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/NCT05993871</url>
    </required_header>
    <id_info>
      <org_study_id>34059/8/20</org_study_id>
      <nct_id>NCT05993871</nct_id>
    </id_info>
    <brief_title>Diabetic Small Fiber Neuropathy: Clinical, Electrophysiological and Neurosonographic Study</brief_title>
    <official_title>Diabetic Small Fiber Neuropathy: Clinical, Electrophysiological and Neurosonographic Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tanta University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Tanta University</source>
    <oversight_info>
      <has_dmc>Yes</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 aim of work is to study the clinical, electrodiagnostic and neurosonographic&#xD;
        characteristics of diabetic patients with small fiber neuropathy in the Egyptian population,&#xD;
        and to evaluate both the diagnostic and the prognostic impact of the studied factors on the&#xD;
        neuropathy severity and quality of life.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This case-control observational study is aiming to evaluate patients with diabetic small&#xD;
        fiber neuropathy in the Egyptian.&#xD;
  &#xD;
        Diabetic small fiber neuropathy was defined as both of the following:&#xD;
  &#xD;
        A. Typical clinical symptoms of SFN such as burning or sharp pain in toes and feet, and on&#xD;
        clinical examination: loss of small fiber modalities (pinprick and temperature),&#xD;
        hyperalgesia, allodynia, and/or autonomic signs.&#xD;
  &#xD;
        B. Reduced intraepidermal nerve fiber density (IENFD) in distal leg skin punch biopsy.&#xD;
  &#xD;
        The study includes 3 groups:&#xD;
  &#xD;
        Group I: Patients with diabetic small fiber neuropathy Group II (Control Group): Patients&#xD;
        with diabetic mixed small and large fiber neuropathy Group III (Control Group): Subjects&#xD;
        without peripheral neuropathy&#xD;
  &#xD;
        Clinical evaluation includes: Neuropathic Pain 4 (DN4) questionnaire, 11-point Numeric Pain&#xD;
        Scale (NPS), Utah Early Neuropathy Scale (UENS), Toronto Clinical Neuropathy Scale (TCNS),&#xD;
        Composite Autonomic Symptom Score (COMPASS-31), an Arabic version, and several anthropometric&#xD;
        measures; including: body weight in kilograms, height in centimeters, waist circumference&#xD;
        measured in centimeters at the top of the iliac crest, and systolic &quot;SBP&quot; and diastolic &quot;DBP&quot;&#xD;
        blood pressure measurement in mmHg.&#xD;
  &#xD;
        Electrodiagnostic evaluation includes: routine nerve conduction study, cutaneous silent&#xD;
        period by stimulating left median nerve and right sural nerve and recording from the abductor&#xD;
        pollicis brevis and tibialis anterior muscles, respectively, bilateral hand-to hand and&#xD;
        foot-to-foot sympathetic skin response, and Ewing battery using R-R interval analysis, in&#xD;
        addition to the blood pressure tests.&#xD;
  &#xD;
        Neurosonographic evaluation includes: bilateral vagal nerve scan at the mid-neck lateral to&#xD;
        the thyroid cartilage, left median and right ulnar nerves scan at the mid-forearm, left&#xD;
        tibial nerve at the distal ankle 2 to 4 fingerbreadths proximal to the medial malleolus, and&#xD;
        right sural nerve 2 to 4 fingerbreadths proximal to the lateral malleolus. Nerves are&#xD;
        evaluated for transverse cross-sectional area (CSA).&#xD;
  &#xD;
        Severity and outcome measures are assessed using: NPS, TCNS, COMPASS-31, and the index score&#xD;
        of Euro Quality of Life -5 Dimensions -5 Levels (EuroQOL-5D-5L), the Arabic version.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">January 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2023</completion_date>
    <primary_completion_date type="Actual">June 30, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Demonstrate the findings of UENS in the studied groups</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of Utah early neuropathy scale in the studied groups to screen for neuropathic symptoms, where overall scores of 4 and more are considered positive.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the findings of TCNS in the studied groups</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of Toronto clinical neuropathy scale in the studied groups, to screen for the neuropathic symptoms where overall scores of 6 and more are considered positive.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the findings of EuroQOL-5D-5L in the studied groups</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of Euro quality of life -5 dimensions -5 levels scale in the studied groups, where lesser scores suggest a lower overall quality of life.