<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/NCT03787511</url>
  </required_header>
  <id_info>
    <org_study_id>RC31/18/0423</org_study_id>
    <secondary_id>2018-A03340-55</secondary_id>
    <nct_id>NCT03787511</nct_id>
  </id_info>
  <brief_title>Chronic Cough and Small Fiber Neuropathy</brief_title>
  <acronym>CHROCOS</acronym>
  <official_title>Chronic Cough and Small Fiber Neuropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Toulouse</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Toulouse</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>
      Diabetic patients with and without chronic cough will be included in this study. After giving&#xD;
      their informed consent, the patients will perform a spirometry, chest X-ray at the inclusion&#xD;
      visit. Cough will be assessed using the cough visual analog scale (VAS) and the Leicester&#xD;
      Cough Questionnaire (LCQ). Within 60 days, the patient will perform neurophysiological tests.&#xD;
      The neurophysiological assessment will be concluded with a skin biopsy to evaluate small&#xD;
      fiber neuropathy. The aim of the study is to compare the proportion of small fiber neuropathy&#xD;
      between diabetic patients with chronic cough and those without chronic cough.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic cough is a very common entity that affects 9.6% people worldwide. Given the high&#xD;
      number of patients with refractory cough, the concept of cough hypersensitivity syndrome&#xD;
      (CHS) has emerged. In CHS, afferent sensory nerves may exhibit a modification of activation&#xD;
      patterns with facilitation of encoding signals in response to irritating stimuli. Similar&#xD;
      patterns with neuropathic pain have been described. Small fiber neuropathy has never been&#xD;
      assessed in chronic cough. Interestingly, diabetic patients experienced cough more frequently&#xD;
      than healthy subject. We hypothesized that small fiber neuropathy may explain chronic cough&#xD;
      is more frequent in diabetic patients.&#xD;
&#xD;
      Within 60 days after inclusion, diabetic patients with and without chronic cough will perform&#xD;
      neurophysiological tests such as electromyography, thermotest, QSART (Quantitative Sudomotor&#xD;
      Axon Reflex Test and Sudoscan), cardio-vascular tests to study the autonomic nervous system.&#xD;
      No risks are expecting with these non-invasive tests. A skin biopsy to evaluate small fiber&#xD;
      neuropathy will also be performed.After the neurophysiological tests, a consultation will be&#xD;
      scheduled at 6 months. A cough VAS and LCQ will be used to assess cough.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 5, 2019</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients with small fiber neuropathy</measure>
    <time_frame>6 month after inclusion visit</time_frame>
    <description>The primary endpoint is the proportion of patients with small fiber neuropathy between diabetic patients with chronic cough and those without chronic cough (defined by at least 2 abnormal neurophysiological tests).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>proportion of patients with abnormal results of the thermotest</measure>
    <time_frame>6 month after inclusion visit</time_frame>
    <description>estimate the proportion of patients with abnormal results of the thermotest in each arm (with and without chronic cough)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of patients with pathological results of the sudori-motor response</measure>
    <time_frame>6 month after inclusion visit</time_frame>
    <description>estimate the proportion of patients with pathological results of the sudori-motor response in each arm (with and without chronic cough)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the proportion of patients with abnormal results of cardiovascular tests</measure>
    <time_frame>6 month after inclusion visit</time_frame>
    <description>estimate the proportion of patients with abnormal results of cardiovascular tests assessing the autonomic nervous system in in each arm (with and without chronic cough)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of patients with abnormal results of laser evoked potentials</measure>
    <time_frame>6 month after inclusion visit</time_frame>
    <description>estimate the proportion of patients with abnormal results of laser evoked potentials in each arm (with and without chronic cough)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of patients with abnormal findings of cutaneous biopsy</measure>
    <time_frame>6 month after inclusion visit</time_frame>
    <description>estimate the proportion of patients with abnormal findings of cutaneous biopsy in in each arm (with and without chronic cough)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>values of Leicester Cough Questionnaire (LCQ) in diabetic patients</measure>
    <time_frame>6 month after inclusion visit</time_frame>
