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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called cryoneurolysis to help individuals with diabetic neuropathy in their feet. The aim is to determine if freezing specific nerves can reduce pain. Participants will receive either the actual cryoneurolysis treatment or a sham procedure for comparison. The trial seeks adults with diabetes who have experienced moderate foot pain daily for the past two months. As an unphased trial, this study offers a unique opportunity to explore a novel approach to pain relief.

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 prior data suggests that cryoneurolysis is safe for treating diabetic neuropathy?

Research has shown that cryoneurolysis, a method used to freeze and block nerves, is generally safe for treating nerve pain. Past studies have found this technique effective and well-tolerated for managing pain from various conditions, such as diabetic neuropathy. The procedure involves inserting a small probe through the skin to freeze the nerve, reducing pain without major side effects.

No reports of serious problems have emerged from using cryoneurolysis. The procedure is quick, taking about six minutes per nerve, and does not affect the entire body. Additionally, cryoneurolysis is not addictive and cannot be misused. These findings suggest that the treatment is safe for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Cryoneurolysis is unique because it targets diabetic neuropathy by freezing affected nerves, offering a novel approach to pain relief. Unlike typical treatments like medications that often focus on managing symptoms or nerve pain through oral or topical routes, cryoneurolysis directly interrupts nerve signaling through a freeze-thaw cycle. Researchers are excited about this treatment because it has the potential to provide targeted, long-lasting pain relief without the need for systemic medications, which can have side effects. This innovative technique might offer a new hope for those with diabetic neuropathy, seeking alternatives to standard pain management strategies.

What evidence suggests that cryoneurolysis might be an effective treatment for diabetic neuropathy?

Studies have shown that cryoneurolysis, one of the treatments tested in this trial, can help reduce pain for people with diabetic neuropathy. In one study, patients experienced pain relief for an average of 11 days after the procedure. This treatment works by freezing the nerves that send pain signals, easing pain without major side effects. Early research suggests it could improve pain relief, especially when doctors use ultrasound to guide the procedure for accuracy. Overall, promising evidence indicates that cryoneurolysis might help people with diabetic neuropathy manage their pain better. Participants in this trial may receive either the active cryoneurolysis treatment or a sham procedure for comparison. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10944322/

Ultrasound-Guided Cryoneurolysis for the Treatment of ... This demonstrates the potential effectiveness and safety of using cryoneurolysis for painful peripheral diabetic neuropathy. Keywords: nerve ...

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

Percutaneous Image-Guided Cryoneurolysis | AJR Sixty-four patients had a median duration of pain relief of 11 days. More recently, CN without image guidance has been studied as a potential treatment for many ...

3. trialx.com trialx.com/clinical-trials/listings/323367/cryoneurolysis-for-painful-diabetic-neuropathy-of-the-foot/

Cryoneurolysis for Painful Diabetic Neuropathy of the Foot We hypothesize that ultrasound-guided cryoneurolysis of the superficial peroneal nerve will improve pain outcomes in research participants with ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06646731

Cryoneurolysis for Painful Diabetic Neuropathy of the Foot The primary outcome measure is the change in pain on the neuropathic pain scale from baseline 1 month following the procedure. Detailed Description. The study ...

5. withpower.com withpower.com/trial/phase-peripheral-nervous-system-diseases-10-2024-2a007

Cryoneurolysis for Diabetic Neuropathy · Info for Participants Trial Overview The study tests if freezing nerves through ultrasound-guided cryoneurolysis can reduce foot pain in diabetic neuropathy patients compared to a ...

6. bostonscientific.com bostonscientific.com/content/dam/bostonscientific/pi/portfolio-group/cryoablation/downloads/Nerve_cryoneurolysis_data_pack_(PI-1173604-AB).pdf

TRANSFORMING PAIN TREATMENTS Outcomes measured include distances from the ablation sites to origins of distal musculature, times to initial clinical recovery and muscle activation, and rate ...