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the findings of nerve conduction studies protocol of the performed nerves in the studied groups.</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of nerve conduction studies (NCS) to define neuropathy in the studied groups, which include: unilateral sensory studies of sural, superficial peroneal and ulnar nerves, and motor studies of tibial, peroneal, and ulnar motor nerves with ulnar and tibial F wave latencies. Nerves were evaluated according to a recommended protocol for NCS postulated by the American Academy of Neurology in conjunction with the American Association of Electrodiagnostic Medicine and the American Academy of Physical Medicine and Rehabilitation, which include an abnormality of any nerve conduction attribute is in two separate nerves, one of which must be the sural nerve.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the findings of cutaneous silent period in the studied groups.</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of cutaneous silent period on stimulating left median nerve and recording from the left abductor pollicis brevis muscle, and on stimulating right sural nerve and recording from the tibialis anterior muscle, where abnormal results in encountered when there is delayed onset and/or end latencies, and/or decreased or absent duration.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the findings of sympathetic skin response in the studied groups.</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of sympathetic skin response on hand-to-hand stimulation of both median nerves, and foot-to-foot stimulation of both tibial nerves, where abnormal result is encountered when there is absent response, or delayed onset latency and/or decreased amplitude.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the findings of Ewing battery in the studied groups.</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of Ewing battery in the studied groups, where findings are recorded in all the 5 domains of the battery as normal or borderline or abnormal. Total score ranges from 0-5, and cardiovascular autonomic neuropathy is diagnosed according to the findings o fthe battery, where the findings are classified as follows&#xD;
  Normal: If all tests are normal, or one test is borderline.&#xD;
  Early: One heart rate test is abnormal or two are borderline.&#xD;
  Definite: At least two heart rate tests are abnormal&#xD;
  Severe: At least two heart rate tests are abnormal plus either at least one blood pressure test is abnormal or both tests are borderline.&#xD;
  Atypical: Any other undefined combination.&#xD;
  Further simplified classification is either normal (including normal or early findings) and abnormal (including definite, severe and atypical findings).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the findings of nerve ultrasound CSA of both vagal nerves.</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of nerve ultrasound cross-sectional area of both vagal nerves scanned opposite to the cricoid cartilage in the studied groups.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the findings of nerve ultrasound CSA of right sural nerve.</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of nerve ultrasound cross-sectional area of right sural nerve at the distal calf in the studied groups.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the findings of nerve ultrasound CSA of left tibial nerve.</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of nerve ultrasound cross-sectional area of left tibial nerve at the distal calf in the studied groups.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the findings of nerve ultrasound CSA of left median nerve.</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of nerve ultrasound cross-sectional area of left median nerve at the mid-forearm in the studied groups.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Demonstrate the findings of nerve ultrasound CSA of right ulnar nerve.</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Demonstrate the findings of nerve ultrasound cross-sectional area of right ulnar nerve at the mid-forearm in the studied groups.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Diabetic neuropathy severity assessment using NPS</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Diabetic neuropathy severity assessment using 11-item Numeric Pain Scale overall score.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diabetic neuropathy severity assessment TCNS</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Diabetic neuropathy severity assessment using Toronto clinical neuropathy scale, overall score.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diabetic neuropathy severity assessment using COMPASS-31</measure>
