xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06030297</url>
    </required_header>
    <id_info>
      <org_study_id>DLss-R61/R33</org_study_id>
      <nct_id>NCT06030297</nct_id>
    </id_info>
    <brief_title>Diode Laser as a Biomarker for Neuropathic Pain of Peripheral Origin.</brief_title>
    <acronym>DLss</acronym>
    <official_title>Diode Laser as a Biomarker for Neuropathic Pain of Peripheral Origin.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Utah</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Stanford University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>National Institutes of Health (NIH)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
      <collaborator>
        <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Utah</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The R61 will perform a four-part double-blind randomized crossover study transitioning from a&#xD;
        pretreatment baseline phase, to randomized treatment with either lidocaine or an identical&#xD;
        placebo patch, washout, and alternate arm. DLss measures will be obtained before and after&#xD;
        each phase. Twice daily report of pain using a visual analogue scale will track severity of&#xD;
        ongoing spontaneous pain in participants. The hybrid biomarker will distinguish between&#xD;
        placebo and active treatment arms, will significantly correlate with extent of neuropathic&#xD;
        pain reduction during lidocaine, but will not change during the placebo phase or no-treatment&#xD;
        lead-in. If preset Go/No-Go criteria are met, the subsequent R33 validation will then compare&#xD;
        lidocaine patch and placebo treatment in a blinded, randomized parallel arm study.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Pain caused by peripheral neuropathy is very common. Understanding patient response to pain&#xD;
        and its treatment is one of the biggest barriers to development of effective medicines to&#xD;
        reduce neuropathic pain. This project will develop and validate a non-invasive test that&#xD;
        correlates with patients' experience of pain caused by peripheral neuropathy, a &quot;pain&#xD;
        biomarker&quot;. The biomarker device applies specialized light energy to skin on the top of the&#xD;
        foot to selectively stimulate the nerve fibers in skin that sense and transmit pain. The test&#xD;
        will determine how much energy is necessary to cause a person to feel the stimulus, or to&#xD;
        first feel the pain of the stimulus. Sensory threshold to the stimulus, and transient&#xD;
        enhancement of blood flow in the skin (flare) will be correlated with patient report of&#xD;
        ongoing foot pain. Use of the experimental device, diagnostic testing, and use of lidocaine&#xD;
        have risks that are explained in this document, but can include allergic reactions,&#xD;
        discomfort, and temporary numbness.&#xD;
  &#xD;
        SUMMARY OF STUDY PROCEDURES This study is being conducted by Drs. J. Robinson Singleton in&#xD;
        the Department of Neurology at the University of Utah, and by Mikhail Nemenov PhD, of&#xD;
        Stanford University, who developed the use of this technique for stimulating nerves in the&#xD;
        skin. Study 1 will correlate the biomarker with patients' reported ongoing neuropathic foot.&#xD;
        You may also be asked to participate in the Study 2, in which change in the biomarker will be&#xD;
        correlated longitudinally to change in pain experience in a brief, randomized crossover trial&#xD;
        of placebo or lidocaine patches applied to the top of the foot.&#xD;
  &#xD;
        Optimization of DLss Biomarker in Healthy Subjects (Stanford)&#xD;
  &#xD;
        Healthy subjects will be screened to exclude neuropathy, foot pain and diabetes then will&#xD;
        have the DLss measures performed over several days. The visit lasts about 3-4 hours.&#xD;
  &#xD;
        Study 1: biomarker correlation with ongoing pain (Utah)&#xD;
  &#xD;
        This study consists of a single visit designed to evaluate possible neuropathy and assess its&#xD;
        severity with history, standardized brief exam, and specialized testing. All participants&#xD;
        will then rate their ongoing foot pain, and biomarker testing will be performed. The entire&#xD;
        visit will take 2-3 hours. The purpose is to correlate the biomarker with patients reported&#xD;
        ongoing neuropathic foot pain.&#xD;
  &#xD;
        People with peripheral neuropathy. A total of 50 people will participate.&#xD;
  &#xD;
        Study 2: biomarker correlation with change in pain during lidocaine treatment (Utah)&#xD;
  &#xD;
        Study 2 is designed to see if change in neuropathic pain from treatment with an effective&#xD;
        pain reducing agent correlates with change in the biomarker. Lidocaine, a locally acting&#xD;
        anesthetic, will be applied to the top of the foot using a patch. The study is structured as&#xD;
        a 4 week blinded and randomized crossover treatment trial and will five consist of 5 brief&#xD;
        weekly study visits, once weekly over the 4 week study period. Crossover means that you will&#xD;
