values represents a better outcome. | change between baseline/screening and 24-weeks following treatment | 
| FAOS - PAIN | FAOS-Pain is a subscale of the Foot and ankle outcome score (FAOS) which is a self-reported outcome score.The sub scale ranges from 0 to 100 where higher values represents a better outcome. | change between baseline/screening and 6-weeks following treatment | 
| FAOS - PAIN | FAOS-Pain is a subscale of the Foot and ankle outcome score (FAOS) which is a self-reported outcome score.The sub scale ranges from 0 to 100 where higher values represents a better outcome. | change between baseline/screening and 24-weeks following treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cryoneurolysis, iovera, Superficial nerves treatment, Deep Fibular Nerve