Peripheral NeuropathyDLssNCT06030297
Diode Laser as a Biomarker for Neuropathic Pain of Peripheral Origin.
A study testing Diode Laser fiber type Selective Stimulator, ZTlido 1.8 % Topical System and PeriCam PSI NR in people with Peripheral Neuropathy, run by University of Utah at 2 sites in United States.
Trial summary
The R61 will perform a four-part double-blind randomized crossover study transitioning from a pretreatment baseline phase, to randomized treatment with either lidocaine or an identical placebo patch, washout, and alternate arm. DLss measures will be obtained before and after each phase. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Peripheral Neuropathy
- What is being tested?
- Diode Laser fiber type Selective Stimulator, ZTlido 1.8 % Topical System and PeriCam PSI NR
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 77 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Sep 2023to 9 Feb 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18-70 years of age
- no complaints of peripheral neuropathy or other foot pain
- no medical history of disease or medication use associated with peripheral neuropathy (e.g. diabetes)
- DLss 3-questions and sharp sensation testing indicate neuropathy is not present.
- 4a Do you have persistent numbness or tingling in your feet? 4b Do you have pain in your feet that is not due to an orthopedic injury or lesions to skin/toenails? 4c Do you have problems with your balance? 5) no known allergy to lidocaine
- . 18 years of age and older
Show all 10Show fewer
- Length dependent, sensory predominant, peripheral neuropathy from any non-acute acquired cause (e.g. diabetes, pre-diabetes, chemotherapy induced), OR musculoskeletal pain from plantar fasciitis or ankle sprain.
- 18 years old or older:
- Pain rating on Average Visual Analog Scale (VAS) > 30mm or Worst Visual Analog Scale (VAS) > 40mm
- UENS score greater than or equal to 4 or a length dependent, sensory predominant, peripheral neuropathy from any non-acute acquired cause based on the opinion of the investigator:
Who cannot join
- Current peripheral neuropathy that is rapidly changing (e.g. Guillain Barre syndrome or glucose correction neuropathy) :
- Severe liver disease (ie: untreated/active hepatitis) :
- Currently receiving chemotherapy:
- Recent or planned change in neuropathic pain medication during study (approximately 7 weeks) :
- Structural defects in foot that result in participant being unable to differentiate between neuropathic pain and another source of pain (ie: plantar fasciitis, arthritis) :
- Unable to comply with protocol requirements or is at undue risk as judged by the investigator :
Show all 10Show fewer
- Known allergy to topical lidocaine or other patch ingredients (ie adhesive, butylated hydroxytoluene, dipropylene glycol, silicon dioxide, styrene/isoprene/sytrene copolymer):
- Use of topical lidocaine patch or other topical neuropathic pain creams on feet (e.g. capsaicin) :
- Taking medications similar to lidocaine or with anti-arrhythmic properties (ie: tocainide or mexiletine) :
- Known allergy to lidocaine or other para-aminobenzoic acid derivative (e.g. procaine, tetracaine, benzocaine) :
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Stanford University
Palo Alto, California, 94305
University of Utah
Salt Lake City, Utah, 84132
About this study
The R61 will perform a four-part double-blind randomized crossover study transitioning from a pretreatment baseline phase, to randomized treatment with either lidocaine or an identical placebo patch, washout, and alternate arm. DLss measures will be obtained before and after each phase. Twice daily report of pain using a visual analogue scale will track severity of ongoing spontaneous pain in participants. The hybrid biomarker will distinguish between placebo and active treatment arms, will significantly correlate with extent of neuropathic pain reduction during lidocaine, but will not change during the placebo phase or no-treatment lead-in. If preset Go/No-Go criteria are met, the subsequent R33 validation will then compare lidocaine patch and placebo treatment in a blinded, randomized parallel arm study.
Read the detailed description
Pain caused by peripheral neuropathy is very common. Understanding patient response to pain and its treatment is one of the biggest barriers to development of effective medicines to reduce neuropathic pain. This project will develop and validate a non-invasive test that correlates with patients' experience of pain caused by peripheral neuropathy, a "pain biomarker". The biomarker device applies specialized light energy to skin on the top of the foot to selectively stimulate the nerve fibers in skin that sense and transmit pain. The test will determine how much energy is necessary to cause a person to feel the stimulus, or to first feel the pain of the stimulus. Sensory threshold to the stimulus, and transient enhancement of blood flow in the skin (flare) will be correlated with patient report of ongoing foot pain. Use of the experimental device, diagnostic testing, and use of lidocaine have risks that are explained in this document, but can include allergic reactions, discomfort, and temporary numbness.