      <time_frame>through study completion, an average of 9 months</time_frame>
      <description>Diabetic neuropathy severity assessment using The Composite Autonomic Symptom Score-31, overall score.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diabetic neuropathy quality of life evaluation using Euro quality of life -5 dimensions -5 levels scale.</measure>
      <time_frame>through study completion, an average of 9 months.</time_frame>
      <description>Diabetic neuropathy quality of life evaluation using EuroQOL-5D-5L index value.</description>
    </secondary_outcome>
    <number_of_groups>3</number_of_groups>
    <enrollment type="Anticipated">45</enrollment>
    <condition>Small Fiber Neuropathy</condition>
    <condition>Diabetic Neuropathies</condition>
    <condition>Autonomic Neuropathy</condition>
    <condition>Diabetic Peripheral Neuropathy</condition>
    <condition>Painful Diabetic Neuropathy</condition>
    <condition>Diabetic Polyneuropathy</condition>
    <arm_group>
      <arm_group_label>Patients with diabetic small fiber neuropathy</arm_group_label>
      <description>Diabetic Patients presented with pure small fiber neuropathy.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Patients with diabetic mixed small and large fiber neuropathy</arm_group_label>
      <description>Diabetic Patients presented with mixed small and large fiber neuropathy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Subjects without neuropathy</arm_group_label>
      <description>Healthy subjects without any symptoms and/or signs suggesting neuropathy, and within average IENFD on skin biopsy.</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Clinical Evaluation/Questionnaires</intervention_name>
      <description>Anthropometric measures, somatosensory assessment (NPS, UENS, TCNS), autonomic assessment (COMPASS-31, Ewing battery), and severity and quality of life evaluation (NPS, TCNS, COMPASS-31, and EuroQOL-5D-5L index score)</description>
      <arm_group_label>Patients with diabetic mixed small and large fiber neuropathy</arm_group_label>
      <arm_group_label>Patients with diabetic small fiber neuropathy</arm_group_label>
      <arm_group_label>Subjects without neuropathy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Nerve Conduction Study</intervention_name>
      <description>Routine Nerve Conduction Study.</description>
      <arm_group_label>Patients with diabetic mixed small and large fiber neuropathy</arm_group_label>
      <arm_group_label>Patients with diabetic small fiber neuropathy</arm_group_label>
      <arm_group_label>Subjects without neuropathy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Small fiber electrodiagnostic tests</intervention_name>
      <description>R-R interval analysis, Cutaneous Silent Period and Sympathetic Skin Response.</description>
      <arm_group_label>Patients with diabetic mixed small and large fiber neuropathy</arm_group_label>
      <arm_group_label>Patients with diabetic small fiber neuropathy</arm_group_label>
      <arm_group_label>Subjects without neuropathy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Nerve Ultrasound</intervention_name>
      <description>Bilateral vagal, left median, right ulnar, left tibial and right sural nerves ultrasound.</description>
      <arm_group_label>Patients with diabetic mixed small and large fiber neuropathy</arm_group_label>
      <arm_group_label>Patients with diabetic small fiber neuropathy</arm_group_label>
      <arm_group_label>Subjects without neuropathy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Skin Biopsy</intervention_name>
      <description>distal leg 3mm punch skin biopsy</description>
      <arm_group_label>Patients with diabetic mixed small and large fiber neuropathy</arm_group_label>
      <arm_group_label>Patients with diabetic small fiber neuropathy</arm_group_label>
      <arm_group_label>Subjects without neuropathy</arm_group_label>
    </intervention>
    <biospec_retention>Samples Without DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Distal leg 3mm punch skin biopsy&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Group I: Patients with diabetic small fiber neuropathy Group II: Patients with diabetic&#xD;
          mixed small and large fiber neuropathy Group III: Subjects without neuropathy&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients diagnosed with diabetes mellitus or impaired glucose intolerance by&#xD;
