Cryoneurolysis for Painful Diabetic Neuropathy of the Foot

Ultrasound-guided Percutaneous Cryoneurolysis for Management of Chronic Painful Diabetic Neuropathy: A Randomized Sham-controlled Pilot Study

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.

Study Overview

• Status: Recruiting
• Conditions: Painful Diabetic Peripheral Neuropathy (PDPN)
• Intervention / Treatment: Device: cryoneurolysis; Device: sham cryoneurolysis

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rodney A Gabriel, MD, MAS; Phone Number: 858-663-7747; Email: ragabriel@health.ucsd.edu
• Study Contact Backup: Name: Kyle Norton, MD; Phone Number: 702-209-9532; Email: kfnorton@health.ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92129
      • Recruiting
      • University of California, San Diego
      • Contact: Rodney A Gabriel, MD, MAS; Phone Number: 858-663-7747; Email: ragabriel@health.ucsd.edu
      • Contact: Kyle Norton, MD; Phone Number: 702-209-9532; Email: kfnorton@health.ucsd.edu
      • Principal Investigator: Rodney A Gabriel, MD, MAS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cryoneurolysis; For participants randomized to active treatment, the probe placed in the research participant will be triggered and the nitrous oxide passed through the probe and then back into the machine, and finally vented out from the console. This will result in a freeze-thaw cycle. This may be repeated, as necessary, to ensure the entire cross-section of each nerve is fully treated.	Device: cryoneurolysis; Peripheral nerve cryoneurolysis of the foot
Sham Comparator: Sham; Patients in this arm will also receive a diagnostic block with local anesthetic. If pain relief is satisfactory, the patients in this arm will undergo the procedure but the cryo probe will simply not be activated.	Device: sham cryoneurolysis; a sham probe will be placed percutaneously proximal to target nerves. No cryoneurolysis will be given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity	Change in pain intensity compared to baseline due to diabetic neuropathy of the foot as measured by the score of the Neuropathic Pain Scale. The primary outcome will be at 1 month following the study procedure. The primary statistic will be comparing the median change in the neuropathic pain scale score between both cohorts.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perception of Well-Being	Perception of well-being will be improved 1 month following one cryoneurolysis procedure (as measured with the Patient Global Impression of Change Scale).	1 month
Physical and Emotional Functioning	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).	1 month
Pain intensity - 1 month	Pain intensity as measured by Brief Pain Inventory	1 month
Pain Intensity - 1 week	Pain intensity as measured by Neuropathic Pain Scale and Brief Pain Inventory)	1 week
Pain Intensity - 3 months	Pain intensity as measured by the Brief Pain Inventory and Neuropathic Pain Scale	3 months
Pain Intensity - 6 months	Pain intensity as measured by the Brief Pain Inventory and Neuropathic Pain Scale	6 months
Opioid consumption - 1 week	opioid consumption as measured by the Quantitative Analgesic Questionnaire	1 week
Opioid consumption - 1 month	opioid consumption as measured by the Quantitative Analgesic Questionnaire	1 month
Opioid consumption - 3 months	opioid consumption as measured by the Quantitative Analgesic Questionnaire	3 months
Opioid consumption - 6 months	opioid consumption as measured by the Quantitative Analgesic Questionnaire	6 months

Collaborators and Investigators

• Sponsor: University of California, San Diego

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: October 15, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: August 29, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Chronic Pain; Cryoneurolysis; Diabetic Peripheral Neuropathy of the Foot; Ultrasound-Guided Percutaneous Cryoneurolysis
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Chronic Pain
• Other Study ID Numbers: 811212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We have not decided if we will share patient data with other researchers. Reasons for not sharing data would be related to patient confidentiality. Reasons to share data would be related to additional research analyses.

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.: Yes