        receive both treatments for a week each. Randomized means that the treatment you receive&#xD;
        first, placebo or Lidocaine patch, will be chosen at random. Blinded means that you will not&#xD;
        be told whether the treatment you receive during the treatment weeks is placebo or Lidocaine.&#xD;
        The patches will look similar or identical. Neither you, nor the study coordinator will be&#xD;
        able to tell the identity of the patches.&#xD;
  &#xD;
        Study Segments: Each weekly segment of the study is proceeded and followed by a visit, in&#xD;
        sequence. Each visit will include review of neuropathic pain and performance of QST and&#xD;
        Biomarker Device assessment. There are four segments:&#xD;
  &#xD;
          1. Baseline neuropathic pain evaluation. Each participant will be screened in clinic, then&#xD;
             record daily pain severity for 7 days.&#xD;
  &#xD;
          2. Treatment period 1. After this baseline period, each participant will be randomized to 7&#xD;
             days of treatment with a patch (either lidocaine or placebo) chosen by the study at&#xD;
             random.&#xD;
  &#xD;
          3. A 7-day wash out period without treatment.&#xD;
  &#xD;
          4. Treatment period 2. Daily treatment with patch not received in the first treatment&#xD;
             period.&#xD;
  &#xD;
        A total of 44 people with neuropathy and associated neuropathic pain will participate&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">November 1, 2022</start_date>
    <completion_date type="Anticipated">August 2025</completion_date>
    <primary_completion_date type="Anticipated">August 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_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.&#xD;
  Evaluate the the Response Biomarker using lidocaine patch as a peripherally acting neuropathic pain agents</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>Unblinded team member will dispense patch masked to patient and investigator</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>CMi:Aδ ratio of amperage for sensory perception threshold following diode laser stimulation</measure>
      <time_frame>4 years</time_frame>
      <description>Participants' will report sensory threshold and pain threshold following diode laser stimulation to foot dorsum of ascending power as measured by amperage.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Area of neurogenic flare response (mm squared) following repetitive subthreshold diode laser stimulation.</measure>
      <time_frame>24 months</time_frame>
      <description>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.</description>
    </primary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">301</enrollment>
    <condition>Peripheral Neuropathy</condition>
    <arm_group>
      <arm_group_label>Biomarker Optimization (Stanford)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Neuropathy assessment and biomarker testing (Utah)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Crossover testing in participants with painful neuropathy (placebo patch)</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Diode Laser fiber type Selective Stimulator</intervention_name>
      <description>-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 &quot;burning pain,&quot; which is from activation of C-fibers and &quot;pinprick&quot; pain from A-fib</description>
      <arm_group_label>Biomarker Optimization (Stanford)</arm_group_label>
      <arm_group_label>Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)</arm_group_label>
      <arm_group_label>Crossover testing in participants with painful neuropathy (placebo patch)</arm_group_label>
      <arm_group_label>Neuropathy assessment and biomarker testing (Utah)</arm_group_label>
      <other_name>DLss</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ZTlido 1.8 % Topical System</intervention_name>
      <description>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-</description>
      <arm_group_label>Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>PeriCam PSI NR</intervention_name>
      <description>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.</description>
      <arm_group_label>Biomarker Optimization (Stanford)</arm_group_label>
      <arm_group_label>Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)</arm_group_label>
      <arm_group_label>Crossover testing in participants with painful neuropathy (placebo patch)</arm_group_label>
      <arm_group_label>Neuropathy assessment and biomarker testing (Utah)</arm_group_label>
      <other_name>speckle imager</other_name>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Medoc Quantitative Sensory Testing</intervention_name>
      <description>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.&#xD;
  Small fiber nerve damage can manifest itself in thermal hypoesthesia (raised perception thresholds) or hyperalgesia (lowered pain thresholds).</description>
      <arm_group_label>Biomarker Optimization (Stanford)</arm_group_label>
      <arm_group_label>Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)</arm_group_label>
      <arm_group_label>Crossover testing in participants with painful neuropathy (placebo patch)</arm_group_label>
      <arm_group_label>Neuropathy assessment and biomarker testing (Utah)</arm_group_label>
