Cryoanalgesia for Phantom Limb Pain

Overseen By Alparslan Turan, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Disqualifiers: Pregnancy, Incarceration, Morbid obesity, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether cryoanalgesia can reduce phantom limb pain, improve mobility, and decrease opioid use in individuals planning a lower leg amputation. Cryoanalgesia uses cold to numb nerves and potentially lessen pain. The study includes two groups: one receives the actual cryoanalgesia treatment, while the other receives a sham (fake) treatment. The trial seeks participants scheduled for a lower leg amputation, including at least one metatarsal bone in the foot, to determine if cryoanalgesia can enhance recovery. As an unphased trial, this study offers a chance to contribute to innovative research that could improve recovery outcomes for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

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

Research has shown that cryoanalgesia, a treatment using cold to numb nerves and reduce pain, is safe for humans. In one case, a patient's severe phantom limb pain decreased from 9 out of 10 to just 1 out of 10 a week after treatment, suggesting cryoanalgesia can effectively manage pain. Another study found that a patient experienced no phantom limb pain even a year after surgery with a similar technique called a cryo nerve block.

Cryoanalgesia has also been used successfully for other pain conditions, such as knee osteoarthritis and various nerve pain syndromes. While these results are promising, cryoanalgesia must be performed carefully to ensure the entire nerve is treated properly, avoiding potential issues. Overall, the treatment appears well-tolerated, with significant pain relief reported in previous cases. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about cryoanalgesia for phantom limb pain because it offers a novel approach to pain relief by using extreme cold to target and disable nerves, potentially providing longer-lasting relief than traditional treatments. Unlike standard options like medications or physical therapy, which can take time to show effects or may require ongoing use, cryoanalgesia uses the iovera° system to deliver targeted cold therapy directly to the nerve, aiming for faster and more sustained pain reduction. This method could transform how phantom limb pain is managed, minimizing reliance on medications and their side effects.

What evidence suggests that cryoanalgesia could be effective for phantom limb pain?

Research has shown that cryoanalgesia, which involves freezing nerves to reduce pain, may help with phantom limb pain. In one review, patients experienced significant pain relief, with a noticeable drop in pain levels on a 10-point scale. Another study suggested that cryo nerve blocks, which work similarly to cryoanalgesia, could reduce pain after surgery and prevent phantom limb pain. However, one study found that cryoanalgesia did not improve pain more than a fake treatment. In this trial, participants will receive either cryoanalgesia or a sham cryoanalgesia treatment to evaluate its effectiveness. Despite these mixed results, cryoanalgesia remains a promising option for those with phantom limb pain. ^{2 3 4 6 7}

Who Is on the Research Team?

Alparslan Turan, MD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are scheduled to have an amputation below the hip and including at least one bone in the foot. It's not suitable for those who don't meet these specific conditions.

Inclusion Criteria

I am scheduled for a leg amputation below the hip that includes part of my foot.

Exclusion Criteria

Pregnancy

Incarceration

My BMI is over 40.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Cryoanalgesia

Participants receive preoperative cryoanalgesia to improve post-amputation outcomes

1 week

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for phantom limb pain, mobility, and opioid consumption

3 months

Weekly assessments (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cryoanalgesia
• Sham Cryoanalgesia

Trial Overview The study tests if pre-amputation cryoanalgesia (a freezing technique to reduce pain) can lessen phantom limb pain after surgery, compared to a sham procedure. The impact on pain, mobility, opioid use, and overall well-being will be measured.

How Is the Trial Designed?

Group I: Cryoanalgesia Experimental Treatment 1 Intervention

Participants will receive cryoanalgesia with the The iovera° system.

Group II: Sham Cryoanalgesia Placebo Group 1 Intervention

Participants will receive Sham cryoanalgesia with the The iovera° system.

