Chronic Obstructive Airway DiseaseNCT01297790
Cough Responses to Tussive Agents in Health and Disease
An observational study of Chronic Obstructive Airway Disease and Asthma, run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
The sensitivity of a persons cough reflex can be measured by getting them to breath in (inhale) irritant chemicals. The purpose of this clinical research study is to test the sensitivity of the cough reflex to a variety of chemicals that can be inhaled to see if coughing responses are different between healthy people… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Obstructive Airway Disease, Asthma, Chronic Cough
- What is being tested?
- Cough Challenge Tests, ambulatory cough recording and Cough questionnaires
- How many people
- 102 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2009to May 2011
- 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 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adults aged 18 and over who are healthy non smokers, or are current smokers with no respiratory conditions and normal spirometry, or have a diagnosis of asthma, chronic cough or COPD.
Who may be able to join
- General
- Adult subjects aged 18 years and over
- Meet criteria for subject groups as outlined below
- Healthy volunteers
- Non-smokers
- No history of respiratory disease
Show all 21Show fewer
- Healthy smokers
- Current smokers with smoking history of ≥10 pack years
- Spirometry within normal limits i.e. FEV1>80% predicted and FEV1/FVC ratio >75% predicted
- Asthma
- Physician diagnosis of asthma
- Airways hyperresponsiveness to methacholine; PC20<16mg/ml (within last 2 years)
- Non-smokers or ex-smoker with smoking history of ≤10 pack years
- COPD
- Physician diagnosis of COPD
- Ex-smokers with smoking history of ≥20 pack years
- Spirometry demonstrating airflow obstruction i.e. FEV1/FVC ratio <70%
- Chronic Cough
- History of a dry cough for >8 weeks
- Normal CXR
- Non-smokers or ex-smoker with smoking history of ≤10 pack years
Who cannot join
- 1) Symptoms of upper respiratory tract infection within the last 6 weeks 2) Participation in another clinical trial of an investigational drug within the last 4 weeks 3) Use of medication likely to alter cough reflex sensitivity i.e. ACE inhibitors, codeine phosphate, morphine sulphate, 4) Patients with severe respiratory disease i.e. FEV1 < 1 litre, 5) Significant medical co-morbidities likely to affect ability to participate in the trial or affect cough reflex sensitivity e.g. diabetes, stroke, Parkinson's disease, multiple sclerosis etc.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospital of South Manchester
Manchester, Lancashire, M23 9LT
About this study
The sensitivity of a persons cough reflex can be measured by getting them to breath in (inhale) irritant chemicals. The purpose of this clinical research study is to test the sensitivity of the cough reflex to a variety of chemicals that can be inhaled to see if coughing responses are different between healthy people and people with respiratory problems that make them cough.
Read the detailed description
Coughing is a distressing symptom which has a major impact on quality of life. It has been estimated that cough costs the UK economy £1 billion each year. Currently there are no effective anti-tussive agents to treat subjects with cough. Although drugs such as morphine may have some anti-tussive effect, side effects unacceptable.
Currently our understanding of the mechanisms which lead to coughing in different diseases is poor. Many mechanistic studies rely on testing the sensitivity of the cough reflex by inhalation of capsaicin (chilli-pepper extract) or citric acid. These challenges do not differentiate well between health and disease or between different disease states. Other agents such as prostaglandins and bradykinin are known to stimulate a coughing but responses to these agents have rarely been used as a measure of cough reflex sensitivity and not been compared to standard challenges.
It is clear that patients with common airway diseases such as COPD and asthma cough significantly more than healthy subjects. Moreover subjects presenting with chronic cough have cough rates an order of magnitude higher than most patients with airway disease. These differences are poorly represented by the differences in current cough challenge tests.
The investigators hypothesize that patterns of cough responses to different tussive agent may better differentiate between health and different disease states. These patterns may also suggest the different mechanisms leading to cough in different diseases.
- Conditions
- Chronic Obstructive Airway Disease, Asthma, Chronic Cough
- Being tested
- Cough Challenge Tests, ambulatory cough recording, Cough questionnaires
- Keywords
- Cough, Inhalational cough challenges, Cough reflex sensitivity, Chronic cough.
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Asthma, Chronic Cough, Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cough Challenge TestsOther
Inhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2
ambulatory cough recordingOther
Cough recording with a portable device to capture cough sounds
Cough questionnairesOther
Questionnaires designed to study cough. These include Leicester cough questionnaire, cough visual analogue score and cough quality of life questionnaire.
| Study group | Role | What they receive |
|---|---|---|
| Asthma | Subjects with asthma more than 18 years old with minimal or no smoking history and evidence of bronchial hyperreactivity Receives: Other: Cough Challenge Tests; Other: ambulatory cough recording; Other: Cough questionnaires | |
| Chronic obstructive pulmonary disease | Subjects with diagnosis of COPD who must be ex smokers and have evidence of airflow obstruction on breathing tests. Receives: Other: Cough Challenge Tests; Other: ambulatory cough recording; Other: Cough questionnaires | |
| Healthy Volunteers | Healthy non smoking adults. Receives: Other: Cough Challenge Tests; Other: ambulatory cough recording; Other: Cough questionnaires | |
| Healthy smokers | Current smokers with normal breath tests (spirometry) Receives: Other: Cough Challenge Tests; Other: ambulatory cough recording; Other: Cough questionnaires | |
| Chronic cough | Subjects with idiopathic chronic cough. Receives: Other: Cough Challenge Tests; Other: ambulatory cough recording; Other: Cough questionnaires |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cough response to tussive agents
To measure cough responses to capsaicin, citric acid, prostaglandin E2 (PGE2) and Bradykinin (BK) in healthy volunteers, airway diseases (asthma and COPD) and chronic cough.