SUMMARY OF STUDY PROCEDURES This study is being conducted by Drs. J. Robinson Singleton in the Department of Neurology at the University of Utah, and by Mikhail Nemenov PhD, of Stanford University, who developed the use of this technique for stimulating nerves in the skin. Study 1 will correlate the biomarker with patients' reported ongoing neuropathic foot. You may also be asked to participate in the Study 2, in which change in the biomarker will be correlated longitudinally to change in pain experience in a brief, randomized crossover trial of placebo or lidocaine patches applied to the top of the foot.
Optimization of DLss Biomarker in Healthy Subjects (Stanford and Utah)
Healthy subjects will be screened to exclude neuropathy, foot pain and diabetes then will have the DLss measures performed over several days. The visit lasts about 3-4 hours.
Study 1: biomarker correlation with ongoing pain (Utah)
This study consists of a single visit designed to evaluate possible neuropathy and assess its severity with history, standardized brief exam, and specialized testing. All participants will then rate their ongoing foot pain, and biomarker testing will be performed. The entire visit will take 2-3 hours. The purpose is to correlate the biomarker with patients reported ongoing neuropathic foot pain.
People with peripheral neuropathy. A total of 50 people will participate.
Study 2: biomarker correlation with change in pain during lidocaine treatment (Utah)
Study 2 is designed to see if change in neuropathic pain from treatment with an effective pain reducing agent correlates with change in the biomarker. Lidocaine, a locally acting anesthetic, will be applied to the top of the foot using a patch. The study is structured as a 4 week blinded and randomized crossover treatment trial and will five consist of 5 brief weekly study visits, once weekly over the 4 week study period. Crossover means that you will receive both treatments for a week each. Randomized means that the treatment you receive first, placebo or Lidocaine patch, will be chosen at random. Blinded means that you will not be told whether the treatment you receive during the treatment weeks is placebo or Lidocaine. The patches will look similar or identical. Neither you, nor the study coordinator will be able to tell the identity of the patches.
Study Segments: Each weekly segment of the study is proceeded and followed by a visit, in sequence. Each visit will include review of neuropathic pain and performance of QST and Biomarker Device assessment. There are four segments:
- Baseline neuropathic pain evaluation. Each participant will be screened in clinic, then record daily pain severity for 7 days.
- Treatment period 1. After this baseline period, each participant will be randomized to 7 days of treatment with a patch (either lidocaine or placebo) chosen by the study at random.
- A 7-day wash out period without treatment.
- Treatment period 2. Daily treatment with patch not received in the first treatment period.
A total of 44 people with neuropathy and associated neuropathic pain will participate
- Conditions
- Peripheral Neuropathy
- Being tested
- Diode Laser fiber type Selective Stimulator, ZTlido 1.8 % Topical System, PeriCam PSI NR, Medoc Quantitative Sensory Testing, Inactive Topical System
- Keywords
- Biomarker, neuropathic pain, response biomarker
- Medical subject headings
- Peripheral Nervous System Diseases, Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diode Laser fiber type Selective StimulatorProcedure or surgery
Also called DLss
-Each patient will have an A and C fiber stimulation. Stimulation will be performed on the dorsum of the foot using stimulation previously published parameters to elicit "burning pain," which is from activation of C-fibers and "pinprick" pain from A-fib
ZTlido 1.8 % Topical SystemDrug
ZTLI(diethylamino)-N-(2,6-dimethylphenyl), has an octanol:water partition ratio of 43 at pH 7.4. Each ZTLIDO contains 36 mg of lidocaine (18 mg per gram adhesive) in a non-aqueous base and also contains the following inactive ingredients: butylated hydroxytoluene, dipropylene glycol, isostearic acid, mineral oil, polyisobutylene, silicone dioxide, styrene/isoprene/styrene block copolymer, and terpene resin. DO (lidocaine topical system) 1.8% is a single-layer, drug-in-adhesive topical delivery system comprised of an adhesive material containing 36 mg lidocaine, which is applied to a pliable nonwoven cloth backing and covered with a polyethylene terephthalate film release liner. The release liner is removed prior to application to the skin. The size of ZTLIDO is 10 cm × 14 cm × 0.08 cm. Lidocaine, an amide local anesthetic, is chemically designated as acetamide, 2-
PeriCam PSI NRDiagnostic test
Also called speckle imager
It is a method that visualizes tissue blood perfusion in real time. LASCA provides new means to study the microcirculation in ways that were not possible in the past. PeriCam PSI System combines dynamic response and high spatial resolution in one instrument, providing both real-time graphs and video recordings of the tissue being studied. To further enhance its usability, dedicated application software, PIMSoft, has been developed.
