Cryoneurolysis for Post-Mastectomy Pain

Recruiting at 5 trial locations

Overseen By Baharin Abdullah, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must not be taking: Anticoagulants, Chronic opioids

Disqualifiers: Pulmonary disease, Insulin-dependent diabetes, 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: 5

Duration: Immediate postoperative period

216 Participants Needed

Trial Summary

What is the purpose of this trial?

Breast cancer is the most common type of cancer in women. Removal of the breast, called "mastectomy", is performed either when there is cancer-or an increased risk of cancer-in the breast. This can result in a lot of pain during the months after surgery. Opioids-"narcotics"-are the most common pain control method provided to patients; but they frequently do not relieve enough pain, have undesirable side effects like vomiting and constipation, and are sometimes misused which can lead to addiction. Mastectomy also frequently results in long-term pain which can interfere with physical and emotional functioning; and the more pain patients have immediately after surgery, the greater the risk of developing long-term pain. Numbing the nerves with local anesthetic can decrease the amount of short- and long-term pain experienced by patients, but even the longest types of these nerve blocks last for hours or days, and not the 1-2 months of pain typically following mastectomy. So, there is reason to believe that if the nerve blocks could be extended so that they last longer than the pain from surgery, short- and long-term pain might be avoided completely without the need for opioids. A prolonged nerve block may be provided by freezing the nerve using a technique called "cryoneurolysis". With cryoneurolysis and ultrasound machines, a small needle-like "probe" may be placed through anesthetized skin and guided to the target nerve to allow freezing. The procedure takes about 5 minutes for each nerve, involves little discomfort, has no side effects, and cannot be misused or become addictive. After 2-3 months, the nerve returns to normal functioning. The investigators have completed a small study suggesting that a single cryoneurolysis treatment may provide potent pain relief after mastectomy. The ultimate objectives of the proposed research study are to determine if temporarily freezing the nerves that go to the breast will decrease short-term pain, opioid use, physical and emotional dysfunction, and long-term pain following mastectomy when added to current and customary postoperative analgesics. The current project is a pragmatic, multicenter, randomized, triple-masked (investigators, participants, statisticians), sham/placebo-controlled, parallel-arm, human-subjects, post-market clinical trial to determine if cryoneurolysis is an effective non-opioid treatment for pain following mastectomy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using opioids regularly, you may not be eligible to participate.

What data supports the effectiveness of the treatment Cryoneurolysis for Post-Mastectomy Pain?

Research shows that ultrasound-guided cryoneurolysis, which uses cold temperatures to temporarily block nerve pain, has been effective in reducing pain after thoracic surgeries and in patients with nerve pain from tumors. This suggests it could also help manage pain after a mastectomy. ^{1 2 3 4 5}

Is cryoneurolysis safe for humans?

Cryoneurolysis, which uses low temperatures to temporarily block nerve pain, has been used safely in various procedures with no serious complications reported. It has been shown to provide pain relief for conditions like post-thoracotomy pain and peripheral nerve lesions, making it a safe alternative to other pain management techniques. ^{1 4 6 7 8}

How is the treatment cryoneurolysis unique for post-mastectomy pain?

Cryoneurolysis is unique because it uses extremely cold temperatures to temporarily block pain signals by freezing the nerves, providing pain relief without the need for drugs. This treatment is guided by ultrasound, allowing precise targeting of the nerves, and offers a radiation-free, safe alternative to other pain management techniques. ^{1 2 3 4 6}

Eligibility Criteria

This trial is for adults over 18 years old who are undergoing a mastectomy. It's not suitable for those with infections at the surgery site, chronic opioid users, patients having certain other breast procedures, or individuals unable to stay in contact with researchers. People on blood thinners, needing supplemental oxygen, with cold-triggered diseases or nerve damage in the chest area, and insulin-dependent diabetics can't participate.

Inclusion Criteria

I am 18 years old or older.

I am having or have had a complete or modified breast removal surgery.

Exclusion Criteria

I use insulin to manage my diabetes.

I had surgery on the opposite breast that wasn't a mastectomy.

I have nerve damage in my chest on the same side.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo cryoneurolysis or sham procedure following mastectomy to manage postoperative pain

Immediate postoperative period

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for pain levels and opioid consumption over the first 2 months

8 weeks

Multiple visits (in-person and virtual) on days 1, 2, 3, 4, 7, 14, 21, 30, 45, and 60

Follow-up

Participants are monitored for long-term outcomes including chronic pain and physical/emotional functioning

12 months

Visits at months 3, 6, 9, and 12

Treatment Details

Interventions

• Cryoneurolysis
• Sham Comparator

Trial Overview The study tests if cryoneurolysis—a technique that temporarily freezes nerves—can reduce pain after mastectomy without opioids. Participants will be randomly assigned to receive either cryoneurolysis or a sham procedure (placebo), and neither they nor the investigators know which one they're getting.

