Proximal Nerve Cryoablation Versus Perineuroma Cryoablation for Chronic Neuroma Pain After Combat-Related Amputation (AXON-FREEZE)

atients with combat-related amputations frequently develop chronic neuroma pain that interferes with rehabilitation, prosthesis use, mobility, sleep, and quality of life. Cryoablation is a minimally invasive treatment that produces controlled nerve injury using extreme cold. Although the freezing effect is localized around the cryoprobe, axonal interruption followed by distal Wallerian degeneration may extend functional denervation distal to the ablation site.

This study aims to compare two ultrasound-guided cryoablation strategies for chronic neuroma pain after combat-related amputation: cryoablation performed directly near the neuroma and cryoablation performed proximal to the neuroma along the affected nerve.

The study will evaluate whether proximal nerve cryoablation produces greater or longer-lasting analgesic effects compared with perineuroma cryoablation.

Study Overview

• Status: Not yet recruiting
• Conditions: Neuroma; Cryoablation
• Intervention / Treatment: Procedure: Perineuroma Cryoablation; Procedure: Proximal Nerve Cryoablation

Detailed Description

Chronic neuroma pain is a common and disabling complication following combat-related limb trauma and amputation. Persistent neuroma pain may contribute to residual limb pain, phantom limb pain, impaired prosthesis tolerance, reduced mobility, sleep disturbance, and decreased quality of life. Current treatment strategies frequently provide incomplete or temporary analgesia.

Cryoablation is an ultrasound-guided minimally invasive technique that induces controlled axonal injury using extreme cold temperatures. Although the direct freezing zone extends only a few millimeters around the cryoprobe, cryo-induced axonotmesis may trigger distal Wallerian degeneration along the affected nerve pathway while preserving connective tissue structures that support potential nerve regeneration.

The optimal anatomical target for cryoablation in painful neuromas remains unclear. Cryoablation performed directly adjacent to the neuroma may interrupt local nociceptive signaling, whereas proximal nerve cryoablation may produce broader distal analgesic effects by interrupting axonal conduction proximal to the neuroma-bearing segment.

The AXON-FREEZE Trial is a prospective multicenter controlled study designed to compare proximal nerve cryoablation versus perineuroma cryoablation for chronic neuroma pain after combat-related amputation.

Participants with ultrasound-confirmed painful neuromas will undergo ultrasound-guided cryoablation using one of the two treatment strategies according to study allocation and local clinical practice. Clinical follow-up will include assessment of neuroma pain intensity, neuropathic pain characteristics, phantom limb pain, residual limb pain, prosthesis tolerance, analgesic consumption, patient-reported improvement, and adverse events.

The study aims to improve understanding of cryoablation targeting strategies and evaluate whether proximal nerve cryoablation may provide stronger or longer-lasting pain relief compared with cryoablation performed adjacent to the neuroma.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dmytro Dmytriiev, PhD.Professor; Phone Number: +380674309449; Email: mddmytriiev@gmail.com

Study Locations

• Ukraine
  • Вінницька
    • Vinnytsia, Вінницька, Ukraine, 21000
      • Vinnitsya university hospital
      • Contact: Dmytro Dmytriiev, Phd; Phone Number: 0674309449; Email: mddmytriiev@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years
• Combat-related limb amputation
• Chronic neuroma pain lasting ≥3 months
• Ultrasound-confirmed painful neuroma
• Average pain intensity ≥4/10 on Numeric Rating Scale
• Positive Tinel sign
• Ability to undergo ultrasound-guided cryoablation
• Stable analgesic regimen for at least 14 days
• Ability to provide written informed consent

Exclusion Criteria:

• Active infection at the treatment site
• Open wound preventing safe procedure
• Previous cryoablation of the target nerve within 6 months
• Neuroma surgery within 3 months
• Severe coagulopathy or anticoagulation contraindicating procedure
• Pregnancy or breastfeeding
• Severe uncontrolled systemic disease
• Inability to complete follow-up assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Perineuroma Cryoablation; Ultrasound-guided cryoablation performed adjacent to the painful neuroma.	Procedure: Perineuroma Cryoablation; Ultrasound-guided cryoablation performed adjacent to the painful neuroma.
Active Comparator: Proximal Nerve Cryoablation; Ultrasound-guided cryoablation performed proximal to the neuroma along the affected nerve.	Procedure: Proximal Nerve Cryoablation; Ultrasound-guided cryoablation performed proximal to the neuroma along the affected nerve.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Chronic Neuroma Pain Intensity	Change in average neuroma pain intensity measured using the Numeric Rating Scale (NRS).	Baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DN4 neuropathic pain score	Assessment of neuropathic pain characteristics using the Douleur Neuropathique 4 (DN4) questionnaire. Higher scores indicate greater neuropathic pain involvement associated with chronic neuroma pain after combat-related amputation.	: Baseline to 24 weeks

Collaborators and Investigators

• Sponsor: Ukrainian Society of Regional Anesthesia and Pain Therapy

Study record dates

Study Major Dates

• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): October 15, 2026
• Study Completion (Estimated): October 15, 2026

Study Registration Dates

• First Submitted: May 23, 2026
• First Submitted That Met QC Criteria: May 23, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 30, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cryoablation; peripheral nerve injury; neuroma pain; phantom limb pain; ultrasound-guided intervention; residual limb pain; Wallerian degeneration; military trauma; combat-related amputation
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Wounds and Injuries; Postoperative Complications; Pathologic Processes; Neoplasms; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neoplasms by Histologic Type; Neurobehavioral Manifestations; Neoplasms, Nerve Tissue; Trauma, Nervous System; Nerve Sheath Neoplasms; Perceptual Disorders; Pain, Postoperative; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Nerve Degeneration; Neuroma; Peripheral Nerve Injuries; Phantom Limb; Wallerian Degeneration
• Other Study ID Numbers: 10v213022026; USRA (Other Identifier: Ukranian Society of Regional Anesthesia and Pain Therapy)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data including demographic characteristics, ultrasound findings, neuroma pain intensity scores, DN4 neuropathic pain assessments, phantom limb pain measures, residual limb pain outcomes, prosthesis tolerance assessments, analgesic consumption, adverse events, and follow-up clinical evaluations collected during the study will be available for sharing. The study protocol, statistical analysis plan, and analytic code may also be shared upon reasonable request.
• IPD Sharing Access Criteria: Beginning 6 months after publication of the primary study results and ending 5 years after publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No