Ankle Osteoarthritis
Conditions
Keywords
Cryoneurolysis, iovera, Superficial nerves treatment, Deep Fibular Nerve
Brief summary
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
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).
Interventions
DEVICEiovera
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.
Sponsors
University of Kansas Medical Center
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. * Intra-articular, intravenous or intramuscular 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FAOS - PAIN | Change between baseline/screening and 12-weeks following treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FAOS - ADL(Activity of Daily Living) | change between baseline/screening and 12-weeks following treatment | 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. |
| NRS Pain Over Prior 7 Days | change between baseline/screening and 6-weeks following treatment | The Numeric Rating Scale (NRS) is a numeric scale to rates the pain from 0 (no pain) to 10 (worst pain). |
| FAOS-QoL(Quality of Life) | change between baseline/screening and 12-weeks following treatment | 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. |
| FAOS - PAIN | change between baseline/screening and 6-weeks following treatment | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in 40m Fast Paced Walking Test (40m FPWT) Time Between Baseline/Screening and 24-weeks Following Treatment | change between baseline/screening and 24-weeks following treatment | The 40-meter walk test is one of the three OARSI (Osteoarthritis Research Society International) recommended minimal core set of performance-based outcome measures in OA research and clinical practice.The 40m FPWT will take approximately 2 minutes for each subject to complete. |
| Change in 40m Fast Paced Walking Test (40m FPWT) Time Between Baseline/Screening and 12-weeks Following Treatment | change between baseline/screening and 12-weeks following treatment | The 40-meter walk test is one of the three OARSI (Osteoarthritis Research Society International) recommended minimal core set of performance-based outcome measures in OA research and clinical practice.The 40m FPWT will take approximately 2 minutes for each subject to complete. |
| Change in 40m Fast Paced Walking Test (40m FPWT) Time Between Baseline/Screening and 6-weeks Following Treatment | change between baseline/screening and 6-weeks following treatment | The 40-meter walk test is one of the three OARSI (Osteoarthritis Research Society International) recommended minimal core set of performance-based outcome measures in OA research and clinical practice.The 40m FPWT will take approximately 2 minutes for each subject to complete. |
Countries
United States
Participant flow
Pre-assignment details
Forty-three potentially eligible participants were screened. Of these two were found by radiographs or weight-bearing CT (WBCT) scan to not have tibiotalar osteoarthritis (KL=0) and were excluded. In addition, one participant was excluded due to an unstable ankle that resulted in bracing and opioid therapy. Subsequently, 40 participants with unilateral painful ankle OA were recruited.
Participants by arm
| Arm | Count |
|---|---|
| Iovera 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.
iovera: 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. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 18 |
Baseline characteristics
| Characteristic | Iovera | — |
|---|---|---|
| 40-meter fast-paced walking test | 32.8 sec STANDARD_DEVIATION 9.2 | — |
| Age, Continuous | 63.0 years STANDARD_DEVIATION 12.8 | — |
| BMI | 31.7 kg/m^2 STANDARD_DEVIATION 6.8 | — |
| FAOS-ADL | 53.3 units on a scale STANDARD_DEVIATION 16.4 | — |
| FAOS-Pain | 43.1 units on a scale STANDARD_DEVIATION 14.1 | — |
| FAOS-QOL | 22.0 units on a scale STANDARD_DEVIATION 16.9 | — |
| Index ankle joint, n (% right ) | 27 Participants | — |
| NRS Pain Score | 6.3 units on a scale STANDARD_DEVIATION 1.6 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 40 participants | — |
| Sex: Female, Male Female | 20 Participants | — |
| Sex: Female, Male Male | 20 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 40 |
| other Total, other adverse events | 19 / 40 |
| serious Total, serious adverse events | 0 / 40 |
Outcome results
Primary
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.
Time frame: Change between baseline/screening and 12-weeks following treatment
Population: Twenty seven eligible participants completed 12-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | FAOS - PAIN | 20.8 score on a scale | Standard Error 4.5 |
Secondary
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.
Time frame: change between baseline/screening and 24-weeks following treatment
Population: Twenty two eligible participants completed 24-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | FAOS - ADL(Activity of Daily Living) | 20.1 score on a scale | Standard Error 4.1 |
Secondary
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.
Time frame: change between baseline/screening and 12-weeks following treatment
Population: Twenty seven eligible participants completed 12-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | FAOS - ADL(Activity of Daily Living) | 18.1 score on a scale | Standard Error 4.9 |
Secondary
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.