               laboratory investigations including any of the following: HbA1C, fasting blood sugar&#xD;
               and 2-hour post prandial blood sugar, and/or antidiabetic medication.&#xD;
  &#xD;
            2. Patients presented with small fiber neuropathy (SFN), including all the following:&#xD;
  &#xD;
               A. Typical clinical symptoms of SFN such as burning or sharp pain in toes and feet,&#xD;
               and on clinical examination: loss of small fiber modalities (pinprick and&#xD;
               temperature), hyperalgesia, allodynia, and/or autonomic signs.&#xD;
  &#xD;
               B. Reduced intraepidermal nerve fiber density (IENFD) in distal leg skin punch biopsy.&#xD;
  &#xD;
            3. Age older than 18 years old&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Mental illness that made interviewing ineffective&#xD;
  &#xD;
            2. Physical illness leading to language and/or cognitive barrier&#xD;
  &#xD;
            3. Other conditions that could cause neuropathy (e.g., chemotherapy, alcohol intake,&#xD;
               established vitamin B12 deficiency, established hereditary neuropathy &quot;or first-degree&#xD;
               family members&quot;, active malignancy, chronic advanced liver or kidney diseases thought&#xD;
               to cause neuropathy and history of bariatric surgery).&#xD;
  &#xD;
            4. Atrial Fibrillation&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Ahmed Sami Mahmoud Alkotami</name>
        <address>
          <city>Kafr Ash Shaykh</city>
          <zip>33511</zip>
          <country>Egypt</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Egypt</country>
    </location_countries>
    <reference>
      <citation>Devigili G, Tugnoli V, Penza P, Camozzi F, Lombardi R, Melli G, Broglio L, Granieri E, Lauria G. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain. 2008 Jul;131(Pt 7):1912-25. doi: 10.1093/brain/awn093. Epub 2008 Jun 4.</citation>
      <PMID>18524793</PMID>
    </reference>
    <reference>
      <citation>Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P; Toronto Diabetic Neuropathy Expert Group. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010 Oct;33(10):2285-93. doi: 10.2337/dc10-1303. Erratum In: Diabetes Care. 2010 Dec;33(12):2725.</citation>
      <PMID>20876709</PMID>
    </reference>
    <reference>
      <citation>Tankisi H, Pugdahl K, Beniczky S, Andersen H, Fuglsang-Frederiksen A. Evidence-based recommendations for examination and diagnostic strategies of polyneuropathy electrodiagnosis. Clin Neurophysiol Pract. 2019 Nov 18;4:214-222. doi: 10.1016/j.cnp.2019.10.005. eCollection 2019.</citation>
      <PMID>31886447</PMID>
    </reference>
    <reference>
      <citation>Singleton JR, Bixby B, Russell JW, Feldman EL, Peltier A, Goldstein J, Howard J, Smith AG. The Utah Early Neuropathy Scale: a sensitive clinical scale for early sensory predominant neuropathy. J Peripher Nerv Syst. 2008 Sep;13(3):218-27. doi: 10.1111/j.1529-8027.2008.00180.x.</citation>
      <PMID>18844788</PMID>
    </reference>
    <reference>
      <citation>Terkawi AS, Abolkhair A, Didier B, Alzhahrani T, Alsohaibani M, Terkawi YS, Almoqbali Y, Tolba YY, Pangililan E, Foula F, Tsang S. Development and validation of Arabic version of the douleur neuropathique 4 questionnaire. Saudi J Anaesth. 2017 May;11(Suppl 1):S31-S39. doi: 10.4103/sja.SJA_97_17.</citation>
      <PMID>28616002</PMID>
    </reference>
    <reference>
      <citation>Eldokla AM, Mohamed-Hussein AA, Fouad AM, Abdelnaser MG, Ali ST, Makhlouf NA, Sayed IG, Makhlouf HA, Shah J, Aiash H. Prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome: A cross-sectional study. Ann Clin Transl Neurol. 2022 Jun;9(6):778-785. doi: 10.1002/acn3.51557. Epub 2022 Apr 8.</citation>
      <PMID>35393771</PMID>
    </reference>
    <reference>
      <citation>Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care. 1985 Sep-Oct;8(5):491-8. doi: 10.2337/diacare.8.5.491.</citation>
      <PMID>4053936</PMID>
    </reference>
    <reference>
      <citation>Bril V, Perkins BA. Validation of the Toronto Clinical Scoring System for diabetic polyneuropathy. Diabetes Care. 2002 Nov;25(11):2048-52. doi: 10.2337/diacare.25.11.2048.</citation>
      <PMID>12401755</PMID>
    </reference>
    <reference>
      <citation>Sletten DM, Suarez GA, Low PA, Mandrekar J, Singer W. COMPASS 31: a refined and abbreviated Composite Autonomic Symptom Score. Mayo Clin Proc. 2012 Dec;87(12):1196-201. doi: 10.1016/j.mayocp.2012.10.013.</citation>
      <PMID>23218087</PMID>
    </reference>
    <reference>
