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

20 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Cryoanalgesia for Phantom Limb Pain?

Research shows that cryoanalgesia, which uses cold temperatures to target nerves, can significantly reduce phantom limb pain. In one study, 3 out of 5 patients experienced a 90% or greater reduction in pain, and another study reported profound pain relief after limb amputation with no long-term pain. ^{1 2 3 4 5}

Is cryoanalgesia safe for treating phantom limb pain?

Cryoanalgesia, also known as cryoneurolysis, is generally considered safe with minimal risk of complications when performed using imaging guidance. Studies have shown no adverse events associated with the procedure in treating phantom limb pain. ^{1 2 3 4 6}

How is the treatment Cryoanalgesia unique for phantom limb pain?

Cryoanalgesia is unique because it uses low temperatures to temporarily disable nerves, providing long-term pain relief without the need for ongoing medication. This method targets the peripheral nerves directly, which can lead to significant and lasting reduction in phantom limb pain, unlike traditional treatments that may not address the nerve-specific origin of the pain. ^{1 2 3 7 8}

What is the purpose of this trial?

Investigators will evaluate preamputation cryoanalgesia on pain, mobility, opioid use and general physical and emotional disability using a pilot randomized trial design, to explore the amount and variability of improvement on those outcomes and to investigate the potentiality of conducting a future larger randomized controlled trial, which the investigators will assess quantitatively the benefits of cryoanalgesia.

Research Team

Alparslan Turan, MD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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 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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Ultrasound-guided Percutaneous Cryoneurolysis to Treat Chronic Postamputation Phantom Limb Pain: A Multicenter Randomized Controlled Trial. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment of phantom limb pain by cryoneurolysis of the amputated nerve. [2014]

3. United States pubmed.ncbi.nlm.nih.gov

Ultrasound-Guided Percutaneous Cryoneurolysis for Postoperative Analgesia After Limb Amputation: A Case Series. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Percutaneous Image-Guided Cryoablation for the Treatment of Phantom Limb Pain in Amputees: A Pilot Study. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Treating phantom limb pain: cryoablation of the posterior tibial nerve. [2022]

6. France pubmed.ncbi.nlm.nih.gov

Percutaneous cryoanalgesia for pain palliation: Current status and future trends. [2021]

7. Poland pubmed.ncbi.nlm.nih.gov

Percutaneous cryoanalgesia in pain management: a case-series. [2019]

8. Poland pubmed.ncbi.nlm.nih.gov

Percutaneous cryoanalgesia in pain management: a case-series. [2019]