Cryoanalgesia to Treat Post-Amputation Phantom Limb Pain: A Department of Defense Funded Multicenter Study

NCT03449667 | Completed Results DMC FDA Device

• 3 other identifiers: CRYO for Phantom Pain (DoD)W81XWH-17-2-0051PR160263
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 6

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 research study will include subjects with an existing lower extremity 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 target nerve(s) involved with the phantom pain. Although not required, each subject may return four 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

Post-Amputation Phantom Limb Pain

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Average Daily Phantom Pain Intensity

  The difference in average daily phantom pain intensity at baseline and 4 months following the initial intervention (measured with the numeric rating scale as part of the Brief Pain Inventory with a minimum value of 0 and maximum value of 10, 0=no pain and 10=worst imaginable pain)

  Baseline and 4 months later (difference between the two is the primary end point)

Secondary Outcomes (13)

• Average Daily Phantom Pain Intensity

  Endpoints will be evaluated at baseline and on Days 1 and 7; and Months 1, 2, 3, and 4 after both the initial and subsequently the crossover treatments; and 12 months after the initial treatment

• Worst Daily Phantom Pain Intensity

  Endpoints will be evaluated at baseline and on Days 1 and 7; and Months 1, 2, 3, and 4 after both the initial and subsequently the crossover treatments; and 12 months after the initial treatment

• Residual Limb Pain, Average

  Endpoints will be evaluated at baseline and on Days 1 and 7; and Months 1, 2, 3, and 4 after both the initial and subsequently the crossover treatments; and 12 months after the initial treatment

• Residual Limb Pain, Worst

  Endpoints will be evaluated at baseline and on Days 1 and 7; and Months 1, 2, 3, and 4 after both the initial and subsequently the crossover treatments; and 12 months after the initial treatment

• Patient Global Impression of Change

  Endpoints will be evaluated on Days 1 and 7; and Months 1, 2, 3, and 4 after both the initial and subsequently the crossover treatments; and 12 months after the initial treatment

Study Arms (2)

Cryoneurolysis first, then optional sham crossover treatment

ACTIVE COMPARATOR

Initial treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. Optional sham crossover treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.

Device: Cryoneurolysis; Device: Sham Comparator

Sham Comparator first, then optional cryoneurolysis treatment

SHAM COMPARATOR

Initial treatment: Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis. Optional cryoneurolysis treatment: Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.

Device: Cryoneurolysis; Device: Sham Comparator

Interventions

Cryoneurolysis DEVICE

Cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.

Also known as: Cryoanalgesia

Cryoneurolysis first, then optional sham crossover treatment; Sham Comparator first, then optional cryoneurolysis treatment

Sham Comparator DEVICE

Sham cryoneurolysis of the femoral and sciatic nerves (or their distal counterparts) in the residual limb: The cryoneurolysis device will be triggered using 3 cycles of 2-minute gas activation separated by 1-minute defrost periods. However, for sham probes, the nitrous oxide is not deployed to the tip and therefore there is no drop in temperature resulting in cryoneurolysis.

Also known as: placebo, control

Cryoneurolysis first, then optional sham crossover treatment; Sham Comparator first, then optional cryoneurolysis treatment

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
• with a lower limb traumatic or surgical amputation at least 12 weeks prior to enrollment distal to the hip (femoral head remaining)
• who experience at least moderate phantom limb pain-defined as a 3 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.
• accepting of a cryoneurolysis procedure
• 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
• United States Department of Defense: collaborator

Study Sites (6)

Veterans Affairs Palo Alto Health Care System

Palo Alto, California, 94304, United States

Location

University California San Diego

San Diego, California, 92103, United States

Location

Naval Medical Center San Diego (NMCSD)

San Diego, California, 92134, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• Moesker AA, Karl HW, Trescot AM. Treatment of phantom limb pain by cryoneurolysis of the amputated nerve. Pain Pract. 2014 Jan;14(1):52-6. doi: 10.1111/papr.12020. Epub 2012 Dec 19.

  PMID: 23279331 RESULT

Results Point of Contact

• Title: Brian M. Ilfeld, MD, MS
• Organization: University of California San Diego

bilfeld@health.ucsd.edu

(858) 822-0776

Study Officials

• Brian M Ilfeld, MD, MS

  University California San Diego Department of Anesthesiology

  PRINCIPAL INVESTIGATOR

• Rodney Gabriel, MD, MAS

  University California San Diego Department of Anesthesiology

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, 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, In Residence

Model Details: The primary endpoint at 4 months following the initial treatment will utilize a parallel group study design; however, an optional crossover is offered to subjects following this time point.

Study Record Dates

• First Submitted: February 22, 2018
• First Posted: February 28, 2018
• Study Start: March 23, 2018
• Primary Completion: August 17, 2021
• Study Completion: March 17, 2022
• Last Updated: February 17, 2023
• Results First Posted: February 17, 2023

Record last verified: 2023-02

Locations

US (6)