Cryoneurolysis for Diabetic Neuropathy

Overseen By Kyle Norton, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Disqualifiers: Reynaud syndrome, Cryoglobulinemia, Cold urticaria, 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

Duration: 1 day

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is a single-center, randomized, participant- and observer-masked, human-subjects, post-market clinical pilot study to investigate the use of ultrasound-guided percutaneous cryoneurolysis to treat diabetic neuropathy of the foot. 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 6 minutes for each nerve, involves little discomfort, has no systemic side effects, and cannot be misused or become addictive. Participants will be randomly allocated to one of two possible treatments groups: cryoneurolysis (experimental) or sham (control). The primary outcome measure is the change in pain on the neuropathic pain scale from baseline 1 month following the procedure.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Cryoneurolysis for Diabetic Neuropathy?

Research shows that ultrasound-guided percutaneous cryoneurolysis, which uses extreme cold to target nerve tissue, has been effective in providing long-term pain relief and improving function in patients with painful peripheral nerve lesions. This suggests it could be a useful treatment for managing pain in diabetic neuropathy as well. ^{1 2 3 4 5}

Is cryoneurolysis generally safe for humans?

Cryoneurolysis, which uses extreme cold to treat nerve pain, is generally considered safe with minimal risk of complications when performed using imaging guidance like ultrasound. Studies have not identified any serious complications, and it is seen as a safe alternative to other pain relief methods. ^{1 2 3 6 7}

How is the treatment Cryoneurolysis unique for diabetic neuropathy?

Cryoneurolysis is unique because it uses extreme cold to temporarily block pain signals by freezing the nerves, offering a non-drug alternative for pain relief. This treatment is guided by ultrasound, allowing precise targeting of nerves, and has been shown to provide long-term pain relief without serious complications. ^{1 2 3 4 8}

Eligibility Criteria

This trial is for adults with diabetes who have moderate to severe foot pain from diabetic neuropathy, and a HgbA1c level below 10. They must be able to communicate with researchers and not have any local infection at the treatment site, allergies to local anesthetics, conditions that don't mix well with cryoneurolysis like Reynaud syndrome, or be pregnant.

Inclusion Criteria

HgbA1c <10 (to avoid any increased risk of site infection)

I have diabetes and experience painful nerve pain in my foot or feet.

I have daily foot pain from diabetes rated 3 or higher for the last 2 months.

Exclusion Criteria

Incarceration

Allergy to local anesthetic

My diabetic nerve pain is not in my lower leg or foot.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo ultrasound-guided percutaneous cryoneurolysis or sham procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Multiple visits at 1 week, 1 month, 3 months, and 6 months

Treatment Details

Interventions

• Cryoneurolysis
• Sham Cryoneurolysis

Trial Overview The study tests if freezing nerves through ultrasound-guided cryoneurolysis can reduce foot pain in diabetic neuropathy patients compared to a sham procedure. Participants are randomly assigned to either the real treatment or a fake one without knowing which they receive.

Participant Groups

Group I: Cryoneurolysis Active Control 1 Intervention

For participants randomized to active treatment, the probe placed in the research participant will be triggered and the nitrous oxide passed through the probe and then back into the machine, and finally vented out from the console. This will result in a freeze-thaw cycle. This may be repeated, as necessary, to ensure the entire cross-section of each nerve is fully treated.

Group II: Sham Placebo Group 1 Intervention

Patients in this arm will also receive a diagnostic block with local anesthetic. If pain relief is satisfactory, the patients in this arm will undergo the procedure but the cryo probe will simply not be activated.

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+

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]

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]

In a study involving 113 patients undergoing ultrasound-guided percutaneous cryoneurolysis for spasticity, 96.75% of nerve treatments resulted in no significant pain or dysesthesias beyond the treatment period, indicating a high safety profile.

While a few patients experienced temporary nerve pain or numbness, most adverse effects were manageable and resolved within three months, suggesting that cryoneurolysis could be a safe and effective treatment option for spasticity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Adverse Effects of Cryoneurolysis for the Treatment of Spasticity. Winston, P., MacRae, F., Rajapakshe, S., et al.[2023]

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]

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. 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]

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

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

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

The applications of cryoneurolysis for acute and chronic pain management. [2023]

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

Ultrasound-Guided Percutaneous Cryoneurolysis for Acute Pain Management: A Case Report. [2018]

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

Analysis of Adverse Effects of Cryoneurolysis for the Treatment of Spasticity. [2023]

7. France pubmed.ncbi.nlm.nih.gov

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

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

Percutaneous Image-guided Cryoneurolysis: Applications and Techniques. [2022]