Cryoanalgesia to Treat Phantom Limb Pain Following Above-Knee Amputation

NCT06071715 | Completed Results DMC FDA Device

• 1 other identifier: CRYO Pilot AboveKneeAmputation
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

When a limb is severed, pain perceived in the part of the body that no longer exists often develops and is called "phantom limb" pain. Unfortunately, phantom pain goes away in only 16% of afflicted individuals, and there is currently no reliable definitive treatment. The exact reason that phantom limb pain occurs is unclear, but when a nerve is cut-as happens with an amputation-changes occur in the brain and spinal cord that actually increase with worsening phantom pain. These abnormal changes may often be corrected by putting local anesthetic-called a "nerve block"-on the injured nerve, effectively keeping any "bad signals" from reaching the brain with a simultaneous resolution of the phantom limb pain. However, when the nerve block resolves after a few hours, the phantom pain returns. But, this demonstrates that the brain abnormalities-and phantom pain-that occur with an amputation are not necessarily fixed, and may be dependent upon the "bad" signals being sent from the injured nerve(s), suggesting that a very long peripheral nerve block-lasting many months rather than hours-may permanently reverse the abnormal changes in the brain, and provide definitive relief from phantom pain. A prolonged nerve block lasting a few months may be provided by freezing the nerve using a process called "cryoneurolysis". The ultimate objective of the proposed research study is to determine if cryoanalgesia is an effective treatment for intractable post-amputation phantom limb pain. The proposed pilot study will include subjects with an existing above-knee amputation who experience intractable daily phantom limb pain. A single ultrasound-guided treatment of cryoneurolysis (or sham block-determined randomly like a flip of a coin) will be applied to the major nerves of the thigh. Although not required, each subject may return 4-6 months later for the alternative treatment (if the first treatment is sham, then the second treatment would be cryoneurolysis) so that all participants have the option of receiving the active treatment. Subjects will be followed for a total of 12 months with data collected by telephone.

Conditions

Amputation, Surgical; Amputation, Traumatic; Phantom Limb Pain; Phantom Pain Following Amputation of Lower Limb

Outcome Measures

Primary Outcomes (1)

• Average Pain Intensity Change From Baseline 1 Month Post-intervention

  The "average" pain level measured using the numeric rating scale for the previous 24 hours. This is a 0-10 Likert scale measuring pain level with 0=no pain and 10=worst imaginable pain. The primary outcome will be the change from baseline in average pain intensity as measured with the numeric rating scale 1 month following the initial intervention.

  Baseline and Month 1

Secondary Outcomes (32)

• Average Daily Phantom Pain Intensity Change From Baseline

  Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12

• Worst Daily Phantom Pain Intensity Change From Baseline

  Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12

• Least Daily Phantom Pain Intensity Change From Baseline

  Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12

• Current Daily Phantom Pain Intensity Change From Baseline

  Post-intervention days 1, 7, and Months 1, 2, 3, 4, and 12

• CROSSOVER Average Daily Phantom Pain Intensity Change From Baseline

  Following the CROSSOVER treatment on Days 1 and 7; Months 1, 2, 3, and 4

Study Arms (3)

Cryoneurolysis only

EXPERIMENTAL

Cryoneurolysis of the major nerves of the thigh in the residual limb: The cryoneurolysis device will be triggered using 1 cycle of 5.5-minute argon activation followed by a 30-60 second defrost with helium (Varian) or 2 cycles of 2-minute gas activation with an active probe separated by a 30-60 second defrost (Epimed). For active treatment, the gas will be deployed to the probe tip where a drop in temperature will result in cryoneurolysis.

Device: ACTIVE cryoneurolysis

Sham Comparator only

SHAM COMPARATOR

Sham cryoneurolysis of the major nerves of the thigh in the residual limb: The cryoneurolysis device will be triggered using 1 cycle of 5.5-minute argon activation followed by a 30-60 second defrost period with helium (Varian) or 2 cycles of 2-minute gas activation with a sham probe separated by a 30-60 second defrost (Epimed). However, for sham treatment, the gas is NOT deployed to the probe tip and therefore there is NO drop in temperature with NO resulting cryoneurolysis.

Device: SHAM cryoneurolysis

Sham Comparator first, then optional cryoneurolysis treatment

OTHER

Initial treatment: Sham cryoneurolysis of the major nerves of the thigh in the residual limb: The cryoneurolysis device will be triggered using 1 cycle of 5.5-minute argon activation followed by a 30-60 second defrost period with helium (Varian) or 2 cycles of 2-minute gas activation with a sham probe separated by a 30-60 second defrost (Epimed). However, for sham treatment, the gas is NOT deployed to the probe tip and therefore there is NO drop in temperature with NO resulting cryoneurolysis. Active crossover treatment: Cryoneurolysis of the major nerves of the thigh in the residual limb: The cryoneurolysis device will be triggered using 1 cycle of 5.5-minute argon activation followed by a 30-60 second defrost period with helium (Varian) or 2 cycles of 2-minute gas activation with an active probe separated by a 30-60 second defrost (Epimed). For active treatment, the gas will be deployed to the probe tip where a drop in temperature will result in cryoneurolysis.

