Chronic Refractory CoughMISP COUGHNCT05570981
A Comprehensive Evaluation of the Impact of ATP on Laryngeal Symptoms, Hypersensitivity and Function
An observational study of Chronic Refractory Cough, run by Bispebjerg Hospital at 1 site in Denmark.
Trial summary
OBJECTIVES To deliver a comprehensive model of laryngeal assessment, evaluating both the sensory and motor components of upper airway control and to relate this to symptom disturbance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Refractory Cough
- What is being tested?
- Laryngeal sensitivity testing
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- 28 Nov 2022to 31 Dec 2023
- Phase
- Observational
- 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
- Adult, Older adult
Study population: Adult patients (≥ 18 years) with chronic refractory cough and age-/gender matched healthy controls.
Who may be able to join
- Age ≥ 18 years
- Healthy - with no history of any medical conditions
- No history of asthma / allergies
- Normal spirometric indices
- Non smoker
- Age ≥ 18 years
Show all 10Show fewer
- Chronic cough as per ATS definition (>8 weeks duration)
- High symptom burden (i.e. Cough VAS >= 40 mm at the screening visit)
- Chest radiograph or CT within 3 years of the screening visit with no abnormalities considered to contribute to chronic cough
- For patients with asthma: a confirmed diagnosis of asthma on the basis of asthma symptoms and reversible airflow obstruction (BDR 200mls + 12% change post bronchodilator and/or positive bronchoprovocation test).
Who cannot join
- Current smoker or a smoking history of >10 pack years
- Asthma that is not well-controlled, as per international asthma guidelines as specified by Global Initiative for Asthma (GINA)
- Recent exacerbation of cough or asthma within 4 weeks of inclusion
- Pregnancy or childbearing potential and no contraceptive treatment
- Respiratory tract infection within 4 weeks of inclusion
- Currently taking any of the following medications:
Show all 11Show fewer
- ACE inhibitors and within 3 months of inclusion
- Antitussives (opioids, pregabalin, gabapentin, amitriptyline, nortriptyline or over-the-counter medications) within 2 weeks of inclusion
- Medical treatments for GORD, eosinophilic bronchitis or other cough related conditions, initiated or changed (i.e. not in a stable regimen) for 4 weeks prior to inclusion.
- Medical history of COPD or chronic bronchitis
- Medical conditions/history or other circumstances which, in the judgement of the investigator, could increase the risk of adverse events or bias the study results
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Bispebjerg Hospital
Copenhagen, 2400
Emil Walsted, MD PhD, emil.ingerslev.walsted@regionh.dk
About this study
Official title: A Comprehensive Evaluation of the Impact of ATP on Laryngeal Symptoms, Hypersensitivity and Function - an Observational Controlled Study
OBJECTIVES
- To deliver a comprehensive model of laryngeal assessment, evaluating both the sensory and motor components of upper airway control and to relate this to symptom disturbance.
- Determine if laryngeal control is altered by coughing and the impact of repeated coughing on overall laryngeal control and relaxation to its baseline state.
- Evaluate if cell damage and tissue inflammation (including exposure to ATP) modulates laryngeal hypersensitivity and function, by using a comprehensive array of test modalities.
Read more
AIM To utilise state-of-the-art comprehensive assessment tools to evaluate laryngeal hypersensitivity and function in a cohort of individuals with chronic refractory cough and control subjects. The test modalities utilise direct stimulation of the laryngeal adductor reflex, measurement of laryngeal EMG and assessment of functional laryngeal response to an inhalational challenge with laryngoscopic techniques.
HYPOTHESIS Physiological markers of laryngeal hypersensitivity and dysfunction are highly prevalent in patients with chronic refractory cough and manifestations are driven by ATP stimulation.
OUTCOME MEASURES Measurements of laryngeal symptomatology will be measured over a run-in period and during challenge testing. Laryngeal relaxation will be studied using our novel tracking software capability, combining endoscopic imaging and physiological measurements of diaphragm activation.
- Conditions
- Chronic Refractory Cough
- Being tested
- Laryngeal sensitivity testing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laryngeal sensitivity testingDiagnostic test
Direct stimulation of the laryngeal adductor reflex, measurement of laryngeal EMG and our capability to assess functional laryngeal response to an inhalational challenge with laryngoscopic techniques.
| Study group | Role | What they receive |
|---|---|---|
| Chronic Refractory Cough (CRC) | Individuals with a diagnosis of chronic refractory cough Receives: Diagnostic Test: Laryngeal sensitivity testing | |
| Healthy controls | Healthy control subjects matched to the CRC group by age and gender Receives: Diagnostic Test: Laryngeal sensitivity testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal decrease in glottic anterior angle (degrees) during challenge testing
The maximal decrease in glottic anterior angle during challenge testing
Measured: Baseline measurement is taken immediately before beginning the challenge test. Minimal value is taken from continuously measured glottic anterior angle, from immediately after baseline measurement and until immediately after challenge testing
Maximal increase in glottic anterior angle (degrees) after challenge testing
The difference between the minimal glottic anterior angle observed during challenge testing and the maximal glottic anterior angle observed from immediately after challenge testing and until 5 minutes after challenge testing
Measured: During challenge testing and from immediately after challenge testing until 5 minutes after challenge testing
Maximal laryngeal relaxation time (seconds)
Maximum time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)
Measured: At baseline, during challenge testing and from immediately after challenge testing until 5 minutes after challenge testing
Change in laryngeal relaxation time (seconds) during challenge testing
Change in time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)
Measured: At baseline and immediately after challenge testing
Change in laryngeal relaxation time (seconds) in recovery
Change in time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)
Measured: Immediately after challenge testing and at 5 minutes after challenge testing
Secondary outcomes (2)
Cough VAS (0-100 mm)
This is a descriptive delineation of the ATP/Cough VAS dose/response relationship. The measure is taken at multiple times (see Time Frame) and visualised graphically.