Medoc Quantitative Sensory TestingDiagnostic test
Also called QST
Quantitative sensory testing (QST) is a method through which sensory nerve function is quantitatively measured, based on responses of the subject. The peripheral sensory nervous system responds to specific stimuli of specific modality and intensity in a specific manner, which is well-known through many decades of research into human sensation. Thermal QST provides information about the function of small diameter unmyelinated (C fibers) and thinly myelinated (A-delta fibers) nerve fibers for which no nerve conduction test, or other objective tests exist.
Small fiber nerve damage can manifest itself in thermal hypoesthesia (raised perception thresholds) or hyperalgesia (lowered pain thresholds).
Inactive Topical SystemOther
Also called placebo patch
Inactive, non-medicated topical system comprised of an adhesive material containing, which is applied to a pliable nonwoven cloth backing and covered with a polyethylene terephthalate film release liner. The release liner is removed prior to application to the skin. The size of the system is 10 cm × 14 cm × 0.08 cm.
| Study group | Role | What they receive |
|---|---|---|
| Biomarker Optimization (Stanford) | Experimental | Screening for neuropathy, foot problems and diabetes Diode laser testing of C:Aδ ratio Non-invasive speckle imaging Quantitative sensory testing ZTlido 1.8% lidocaine patch testing in some subjects Receives: Procedure: Diode Laser fiber type Selective Stimulator; Diagnostic Test: PeriCam PSI NR; Diagnostic Test: Medoc Quantitative Sensory Testing |
| Neuropathy assessment and biomarker testing (Utah) | Experimental | History, physical, and neurological exam Nerve conduction study Medical record review of neuropathy history PROMIS pain severity and interference testing Brief pain inventory Norfolk quality of life questionnaire Quantitative sensory testing 3mm skin punch biopsy Diode laser testing of C:Aδ ratio Non-invasive speckle imaging Receives: Procedure: Diode Laser fiber type Selective Stimulator; Diagnostic Test: PeriCam PSI NR; Diagnostic Test: Medoc Quantitative Sensory Testing |
| Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch) | Active comparator | History, physical, and neurological exam Nerve conduction study Medical record review of neuropathy history PROMIS pain severity and interference testing Brief pain inventory Norfolk quality of life questionnaire Quantitative sensory testing 3mm skin punch biopsy Diode laser testing of C:Aδ ratio Non-invasive speckle imaging ZTlido 1.8% lidocaine patch application to both feet for 7 days up to 12 hours per day. Receives: Procedure: Diode Laser fiber type Selective Stimulator; Drug: ZTlido 1.8 % Topical System; Diagnostic Test: PeriCam PSI NR; Diagnostic Test: Medoc Quantitative Sensory Testing |
| Crossover testing in participants with painful neuropathy (placebo patch) | Placebo comparator | History, physical, and neurological exam Nerve conduction study Medical record review of neuropathy history PROMIS pain severity and interference testing Brief pain inventory Norfolk quality of life questionnaire Quantitative sensory testing 3mm skin punch biopsy Diode laser testing of C:Aδ ratio Non-invasive speckle imaging Placebo patch application to both feet for 7 days up to 12 hours per day. Receives: Procedure: Diode Laser fiber type Selective Stimulator; Diagnostic Test: PeriCam PSI NR; Diagnostic Test: Medoc Quantitative Sensory Testing; Other: Inactive Topical System |
What is being measured
The primary outcome is the main question the study is designed to answer.
CMi:Aδ ratio of amperage for sensory perception threshold following diode laser stimulation
Participants' will report sensory threshold and pain threshold following diode laser stimulation to foot dorsum of ascending power as measured by amperage.
Measured: 4 years
Area of neurogenic flare response (mm squared) following repetitive subthreshold diode laser stimulation.