      <citation>Al Shabasy S, Abbassi M, Finch A, Roudijk B, Baines D, Farid S. The EQ-5D-5L Valuation Study in Egypt. Pharmacoeconomics. 2022 Apr;40(4):433-447. doi: 10.1007/s40273-021-01100-y. Epub 2021 Nov 17.</citation>
      <PMID>34786590</PMID>
    </reference>
    <reference>
      <citation>Bekairy AM, Bustami RT, Almotairi M, Jarab A, Katheri AM, Aldebasi TM, Aburuz S. Validity and reliability of the Arabic version of the the EuroQOL (EQ-5D). A study from Saudi Arabia. Int J Health Sci (Qassim). 2018 Mar-Apr;12(2):16-20.</citation>
      <PMID>29599689</PMID>
    </reference>
    <reference>
      <citation>Vetrugno R, Liguori R, Cortelli P, Montagna P. Sympathetic skin response: basic mechanisms and clinical applications. Clin Auton Res. 2003 Aug;13(4):256-70. doi: 10.1007/s10286-003-0107-5.</citation>
      <PMID>12955550</PMID>
    </reference>
    <reference>
      <citation>Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Nolano M, Merkies IS, Polydefkis M, Smith AG, Sommer C, Valls-Sole J; European Federation of Neurological Societies; Peripheral Nerve Society. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2010 Jul;17(7):903-12, e44-9. doi: 10.1111/j.1468-1331.2010.03023.x.</citation>
      <PMID>20642627</PMID>
    </reference>
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      <citation>Telleman JA, Herraets IJ, Goedee HS, van Asseldonk JT, Visser LH. Ultrasound scanning in the diagnosis of peripheral neuropathies. Pract Neurol. 2021 Jun;21(3):186-195. doi: 10.1136/practneurol-2020-002645. Epub 2021 Feb 4.</citation>
      <PMID>33541914</PMID>
    </reference>
    <reference>
      <citation>Tawfik EA, Walker FO, Cartwright MS, El-Hilaly RA. Diagnostic Ultrasound of the Vagus Nerve in Patients with Diabetes. J Neuroimaging. 2017 Nov;27(6):589-593. doi: 10.1111/jon.12452. Epub 2017 May 19.</citation>
      <PMID>28524416</PMID>
    </reference>
    <reference>
      <citation>Ebadi H, Siddiqui H, Ebadi S, Ngo M, Breiner A, Bril V. Peripheral Nerve Ultrasound in Small Fiber Polyneuropathy. Ultrasound Med Biol. 2015 Nov;41(11):2820-6. doi: 10.1016/j.ultrasmedbio.2015.06.011. Epub 2015 Aug 28.</citation>
      <PMID>26318562</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>May 21, 2023</study_first_submitted>
    <study_first_submitted_qc>August 13, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 13, 2023</last_update_submitted>
    <last_update_submitted_qc>August 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Tanta University</investigator_affiliation>
      <investigator_full_name>Ahmed Sami Alkotami</investigator_full_name>
      <investigator_title>Assistant Lecturer of Neurology</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Peripheral Nervous System Diseases</mesh_term>
      <mesh_term>Diabetic Neuropathies</mesh_term>
      <mesh_term>Polyneuropathies</mesh_term>
      <mesh_term>Small Fiber Neuropathy</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05993871
  org study id: 34059/8/20
  nct id: NCT05993871
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The aim of work is to study the clinical, electrodiagnostic and neurosonographic
        characteristics of diabetic patients with small fiber neuropathy in the Egyptian population,
        and to evaluate both the diagnostic and the prognostic impact of the studied factors on the
        neuropathy severity and quality of life.
  This case-control observational study is aiming to evaluate patients with diabetic small
        fiber neuropathy in the Egyptian.
  
        Diabetic small fiber neuropathy was defined as both of the following:
  
        A. Typical clinical symptoms of SFN such as burning or sharp pain in toes and feet, and on
        clinical examination: loss of small fiber modalities (pinprick and temperature),
        hyperalgesia, allodynia, and/or autonomic signs.
  
        B. Reduced intraepidermal nerve fiber density (IENFD) in distal leg skin punch biopsy.
  
        The study includes 3 groups:
  
        Group I: Patients with diabetic small fiber neuropathy Group II (Control Group): Patients
        with diabetic mixed small and large fiber neuropathy Group III (Control Group): Subjects
        without peripheral neuropathy
  
        Clinical evaluation includes: Neuropathic Pain 4 (DN4) questionnaire, 11-point Numeric Pain
        Scale (NPS), Utah Early Neuropathy Scale (UENS), Toronto Clinical Neuropathy Scale (TCNS),
        Composite Autonomic Symptom Score (COMPASS-31), an Arabic version, and several anthropometric
        measures; including: body weight in kilograms, height in centimeters, waist circumference
        measured in centimeters at the top of the iliac crest, and systolic "SBP" and diastolic "DBP"
        blood pressure measurement in mmHg.
