Cryoneurolysis for Post-Mastectomy Pain

Enrolling by invitation 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if freezing certain nerves with cryoneurolysis, a type of nerve treatment, can reduce pain after a mastectomy, which is surgery to remove the breast. The trial tests whether this method can lessen the need for opioids, which are often used for pain but can cause side effects like nausea and addiction risks. Participants will receive either the actual cryoneurolysis treatment or a placebo version to compare results. This trial suits adults undergoing mastectomy surgery who seek non-opioid pain relief options. As an unphased trial, it offers a unique opportunity for patients to explore innovative pain management strategies without the constraints of traditional trial phases.

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 prior data suggests that cryoneurolysis is safe for post-mastectomy pain relief?

Research shows that cryoneurolysis is a safe and promising method for managing pain after a mastectomy. Studies have found that this technique greatly reduces pain and improves patients' quality of life. Cryoneurolysis temporarily freezes the nerves, numbing pain without the risks linked to opioid use. The procedure is quick, causes little discomfort, and avoids side effects like addiction. Participants in previous studies experienced significant pain relief, indicating that the treatment is well-tolerated. This evidence supports the safety of cryoneurolysis for post-surgical pain management. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for post-mastectomy pain involve medications like opioids or nerve blocks, which can have significant side effects or require repeated administration. Cryoneurolysis is unique because it directly targets and "freezes" the nerves responsible for transmitting pain, potentially providing longer-lasting relief without the need for frequent doses. This technique uses a cryoneurolysis device to cool the nerves to around -70°C, which can interrupt pain signals more effectively than conventional methods. Researchers are excited about this approach because it offers a non-drug alternative that could reduce reliance on opioids and their associated risks.

What evidence suggests that cryoneurolysis is effective for post-mastectomy pain?

Research has shown that cryoneurolysis, which participants in this trial may receive, can greatly reduce pain after a mastectomy. One study found that this treatment lowered pain levels and improved patients' quality of life. Other research has demonstrated that cryoneurolysis reduced pain 10, 90, and 180 days after surgery. It is also recognized as a non-opioid method for pain management. Overall, evidence suggests cryoneurolysis is a promising option for managing pain after a mastectomy. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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-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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39716781/

Cryoneurolysis for management of post-mastectomy pain Conclusion: Cryoneurolysis intervention shows promising and clinically significant relief in post-mastectomy pain in patients and further ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1051044322018929

Percutaneous CT-Guided Cryoneurolysis of the ... This study demonstrated that percutaneous CT-guided cryoneurolysis of the ICBN significantly reduced severity of pain and improved quality of life in patients.

3. jvir.org jvir.org/article/S1051-0443(22)01892-9/fulltext

Percutaneous CT-Guided Cryoneurolysis of the ... Cryoneurolysis of the intercostobrachial nerve significantly decreased mean pain in patients with postmastectomy pain syndrome 10, 90, and 180 days after ...

4. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/rg.220082

Percutaneous Image-guided Cryoneurolysis: Applications ... Cryoneurolysis has societal and legislative endorsement as an effective nonopioid procedural option for pain palliation.

5. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT05444361

Ultrasound-Guided Percutaneous Cryoneurolysis to Treat ... The investigators have completed a small study suggesting that a single cryoneurolysis treatment may provide potent pain relief after mastectomy.

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

Percutaneous Image-Guided Cryoneurolysis | AJR Percutaneous image-guided cryoneurolysis is safe and effective for the management of several well-described syndromes involving neuropathic pain.