Foot dorsum skin will be repeatedly stimulated by diode laser and area of neurogenic flare measured using red blood cell reflectance using a speckle imager.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2023
- Study start1 Sep 2023
- Primary completion9 Feb 2026
- Study completion9 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (134)Papers the sponsor has linked to this study.
- Other trials for Peripheral NeuropathyStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Response biomarker set-up and optimization in Healthy Subjects Examination of the relationship between Response Biomarker measures and severity of neuropathic pain in patients with peripheral neuropathy. Evaluate the the Response Biomarker using lidocaine patch as a peripherally acting neuropathic pain agents
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Stanford University, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Rob Singleton, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06030297
- Sponsor's protocol ID
- DLss-R61/R33
- Acronym
- DLss
- Status last verified
- Apr 2026
- First submitted
- 4 Aug 2023
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. Available from http://www.ncbi.nlm.nih.gov/books/NBK326791/
PubMed 27010052DiBonaventura MD, Sadosky A, Concialdi K, Hopps M, Kudel I, Parsons B, Cappelleri JC, Hlavacek P, Alexander AH, Stacey BR, Markman JD, Farrar JT. The prevalence of probable neuropathic pain in the US: results from a multimodal general-population health survey. J Pain Res. 2017 Nov 1;10:2525-2538. doi: 10.2147/JPR.S127014. eCollection 2017.
PubMed 29138590Brix Finnerup N, Hein Sindrup S, Staehelin Jensen T. Management of painful neuropathies. Handb Clin Neurol. 2013;115:279-90. doi: 10.1016/B978-0-444-52902-2.00017-5.
PubMed 23931787Tracey I, Woolf CJ, Andrews NA. Composite Pain Biomarker Signatures for Objective Assessment and Effective Treatment. Neuron. 2019 Mar 6;101(5):783-800. doi: 10.1016/j.neuron.2019.02.019.
PubMed 30844399Davis KD, Aghaeepour N, Ahn AH, Angst MS, Borsook D, Brenton A, Burczynski ME, Crean C, Edwards R, Gaudilliere B, Hergenroeder GW, Iadarola MJ, Iyengar S, Jiang Y, Kong JT, Mackey S, Saab CY, Sang CN, Scholz J, Segerdahl M, Tracey I, Veasley C, Wang J, Wager TD, Wasan AD, Pelleymounter MA. Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: challenges and opportunities. Nat Rev Neurol. 2020 Jul;16(7):381-400. doi: 10.1038/s41582-020-0362-2. Epub 2020 Jun 15.
PubMed 32541893Cuellar JM, Manering NA, Klukinov M, Nemenov MI, Yeomans DC. Thermal nociceptive properties of trigeminal afferent neurons in rats. Mol Pain. 2010 Jul 7;6:39. doi: 10.1186/1744-8069-6-39.
PubMed 20609212Veldhuijzen DS, Nemenov MI, Keaser M, Zhuo J, Gullapalli RP, Greenspan JD. Differential brain activation associated with laser-evoked burning and pricking pain: An event-related fMRI study. Pain. 2009 Jan;141(1-2):104-13. doi: 10.1016/j.pain.2008.10.027. Epub 2008 Dec 5.
PubMed 19058914Moeller-Bertram T, Schilling JM, Backonja MM, Nemenov MI. Sensory small fiber function differentially assessed with diode laser (DL) quantitative sensory testing (QST) in painful neuropathy (PN). Pain Med. 2013 Mar;14(3):417-21. doi: 10.1111/pme.12049. Epub 2013 Feb 22.
PubMed 23433028Rowbotham MC, Davies PS, Verkempinck C, Galer BS. Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia. Pain. 1996 Apr;65(1):39-44. doi: 10.1016/0304-3959(95)00146-8.
PubMed 8826488Devers A, Galer BS. Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open-label study. Clin J Pain. 2000 Sep;16(3):205-8. doi: 10.1097/00002508-200009000-00005.
PubMed 11014393Argoff CE. New analgesics for neuropathic pain: the lidocaine patch. Clin J Pain. 2000 Jun;16(2 Suppl):S62-6. doi: 10.1097/00002508-200006001-00011.
PubMed 10870742Katz NP, Gammaitoni AR, Davis MW, Dworkin RH; Lidoderm Patch Study Group. Lidocaine patch 5% reduces pain intensity and interference with quality of life in patients with postherpetic neuralgia: an effectiveness trial. Pain Med. 2002 Dec;3(4):324-32. doi: 10.1046/j.1526-4637.2002.02050.x.