  
        Electrodiagnostic evaluation includes: routine nerve conduction study, cutaneous silent
        period by stimulating left median nerve and right sural nerve and recording from the abductor
        pollicis brevis and tibialis anterior muscles, respectively, bilateral hand-to hand and
        foot-to-foot sympathetic skin response, and Ewing battery using R-R interval analysis, in
        addition to the blood pressure tests.
  
        Neurosonographic evaluation includes: bilateral vagal nerve scan at the mid-neck lateral to
        the thyroid cartilage, left median and right ulnar nerves scan at the mid-forearm, left
        tibial nerve at the distal ankle 2 to 4 fingerbreadths proximal to the medial malleolus, and
        right sural nerve 2 to 4 fingerbreadths proximal to the lateral malleolus. Nerves are
        evaluated for transverse cross-sectional area (CSA).
  
        Severity and outcome measures are assessed using: NPS, TCNS, COMPASS-31, and the index score
        of Euro Quality of Life -5 Dimensions -5 Levels (EuroQOL-5D-5L), the Arabic version.
  observational model: Case-Control
  time perspective: Retrospective
  measure: Demonstrate the findings of UENS in the studied groups
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of Utah early neuropathy scale in the studied groups to screen for neuropathic symptoms, where overall scores of 4 and more are considered positive.
  measure: Demonstrate the findings of TCNS in the studied groups
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of Toronto clinical neuropathy scale in the studied groups, to screen for the neuropathic symptoms where overall scores of 6 and more are considered positive.
  measure: Demonstrate the findings of EuroQOL-5D-5L in the studied groups
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of Euro quality of life -5 dimensions -5 levels scale in the studied groups, where lesser scores suggest a lower overall quality of life.
  measure: Demonstrate the findings of nerve conduction studies protocol of the performed nerves in the studied groups.
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of nerve conduction studies (NCS) to define neuropathy in the studied groups, which include: unilateral sensory studies of sural, superficial peroneal and ulnar nerves, and motor studies of tibial, peroneal, and ulnar motor nerves with ulnar and tibial F wave latencies. Nerves were evaluated according to a recommended protocol for NCS postulated by the American Academy of Neurology in conjunction with the American Association of Electrodiagnostic Medicine and the American Academy of Physical Medicine and Rehabilitation, which include an abnormality of any nerve conduction attribute is in two separate nerves, one of which must be the sural nerve.
  measure: Demonstrate the findings of cutaneous silent period in the studied groups.
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of cutaneous silent period on stimulating left median nerve and recording from the left abductor pollicis brevis muscle, and on stimulating right sural nerve and recording from the tibialis anterior muscle, where abnormal results in encountered when there is delayed onset and/or end latencies, and/or decreased or absent duration.
  measure: Demonstrate the findings of sympathetic skin response in the studied groups.
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of sympathetic skin response on hand-to-hand stimulation of both median nerves, and foot-to-foot stimulation of both tibial nerves, where abnormal result is encountered when there is absent response, or delayed onset latency and/or decreased amplitude.
  measure: Demonstrate the findings of Ewing battery in the studied groups.
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of Ewing battery in the studied groups, where findings are recorded in all the 5 domains of the battery as normal or borderline or abnormal. Total score ranges from 0-5, and cardiovascular autonomic neuropathy is diagnosed according to the findings o fthe battery, where the findings are classified as follows
  Normal: If all tests are normal, or one test is borderline.
  Early: One heart rate test is abnormal or two are borderline.
  Definite: At least two heart rate tests are abnormal
  Severe: At least two heart rate tests are abnormal plus either at least one blood pressure test is abnormal or both tests are borderline.
  Atypical: Any other undefined combination.
  Further simplified classification is either normal (including normal or early findings) and abnormal (including definite, severe and atypical findings).
  measure: Demonstrate the findings of nerve ultrasound CSA of both vagal nerves.
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of nerve ultrasound cross-sectional area of both vagal nerves scanned opposite to the cricoid cartilage in the studied groups.
  measure: Demonstrate the findings of nerve ultrasound CSA of right sural nerve.
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of nerve ultrasound cross-sectional area of right sural nerve at the distal calf in the studied groups.
  measure: Demonstrate the findings of nerve ultrasound CSA of left tibial nerve.