    <description>estimate the values of Leicester Cough Questionnaire in diabetic patients with and without chronic cough. The Leicester Cough Questionnaire comprises 19 items and takes 5 to 10 minutes to complete. Each item assesses symptoms, or the impact of symptoms, over the last 2 weeks on a seven-point Likert scale. Scores in three domains (physical, psychological and social) are calculated as a mean for each domain (range 1 to 7). A total score (range 3 to 21) is also calculated by adding the domain scores together. Higher scores indicate better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>values of the DN4 questionnaire in diabetic patients</measure>
    <time_frame>6 month after inclusion visit</time_frame>
    <description>estimate the values of the DN4 questionnaire in diabetic patients with and without chronic cough.&#xD;
It allows to estimate the probability of neuropathic pain in a patient, through 4 questions divided into 10 check items. The practitioner questions or examines the patient and completes the questionnaire himself. He notes a response (&quot;yes&quot;, &quot;no&quot;) to each item. At the end of the questionnaire, he counts the answers and assigns the note 1 for each &quot;yes&quot;, and the score 0 for each &quot;no&quot;. The sum obtained gives the score of the patient, scored out of 10.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Chronic Cough</condition>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Diabetic patients with chronic cough</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Diabetic patients with chronic cough defined by cough lasting for more than 8 weeks. Cough assessment, neurological tests and cardiovascular tests and skin biopsy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetic patients without chronic cough</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Diabetic patients without chronic cough defined by cough lasting for more than 8 weeks. Cough assessment, neurological tests and cardiovascular tests and skin biopsy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cough assessment</intervention_name>
    <description>Cough assessment with cough visual analog scale (VAS), and Leicester Cough Questionnaire (LCQ) for Diabetic patients with chronic cough and Diabetic patients without chronic cough</description>
    <arm_group_label>Diabetic patients with chronic cough</arm_group_label>
    <arm_group_label>Diabetic patients without chronic cough</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Neurological tests and cardiovascular tests</intervention_name>
    <description>Neurological tests : electromyography, thermotest, QSAR + cardiovascular test for Diabetic patients with chronic cough and Diabetic patients without chronic cough</description>
    <arm_group_label>Diabetic patients with chronic cough</arm_group_label>
    <arm_group_label>Diabetic patients without chronic cough</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Skin biopsy</intervention_name>
    <description>Skin biopsy to evaluate small fiber neuropathy for Diabetic patients with chronic cough and Diabetic patients without chronic cough</description>
    <arm_group_label>Diabetic patients with chronic cough</arm_group_label>
    <arm_group_label>Diabetic patients without chronic cough</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        In diabetic patients with chronic cough:&#xD;
&#xD;
          -  Chronic cough defined by cough for more than 8 weeks.&#xD;
&#xD;
          -  Normal chest X-ray&#xD;
&#xD;
          -  history of type 2 diabetes&#xD;
&#xD;
          -  Age of diabetes onset&gt; 40 years&#xD;
&#xD;
          -  Affiliated or beneficiary person of social security&#xD;
&#xD;
          -  Free, informed and written consent&#xD;
&#xD;
        In diabetic patients without chronic cough&#xD;
&#xD;
          -  History of type 2 diabetes&#xD;
&#xD;
          -  Age of discovery of diabetes&gt; 40 years&#xD;
&#xD;
          -  Affiliated or beneficiary person of social security&#xD;
&#xD;
          -  Free, informed and written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of physical signs of peripheral neuropathy&#xD;
&#xD;
          -  Active smoking or smoking cessation within the last 12 months&#xD;
&#xD;
          -  Pregnant or lactating woman&#xD;
&#xD;
          -  History of non-type 2 diabetes (type I, secondary diabetes, monogenic ...)&#xD;
&#xD;
          -  Cancer within the last 5 years (except cutaneous squamous cell carcinoma)&#xD;
&#xD;
          -  History of anti-cancer chemotherapy&#xD;
&#xD;
          -  Suspicion of autoimmune pathology&#xD;
&#xD;
          -  Active neurological pathology&#xD;
&#xD;
          -  Electromyography in favor of large fiber neuropathy&#xD;
&#xD;
          -  Chronic pathology that may interfere with the neurophysiological assessment&#xD;
&#xD;
          -  Patient who were given anticoagulation drug therapy, anti-cholinergic drugs,&#xD;
             beta-blocker and impossibility to withdraw the treatment before neurophysiological&#xD;
             tests&#xD;
&#xD;
        In diabetic patients without chronic cough, another non-inclusion criteria is acute or&#xD;
        chronic cough&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Laurent Guilleminault, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Toulouse</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Laurent Guilleminault, MD</last_name>