PubMed 15099237Galer BS, Jensen MP, Ma T, Davies PS, Rowbotham MC. The lidocaine patch 5% effectively treats all neuropathic pain qualities: results of a randomized, double-blind, vehicle-controlled, 3-week efficacy study with use of the neuropathic pain scale. Clin J Pain. 2002 Sep-Oct;18(5):297-301. doi: 10.1097/00002508-200209000-00004.
PubMed 12218500Meier T, Wasner G, Faust M, Kuntzer T, Ochsner F, Hueppe M, Bogousslavsky J, Baron R. Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic pain syndromes: a randomized, double-blind, placebo-controlled study. Pain. 2003 Nov;106(1-2):151-8. doi: 10.1016/s0304-3959(03)00317-8.
PubMed 14581122Gammaitoni AR, Alvarez NA, Galer BS. Safety and tolerability of the lidocaine patch 5%, a targeted peripheral analgesic: a review of the literature. J Clin Pharmacol. 2003 Feb;43(2):111-7. doi: 10.1177/0091270002239817.
PubMed 12616661
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diode Laser as a Biomarker for Neuropathic Pain of Peripheral Origin.
- ClinicalTrials.gov ID
- NCT06030297
- Acronym / sponsor ID
- DLss / DLss-R61/R33
- Conditions
- Peripheral Neuropathy
- Keywords
- Biomarker, neuropathic pain, response biomarker
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Stanford University, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 9 Feb 2026 (actual)
- Study completion
- 9 Feb 2026 (actual)
- First posted
- 8 Sep 2023 (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 R61 will perform a four-part double-blind randomized crossover study transitioning from a pretreatment baseline phase, to randomized treatment with either lidocaine or an identical placebo patch, washout, and alternate arm. DLss measures will be obtained before and after each phase. Twice daily report of pain using a visual analogue scale will track severity of ongoing spontaneous pain in participants. The hybrid biomarker will distinguish between placebo and active treatment arms, will significantly correlate with extent of neuropathic pain reduction during lidocaine, but will not change during the placebo phase or no-treatment lead-in. If preset Go/No-Go criteria are met, the subsequent R33 validation will then compare lidocaine patch and placebo treatment in a blinded, randomized parallel arm study.
Detailed description
Pain caused by peripheral neuropathy is very common. Understanding patient response to pain and its treatment is one of the biggest barriers to development of effective medicines to reduce neuropathic pain. This project will develop and validate a non-invasive test that correlates with patients' experience of pain caused by peripheral neuropathy, a "pain biomarker". The biomarker device applies specialized light energy to skin on the top of the foot to selectively stimulate the nerve fibers in skin that sense and transmit pain. The test will determine how much energy is necessary to cause a person to feel the stimulus, or to first feel the pain of the stimulus. Sensory threshold to the stimulus, and transient enhancement of blood flow in the skin (flare) will be correlated with patient report of ongoing foot pain. Use of the experimental device, diagnostic testing, and use of lidocaine have risks that are explained in this document, but can include allergic reactions, discomfort, and temporary numbness.
SUMMARY OF STUDY PROCEDURES This study is being conducted by Drs. J. Robinson Singleton in the Department of Neurology at the University of Utah, and by Mikhail Nemenov PhD, of Stanford University, who developed the use of this technique for stimulating nerves in the skin. Study 1 will correlate the biomarker with patients' reported ongoing neuropathic foot. You may also be asked to participate in the Study 2, in which change in the biomarker will be correlated longitudinally to change in pain experience in a brief, randomized crossover trial of placebo or lidocaine patches applied to the top of the foot.
Optimization of DLss Biomarker in Healthy Subjects (Stanford and Utah)
Healthy subjects will be screened to exclude neuropathy, foot pain and diabetes then will have the DLss measures performed over several days. The visit lasts about 3-4 hours.
Study 1: biomarker correlation with ongoing pain (Utah)
This study consists of a single visit designed to evaluate possible neuropathy and assess its severity with history, standardized brief exam, and specialized testing. All participants will then rate their ongoing foot pain, and biomarker testing will be performed. The entire visit will take 2-3 hours. The purpose is to correlate the biomarker with patients reported ongoing neuropathic foot pain.
People with peripheral neuropathy. A total of 50 people will participate.