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of nerve ultrasound cross-sectional area of left tibial nerve at the distal calf in the studied groups.
  measure: Demonstrate the findings of nerve ultrasound CSA of left median nerve.
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of nerve ultrasound cross-sectional area of left median nerve at the mid-forearm in the studied groups.
  measure: Demonstrate the findings of nerve ultrasound CSA of right ulnar nerve.
  time frame: through study completion, an average of 9 months
  description: Demonstrate the findings of nerve ultrasound cross-sectional area of right ulnar nerve at the mid-forearm in the studied groups.
  measure: Diabetic neuropathy severity assessment using NPS
  time frame: through study completion, an average of 9 months
  description: Diabetic neuropathy severity assessment using 11-item Numeric Pain Scale overall score.
  measure: Diabetic neuropathy severity assessment TCNS
  time frame: through study completion, an average of 9 months
  description: Diabetic neuropathy severity assessment using Toronto clinical neuropathy scale, overall score.
  measure: Diabetic neuropathy severity assessment using COMPASS-31
  time frame: through study completion, an average of 9 months
  description: Diabetic neuropathy severity assessment using The Composite Autonomic Symptom Score-31, overall score.
  measure: Diabetic neuropathy quality of life evaluation using Euro quality of life -5 dimensions -5 levels scale.
  time frame: through study completion, an average of 9 months.
  description: Diabetic neuropathy quality of life evaluation using EuroQOL-5D-5L index value.
  arm group label: Patients with diabetic small fiber neuropathy
  description: Diabetic Patients presented with pure small fiber neuropathy.
  arm group label: Patients with diabetic mixed small and large fiber neuropathy
  description: Diabetic Patients presented with mixed small and large fiber neuropathy
  arm group label: Subjects without neuropathy
  description: Healthy subjects without any symptoms and/or signs suggesting neuropathy, and within average IENFD on skin biopsy.
  intervention type: Diagnostic Test
  intervention name: Clinical Evaluation/Questionnaires
  description: Anthropometric measures, somatosensory assessment (NPS, UENS, TCNS), autonomic assessment (COMPASS-31, Ewing battery), and severity and quality of life evaluation (NPS, TCNS, COMPASS-31, and EuroQOL-5D-5L index score)
  arm group label: Patients with diabetic mixed small and large fiber neuropathy
  arm group label: Patients with diabetic small fiber neuropathy
  arm group label: Subjects without neuropathy
  intervention type: Diagnostic Test
  intervention name: Nerve Conduction Study
  description: Routine Nerve Conduction Study.
  arm group label: Patients with diabetic mixed small and large fiber neuropathy
  arm group label: Patients with diabetic small fiber neuropathy
  arm group label: Subjects without neuropathy
  intervention type: Diagnostic Test
  intervention name: Small fiber electrodiagnostic tests
  description: R-R interval analysis, Cutaneous Silent Period and Sympathetic Skin Response.
  arm group label: Patients with diabetic mixed small and large fiber neuropathy
  arm group label: Patients with diabetic small fiber neuropathy
  arm group label: Subjects without neuropathy
  intervention type: Diagnostic Test
  intervention name: Nerve Ultrasound
  description: Bilateral vagal, left median, right ulnar, left tibial and right sural nerves ultrasound.
  arm group label: Patients with diabetic mixed small and large fiber neuropathy
  arm group label: Patients with diabetic small fiber neuropathy
  arm group label: Subjects without neuropathy
  intervention type: Diagnostic Test
  intervention name: Skin Biopsy
  description: distal leg 3mm punch skin biopsy
  arm group label: Patients with diabetic mixed small and large fiber neuropathy
  arm group label: Patients with diabetic small fiber neuropathy
  arm group label: Subjects without neuropathy
  Distal leg 3mm punch skin biopsy
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  facility: 
  country: Egypt
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  PMID: 26318562
  responsible party type: Principal Investigator
  investigator affiliation: Tanta University
  investigator full name: Ahmed Sami Alkotami
  investigator title: Assistant Lecturer of Neurology
  mesh term: Peripheral Nervous System Diseases
  mesh term: Diabetic Neuropathies
  mesh term: Polyneuropathies
  mesh term: Small Fiber Neuropathy
  sharing ipd: Undecided