Cryoanalgesia is already approved in United States, European Union for the following indications:

Approved in United States as Cryoanalgesia for:

• Chronic pain management
• Phantom limb pain
• Intercostal neuralgia
• Lumbar facet pain
• Trigeminal neuralgia

Approved in European Union as Cryoanalgesia for:

• Chronic pain management
• Phantom limb pain
• Intercostal neuralgia
• Lumbar facet pain
• Trigeminal neuralgia

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Pacira Pharmaceuticals, Inc

Industry Sponsor

Trials

142

Recruited

14,300+

Headquarters

Tampa, USA

Known For

Non-opioid Pain Management

Top Products

Exparel, Zilretta, iovera

Dr. Jonathan Slonin

Pacira Pharmaceuticals, Inc

Chief Medical Officer since 2020

BSc in Biomedical Engineering and MD from University of Miami, MBA from George Washington University

Frank D. Lee

Pacira Pharmaceuticals, Inc

Chief Executive Officer since 2024

BSc in Chemical Engineering from Vanderbilt University, MBA from Wharton Graduate School of Business

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]

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]

A case report highlights the successful reduction of phantom limb pain (PLP) in a patient with bilateral phantom toe pain through the use of nerve blockade followed by cryoablation of the posterior tibial nerves.

This approach offers a potential treatment strategy for PLP, which affects a significant number of amputees, as up to 80% of individuals with amputated limbs experience this type of pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating phantom limb pain: cryoablation of the posterior tibial nerve. Fiala, M., Azariah, A., Woo, J., 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]

In a retrospective study of 18 patients, cryoanalgesia provided significant long-term pain relief for conditions like lumbar facet pain, sacroiliac pain, and knee pain, with the best results observed at three months post-treatment.

Most patients reported a clinically meaningful improvement in pain and function, with only three individuals experiencing a decline in their condition after one month.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous cryoanalgesia in pain management: a case-series. Bellini, M., Barbieri, M.[2019]

In a study of 5 patients with phantom limb pain (PLP), targeted treatment at the peripheral nerve location significantly reduced pain, with 3 patients experiencing over 90% relief after cryoanalgesia.

The findings suggest that identifying and treating peripheral pain sources can lead to long-term relief from PLP, highlighting the importance of addressing both central and peripheral factors in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of phantom limb pain by cryoneurolysis of the amputated nerve. Moesker, AA., Karl, HW., Trescot, AM.[2014]

In a study of 18 patients suffering from articular lumbar facet pain, knee pain, and sacroiliac pain, cryoanalgesia provided significant pain relief and improved function, with most patients reporting satisfaction as early as one month after the procedure.

The best results were observed at three months post-treatment, indicating that cryoanalgesia can be an effective long-term pain management option, as only three patients reported a decline in their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous cryoanalgesia in pain management: a case-series. Bellini, M., Barbieri, M.[2019]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39707720/

Cryoneurolysis for phantom limb pain: a systematic review On a 10-point pain scale, patients reported significant pain relief, with the pooled data showing a strong reduction in pain scores. In the case ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06071715

Cryoanalgesia to Treat Phantom Limb Pain Following ... The ultimate objective of the proposed research study is to determine if cryoanalgesia is an effective treatment for intractable post-amputation phantom limb ...

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

Ultrasound-Guided Percutaneous Cryoneurolysis to Treat ... Descriptively, cryoneurolysis did not demonstrably improve phantom and residual limb pain outcomes at any time point compared with the sham ...

4. tandfonline.com tandfonline.com/doi/abs/10.1080/17581869.2024.2441650

Cryoneurolysis for phantom limb pain: a systematic review On a 10-point pain scale, patients reported significant pain relief, with the pooled data showing a strong reduction in pain scores. In the case report, the ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2468428725001595

Intraoperative cryo nerve block during lower extremity ... This case highlights the potential benefits of cryo nerve block for postoperative pain reduction and prevention of phantom limb pain.

6. rapm.bmj.com rapm.bmj.com/content/early/2025/10/13/rapm-2025-107116

Cryoanalgesia to treat phantom limb pain following a trans ... Results After 1-month, average phantom limb pain intensity (primary outcome) was 5.0 (5.0, 6.0) in patients given cryoneurolysis (n=11) vs 5.0 ...

7. cureus.com cureus.com/articles/337006-cryoneurolysis-a-comprehensive-review-of-applications-in-pain-management

Cryoneurolysis: A Comprehensive Review of Applications ... Multiple studies have reported successful pain management for osteoarthritis of the knee and various neuropathic pain syndromes, including ...