Study 2: biomarker correlation with change in pain during lidocaine treatment (Utah)
Study 2 is designed to see if change in neuropathic pain from treatment with an effective pain reducing agent correlates with change in the biomarker. Lidocaine, a locally acting anesthetic, will be applied to the top of the foot using a patch. The study is structured as a 4 week blinded and randomized crossover treatment trial and will five consist of 5 brief weekly study visits, once weekly over the 4 week study period. Crossover means that you will receive both treatments for a week each. Randomized means that the treatment you receive first, placebo or Lidocaine patch, will be chosen at random. Blinded means that you will not be told whether the treatment you receive during the treatment weeks is placebo or Lidocaine. The patches will look similar or identical. Neither you, nor the study coordinator will be able to tell the identity of the patches.
Study Segments: Each weekly segment of the study is proceeded and followed by a visit, in sequence. Each visit will include review of neuropathic pain and performance of QST and Biomarker Device assessment. There are four segments:
- Baseline neuropathic pain evaluation. Each participant will be screened in clinic, then record daily pain severity for 7 days.
- Treatment period 1. After this baseline period, each participant will be randomized to 7 days of treatment with a patch (either lidocaine or placebo) chosen by the study at random.
- A 7-day wash out period without treatment.
- Treatment period 2. Daily treatment with patch not received in the first treatment period.
A total of 44 people with neuropathy and associated neuropathic pain will participate
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- Response biomarker set-up and optimization in Healthy Subjects Examination of the relationship between Response Biomarker measures and severity of neuropathic pain in patients with peripheral neuropathy. Evaluate the the Response Biomarker using lidocaine patch as a peripherally acting neuropathic pain agents
| Arm | Type | Receives |
|---|---|---|
| Biomarker Optimization (Stanford) | Experimental | Procedure: Diode Laser fiber type Selective Stimulator, Diagnostic Test: PeriCam PSI NR, Diagnostic Test: Medoc Quantitative Sensory TestingScreening for neuropathy, foot problems and diabetes Diode laser testing of C:Aδ ratio Non-invasive speckle imaging Quantitative sensory testing ZTlido 1.8% lidocaine patch testing in some subjects |
| Neuropathy assessment and biomarker testing (Utah) | Experimental | Procedure: Diode Laser fiber type Selective Stimulator, Diagnostic Test: PeriCam PSI NR, Diagnostic Test: Medoc Quantitative Sensory TestingHistory, physical, and neurological exam Nerve conduction study Medical record review of neuropathy history PROMIS pain severity and interference testing Brief pain inventory Norfolk quality of life questionnaire Quantitative sensory testing 3mm skin punch biopsy Diode laser testing of C:Aδ ratio Non-invasive speckle imaging |
| Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch) | Active comparator | Procedure: Diode Laser fiber type Selective Stimulator, Drug: ZTlido 1.8 % Topical System, Diagnostic Test: PeriCam PSI NR, Diagnostic Test: Medoc Quantitative Sensory TestingHistory, physical, and neurological exam Nerve conduction study Medical record review of neuropathy history PROMIS pain severity and interference testing Brief pain inventory Norfolk quality of life questionnaire Quantitative sensory testing 3mm skin punch biopsy Diode laser testing of C:Aδ ratio Non-invasive speckle imaging ZTlido 1.8% lidocaine patch application to both feet for 7 days up to 12 hours per day. |
| Crossover testing in participants with painful neuropathy (placebo patch) | Placebo comparator | Procedure: Diode Laser fiber type Selective Stimulator, Diagnostic Test: PeriCam PSI NR, Diagnostic Test: Medoc Quantitative Sensory Testing, Other: Inactive Topical SystemHistory, physical, and neurological exam Nerve conduction study Medical record review of neuropathy history PROMIS pain severity and interference testing Brief pain inventory Norfolk quality of life questionnaire Quantitative sensory testing 3mm skin punch biopsy Diode laser testing of C:Aδ ratio Non-invasive speckle imaging Placebo patch application to both feet for 7 days up to 12 hours per day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 18-70 years of age
- no complaints of peripheral neuropathy or other foot pain
- no medical history of disease or medication use associated with peripheral neuropathy (e.g. diabetes)
- DLss 3-questions and sharp sensation testing indicate neuropathy is not present.