    <phone>05-67-77-18-50</phone>
    <phone_ext>33</phone_ext>
    <email>guilleminault.a@chu-toulouse.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital Larrey</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurent Guilleminault, MD</last_name>
    </contact>
    <investigator>
      <last_name>Laurent Guilleminault, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alain Didier, PH</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Marion Dupuis, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Danielle Brouiquieres, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Vincent Fabry, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Anne Pavy-Le Traon, PH</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Pascal Cintas, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Blandine Acket, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Chung KF. Chronic 'cough hypersensitivity syndrome': a more precise label for chronic cough. Pulm Pharmacol Ther. 2011 Jun;24(3):267-71. doi: 10.1016/j.pupt.2011.01.012. Epub 2011 Feb 1.</citation>
    <PMID>21292019</PMID>
  </reference>
  <reference>
    <citation>De Santi F, Zoppini G, Locatelli F, Finocchio E, Cappa V, Dauriz M, Verlato G. Type 2 diabetes is associated with an increased prevalence of respiratory symptoms as compared to the general population. BMC Pulm Med. 2017 Jul 17;17(1):101. doi: 10.1186/s12890-017-0443-1.</citation>
    <PMID>28716044</PMID>
  </reference>
  <reference>
    <citation>Pavy-Le Traon A, Fontaine S, Tap G, Guidolin B, Senard JM, Hanaire H. Cardiovascular autonomic neuropathy and other complications in type 1 diabetes. Clin Auton Res. 2010 Jun;20(3):153-60. doi: 10.1007/s10286-010-0062-x. Epub 2010 Mar 31.</citation>
    <PMID>20354891</PMID>
  </reference>
  <reference>
    <citation>Casellini CM, Parson HK, Richardson MS, Nevoret ML, Vinik AI. Sudoscan, a noninvasive tool for detecting diabetic small fiber neuropathy and autonomic dysfunction. Diabetes Technol Ther. 2013 Nov;15(11):948-53. doi: 10.1089/dia.2013.0129. Epub 2013 Jul 27.</citation>
    <PMID>23889506</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>December 24, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 26, 2018</study_first_posted>
  <last_update_submitted>July 21, 2023</last_update_submitted>
  <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cough</keyword>
  <keyword>diabetes</keyword>
  <keyword>small fiber neuropathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cough</mesh_term>
    <mesh_term>Small Fiber Neuropathy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03787511
org study id: RC31/18/0423
secondary id: 2018-A03340-55
nct id: NCT03787511
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Diabetic patients with and without chronic cough will be included in this study. After giving
      their informed consent, the patients will perform a spirometry, chest X-ray at the inclusion
      visit. Cough will be assessed using the cough visual analog scale (VAS) and the Leicester
      Cough Questionnaire (LCQ). Within 60 days, the patient will perform neurophysiological tests.
      The neurophysiological assessment will be concluded with a skin biopsy to evaluate small
      fiber neuropathy. The aim of the study is to compare the proportion of small fiber neuropathy
      between diabetic patients with chronic cough and those without chronic cough.
Chronic cough is a very common entity that affects 9.6% people worldwide. Given the high
      number of patients with refractory cough, the concept of cough hypersensitivity syndrome
      (CHS) has emerged. In CHS, afferent sensory nerves may exhibit a modification of activation
      patterns with facilitation of encoding signals in response to irritating stimuli. Similar
      patterns with neuropathic pain have been described. Small fiber neuropathy has never been
      assessed in chronic cough. Interestingly, diabetic patients experienced cough more frequently
      than healthy subject. We hypothesized that small fiber neuropathy may explain chronic cough
      is more frequent in diabetic patients.

      Within 60 days after inclusion, diabetic patients with and without chronic cough will perform
      neurophysiological tests such as electromyography, thermotest, QSART (Quantitative Sudomotor
      Axon Reflex Test and Sudoscan), cardio-vascular tests to study the autonomic nervous system.
      No risks are expecting with these non-invasive tests. A skin biopsy to evaluate small fiber
      neuropathy will also be performed.After the neurophysiological tests, a consultation will be
      scheduled at 6 months. A cough VAS and LCQ will be used to assess cough.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Proportion of patients with small fiber neuropathy
time frame: 6 month after inclusion visit
description: The primary endpoint is the proportion of patients with small fiber neuropathy between diabetic patients with chronic cough and those without chronic cough (defined by at least 2 abnormal neurophysiological tests).