      <other_name>QST</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Inactive Topical System</intervention_name>
      <description>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.</description>
      <arm_group_label>Crossover testing in participants with painful neuropathy (placebo patch)</arm_group_label>
      <other_name>placebo patch</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Inclusion criteria for Objective 1 (Stanford)&#xD;
  &#xD;
            1. 18 -70 years of age&#xD;
  &#xD;
            2. no complaints of peripheral neuropathy or other foot pain&#xD;
  &#xD;
            3. no medical history of disease or medication use associated with peripheral neuropathy&#xD;
               (e.g. diabetes)&#xD;
  &#xD;
            4. no known allergy to lidocaine&#xD;
  &#xD;
          Inclusion Criteria for Objective 2&#xD;
  &#xD;
            1. . 18 years of age and older&#xD;
  &#xD;
            2. Length dependent, sensory predominant, peripheral neuropathy from any non-acute&#xD;
               acquired cause (e.g. diabetes, pre-diabetes, chemotherapy induced), OR musculoskeletal&#xD;
               pain from plantar fasciitis or ankle sprain.&#xD;
  &#xD;
          Inclusion Criteria for Objective 3&#xD;
  &#xD;
            1. 18 years of age and older&#xD;
  &#xD;
            2. Length dependent, sensory predominant, peripheral neuropathy from any non-acute&#xD;
               acquired cause (e.g. diabetes, pre-diabetes, chemotherapy induced) .&#xD;
  &#xD;
            3. Pain rating on Visual Analog Scale (VAS) &gt; 30mm&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Exclusion criteria Objective 1 (Stanford)&#xD;
  &#xD;
            1. complaints of peripheral neuropathy or other foot pain&#xD;
  &#xD;
            2. medical history of disease or medication use associated with peripheral neuropathy&#xD;
               (e.g. diabetes)&#xD;
  &#xD;
            3. known allergy to lidocaine or other para-aminobenzioc acid derivative (ie: procaine,&#xD;
               tetracaine, benzocaine)&#xD;
  &#xD;
          Exclusion Criteria Objective 2 and 3&#xD;
  &#xD;
            1. Acute peripheral neuropathy (e.g. Guillain Barre Syndrome, glucose correction&#xD;
               neuropathy) because of concerns for stability of neuropathic pain over the period of&#xD;
               study participation.&#xD;
  &#xD;
            2. Bleeding diathesis, or history of severe bleeding with skin wounds.&#xD;
  &#xD;
            3. known allergy to lidocaine or other para-aminobenzioc acid derivative (ie: procaine,&#xD;
               tetracaine, benzocaine)&#xD;
  &#xD;
          4. Taking exclusionary medications related to lidocaine, or with anti-arrhythmic&#xD;
          properties, such as tocainide or mexilitine.&#xD;
  &#xD;
          5. Severe liver disease&#xD;
  &#xD;
          6. People currently receiving chemotherapy.&#xD;
  &#xD;
          7. Unable to complete protocol requirements in the judgement of the investigator.-&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>69 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Cathy Revere</last_name>
      <phone>8015585503</phone>
      <email>cathy.revere@hsc.utah.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Stanford University</name>
        <address>
          <city>Palo Alto</city>
          <state>California</state>
          <zip>94305</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Michael Klukinov</last_name>
        <phone>650-736-1778</phone>
        <email>klukinov@stanford.edu</email>
      </contact>
      <investigator>
        <last_name>David Yeomans, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>University of Utah</name>
        <address>
          <city>Salt Lake City</city>
          <state>Utah</state>
          <zip>84132</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Cathy Revere</last_name>
        <phone>801-558-5503</phone>
        <email>cathy.revere@hsc.utah.edu</email>
      </contact>
      <contact_backup>
        <last_name>Miguel Numa</last_name>
        <email>miguel.numa@hsc.utah.edu</email>
      </contact_backup>
      <investigator>
        <last_name>J R Singleton, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
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    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 4, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Utah</investigator_affiliation>
      <investigator_full_name>Rob Singleton</investigator_full_name>
      <investigator_title>Professor and Vice Chair of Neurology</investigator_title>
    </responsible_party>
    <keyword>Biomarker</keyword>
    <keyword>neuropathic pain</keyword>
    <keyword>response biomarker</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neuralgia</mesh_term>
      <mesh_term>Peripheral Nervous System Diseases</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06030297
  org study id: DLss-R61/R33
  nct id: NCT06030297
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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)
  
        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:
  
          1. Baseline neuropathic pain evaluation. Each participant will be screened in clinic, then
             record daily pain severity for 7 days.