Time frame: change between baseline/screening and 6-weeks following treatment
Population: Thirty five eligible participants completed 6-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | FAOS - ADL(Activity of Daily Living) | 16.6 score on a scale | Standard Error 4.3 |
Secondary
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.
Time frame: change between baseline/screening and 6-weeks following treatment
Population: Thirty five eligible participants completed 6-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | FAOS - PAIN | 17.4 score on a scale | Standard Error 4.1 |
Secondary
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.
Time frame: change between baseline/screening and 24-weeks following treatment
Population: Twenty two eligible participants completed 24-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | FAOS - PAIN | 21.7 score on a scale | Standard Error 4.3 |
Secondary
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.
Time frame: change between baseline/screening and 6-weeks following treatment
Population: Thirty five eligible participants completed 6-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | FAOS-QoL(Quality of Life) | 22.4 score on a scale | Standard Error 4.4 |
Secondary
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.
Time frame: change between baseline/screening and 24-weeks following treatment
Population: Twenty two eligible participants completed 24-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | FAOS-QoL(Quality of Life) | 25.4 score on a scale | Standard Error 4.8 |
Secondary
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.
Time frame: change between baseline/screening and 12-weeks following treatment
Population: Twenty seven eligible participants completed 12-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | FAOS-QoL(Quality of Life) | 19.9 score on a scale | Standard Error 5.3 |
Secondary
NRS Pain Over Prior 7 Days
The Numeric Rating Scale (NRS) is a numeric scale to rates the pain from 0 (no pain) to 10 (worst pain).
Time frame: change between baseline/screening and 6-weeks following treatment
Population: Thirty five eligible participants completed 6-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | NRS Pain Over Prior 7 Days | -2.7 score on a scale | Standard Error 0.5 |
Secondary
NRS Pain Over Prior 7 Days
The Numeric Rating Scale (NRS) is a numeric scale to rates the pain from 0 (no pain) to 10 (worst pain).
Time frame: change between baseline/screening and 24-weeks following treatment
Population: Twenty two eligible participants completed 24-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | NRS Pain Over Prior 7 Days | -2.8 score on a scale | Standard Error 0.5 |
Secondary
NRS Pain Over Prior 7 Days
The Numeric Rating Scale (NRS) is a numeric scale to rates the pain from 0 (no pain) to 10 (worst pain).
Time frame: change between baseline/screening and 12-weeks following treatment
Population: Twenty seven eligible participants completed 12-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | NRS Pain Over Prior 7 Days | -2.6 score on a scale | Standard Error 0.6 |
Other Pre-specified
Change in 40m Fast Paced Walking Test (40m FPWT) Time Between Baseline/Screening and 12-weeks Following Treatment
The 40-meter walk test is one of the three OARSI (Osteoarthritis Research Society International) recommended minimal core set of performance-based outcome measures in OA research and clinical practice.The 40m FPWT will take approximately 2 minutes for each subject to complete.
Time frame: change between baseline/screening and 12-weeks following treatment
Population: Twenty seven eligible participants completed 12-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | Change in 40m Fast Paced Walking Test (40m FPWT) Time Between Baseline/Screening and 12-weeks Following Treatment | -1.2 seconds | Standard Error 2.2 |
Other Pre-specified
Change in 40m Fast Paced Walking Test (40m FPWT) Time Between Baseline/Screening and 24-weeks Following Treatment
The 40-meter walk test is one of the three OARSI (Osteoarthritis Research Society International) recommended minimal core set of performance-based outcome measures in OA research and clinical practice.The 40m FPWT will take approximately 2 minutes for each subject to complete.
Time frame: change between baseline/screening and 24-weeks following treatment
Population: Twenty two eligible participants completed 24-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | Change in 40m Fast Paced Walking Test (40m FPWT) Time Between Baseline/Screening and 24-weeks Following Treatment | -1.8 seconds | Standard Error 2.6 |
Other Pre-specified
Change in 40m Fast Paced Walking Test (40m FPWT) Time Between Baseline/Screening and 6-weeks Following Treatment
The 40-meter walk test is one of the three OARSI (Osteoarthritis Research Society International) recommended minimal core set of performance-based outcome measures in OA research and clinical practice.The 40m FPWT will take approximately 2 minutes for each subject to complete.
Time frame: change between baseline/screening and 6-weeks following treatment
Population: Thirty five eligible participants completed 6-weeks follow-up treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iovera | Change in 40m Fast Paced Walking Test (40m FPWT) Time Between Baseline/Screening and 6-weeks Following Treatment | -0.1 seconds | Standard Error 2.3 |