measure: proportion of patients with abnormal results of the thermotest
time frame: 6 month after inclusion visit
description: estimate the proportion of patients with abnormal results of the thermotest in each arm (with and without chronic cough)
measure: proportion of patients with pathological results of the sudori-motor response
time frame: 6 month after inclusion visit
description: estimate the proportion of patients with pathological results of the sudori-motor response in each arm (with and without chronic cough)
measure: the proportion of patients with abnormal results of cardiovascular tests
time frame: 6 month after inclusion visit
description: estimate the proportion of patients with abnormal results of cardiovascular tests assessing the autonomic nervous system in in each arm (with and without chronic cough)
measure: proportion of patients with abnormal results of laser evoked potentials
time frame: 6 month after inclusion visit
description: estimate the proportion of patients with abnormal results of laser evoked potentials in each arm (with and without chronic cough)
measure: proportion of patients with abnormal findings of cutaneous biopsy
time frame: 6 month after inclusion visit
description: estimate the proportion of patients with abnormal findings of cutaneous biopsy in in each arm (with and without chronic cough)
measure: values of Leicester Cough Questionnaire (LCQ) in diabetic patients
time frame: 6 month after inclusion visit
description: estimate the values of Leicester Cough Questionnaire in diabetic patients with and without chronic cough. The Leicester Cough Questionnaire comprises 19 items and takes 5 to 10 minutes to complete. Each item assesses symptoms, or the impact of symptoms, over the last 2 weeks on a seven-point Likert scale. Scores in three domains (physical, psychological and social) are calculated as a mean for each domain (range 1 to 7). A total score (range 3 to 21) is also calculated by adding the domain scores together. Higher scores indicate better quality of life.
measure: values of the DN4 questionnaire in diabetic patients
time frame: 6 month after inclusion visit
description: estimate the values of the DN4 questionnaire in diabetic patients with and without chronic cough.
It allows to estimate the probability of neuropathic pain in a patient, through 4 questions divided into 10 check items. The practitioner questions or examines the patient and completes the questionnaire himself. He notes a response ("yes", "no") to each item. At the end of the questionnaire, he counts the answers and assigns the note 1 for each "yes", and the score 0 for each "no". The sum obtained gives the score of the patient, scored out of 10.
arm group label: Diabetic patients with chronic cough
arm group type: Other
description: Diabetic patients with chronic cough defined by cough lasting for more than 8 weeks. Cough assessment, neurological tests and cardiovascular tests and skin biopsy.
arm group label: Diabetic patients without chronic cough
arm group type: Other
description: Diabetic patients without chronic cough defined by cough lasting for more than 8 weeks. Cough assessment, neurological tests and cardiovascular tests and skin biopsy.
intervention type: Other
intervention name: Cough assessment
description: Cough assessment with cough visual analog scale (VAS), and Leicester Cough Questionnaire (LCQ) for Diabetic patients with chronic cough and Diabetic patients without chronic cough
arm group label: Diabetic patients with chronic cough
arm group label: Diabetic patients without chronic cough
intervention type: Other
intervention name: Neurological tests and cardiovascular tests
description: Neurological tests : electromyography, thermotest, QSAR + cardiovascular test for Diabetic patients with chronic cough and Diabetic patients without chronic cough
arm group label: Diabetic patients with chronic cough
arm group label: Diabetic patients without chronic cough
intervention type: Other
intervention name: Skin biopsy
description: Skin biopsy to evaluate small fiber neuropathy for Diabetic patients with chronic cough and Diabetic patients without chronic cough
arm group label: Diabetic patients with chronic cough
arm group label: Diabetic patients without chronic cough
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Laurent Guilleminault, MD
role: Principal Investigator
affiliation: University Hospital, Toulouse
last name: Laurent Guilleminault, MD
phone: 05-67-77-18-50
phone ext: 33
email: guilleminault.a@chu-toulouse.fr
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: France
citation: Chung KF. Chronic 'cough hypersensitivity syndrome': a more precise label for chronic cough. Pulm Pharmacol Ther. 2011 Jun;24(3):267-71. doi: 10.1016/j.pupt.2011.01.012. Epub 2011 Feb 1.
PMID: 21292019
citation: De Santi F, Zoppini G, Locatelli F, Finocchio E, Cappa V, Dauriz M, Verlato G. Type 2 diabetes is associated with an increased prevalence of respiratory symptoms as compared to the general population. BMC Pulm Med. 2017 Jul 17;17(1):101. doi: 10.1186/s12890-017-0443-1.
PMID: 28716044
citation: Pavy-Le Traon A, Fontaine S, Tap G, Guidolin B, Senard JM, Hanaire H. Cardiovascular autonomic neuropathy and other complications in type 1 diabetes. Clin Auton Res. 2010 Jun;20(3):153-60. doi: 10.1007/s10286-010-0062-x. Epub 2010 Mar 31.
PMID: 20354891
citation: Casellini CM, Parson HK, Richardson MS, Nevoret ML, Vinik AI. Sudoscan, a noninvasive tool for detecting diabetic small fiber neuropathy and autonomic dysfunction. Diabetes Technol Ther. 2013 Nov;15(11):948-53. doi: 10.1089/dia.2013.0129. Epub 2013 Jul 27.
PMID: 23889506
responsible party type: Sponsor
mesh term: Cough
mesh term: Small Fiber Neuropathy
sharing ipd: No