Clinical trial NCT03787511: Chronic Cough and Small Fiber Neuropathy
Official title: Chronic Cough and Small Fiber Neuropathy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Chronic Cough
Type 2 Diabetes
Keywords: cough
diabetes
small fiber neuropathy
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2018-12-26
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

In diabetic patients with chronic cough:

* Chronic cough defined by cough for more than 8 weeks.
* Normal chest X-ray
* history of type 2 diabetes
* Age of diabetes onset\> 40 years
* Affiliated or beneficiary person of social security
* Free, informed and written consent

In diabetic patients without chronic cough

* History of type 2 diabetes
* Age of discovery of diabetes\> 40 years
* Affiliated or beneficiary person of social security
* Free, informed and written consent

Exclusion Criteria:

* Presence of physical signs of peripheral neuropathy
* Active smoking or smoking cessation within the last 12 months
* Pregnant or lactating woman
* History of non-type 2 diabetes (type I, secondary diabetes, monogenic ...)
* Cancer within the last 5 years (except cutaneous squamous cell carcinoma)
* History of anti-cancer chemotherapy
* Suspicion of autoimmune pathology
* Active neurological pathology
* Electromyography in favor of large fiber neuropathy
* Chronic pathology that may interfere with the neurophysiological assessment
* Patient who were given anticoagulation drug therapy, anti-cholinergic drugs, beta-blocker and impossibility to withdraw the treatment before neurophysiological tests

In diabetic patients without chronic cough, another non-inclusion criteria is acute or chronic cough

Primary outcomes:
measure: Proportion of patients with small fiber neuropathy
timeFrame: 6 month after inclusion visit
Secondary outcomes:
measure: proportion of patients with abnormal results of the thermotest
timeFrame: 6 month after inclusion visit
measure: proportion of patients with pathological results of the sudori-motor response
timeFrame: 6 month after inclusion visit
measure: the proportion of patients with abnormal results of cardiovascular tests
timeFrame: 6 month after inclusion visit
measure: proportion of patients with abnormal results of laser evoked potentials
timeFrame: 6 month after inclusion visit
measure: proportion of patients with abnormal findings of cutaneous biopsy
timeFrame: 6 month after inclusion visit
measure: values of Leicester Cough Questionnaire (LCQ) in diabetic patients
timeFrame: 6 month after inclusion visit
measure: values of the DN4 questionnaire in diabetic patients
timeFrame: 6 month after inclusion visit
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Hôpital Larrey
Study officials:
affiliation: University Hospital, Toulouse
name: Laurent Guilleminault, MD
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: 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: 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.