Measured: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
Cough count and frequency
This is a descriptive delineation of the ATP/Cough count dose/response relationship. The measure is taken at multiple times (see Time Frame) and visualised graphically.
Measured: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2022
- Study start28 Nov 2022
- Primary completion31 Jul 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Refractory CoughStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bispebjerg Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Responsible party
- Principal investigator, Emil Walsted, Bispebjerg Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05570981
- Sponsor's protocol ID
- H-21076805
- Acronym
- MISP COUGH
- Status last verified
- Nov 2022
- First submitted
- 14 Sep 2022
- Last updated
- 1 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comprehensive Evaluation of the Impact of ATP on Laryngeal Symptoms, Hypersensitivity and Function - an Observational Controlled Study
- ClinicalTrials.gov ID
- NCT05570981
- Acronym / sponsor ID
- MISP COUGH / H-21076805
- Conditions
- Chronic Refractory Cough
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Bispebjerg HospitalUniversity, hospital or other
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Study start
- 28 Nov 2022 (actual)
- Primary completion
- 31 Jul 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 7 Oct 2022 (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.
OBJECTIVES
- To deliver a comprehensive model of laryngeal assessment, evaluating both the sensory and motor components of upper airway control and to relate this to symptom disturbance.
- Determine if laryngeal control is altered by coughing and the impact of repeated coughing on overall laryngeal control and relaxation to its baseline state.
- Evaluate if cell damage and tissue inflammation (including exposure to ATP) modulates laryngeal hypersensitivity and function, by using a comprehensive array of test modalities.
AIM To utilise state-of-the-art comprehensive assessment tools to evaluate laryngeal hypersensitivity and function in a cohort of individuals with chronic refractory cough and control subjects. The test modalities utilise direct stimulation of the laryngeal adductor reflex, measurement of laryngeal EMG and assessment of functional laryngeal response to an inhalational challenge with laryngoscopic techniques.
HYPOTHESIS Physiological markers of laryngeal hypersensitivity and dysfunction are highly prevalent in patients with chronic refractory cough and manifestations are driven by ATP stimulation.
OUTCOME MEASURES Measurements of laryngeal symptomatology will be measured over a run-in period and during challenge testing. Laryngeal relaxation will be studied using our novel tracking software capability, combining endoscopic imaging and physiological measurements of diaphragm activation.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chronic Refractory Cough (CRC) | – | Diagnostic Test: Laryngeal sensitivity testingIndividuals with a diagnosis of chronic refractory cough |
| Healthy controls | – | Diagnostic Test: Laryngeal sensitivity testingHealthy control subjects matched to the CRC group by age and gender |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Adult patients (≥ 18 years) with chronic refractory cough and age-/gender matched healthy controls.
Key inclusion criteria (10 listed)
- Age ≥ 18 years
- Healthy - with no history of any medical conditions
- No history of asthma / allergies
- Normal spirometric indices
- Non smoker
Key exclusion criteria (11 listed)
- Current smoker or a smoking history of >10 pack years
- Asthma that is not well-controlled, as per international asthma guidelines as specified by Global Initiative for Asthma (GINA)
- Recent exacerbation of cough or asthma within 4 weeks of inclusion
- Pregnancy or childbearing potential and no contraceptive treatment
- Respiratory tract infection within 4 weeks of inclusion
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 |
|---|---|---|
| Laryngeal sensitivity testingDirect stimulation of the laryngeal adductor reflex, measurement of laryngeal EMG and our capability to assess functional laryngeal response to an inhalational challenge with laryngoscopic techniques. | Diagnostic test | Chronic Refractory Cough (CRC), Healthy controls |
Primary outcome
Maximal decrease in glottic anterior angle (degrees) during challenge testing
Time frame: Baseline measurement is taken immediately before beginning the challenge test. Minimal value is taken from continuously measured glottic anterior angle, from immediately after baseline measurement and until immediately after challenge testing
The maximal decrease in glottic anterior angle during challenge testing
Maximal increase in glottic anterior angle (degrees) after challenge testing
Time frame: During challenge testing and from immediately after challenge testing until 5 minutes after challenge testing
The difference between the minimal glottic anterior angle observed during challenge testing and the maximal glottic anterior angle observed from immediately after challenge testing and until 5 minutes after challenge testing
Maximal laryngeal relaxation time (seconds)
Time frame: At baseline, during challenge testing and from immediately after challenge testing until 5 minutes after challenge testing
Maximum time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)
Change in laryngeal relaxation time (seconds) during challenge testing
Time frame: At baseline and immediately after challenge testing
Change in time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)
Change in laryngeal relaxation time (seconds) in recovery
Time frame: Immediately after challenge testing and at 5 minutes after challenge testing
Change in time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)
2 secondary outcomes
Cough VAS (0-100 mm)
Time frame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
Cough count and frequency
Time frame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2022.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Refractory Cough, run by Bispebjerg Hospital at 1 site in Denmark.
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 10 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 1 Dec 2022. 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 Denmark. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Emil Walsted, MD PhD ((+45)30338750, emilwalsted@dadlnet.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal decrease in glottic anterior angle (degrees) during challenge testing (time frame: Baseline measurement is taken immediately before beginning the challenge test. Minimal value is taken from continuously measured glottic anterior angle, from immediately after baseline measurement and until immediately after challenge testing). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Dec 2022.