Painful Diabetic Peripheral Neuropathy (PDPN)NCT06646731
Cryoneurolysis for Painful Diabetic Neuropathy of the Foot
A study testing cryoneurolysis in people with Painful Diabetic Peripheral Neuropathy (PDPN), run by University of California, San Diego at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Painful Diabetic Peripheral Neuropathy (PDPN)
- What is being tested?
- cryoneurolysis
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Aug 2025to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Research participants with diabetes mellitus and painful diabetic neuropathy of the foot (unilateral or bilateral)
- HgbA1c <10 (to avoid any increased risk of site infection)
- Adult patients of at least 18 years of age
- Experiencing at least moderate diabetic neuropathic pain in the foot - defined as 3 or higher on the numeric rating scale (NRS; 0-10, 0=no pain; 10=worse imaginable pain) - at least daily for the previous 2 months.
Who cannot join
- Diabetic neuropathy not in the distribution of the superficial peroneal nerve, sural nerve, deep peroneal, and/or distal saphenous nerve.
- Comorbidities that are contraindication to cryoneurolysis (e.g., Reynaud syndrome, cryoglobulinemia, cold urticaria)
- Allergy to local anesthetic
- Pregnancy
- Incarceration
- Inability to communicate to investigators due to lack of capacity
- Local infection in the foot/ankle where cryoneurolysis will be performed
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
La Jolla, California, 92129
About this study
Official title: Ultrasound-guided Percutaneous Cryoneurolysis for Management of Chronic Painful Diabetic Neuropathy: A Randomized Sham-controlled Pilot Study
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.
Read the detailed description
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. After 2-3 months, the nerve returns to normal functioning. 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.
Our objective is to investigate the therapeutic benefits of cryoneurolysis for research participants with painful diabetic neuropathy of the feet via a pilot study of 30 research participants. We hypothesize that ultrasound-guided cryoneurolysis of the superficial peroneal nerve will improve pain outcomes in research participants with painful diabetic neuropathy of the foot. The aims of this study will be to:
Primary Specific Aim. Demonstrate the potential efficacy of ultrasound-guided percutaneous cryoneurolysis of the superficial peroneal nerve, sural, distal saphenous, and/or deep peroneal nerve to treat painful diabetic neuropathy of the foot in reducing neuropathic pain 1 month after the procedure compared to baseline. This will be performed as a pilot study and executed as a randomized sham-controlled clinical trial of 30 subjects.
Hypothesis 1: Diabetic neuropathic pain intensity will be decreased relative to baseline 1 month following a cryoneurolysis procedure (as measured by the Neuropathic Pain Scale).
Secondary Specific Aim: To test the influence of a cryoanalgesia treatment as compared to sham/placebo on the long term measurements related to pain, quality of life, and analgesic usage.
Hypothesis 2a: Perception of well-being will be improved 1 month following one cryoneurolysis procedure (as measured with the Patient Global Impression of Change Scale).
Hypothesis 2b: Physical and emotional functioning will be improved relative to baseline 1 month following one cryoneurolysis procedure (as measured with the Interference Subscale of the Brief Pain Inventory).
Hypothesis 2c: Pain and opioid consumption will be reduced in the cryoneurolysis group compare to sham at multiple post-procedure time points, including 1 week, 1 month, 3 months, and 6 months after.
- Being tested
- cryoneurolysis, sham cryoneurolysis
- Keywords
- Cryoneurolysis, Diabetic Peripheral Neuropathy of the Foot, Chronic Pain, Ultrasound-Guided Percutaneous Cryoneurolysis
- Medical subject headings
- Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cryoneurolysisDevice
Peripheral nerve cryoneurolysis of the foot
sham cryoneurolysisDevice
a sham probe will be placed percutaneously proximal to target nerves. No cryoneurolysis will be given.
| Study group | Role | What they receive |
|---|---|---|
| Cryoneurolysis | Active comparator | 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. Receives: Device: cryoneurolysis |
| Sham | Sham comparator | 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. Receives: Device: sham cryoneurolysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain Intensity
Change in pain intensity compared to baseline due to diabetic neuropathy of the foot as measured by the score of the Neuropathic Pain Scale. The primary outcome will be at 1 month following the study procedure. The primary statistic will be comparing the median change in the neuropathic pain scale score between both cohorts.
Measured: 1 month
Secondary outcomes (10)
Perception of Well-Being
Perception of well-being will be improved 1 month following one cryoneurolysis procedure (as measured with the Patient Global Impression of Change Scale).
Measured: 1 month
Physical and Emotional Functioning
Physical and emotional functioning will be improved relative to baseline 1 month following one cryoneurolysis procedure (as measured with the Interference Subscale of the Brief Pain Inventory).
