Cryoanalgesia for Phantom Limb Pain

Overseen By Brian Ilfeld, MD, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Disqualifiers: Allergy to anesthetics, pregnancy, incarceration, morbid obesity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called cryoneurolysis, which involves freezing nerves, for individuals experiencing phantom limb pain after an above-knee amputation. Phantom limb pain occurs when pain is felt in a limb that is no longer present. The trial aims to determine if freezing the nerves can provide long-term relief. Participants will receive either the cryoneurolysis treatment or a sham (fake) treatment, with the option to try the other treatment later. Individuals who have had an above-knee amputation and experience moderate phantom pain daily for at least two months might be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to explore a novel treatment approach for phantom limb pain.

Will I have to stop taking my current medications?

You will need to keep your current pain medication routine the same from one month before to at least four months after the initial procedure.

What prior data suggests that cryoneurolysis is safe for treating phantom limb pain?

Research has shown that cryoneurolysis is generally safe for people. Studies have found that this treatment is well-tolerated and can help manage nerve pain. In one study, imaging-guided cryoneurolysis safely treated nerve pain caused by nerve damage. Another study found it to be a safe option for people with phantom limb pain, which is pain felt in a limb that has been amputated.

While these studies suggest that cryoneurolysis is safe, individual experiences can vary. Some people might experience mild side effects, such as numbness or tingling, but serious issues are rare. Overall, the research supports cryoneurolysis as a promising and safe option for treating phantom limb pain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about cryoneurolysis for phantom limb pain because it uses a novel approach to target nerve pain at its source. Unlike standard treatments such as medications or nerve blocks that often address symptoms more generally, cryoneurolysis works by applying extreme cold directly to the nerve, which can potentially offer longer-lasting relief. This technique aims to reduce pain by interrupting the pain signals from the nerves in the residual limb, offering a targeted and potentially more effective treatment option. Additionally, the precision of this method may lead to fewer side effects compared to systemic pain medications.

What evidence suggests that cryoneurolysis might be an effective treatment for phantom limb pain?

This trial will compare the effects of cryoneurolysis and sham treatment on phantom limb pain. Research suggests that cryoneurolysis, which participants in this trial may receive, might reduce phantom limb pain by freezing nerves to stop pain signals. However, results from past studies are mixed. One study found no significant pain reduction four months after treatment, while another reported pain relief lasting only about 11 days. Although promising, the long-term effectiveness of cryoneurolysis for phantom limb pain remains uncertain based on current evidence. ^{1 2 4 5 6}

Who Is on the Research Team?

Brian Ilfeld, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for adults over 18 who have had an above-knee amputation at least 12 weeks ago and suffer from moderate to severe phantom limb pain daily. Participants should not change their pain medication or undergo elective surgeries from one month before until four months after the initial treatment.

Inclusion Criteria

I had a leg amputation above the knee more than 12 weeks ago.

I experience daily phantom limb pain rated 4 or higher for the last 2 months.

I agree not to change my pain medication or have elective surgery for 5 months around my cryoneurolysis procedure.

Exclusion Criteria

My BMI is over 40.

You are currently in jail or prison.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive either cryoneurolysis or sham procedure on the major nerves of the thigh

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Data collected by telephone

Optional Crossover Treatment

Participants may opt for a crossover treatment with the alternative procedure (either active cryoneurolysis or sham)

4-6 months after initial treatment

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cryoneurolysis

Trial Overview The study tests cryoanalgesia, a prolonged nerve block achieved by freezing nerves, against a sham procedure to see if it can provide long-term relief from phantom limb pain in individuals with above-knee amputations. Each participant may receive both treatments over the course of the study.

How Is the Trial Designed?

Group I: Sham Comparator first, then optional cryoneurolysis treatment Experimental Treatment 2 Interventions

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. Optional 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.

Group II: Cryoneurolysis first, then optional sham crossover treatment Experimental Treatment 2 Interventions

Initial 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 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. Optional sham crossover 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.

Cryoneurolysis is already approved in United States for the following indications:

Approved in United States as Cryoneurolysis for:

• Pain management for traumatic rib fractures
• Postoperative pain relief

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Epimed International

Collaborator

Trials

2

Recruited

110+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Published Research Related to This Trial

A study involving 144 patients with lower-limb amputations found that cryoneurolysis did not significantly reduce phantom pain intensity compared to a sham treatment after 4 months, indicating limited efficacy for this intervention.

One serious adverse event occurred due to a protocol deviation, highlighting potential safety concerns associated with the procedure, particularly if not performed correctly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-guided Percutaneous Cryoneurolysis to Treat Chronic Postamputation Phantom Limb Pain: A Multicenter Randomized Controlled Trial. Ilfeld, BM., Smith, CR., Turan, A., et al.[2023]

Ultrasound guidance during cryoneurolysis allows for real-time monitoring of needle placement, leading to more accurate targeting of peripheral nerves and improved outcomes in pain relief.