  
          2. 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.
  
          3. A 7-day wash out period without treatment.
  
          4. 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
  allocation: Randomized
  intervention model: Sequential Assignment
  intervention 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
  primary purpose: Basic Science
  masking: Double (Participant, Investigator)
  masking description: Unblinded team member will dispense patch masked to patient and investigator
  measure: CMi:Aδ ratio of amperage for sensory perception threshold following diode laser stimulation
  time frame: 4 years
  description: Participants' will report sensory threshold and pain threshold following diode laser stimulation to foot dorsum of ascending power as measured by amperage.
  measure: Area of neurogenic flare response (mm squared) following repetitive subthreshold diode laser stimulation.
  time frame: 24 months
  description: 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.
  arm group label: Biomarker Optimization (Stanford)
  arm group type: Experimental
  description: 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
  arm group label: Neuropathy assessment and biomarker testing (Utah)
  arm group type: Experimental
  description: 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
  arm group label: Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)
  arm group type: Active Comparator
  description: 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.
  arm group label: Crossover testing in participants with painful neuropathy (placebo patch)
  arm group type: Placebo Comparator
  description: 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 type: Procedure
  intervention name: Diode Laser fiber type Selective Stimulator
  description: -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
  arm group label: Biomarker Optimization (Stanford)
  arm group label: Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)
  arm group label: Crossover testing in participants with painful neuropathy (placebo patch)
  arm group label: Neuropathy assessment and biomarker testing (Utah)
  other name: DLss
  intervention type: Drug
  intervention name: ZTlido 1.8 % Topical System
  description: 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-
  arm group label: Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)
  intervention type: Diagnostic Test
  intervention name: PeriCam PSI NR
  description: 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.
  arm group label: Biomarker Optimization (Stanford)
  arm group label: Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)
  arm group label: Crossover testing in participants with painful neuropathy (placebo patch)
  arm group label: Neuropathy assessment and biomarker testing (Utah)
  other name: speckle imager
  intervention type: Diagnostic Test
  intervention name: Medoc Quantitative Sensory Testing
  description: 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).
  arm group label: Biomarker Optimization (Stanford)
  arm group label: Crossover testing in participants with painful neuropathy (ZTlido 1.8% lidocaine patch)
  arm group label: Crossover testing in participants with painful neuropathy (placebo patch)
  arm group label: Neuropathy assessment and biomarker testing (Utah)
  other name: QST
  intervention type: Other
  intervention name: Inactive Topical System
  description: 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.
  arm group label: Crossover testing in participants with painful neuropathy (placebo patch)
  other name: placebo patch
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 69 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Cathy Revere
  phone: 8015585503
  email: cathy.revere@hsc.utah.edu
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  facility: 
  status: Not yet recruiting
  contact: 
  contact backup: 
  investigator: 
  country: United States
  citation: 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/
  PMID: 27010052
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  responsible party type: Principal Investigator
  investigator affiliation: University of Utah
  investigator full name: Rob Singleton
  investigator title: Professor and Vice Chair of Neurology
  mesh term: Neuralgia
  mesh term: Peripheral Nervous System Diseases