NCT06030297

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
75

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Sep 2023

Typical duration for not_applicable

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 4, 2023

Completed
28 days until next milestone

Study Start

First participant enrolled

September 1, 2023

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 8, 2023

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 9, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 9, 2026

Completed
Last Updated

April 17, 2026

Status Verified

April 1, 2026

Enrollment Period

2.4 years

First QC Date

August 4, 2023

Last Update Submit

April 15, 2026

Conditions

Peripheral Neuropathy

Keywords

Biomarkerneuropathic painresponse biomarker

Outcome Measures

Primary Outcomes (2)

  • 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.

    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.

    24 months

Study Arms (4)

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

Procedure: Diode Laser fiber type Selective StimulatorDiagnostic Test: PeriCam PSI NRDiagnostic 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

Procedure: Diode Laser fiber type Selective StimulatorDiagnostic Test: PeriCam PSI NRDiagnostic 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.

Procedure: Diode Laser fiber type Selective StimulatorDrug: ZTlido 1.8 % Topical SystemDiagnostic Test: PeriCam PSI NRDiagnostic 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.

Procedure: Diode Laser fiber type Selective StimulatorDiagnostic Test: PeriCam PSI NRDiagnostic Test: Medoc Quantitative Sensory TestingOther: Inactive Topical System

Interventions

Diode Laser fiber type Selective StimulatorPROCEDURE

-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

Also known as: DLss
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 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 Ă— 14 cm Ă— 0.08 cm. Lidocaine, an amide local anesthetic, is chemically designated as acetamide, 2-

Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)
PeriCam PSI NRDIAGNOSTIC_TEST

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.

Also known as: speckle imager
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 TestingDIAGNOSTIC_TEST

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).

Also known as: QST
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 SystemOTHER

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 Ă— 14 cm Ă— 0.08 cm.

Also known as: placebo patch
Crossover testing in participants with painful neuropathy (placebo patch)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • a 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
  • years of age and older
  • 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.
  • 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:

You may not qualify if:

  • 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 :
  • 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) :

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Stanford University

Palo Alto, California, 94305, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (134)

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MeSH Terms

Conditions

Peripheral Nervous System DiseasesNeuralgia

Interventions

LidocaineDrug Delivery Systems

Condition Hierarchy (Ancestors)

Neuromuscular DiseasesNervous System DiseasesPainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AcetanilidesAnilidesAmidesOrganic ChemicalsAniline CompoundsAminesDrug TherapyTherapeutics

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
Unblinded team member will dispense patch masked to patient and investigator
Purpose
BASIC SCIENCE
Intervention Model
SEQUENTIAL
Model Details: 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
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor and Vice Chair of Neurology

Study Record Dates

First Submitted

August 4, 2023

First Posted

September 8, 2023

Study Start

September 1, 2023

Primary Completion

February 9, 2026

Study Completion

February 9, 2026

Last Updated

April 17, 2026

Record last verified: 2026-04

Locations

US(2)