Diode Laser as a Biomarker for Neuropathic Pain of Peripheral Origin.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Utah
- Enrollment
- 75
- Locations
- 2
- Primary Endpoint
- CMi:Aδ ratio of amperage for sensory perception threshold following diode laser stimulation
Study Overview
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.
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)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Masking Description
Unblinded team member will dispense patch masked to patient and investigator
Eligibility Criteria
- Ages
- 18 Years to 69 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Inclusion criteria for Objective 1 (Healthy Controls)
- •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
- •Inclusion Criteria for Objective 2 - Neuropathy Correlation
- •. 18 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.
- •Inclusion Criteria for Cross Over
- •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:
Exclusion Criteria
- •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 :
- •Exclusion Criteria for Patch Cross Over
- •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) :
Arms & Interventions
Crossover testing in participants with painful neuropathy (placebo patch)
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.
Intervention: Diode Laser fiber type Selective Stimulator (Procedure)
Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)
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.
Intervention: Medoc Quantitative Sensory Testing (Diagnostic Test)
Crossover testing in participants with painful neuropathy (placebo patch)
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.
Intervention: Medoc Quantitative Sensory Testing (Diagnostic Test)
Biomarker Optimization (Stanford)
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
Intervention: Diode Laser fiber type Selective Stimulator (Procedure)
Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)
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.
Intervention: PeriCam PSI NR (Diagnostic Test)
Neuropathy assessment and biomarker testing (Utah)
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
Intervention: PeriCam PSI NR (Diagnostic Test)
Crossover testing in participants with painful neuropathy (placebo patch)
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.
Intervention: Inactive Topical System (Other)
Biomarker Optimization (Stanford)
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
Intervention: PeriCam PSI NR (Diagnostic Test)
Neuropathy assessment and biomarker testing (Utah)
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
Intervention: Diode Laser fiber type Selective Stimulator (Procedure)
Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)
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.
Intervention: Diode Laser fiber type Selective Stimulator (Procedure)
Biomarker Optimization (Stanford)
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
Intervention: Medoc Quantitative Sensory Testing (Diagnostic Test)
Neuropathy assessment and biomarker testing (Utah)
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
Intervention: Medoc Quantitative Sensory Testing (Diagnostic Test)
Crossover testing in participants with painful neuropathy (placebo patch)
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.
Intervention: PeriCam PSI NR (Diagnostic Test)
Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)
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.
Intervention: ZTlido 1.8 % Topical System (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
No secondary outcomes reported
Investigators
Rob Singleton
Professor and Vice Chair of Neurology
University of Utah