Measured: 1 month
Pain intensity - 1 month
Pain intensity as measured by Brief Pain Inventory
Measured: 1 month
Pain Intensity - 1 week
Pain intensity as measured by Neuropathic Pain Scale and Brief Pain Inventory)
Measured: 1 week
Pain Intensity - 3 months
Pain intensity as measured by the Brief Pain Inventory and Neuropathic Pain Scale
Measured: 3 months
Pain Intensity - 6 months
Pain intensity as measured by the Brief Pain Inventory and Neuropathic Pain Scale
Measured: 6 months
Opioid consumption - 1 week
opioid consumption as measured by the Quantitative Analgesic Questionnaire
Measured: 1 week
Opioid consumption - 1 month
opioid consumption as measured by the Quantitative Analgesic Questionnaire
Measured: 1 month
Opioid consumption - 3 months
opioid consumption as measured by the Quantitative Analgesic Questionnaire
Measured: 3 months
Opioid consumption - 6 months
opioid consumption as measured by the Quantitative Analgesic Questionnaire
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2024
- Study start25 Aug 2025
- Primary completionAug 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Painful Diabetic Peripheral Neuropathy (PDPN)Studies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study is a single-center, randomized, participant- and observer-masked, human-subjects, post-market clinical pilot study
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rodney Gabriel, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06646731
- Sponsor's protocol ID
- 811212
- Status last verified
- Aug 2025
- First submitted
- 15 Oct 2024
- Last updated
- 6 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: We have not decided if we will share patient data with other researchers. Reasons for not sharing data would be related to patient confidentiality. Reasons to share data would be related to additional research analyses.
Publications
Yoon JH, Grechushkin V, Chaudhry A, Bhattacharji P, Durkin B, Moore W. Cryoneurolysis in Patients with Refractory Chronic Peripheral Neuropathic Pain. J Vasc Interv Radiol. 2016 Feb;27(2):239-43. doi: 10.1016/j.jvir.2015.11.027. Epub 2015 Dec 17.
PubMed 26710969Jay GW, Barkin RL. Neuropathic pain: etiology, pathophysiology, mechanisms, and evaluations. Dis Mon. 2014 Jan;60(1):6-47. doi: 10.1016/j.disamonth.2013.12.001. No abstract available.
PubMed 24507705Gabriel RA, Seng EC, Curran BP, Winston P, Trescot AM, Filipovski I. A Narrative Review of Ultrasound-Guided and Landmark-based Percutaneous Cryoneurolysis for the Management of Acute and Chronic Pain. Curr Pain Headache Rep. 2024 Nov;28(11):1097-1104. doi: 10.1007/s11916-024-01281-z. Epub 2024 Jul 4.
PubMed 38963513Filipovski I, Gabriel RA, Kestenholz R. Ultrasound-Guided Cryoneurolysis for the Treatment of Painful Diabetic Neuropathy of the Foot: A Case Series. Cureus. 2024 Mar 16;16(3):e56267. doi: 10.7759/cureus.56267. eCollection 2024 Mar.
PubMed 38495961
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ultrasound-guided Percutaneous Cryoneurolysis for Management of Chronic Painful Diabetic Neuropathy: A Randomized Sham-controlled Pilot Study
- ClinicalTrials.gov ID
- NCT06646731
- Acronym / sponsor ID
- 811212
- Keywords
- Cryoneurolysis, Diabetic Peripheral Neuropathy of the Foot, Chronic Pain, Ultrasound-Guided Percutaneous Cryoneurolysis
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- 25 Aug 2025 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 17 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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. After 2-3 months, the nerve returns to normal functioning. 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.
Our objective is to investigate the therapeutic benefits of cryoneurolysis for research participants with painful diabetic neuropathy of the feet via a pilot study of 30 research participants. We hypothesize that ultrasound-guided cryoneurolysis of the superficial peroneal nerve will improve pain outcomes in research participants with painful diabetic neuropathy of the foot. The aims of this study will be to:
Primary Specific Aim. Demonstrate the potential efficacy of ultrasound-guided percutaneous cryoneurolysis of the superficial peroneal nerve, sural, distal saphenous, and/or deep peroneal nerve to treat painful diabetic neuropathy of the foot in reducing neuropathic pain 1 month after the procedure compared to baseline. This will be performed as a pilot study and executed as a randomized sham-controlled clinical trial of 30 subjects.
Hypothesis 1: Diabetic neuropathic pain intensity will be decreased relative to baseline 1 month following a cryoneurolysis procedure (as measured by the Neuropathic Pain Scale).
Secondary Specific Aim: To test the influence of a cryoanalgesia treatment as compared to sham/placebo on the long term measurements related to pain, quality of life, and analgesic usage.