- 4a Do you have persistent numbness or tingling in your feet? 4b Do you have pain in your feet that is not due to an orthopedic injury or lesions to skin/toenails? 4c Do you have problems with your balance? 5) no known allergy to lidocaine
Key exclusion criteria (10 listed)
- Current peripheral neuropathy that is rapidly changing (e.g. Guillain Barre syndrome or glucose correction neuropathy) :
- Severe liver disease (ie: untreated/active hepatitis) :
- Currently receiving chemotherapy:
- Recent or planned change in neuropathic pain medication during study (approximately 7 weeks) :
- Structural defects in foot that result in participant being unable to differentiate between neuropathic pain and another source of pain (ie: plantar fasciitis, arthritis) :
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 |
|---|---|---|
| Diode Laser fiber type Selective StimulatorAlso: DLss-Each patient will have an A and C fiber stimulation. Stimulation will be performed on the dorsum of the foot using stimulation previously published parameters to elicit "burning pain," which is from activation of C-fibers and "pinprick" pain from A-fib | Procedure or surgery | Biomarker Optimization (Stanford), Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch), Crossover testing in participants with painful neuropathy (placebo patch), Neuropathy assessment and biomarker testing (Utah) |
| ZTlido 1.8 % Topical SystemZTLI(diethylamino)-N-(2,6-dimethylphenyl), has an octanol:water partition ratio of 43 at pH 7.4. Each ZTLIDO contains 36 mg of lidocaine (18 mg per gram adhesive) in a non-aqueous base and also contains the following inactive ingredients: butylated hydroxytoluene, dipropylene glycol, isostearic acid, mineral oil, polyisobutylene, silicone dioxide, styrene/isoprene/styrene block copolymer, and terpene resin. DO (lidocaine topical system) 1.8% is a single-layer, drug-in-adhesive topical delivery system comprised of an adhesive material containing 36 mg lidocaine, which is applied to a pliable nonwoven cloth backing and covered with a polyethylene terephthalate film release liner. The release liner is removed prior to application to the skin. The size of ZTLIDO is 10 cm × 14 cm × 0.08 cm. Lidocaine, an amide local anesthetic, is chemically designated as acetamide, 2- | Drug | Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch) |
| PeriCam PSI NRAlso: speckle imagerIt is a method that visualizes tissue blood perfusion in real time. LASCA provides new means to study the microcirculation in ways that were not possible in the past. PeriCam PSI System combines dynamic response and high spatial resolution in one instrument, providing both real-time graphs and video recordings of the tissue being studied. To further enhance its usability, dedicated application software, PIMSoft, has been developed. | Diagnostic test | Biomarker Optimization (Stanford), Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch), Crossover testing in participants with painful neuropathy (placebo patch), Neuropathy assessment and biomarker testing (Utah) |
| Medoc Quantitative Sensory TestingAlso: QSTQuantitative sensory testing (QST) is a method through which sensory nerve function is quantitatively measured, based on responses of the subject. The peripheral sensory nervous system responds to specific stimuli of specific modality and intensity in a specific manner, which is well-known through many decades of research into human sensation. Thermal QST provides information about the function of small diameter unmyelinated (C fibers) and thinly myelinated (A-delta fibers) nerve fibers for which no nerve conduction test, or other objective tests exist. Small fiber nerve damage can manifest itself in thermal hypoesthesia (raised perception thresholds) or hyperalgesia (lowered pain thresholds). | Diagnostic test | Biomarker Optimization (Stanford), Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch), Crossover testing in participants with painful neuropathy (placebo patch), Neuropathy assessment and biomarker testing (Utah) |
| Inactive Topical SystemAlso: placebo patchInactive, non-medicated topical system comprised of an adhesive material containing, which is applied to a pliable nonwoven cloth backing and covered with a polyethylene terephthalate film release liner. The release liner is removed prior to application to the skin. The size of the system is 10 cm × 14 cm × 0.08 cm. | Other | Crossover testing in participants with painful neuropathy (placebo patch) |
Primary outcome
CMi:Aδ ratio of amperage for sensory perception threshold following diode laser stimulation
Time frame: 4 years
Participants' will report sensory threshold and pain threshold following diode laser stimulation to foot dorsum of ascending power as measured by amperage.
Area of neurogenic flare response (mm squared) following repetitive subthreshold diode laser stimulation.
