Chronic CoughCHROCOSNCT03787511
Chronic Cough and Small Fiber Neuropathy
A study testing Cough assessment, Neurological tests and cardiovascular tests and Skin biopsy in people with Chronic Cough and Type 2 Diabetes, run by University Hospital, Toulouse at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Cough, Type 2 Diabetes
- What is being tested?
- Cough assessment, Neurological tests and cardiovascular tests and Skin biopsy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteFrance
- Study dates
- 14 Jun 2022to 31 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Chronic Cough, Type 2 Diabetes
- Being tested
- Cough assessment, Neurological tests and cardiovascular tests, Skin biopsy
- Keywords
- cough, diabetes, small fiber neuropathy
- Medical subject headings
- Chronic Cough, Diabetes Mellitus, Type 2, Cough, Diabetes Mellitus, Small Fiber Neuropathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cough assessmentOther
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
Neurological tests and cardiovascular testsOther
Neurological tests : electromyography, thermotest, QSAR + cardiovascular test for Diabetic patients with chronic cough and Diabetic patients without chronic cough
Skin biopsyOther
Skin biopsy to evaluate small fiber neuropathy for Diabetic patients with chronic cough and Diabetic patients without chronic cough
| Study group | Role | What they receive |
|---|---|---|
| Diabetic patients with chronic cough | Other | Diabetic patients with chronic cough defined by cough lasting for more than 8 weeks. Cough assessment, neurological tests and cardiovascular tests and skin biopsy. Receives: Other: Cough assessment; Other: Neurological tests and cardiovascular tests; Other: Skin biopsy |
| Diabetic patients without chronic cough | Other | Diabetic patients without chronic cough defined by cough lasting for more than 8 weeks. Cough assessment, neurological tests and cardiovascular tests and skin biopsy. Receives: Other: Cough assessment; Other: Neurological tests and cardiovascular tests; Other: Skin biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with small fiber neuropathy
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).
Measured: 6 month after inclusion visit
Secondary outcomes (7)
proportion of patients with abnormal results of the thermotest
estimate the proportion of patients with abnormal results of the thermotest in each arm (with and without chronic cough)
Measured: 6 month after inclusion visit
proportion of patients with pathological results of the sudori-motor response
estimate the proportion of patients with pathological results of the sudori-motor response in each arm (with and without chronic cough)
Measured: 6 month after inclusion visit
the proportion of patients with abnormal results of cardiovascular tests
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)
Measured: 6 month after inclusion visit
proportion of patients with abnormal results of laser evoked potentials
estimate the proportion of patients with abnormal results of laser evoked potentials in each arm (with and without chronic cough)
Measured: 6 month after inclusion visit
proportion of patients with abnormal findings of cutaneous biopsy
estimate the proportion of patients with abnormal findings of cutaneous biopsy in in each arm (with and without chronic cough)
Measured: 6 month after inclusion visit
values of Leicester Cough Questionnaire (LCQ) in diabetic patients
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.
Measured: 6 month after inclusion visit
values of the DN4 questionnaire in diabetic patients
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.
Measured: 6 month after inclusion visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2018
- Study start14 Jun 2022
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Why it stopped: patients difficult to recruit
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic CoughStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laurent Guilleminault, MD, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03787511
- Sponsor's protocol ID
- RC31/18/0423
- Other IDs
- 2018-A03340-55
- Acronym
- CHROCOS
- Status last verified
- May 2026
- First submitted
- 21 Dec 2018
- Last updated
- 1 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21292019De 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.
PubMed 28716044Pavy-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.
PubMed 20354891Casellini 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.
PubMed 23889506
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chronic Cough and Small Fiber Neuropathy
- ClinicalTrials.gov ID
- NCT03787511
- Acronym / sponsor ID
- CHROCOS / RC31/18/0423
- Conditions
- Chronic Cough, Type 2 Diabetes
- Keywords
- cough, diabetes, small fiber neuropathy
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: patients difficult to recruit
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 14 Jun 2022 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 26 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diabetic patients with chronic cough | Other | Other: Cough assessment, Other: Neurological tests and cardiovascular tests, Other: Skin biopsyDiabetic patients with chronic cough defined by cough lasting for more than 8 weeks. Cough assessment, neurological tests and cardiovascular tests and skin biopsy. |
| Diabetic patients without chronic cough | Other | Other: Cough assessment, Other: Neurological tests and cardiovascular tests, Other: Skin biopsyDiabetic patients without chronic cough defined by cough lasting for more than 8 weeks. Cough assessment, neurological tests and cardiovascular tests and skin biopsy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cough assessmentCough assessment with cough visual analog scale (VAS), and Leicester Cough Questionnaire (LCQ) for Diabetic patients with chronic cough and Diabetic patients without chronic cough | Other | Diabetic patients with chronic cough, Diabetic patients without chronic cough |
| Neurological tests and cardiovascular testsNeurological tests : electromyography, thermotest, QSAR + cardiovascular test for Diabetic patients with chronic cough and Diabetic patients without chronic cough | Other | Diabetic patients with chronic cough, Diabetic patients without chronic cough |
| Skin biopsySkin biopsy to evaluate small fiber neuropathy for Diabetic patients with chronic cough and Diabetic patients without chronic cough | Other | Diabetic patients with chronic cough, Diabetic patients without chronic cough |
Primary outcome
Proportion of patients with small fiber neuropathy
Time frame: 6 month after inclusion visit
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).
7 secondary outcomes
proportion of patients with abnormal results of the thermotest
Time frame: 6 month after inclusion visit
proportion of patients with pathological results of the sudori-motor response
Time frame: 6 month after inclusion visit
the proportion of patients with abnormal results of cardiovascular tests
Time frame: 6 month after inclusion visit
proportion of patients with abnormal results of laser evoked potentials
Time frame: 6 month after inclusion visit
proportion of patients with abnormal findings of cutaneous biopsy
Time frame: 6 month after inclusion visit
values of Leicester Cough Questionnaire (LCQ) in diabetic patients
Time frame: 6 month after inclusion visit
values of the DN4 questionnaire in diabetic patients
Time frame: 6 month after inclusion visit
Results and safety
The study was stopped early (reason given: patients difficult to recruit). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2026.
- Background: PubMed 21292019Chung 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.
- Background: PubMed 28716044De 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.
- Background: PubMed 20354891Pavy-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.
- Background: PubMed 23889506Casellini 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laurent Guilleminault, MD principal investigator
University Hospital, Toulouse
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cough assessment, Neurological tests and cardiovascular tests and Skin biopsy in people with Chronic Cough and Type 2 Diabetes, run by University Hospital, Toulouse at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: patients difficult to recruit). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with small fiber neuropathy (time frame: 6 month after inclusion visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03787511, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.