Participant Groups

Group I: Cryoneurolysis Active Control 1 Intervention

Cryoneurolysis of the 2nd-6th thoracic intercostal nerves will be treated on the ipsilateral surgical side (bilaterally for bilateral surgical procedures): for each nerve the cryoneurolysis device will be triggered using 1 cycle of 5.5-minute \[all but 4 participants: 064-067\] or 3 minutes \[only 4 participants 064-067; change based on new laboratory data, then changed back based on inadequate freeze\] argon activation (2000 psi and 100% power) followed by a 30-second helium defrost. For active probes, the gas will be deployed to the tip where a drop in temperature to approximately -70°C will result in cryoneurolysis.

Group II: Sham Procedure Placebo Group 1 Intervention

Sham cryoneurolysis of the 2nd-6th thoracic intercostal nerves will be applied on the ipsilateral surgical side (bilaterally for bilateral surgical procedures): for each nerve the cryoneurolysis device will be triggered using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods (Epimed) or 1 cycle of 5.5 minutes \[all but 4 participants: 064-067\] or 3 minutes \[only 4 participants 064-067; change based on new laboratory data, then changed back based on inadequate freeze\] of argon and 30 seconds of helium (Varian). However, for sham probes, the gas is not deployed to the tip and therefore there is no drop in temperature resulting in 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+

Department of Defense Congressionally Directed Medical Research Program

Collaborator

Trials

3

Recruited

640+

Findings from Research

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]

Ultrasound-guided percutaneous cryoanalgesia effectively targets intercostal nerves to provide postoperative pain relief after thoracic surgery, which is crucial for improving lung function and reducing complications.

Using a high-frequency ultrasound probe allows for precise placement of the cryoprobe near the intercostal nerve, confirmed by specific ultrasound signs, enhancing the efficacy of the cryoanalgesia technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short communication: ultrasound-guided percutaneous cryoanalgesia of intercostal nerves for uniportal video-assisted thoracic surgery. Nicolás, M., Acosta, CM., Martinez Ferro, M., et al.[2022]

The size of the ice ball created during ultrasound-guided percutaneous cryoneurolysis is significantly influenced by the gauge of the cryoprobe used, with larger probes (14 gauge) producing ice balls that are up to 512% larger and achieving much lower temperatures compared to smaller probes (18 gauge).

Visualizing a nerve fully encompassed in an ice ball does not guarantee effective treatment, as temperatures within the ice ball may not reach the levels necessary to induce Wallerian degeneration, highlighting the need for further research to understand the implications for human tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Said, ET., Marsh-Armstrong, BP., Fischer, SJ., 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 of the intercostal nerves was successfully used to treat a 40-year-old male with severe post-thoracotomy pain syndrome (PTPS) that had persisted for two years.

The treatment resulted in a 75% reduction in pain immediately after the procedure, with sustained 50% pain relief for eight weeks, suggesting that this method is a safe and effective option for managing chronic PTPS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-Guided Percutaneous Cryoneurolysis for Post-Thoracotomy Pain Syndrome: A Case Report. Perese, J., Oswald, J., Gabriel, RA.[2023]

Ultrasound-guided cryoablation of intercostal nerves has been successfully performed in four patients with postthoracotomy pain syndrome, providing pain relief for at least one month without any complications.

The use of ultrasound enhances the safety of the procedure by allowing visualization of the pleura, which is particularly beneficial in thin patients, potentially reducing the risk of pneumothorax and improving the success rate of cryoablation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-guided intercostal nerve cryoablation. Byas-Smith, MG., Gulati, A.[2016]

References

1. United States 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. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

Short communication: ultrasound-guided percutaneous cryoanalgesia of intercostal nerves for uniportal video-assisted thoracic surgery. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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. [2023]

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

Ultrasound-Guided Cryoanalgesia of Peripheral Nerve Lesions. [2017]

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

Cryoneurolysis in Patients with Dorsal Neuropathic Pain Secondary to Tumor Invasion. [2020]

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

Ultrasound-Guided Percutaneous Cryoneurolysis for Post-Thoracotomy Pain Syndrome: A Case Report. [2023]

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

Ultrasound-guided intercostal nerve cryoablation. [2016]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Ultrasound-guided percutaneous cryoneurolysis providing postoperative analgesia lasting many weeks following a single administration: a replacement for continuous peripheral nerve blocks?: a case report. [2019]