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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Ankle Osteoarthritis
• Intervention / Treatment: Device: iovera

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).

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Device: 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
40m fast paced walking test (40m FPWT)	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 between baseline/screening and 6-weeks following treatment
40m fast paced walking test (40m FPWT)	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 between baseline/screening and 12-weeks following treatment
40m fast paced walking test (40m FPWT)	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 between baseline/screening and 24-weeks following treatment
Standing Balance Test	The standing balance test outcome is measured with the feet side by side, then in semi-tandem stance (heel of one foot in front and beside the big toe of the other foot), and then in tandem stance (heel of one foot directly in front of the other foot); each stance was held for up to 10s. These test results are converted to scores (range 0-4).	change between baseline/screening and 6-weeks following treatment
Standing Balance Test	The standing balance test outcome is measured with the feet side by side, then in semi-tandem stance (heel of one foot in front and beside the big toe of the other foot), and then in tandem stance (heel of one foot directly in front of the other foot); each stance was held for up to 10s. These test results are converted to scores (range 0-4).	change between baseline/screening and 12-weeks following treatment
Standing Balance Test	The standing balance test outcome is measured with the feet side by side, then in semi-tandem stance (heel of one foot in front and beside the big toe of the other foot), and then in tandem stance (heel of one foot directly in front of the other foot); each stance was held for up to 10s. These test results are converted to scores (range 0-4).	change between baseline/screening and 24-weeks following treatment

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Investigators: Principal Investigator: Neil A Segal, MD, University of Kansas Medical Center

Publications and helpful links

General Publications

• Trescot AM. Cryoanalgesia in interventional pain management. Pain Physician. 2003 Jul;6(3):345-60.
• Dobson F, Hinman RS, Roos EM, Abbott JH, Stratford P, Davis AM, Buchbinder R, Snyder-Mackler L, Henrotin Y, Thumboo J, Hansen P, Bennell KL. OARSI recommended performance-based tests to assess physical function in people diagnosed with hip or knee osteoarthritis. Osteoarthritis Cartilage. 2013 Aug;21(8):1042-52. doi: 10.1016/j.joca.2013.05.002. Epub 2013 May 13.
• Holzer N, Salvo D, Marijnissen AC, Vincken KL, Ahmad AC, Serra E, Hoffmeyer P, Stern R, Lubbeke A, Assal M. Radiographic evaluation of posttraumatic osteoarthritis of the ankle: the Kellgren-Lawrence scale is reliable and correlates with clinical symptoms. Osteoarthritis Cartilage. 2015 Mar;23(3):363-9. doi: 10.1016/j.joca.2014.11.010. Epub 2014 Nov 15.
• Ward ST, Williams PL, Purkayastha S. Intra-articular corticosteroid injections in the foot and ankle: a prospective 1-year follow-up investigation. J Foot Ankle Surg. 2008 Mar-Apr;47(2):138-44. doi: 10.1053/j.jfas.2007.12.007.
• Valderrabano V, Horisberger M, Russell I, Dougall H, Hintermann B. Etiology of ankle osteoarthritis. Clin Orthop Relat Res. 2009 Jul;467(7):1800-6. doi: 10.1007/s11999-008-0543-6. Epub 2008 Oct 2.
• Repetto I, Biti B, Cerruti P, Trentini R, Felli L. Conservative Treatment of Ankle Osteoarthritis: Can Platelet-Rich Plasma Effectively Postpone Surgery? J Foot Ankle Surg. 2017 Mar-Apr;56(2):362-365. doi: 10.1053/j.jfas.2016.11.015.
• Evans PJ, Lloyd JW, Green CJ. Cryoanalgesia: the response to alterations in freeze cycle and temperature. Br J Anaesth. 1981 Nov;53(11):1121-7. doi: 10.1093/bja/53.11.1121.
• Golightly YM, Devellis RF, Nelson AE, Hannan MT, Lohmander LS, Renner JB, Jordan JM. Psychometric properties of the foot and ankle outcome score in a community-based study of adults with and without osteoarthritis. Arthritis Care Res (Hoboken). 2014 Mar;66(3):395-403. doi: 10.1002/acr.22162.
• Mani SB, Do H, Vulcano E, Hogan MV, Lyman S, Deland JT, Ellis SJ. Evaluation of the foot and ankle outcome score in patients with osteoarthritis of the ankle. Bone Joint J. 2015 May;97-B(5):662-7. doi: 10.1302/0301-620X.97B5.33940.
• Roos EM, Brandsson S, Karlsson J. Validation of the foot and ankle outcome score for ankle ligament reconstruction. Foot Ankle Int. 2001 Oct;22(10):788-94. doi: 10.1177/107110070102201004.
• Hunt KJ, Hurwit D. Use of patient-reported outcome measures in foot and ankle research. J Bone Joint Surg Am. 2013 Aug 21;95(16):e118(1-9). doi: 10.2106/JBJS.L.01476.
• McDaniel G, Renner JB, Sloane R, Kraus VB. Association of knee and ankle osteoarthritis with physical performance. Osteoarthritis Cartilage. 2011 Jun;19(6):634-8. doi: 10.1016/j.joca.2011.01.016. Epub 2011 Feb 19.
• Radnovich R, Scott D, Patel AT, Olson R, Dasa V, Segal N, Lane NE, Shrock K, Naranjo J, Darr K, Surowitz R, Choo J, Valadie A, Harrell R, Wei N, Metyas S. Cryoneurolysis to treat the pain and symptoms of knee osteoarthritis: a multicenter, randomized, double-blind, sham-controlled trial. Osteoarthritis Cartilage. 2017 Aug;25(8):1247-1256. doi: 10.1016/j.joca.2017.03.006. Epub 2017 Mar 20.

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2018
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): March 1, 2021

Study Registration Dates

• First Submitted: June 12, 2018
• First Submitted That Met QC Criteria: June 21, 2018
• First Posted (Actual): June 25, 2018

Study Record Updates

• Last Update Posted (Actual): September 24, 2020
• Last Update Submitted That Met QC Criteria: September 22, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Cryoneurolysis; iovera; Superficial nerves treatment; Deep Fibular Nerve
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: STUDY00142298

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No