Clinical trial NCT06646731: Cryoneurolysis for Painful Diabetic Neuropathy of the Foot
Official title: Ultrasound-guided Percutaneous Cryoneurolysis for Management of Chronic Painful Diabetic Neuropathy: a Randomized Sham-controlled Pilot Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Painful Diabetic Peripheral Neuropathy (PDPN)
Keywords: Cryoneurolysis
Diabetic Peripheral Neuropathy of the Foot
Chronic Pain
Ultrasound-Guided Percutaneous Cryoneurolysis
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2024-10-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is a single-center, randomized, participant- and observer-masked, human-subjects, post-market clinical pilot study
Primary purpose: TREATMENT

Brief summary: The study is a single-center, randomized, participant- and observer-masked, human-subjects, post-market clinical pilot study to investigate the use of ultrasound-guided percutaneous cryoneurolysis to treat diabetic neuropathy of the foot. A prolonged nerve block may be provided by freezing the nerve using a technique called "cryoneurolysis". With cryoneurolysis and ultrasound machines, a small needle-like "probe" may be placed through anesthetized skin and guided to the target nerve to allow freezing. The procedure takes about 6 minutes for each nerve, involves little discomfort, has no systemic side effects, and cannot be misused or become addictive. Participants will be randomly allocated to one of two possible treatments groups: cryoneurolysis (experimental) or sham (control). The primary outcome measure is the change in pain on the neuropathic pain scale from baseline 1 month following the procedure.

Detailed description: The study is a single-center, randomized, participant- and observer-masked, human-subjects, post-market clinical pilot study to investigate the use of ultrasound-guided percutaneous cryoneurolysis to treat diabetic neuropathy of the foot. A prolonged nerve block may be provided by freezing the nerve using a technique called "cryoneurolysis". With cryoneurolysis and ultrasound machines, a small needle-like "probe" may be placed through anesthetized skin and guided to the target nerve to allow freezing. The procedure takes about 6 minutes for each nerve, involves little discomfort, has no systemic side effects, and cannot be misused or become addictive. After 2-3 months, the nerve returns to normal functioning. Participants will be randomly allocated to one of two possible treatments groups: cryoneurolysis (experimental) or sham (control). The primary outcome measure is the change in pain on the neuropathic pain scale from baseline 1 month following the procedure.

Our objective is to investigate the therapeutic benefits of cryoneurolysis for research participants with painful diabetic neuropathy of the feet via a pilot study of 30 research participants. We hypothesize that ultrasound-guided cryoneurolysis of the superficial peroneal nerve will improve pain outcomes in research participants with painful diabetic neuropathy of the foot. The aims of this study will be to:

Primary Specific Aim. Demonstrate the potential efficacy of ultrasound-guided percutaneous cryoneurolysis of the superficial peroneal nerve, sural, distal saphenous, and/or deep peroneal nerve to treat painful diabetic neuropathy of the foot in reducing neuropathic pain 1 month after the procedure compared to baseline. This will be performed as a pilot study and executed as a randomized sham-controlled clinical trial of 30 subjects.

Hypothesis 1: Diabetic neuropathic pain intensity will be decreased relative to baseline 1 month following a cryoneurolysis procedure (as measured by the Neuropathic Pain Scale).

Secondary Specific Aim: To test the influence of a cryoanalgesia treatment as compared to sham/placebo on the long term measurements related to pain, quality of life, and analgesic usage.

Hypothesis 2a: Perception of well-being will be improved 1 month following one cryoneurolysis procedure (as measured with the Patient Global Impression of Change Scale).

Hypothesis 2b: Physical and emotional functioning will be improved relative to baseline 1 month following one cryoneurolysis procedure (as measured with the Interference Subscale of the Brief Pain Inventory).

Hypothesis 2c: Pain and opioid consumption will be reduced in the cryoneurolysis group compare to sham at multiple post-procedure time points, including 1 week, 1 month, 3 months, and 6 months after.

Eligibility criteria: Inclusion Criteria:

* Research participants with diabetes mellitus and painful diabetic neuropathy of the foot (unilateral or bilateral)
* HgbA1c \<10 (to avoid any increased risk of site infection)
* Adult patients of at least 18 years of age
* Experiencing at least moderate diabetic neuropathic pain in the foot - defined as 3 or higher on the numeric rating scale (NRS; 0-10, 0=no pain; 10=worse imaginable pain) - at least daily for the previous 2 months.

Exclusion Criteria:

* Diabetic neuropathy not in the distribution of the superficial peroneal nerve, sural nerve, deep peroneal, and/or distal saphenous nerve.
* Comorbidities that are contraindication to cryoneurolysis (e.g., Reynaud syndrome, cryoglobulinemia, cold urticaria)
* Allergy to local anesthetic
* Pregnancy
* Incarceration
* Inability to communicate to investigators due to lack of capacity
* Local infection in the foot/ankle where cryoneurolysis will be performed

Primary outcomes:
measure: Pain Intensity
timeFrame: 1 month
Secondary outcomes:
measure: Perception of Well-Being
timeFrame: 1 month
measure: Physical and Emotional Functioning
timeFrame: 1 month
measure: Pain intensity - 1 month
timeFrame: 1 month
measure: Pain Intensity - 1 week
timeFrame: 1 week
measure: Pain Intensity - 3 months
timeFrame: 3 months
measure: Pain Intensity - 6 months
timeFrame: 6 months
measure: Opioid consumption - 1 week
timeFrame: 1 week
measure: Opioid consumption - 1 month
timeFrame: 1 month
measure: Opioid consumption - 3 months
timeFrame: 3 months
measure: Opioid consumption - 6 months
timeFrame: 6 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
Study officials:
References:
citation: Yoon JH, Grechushkin V, Chaudhry A, Bhattacharji P, Durkin B, Moore W. Cryoneurolysis in Patients with Refractory Chronic Peripheral Neuropathic Pain. J Vasc Interv Radiol. 2016 Feb;27(2):239-43. doi: 10.1016/j.jvir.2015.11.027. Epub 2015 Dec 17.
citation: Jay GW, Barkin RL. Neuropathic pain: etiology, pathophysiology, mechanisms, and evaluations. Dis Mon. 2014 Jan;60(1):6-47. doi: 10.1016/j.disamonth.2013.12.001. No abstract available.
citation: Gabriel RA, Seng EC, Curran BP, Winston P, Trescot AM, Filipovski I. A Narrative Review of Ultrasound-Guided and Landmark-based Percutaneous Cryoneurolysis for the Management of Acute and Chronic Pain. Curr Pain Headache Rep. 2024 Nov;28(11):1097-1104. doi: 10.1007/s11916-024-01281-z. Epub 2024 Jul 4.
citation: Filipovski I, Gabriel RA, Kestenholz R. Ultrasound-Guided Cryoneurolysis for the Treatment of Painful Diabetic Neuropathy of the Foot: A Case Series. Cureus. 2024 Mar 16;16(3):e56267. doi: 10.7759/cureus.56267. eCollection 2024 Mar.