Cryoneurolysis for Painful Diabetic Neuropathy of the Foot

NCT ID: NCT06646731

Last Updated: 2025-09-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-25
• Study Completion Date: 2026-06-30

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.

Conditions

Painful Diabetic Peripheral Neuropathy (PDPN)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

cryoneurolysis

Intervention Type: DEVICE

Peripheral nerve cryoneurolysis of the foot

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.

Group Type: SHAM_COMPARATOR

sham cryoneurolysis

Intervention Type: DEVICE

a sham probe will be placed percutaneously proximal to target nerves. No cryoneurolysis will be given.

Interventions

cryoneurolysis

Peripheral nerve cryoneurolysis of the foot

Intervention Type: DEVICE

sham cryoneurolysis

a sham probe will be placed percutaneously proximal to target nerves. No cryoneurolysis will be given.

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Rodney Gabriel

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of California, San Diego

La Jolla, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Rodney A Gabriel, MD, MAS

Role: CONTACT

ragabriel@health.ucsd.edu

858-663-7747

Kyle Norton, MD

Role: CONTACT

kfnorton@health.ucsd.edu

702-209-9532

Facility Contacts

Rodney A Gabriel, MD, MAS

Role: primary

ragabriel@health.ucsd.edu

858-663-7747

Kyle Norton, MD

Role: backup

kfnorton@health.ucsd.edu

702-209-9532

References

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.

Reference Type: BACKGROUND

PMID: 26710969 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24507705 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 38963513 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 38495961 (View on PubMed)

Other Identifiers

811212

Identifier Type: -

Identifier Source: org_study_id