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Not yet recruitingNCT07618689AXON-FREEZEUpdated Jun 2, 2026

Proximal Nerve Cryoablation Versus Perineuroma Cryoablation for Chronic Neuroma Pain After Combat-Related Amputation

An interventional study of Perineuroma Cryoablation and Proximal Nerve Cryoablation in Neuroma and Cryoablation, sponsored by Ukrainian Society of Regional Anesthesia and Pain Therapy. Not yet recruiting at 1 site in Ukraine. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-06-02.

Sponsored by Ukrainian Society of Regional Anesthesia and Pain Therapy · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
50
Allocation
Non-randomized
Ages
18 Years to 60 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Neuroma
  • Cryoablation

Keywords

  • Cryoablation
  • neuroma pain
  • combat-related amputation
  • phantom limb pain
  • residual limb pain
  • peripheral nerve injury
  • Wallerian degeneration
  • ultrasound-guided intervention
  • military trauma
03

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
50 participants (estimated)

Study arms

  • Experimental
    Perineuroma Cryoablation

    Ultrasound-guided cryoablation performed adjacent to the painful neuroma.

    Procedure: Perineuroma Cryoablation

  • Active comparator
    Proximal Nerve Cryoablation

    Ultrasound-guided cryoablation performed proximal to the neuroma along the affected nerve.

    Procedure: Proximal Nerve Cryoablation

Interventions

  • ProcedurePerineuroma Cryoablation

    Ultrasound-guided cryoablation performed adjacent to the painful neuroma.

  • ProcedureProximal Nerve Cryoablation

    Ultrasound-guided cryoablation performed proximal to the neuroma along the affected nerve.

05

What researchers measure

Primary outcomes

  1. Change in Chronic Neuroma Pain Intensity

    Change in average neuroma pain intensity measured using the Numeric Rating Scale (NRS).

    Time frame: Baseline to 12 weeks

Secondary outcomes

  1. 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.

    Time frame: : Baseline to 24 weeks

06

Study locations

1 site
  • Vinnitsya university hospital
    Vinnytsia, Вінницька 21000, Ukraine
07

References and documents

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07618689
Lead sponsor
Ukrainian Society of Regional Anesthesia and Pain Therapy
Responsible party
Dmytro Dmytriiev (PhD, Professor, Ukrainian Society of Regional Anesthesia and Pain Therapy) — Principal investigator
First posted
Jun 1, 2026
Start date
Oct 15, 2026 (estimated)
Primary completion
Oct 15, 2026 (estimated)
Completion
Oct 15, 2026 (estimated)
Last update
Jun 2, 2026

Study contacts

Dmytro Dmytriiev, PhD.Professor
Contact
mddmytriiev@gmail.com
+380674309449

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is not yet recruiting, as verified in May 2026. You cannot join it, but the record below documents what was studied.

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