Device: ACTIVE cryoneurolysis; Device: SHAM cryoneurolysis

Interventions

ACTIVE cryoneurolysis DEVICE

Cryoneurolysis of the major nerves of the thigh (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 1 cycle of 5.5-minute argon activation followed by a 30-60 second defrost period with helium Initial treatment: Cryoneurolysis of the major nerves of the thigh (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 1 cycle of 5.5-minute argon activation followed by a 30-60 second defrost period with helium (Varian) or 2 cycles of 2-minute gas activation with an active probe separated by a 30-60 second defrost (Epimed). For active treatment, the gas will be deployed to the probe tip where a drop in temperature will result in cryoneurolysis.

Also known as: cryoablation

Cryoneurolysis only; Sham Comparator first, then optional cryoneurolysis treatment

SHAM cryoneurolysis DEVICE

SHAM cryoneurolysis of the major nerves of the thigh (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 1 cycle of 5.5-minute argon activation followed by a 30-60 second defrost period with helium (Varian) or 2 cycles of 2-minute gas activation with a sham probe separated by a 30-60 second defrost (Epimed). However, for sham treatment, the gas is NOT deployed to the probe tip and therefore there is NO drop in temperature with NO resulting cryoneurolysis.

Also known as: sham cryoablation

Sham Comparator first, then optional cryoneurolysis treatment; Sham Comparator only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients of at least 18 years of age
• Trans-femoral traumatic or surgical amputation at least 12 weeks prior to enrollment distal to the hip (femoral head remaining)
• Experiencing at least moderate phantom limb pain-defined as a 4 or higher on the Numeric Rating Scale (NRS; 0-10, 0= no pain; 10=worst imaginable pain)-at least daily for the previous 2 months
• willing to avoid both changes to their analgesic regimen as well as elective surgical procedures from 1 month prior to and at least 4 months following the initial cryoneurolysis procedure.

You may not qualify if:

• allergy to amide local anesthetics
• pregnancy
• incarceration
• inability to communicate with the investigators
• morbid obesity (body mass index \> 40 kg/m2)
• possessing any contraindication specific to cryoneurolysis such as a localized infection at the treatment site, cryoglobulinemia, cold urticaria and Reynaud's Syndrome

Sponsors & Collaborators

• University of California, San Diego: lead
• Varian Medical Systems: collaborator

Study Sites (1)

University of California San Diego

La Jolla, California, 92037, United States

Location

Related Publications (3)

• Gabriel RA, Finneran JJ 4th, Trescot AM, Ilfeld BM. Ultrasound-Guided Percutaneous Cryoneurolysis for Postoperative Analgesia After Limb Amputation: A Case Series. A A Pract. 2019 Apr 1;12(7):231-234. doi: 10.1213/XAA.0000000000000893.

  PMID: 30234513 BACKGROUND

• Said ET, Marsh-Armstrong BP, Fischer SJ, Suresh PJ, Swisher MW, Trescot AM, Prologo JD, Abdullah B, Ilfeld BM. Relative Effects of Various Factors on Ice Ball Formation and Ablation Zone Size During Ultrasound-Guided Percutaneous Cryoneurolysis: A Laboratory Investigation to Inform Clinical Practice and Future Research. Pain Ther. 2023 Jun;12(3):771-783. doi: 10.1007/s40122-023-00497-y. Epub 2023 Mar 31.

  PMID: 37000371 BACKGROUND

• Ilfeld BM, Finneran JJ, Abdullah B, Vadakkan S, Alkabalan RA, Gabriel RA. Cryoanalgesia to treat phantom limb pain following a trans-femoral (above-knee) amputation: a randomized, sham-controlled pilot study. Reg Anesth Pain Med. 2025 Oct 13:rapm-2025-107116. doi: 10.1136/rapm-2025-107116. Online ahead of print.

  PMID: 41033797 DERIVED

MeSH Terms

Conditions

Amputation, Traumatic; Phantom Limb

Interventions

Cryosurgery

Condition Hierarchy (Ancestors)

Wounds and Injuries; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Results Point of Contact

• Title: Baharin Abdullah
• Organization: University of California San Diego

baabdullah@health.ucsd.edu

+1 858-220-5714

Study Officials

• Brian Ilfeld, MD, MS

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All individuals will be masked to treatment with the exception of the anesthesiologist administering the procedure who will choose which probe to use: the functional or sham. Of note, this individual could not be masked to treatment since the cryoneurolysis ice ball is visualized on ultrasound; and, the practitioner would see a lack of ice ball formation for the sham probes.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology

Model Details: The primary endpoint at 1 month following the initial treatment will utilize a parallel group study design; however, an optional crossover is offered to subjects between 4-6 months following the initial treatment.

Study Record Dates

• First Submitted: October 1, 2023
• First Posted: October 6, 2023
• Study Start: February 12, 2024
• Primary Completion: October 9, 2025
• Study Completion: October 9, 2025
• Last Updated: April 8, 2026
• Results First Posted: April 8, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)