Hypothesis 2a: Perception of well-being will be improved 1 month following one cryoneurolysis procedure (as measured with the Patient Global Impression of Change Scale).
Hypothesis 2b: Physical and emotional functioning will be improved relative to baseline 1 month following one cryoneurolysis procedure (as measured with the Interference Subscale of the Brief Pain Inventory).
Hypothesis 2c: Pain and opioid consumption will be reduced in the cryoneurolysis group compare to sham at multiple post-procedure time points, including 1 week, 1 month, 3 months, and 6 months after.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- The study is a single-center, randomized, participant- and observer-masked, human-subjects, post-market clinical pilot study
| Arm | Type | Receives |
|---|---|---|
| Cryoneurolysis | Active comparator | Device: cryoneurolysisFor 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. |
| Sham | Sham comparator | Device: sham cryoneurolysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Research participants with diabetes mellitus and painful diabetic neuropathy of the foot (unilateral or bilateral)
- HgbA1c <10 (to avoid any increased risk of site infection)
- Adult patients of at least 18 years of age
- Experiencing at least moderate diabetic neuropathic pain in the foot - defined as 3 or higher on the numeric rating scale (NRS; 0-10, 0=no pain; 10=worse imaginable pain) - at least daily for the previous 2 months.
Key exclusion criteria (7 listed)
- Diabetic neuropathy not in the distribution of the superficial peroneal nerve, sural nerve, deep peroneal, and/or distal saphenous nerve.
- Comorbidities that are contraindication to cryoneurolysis (e.g., Reynaud syndrome, cryoglobulinemia, cold urticaria)
- Allergy to local anesthetic
- Pregnancy
- Incarceration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cryoneurolysisPeripheral nerve cryoneurolysis of the foot | Device | Cryoneurolysis |
| sham cryoneurolysisa sham probe will be placed percutaneously proximal to target nerves. No cryoneurolysis will be given. | Device | Sham |
Primary outcome
Pain Intensity
Time frame: 1 month
Change in pain intensity compared to baseline due to diabetic neuropathy of the foot as measured by the score of the Neuropathic Pain Scale. The primary outcome will be at 1 month following the study procedure. The primary statistic will be comparing the median change in the neuropathic pain scale score between both cohorts.
10 secondary outcomes
Perception of Well-Being
Time frame: 1 month
Physical and Emotional Functioning
Time frame: 1 month
Pain intensity - 1 month
Time frame: 1 month
Pain Intensity - 1 week
Time frame: 1 week
Pain Intensity - 3 months
Time frame: 3 months
Pain Intensity - 6 months
Time frame: 6 months
Opioid consumption - 1 week
Time frame: 1 week
Opioid consumption - 1 month
Time frame: 1 month
Opioid consumption - 3 months
Time frame: 3 months
Opioid consumption - 6 months
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2026.
- Background: PubMed 26710969Yoon JH, Grechushkin V, Chaudhry A, Bhattacharji P, Durkin B, Moore W. Cryoneurolysis in Patients with Refractory Chronic Peripheral Neuropathic Pain. J Vasc Interv Radiol. 2016 Feb;27(2):239-43. doi: 10.1016/j.jvir.2015.11.027. Epub 2015 Dec 17.
- Background: PubMed 24507705Jay GW, Barkin RL. Neuropathic pain: etiology, pathophysiology, mechanisms, and evaluations. Dis Mon. 2014 Jan;60(1):6-47. doi: 10.1016/j.disamonth.2013.12.001. No abstract available.
- Background: PubMed 38963513Gabriel RA, Seng EC, Curran BP, Winston P, Trescot AM, Filipovski I. A Narrative Review of Ultrasound-Guided and Landmark-based Percutaneous Cryoneurolysis for the Management of Acute and Chronic Pain. Curr Pain Headache Rep. 2024 Nov;28(11):1097-1104. doi: 10.1007/s11916-024-01281-z. Epub 2024 Jul 4.
- Background: PubMed 38495961Filipovski I, Gabriel RA, Kestenholz R. Ultrasound-Guided Cryoneurolysis for the Treatment of Painful Diabetic Neuropathy of the Foot: A Case Series. Cureus. 2024 Mar 16;16(3):e56267. doi: 10.7759/cureus.56267. eCollection 2024 Mar.
- Individual participant dataSharing planned: Undecided. We have not decided if we will share patient data with other researchers. Reasons for not sharing data would be related to patient confidentiality. Reasons to share data would be related to additional research analyses.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing cryoneurolysis in people with Painful Diabetic Peripheral Neuropathy (PDPN), run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain Intensity (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06646731, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2026.