Time frame: 24 months
Foot dorsum skin will be repeatedly stimulated by diode laser and area of neurogenic flare measured using red blood cell reflectance using a speckle imager.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- Background: PubMed 27010052FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. Available from http://www.ncbi.nlm.nih.gov/books/NBK326791/
- Background: PubMed 29138590DiBonaventura MD, Sadosky A, Concialdi K, Hopps M, Kudel I, Parsons B, Cappelleri JC, Hlavacek P, Alexander AH, Stacey BR, Markman JD, Farrar JT. The prevalence of probable neuropathic pain in the US: results from a multimodal general-population health survey. J Pain Res. 2017 Nov 1;10:2525-2538. doi: 10.2147/JPR.S127014. eCollection 2017.
- Background: PubMed 23931787Brix Finnerup N, Hein Sindrup S, Staehelin Jensen T. Management of painful neuropathies. Handb Clin Neurol. 2013;115:279-90. doi: 10.1016/B978-0-444-52902-2.00017-5.
- Background: PubMed 30844399Tracey I, Woolf CJ, Andrews NA. Composite Pain Biomarker Signatures for Objective Assessment and Effective Treatment. Neuron. 2019 Mar 6;101(5):783-800. doi: 10.1016/j.neuron.2019.02.019.
- Background: PubMed 32541893Davis KD, Aghaeepour N, Ahn AH, Angst MS, Borsook D, Brenton A, Burczynski ME, Crean C, Edwards R, Gaudilliere B, Hergenroeder GW, Iadarola MJ, Iyengar S, Jiang Y, Kong JT, Mackey S, Saab CY, Sang CN, Scholz J, Segerdahl M, Tracey I, Veasley C, Wang J, Wager TD, Wasan AD, Pelleymounter MA. Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: challenges and opportunities. Nat Rev Neurol. 2020 Jul;16(7):381-400. doi: 10.1038/s41582-020-0362-2. Epub 2020 Jun 15.
- Background: PubMed 20609212Cuellar JM, Manering NA, Klukinov M, Nemenov MI, Yeomans DC. Thermal nociceptive properties of trigeminal afferent neurons in rats. Mol Pain. 2010 Jul 7;6:39. doi: 10.1186/1744-8069-6-39.
- Background: PubMed 19058914Veldhuijzen DS, Nemenov MI, Keaser M, Zhuo J, Gullapalli RP, Greenspan JD. Differential brain activation associated with laser-evoked burning and pricking pain: An event-related fMRI study. Pain. 2009 Jan;141(1-2):104-13. doi: 10.1016/j.pain.2008.10.027. Epub 2008 Dec 5.
- Background: PubMed 23433028Moeller-Bertram T, Schilling JM, Backonja MM, Nemenov MI. Sensory small fiber function differentially assessed with diode laser (DL) quantitative sensory testing (QST) in painful neuropathy (PN). Pain Med. 2013 Mar;14(3):417-21. doi: 10.1111/pme.12049. Epub 2013 Feb 22.
- Background: PubMed 8826488Rowbotham MC, Davies PS, Verkempinck C, Galer BS. Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia. Pain. 1996 Apr;65(1):39-44. doi: 10.1016/0304-3959(95)00146-8.
- Background: PubMed 11014393Devers A, Galer BS. Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open-label study. Clin J Pain. 2000 Sep;16(3):205-8. doi: 10.1097/00002508-200009000-00005.
- Background: PubMed 10870742Argoff CE. New analgesics for neuropathic pain: the lidocaine patch. Clin J Pain. 2000 Jun;16(2 Suppl):S62-6. doi: 10.1097/00002508-200006001-00011.
- Background: PubMed 15099237Katz NP, Gammaitoni AR, Davis MW, Dworkin RH; Lidoderm Patch Study Group. Lidocaine patch 5% reduces pain intensity and interference with quality of life in patients with postherpetic neuralgia: an effectiveness trial. Pain Med. 2002 Dec;3(4):324-32. doi: 10.1046/j.1526-4637.2002.02050.x.
- Individual participant dataSharing planned: Undecided
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Diode Laser fiber type Selective Stimulator, ZTlido 1.8 % Topical System and PeriCam PSI NR in people with Peripheral Neuropathy, run by University of Utah at 2 sites 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 10 inclusion and 10 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: finished, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
CMi:Aδ ratio of amperage for sensory perception threshold following diode laser stimulation (time frame: 4 years). The study lists 2 primary outcomes in all. 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 NCT06030297, which also lists 134 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 19 Oct 2026.