Patients have reported varying degrees of long-term pain relief and functional improvement from cryoneurolysis, with no serious complications noted, suggesting it is a safe alternative to other pain management techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-Guided Cryoanalgesia of Peripheral Nerve Lesions. Djebbar, S., Rossi, IM., Adler, RS.[2017]

Ultrasound-guided percutaneous cryoneurolysis significantly reduced pain levels on postoperative day 2 after mastectomy, with active treatment participants reporting a median pain score of 0 compared to 3 in the sham group (P < 0.001).

The technique also led to a dramatic reduction in opioid use during the first three weeks post-surgery, with the active group using only 1.5 mg of oxycodone compared to 72 mg in the sham group, and resulted in lower rates of chronic pain after one year (3% in active vs 17% in sham, P < 0.001).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative Ultrasound-guided Percutaneous Cryoneurolysis for the Treatment of Pain after Mastectomy: A Randomized, Participant- and Observer-masked, Sham-controlled Study. Ilfeld, BM., Finneran, JJ., Swisher, MW., et al.[2023]

In three cases of limb amputation, ultrasound-guided percutaneous cryoneurolysis provided effective pain relief in the immediate postoperative period without leading to persistent postsurgical or phantom limb pain.

The procedure was safe, with no reported adverse events, suggesting that cryoneurolysis could be a promising alternative to traditional local anesthetic techniques for managing post-amputation pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-Guided Percutaneous Cryoneurolysis for Postoperative Analgesia After Limb Amputation: A Case Series. Gabriel, RA., Finneran, JJ., Trescot, AM., et al.[2021]

Image-guided percutaneous intercostal nerve cryoablation, using cone-beam computed tomography and software-assisted planning, is a feasible method for treating chronic post-thoracotomy pain syndrome (PTPS).

In a case study, this technique provided approximately 8 weeks of significant pain relief for a patient suffering from intractable PTPS, suggesting it may be a valuable option for managing this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided nerve cryoablation for post-thoracotomy pain syndrome. Koethe, Y., Mannes, AJ., Wood, BJ.[2021]

In a pilot study involving 21 patients with refractory phantom limb pain, image-guided percutaneous nerve cryoablation demonstrated a 100% technical success rate and was found to be a feasible and safe procedure.

Patients experienced significant reductions in pain intensity, from a mean score of 6.2 to 2.0, and improvements in disability scores, from 11.3 to 3.3, indicating that this treatment may be an effective option for managing phantom limb pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Image-Guided Cryoablation for the Treatment of Phantom Limb Pain in Amputees: A Pilot Study. Prologo, JD., Gilliland, CA., Miller, M., et al.[2022]

Cryoanalgesia, or cryoneurolysis, is a safe and effective method for relieving pain by applying extreme cold to peripheral nerves, interrupting pain signals without causing permanent nerve damage.

This technique, guided by imaging methods like ultrasound or CT, offers a minimally invasive alternative to traditional pain management approaches, especially important in the context of the opioid crisis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous cryoanalgesia for pain palliation: Current status and future trends. Filippiadis, D., Efthymiou, E., Tsochatzis, A., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02366832

NCT02366832 | Cryoablation for Phantom Limb Pain A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes. Participants may ...

2. bostonscientific.com bostonscientific.com/content/dam/bostonscientific/pi/portfolio-group/cryoablation/downloads/Nerve_cryoneurolysis_data_pack_(PI-1173604-AB).pdf

cryoneurolysis i clinical review Outcomes measured include distances from the ablation sites to origins of distal musculature, times to initial clinical recovery and muscle activation, and rate ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10374196/

Ultrasound-Guided Percutaneous Cryoneurolysis to Treat ... Percutaneous cryoneurolysis did not decrease chronic lower extremity phantom limb pain 4 months following treatment. However, these results were ...

4. ajronline.org ajronline.org/doi/10.2214/AJR.17.18452

Percutaneous Image-Guided Cryoneurolysis | AJR Sixty-four patients had a median duration of pain relief of 11 days. More recently, CN without image guidance has been studied as a potential treatment for many ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5746047/

Percutaneous Image-Guided Cryoablation for the Treatment of ... To prospectively evaluate percutaneous image-guided nerve cryoablation for treatment of refractory phantom limb pain (PLP) in a pilot cohort ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1051044316305371

Percutaneous Image-Guided Cryoablation for the ... Conclusions. Image-guided percutaneous nerve cryoablation is feasible and safe and may represent a new efficacious therapeutic option for patients with phantom ...