To compare the ability of individual challenges and patterns of challenge response to discriminate between diagnostic groups.
Measured: 45 minutes
Objective cough recording
To perform ambulatory cough recording over 24 hours to assess if there are any differences
Measured: 24 Hours
Secondary outcomes (1)
C2 to inhaled tussive agents
C2 concentration difference between different diagnostic groups after inhalation of tussive agents
Measured: 45 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2011 (estimated)
- Study startNov 2009
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Airway DiseaseStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Manchester University NHS Foundation Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Ashley A Woodcock, FRCP, MD, Principal investigator, University Hospital of South Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01297790
- Sponsor's protocol ID
- JAS Protocol 2
- Status last verified
- Sep 2011
- First submitted
- 15 Feb 2011
- Last updated
- 16 Sep 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Belvisi MG, Birrell MA, Khalid S, Wortley MA, Dockry R, Coote J, Holt K, Dubuis E, Kelsall A, Maher SA, Bonvini S, Woodcock A, Smith JA. Neurophenotypes in Airway Diseases. Insights from Translational Cough Studies. Am J Respir Crit Care Med. 2016 Jun 15;193(12):1364-72. doi: 10.1164/rccm.201508-1602OC.
PubMed 26741046
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cough Responses to Tussive Agents in Health and Disease
- ClinicalTrials.gov ID
- NCT01297790
- Acronym / sponsor ID
- JAS Protocol 2
- Conditions
- Chronic Obstructive Airway Disease, Asthma, Chronic Cough
- Keywords
- Cough, Inhalational cough challenges, Cough reflex sensitivity, Chronic cough.
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Manchester University NHS Foundation TrustOther government
- Study start
- Nov 2009
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 17 Feb 2011 (estimated)
- 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.
The sensitivity of a persons cough reflex can be measured by getting them to breath in (inhale) irritant chemicals. The purpose of this clinical research study is to test the sensitivity of the cough reflex to a variety of chemicals that can be inhaled to see if coughing responses are different between healthy people and people with respiratory problems that make them cough.
Detailed description
Coughing is a distressing symptom which has a major impact on quality of life. It has been estimated that cough costs the UK economy £1 billion each year. Currently there are no effective anti-tussive agents to treat subjects with cough. Although drugs such as morphine may have some anti-tussive effect, side effects unacceptable.
Currently our understanding of the mechanisms which lead to coughing in different diseases is poor. Many mechanistic studies rely on testing the sensitivity of the cough reflex by inhalation of capsaicin (chilli-pepper extract) or citric acid. These challenges do not differentiate well between health and disease or between different disease states. Other agents such as prostaglandins and bradykinin are known to stimulate a coughing but responses to these agents have rarely been used as a measure of cough reflex sensitivity and not been compared to standard challenges.
It is clear that patients with common airway diseases such as COPD and asthma cough significantly more than healthy subjects. Moreover subjects presenting with chronic cough have cough rates an order of magnitude higher than most patients with airway disease. These differences are poorly represented by the differences in current cough challenge tests.
The investigators hypothesize that patterns of cough responses to different tussive agent may better differentiate between health and different disease states. These patterns may also suggest the different mechanisms leading to cough in different diseases.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Asthma | – | Other: Cough Challenge Tests, Other: ambulatory cough recording, Other: Cough questionnairesSubjects with asthma more than 18 years old with minimal or no smoking history and evidence of bronchial hyperreactivity |
| Chronic obstructive pulmonary disease | – | Other: Cough Challenge Tests, Other: ambulatory cough recording, Other: Cough questionnairesSubjects with diagnosis of COPD who must be ex smokers and have evidence of airflow obstruction on breathing tests. |
| Healthy Volunteers | – | Other: Cough Challenge Tests, Other: ambulatory cough recording, Other: Cough questionnairesHealthy non smoking adults. |
| Healthy smokers | – | Other: Cough Challenge Tests, Other: ambulatory cough recording, Other: Cough questionnairesCurrent smokers with normal breath tests (spirometry) |
| Chronic cough | – | Other: Cough Challenge Tests, Other: ambulatory cough recording, Other: Cough questionnairesSubjects with idiopathic chronic cough. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adults aged 18 and over who are healthy non smokers, or are current smokers with no respiratory conditions and normal spirometry, or have a diagnosis of asthma, chronic cough or COPD.
Key inclusion criteria (21 listed)
- General
Key exclusion criteria (1 listed)
- 1) Symptoms of upper respiratory tract infection within the last 6 weeks 2) Participation in another clinical trial of an investigational drug within the last 4 weeks 3) Use of medication likely to alter cough reflex sensitivity i.e. ACE inhibitors, codeine phosphate, morphine sulphate, 4) Patients with severe respiratory disease i.e. FEV1 < 1 litre, 5) Significant medical co-morbidities likely to affect ability to participate in the trial or affect cough reflex sensitivity e.g. diabetes, stroke, Parkinson's disease, multiple sclerosis etc.
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 Challenge TestsInhalational cough challenge tests with capsaicin, bradykinin, Citric acid and prostaglandin E2 | Other | Asthma, Chronic cough, Chronic obstructive pulmonary disease, Healthy Volunteers, Healthy smokers |
| ambulatory cough recordingCough recording with a portable device to capture cough sounds | Other | Asthma, Chronic cough, Chronic obstructive pulmonary disease, Healthy Volunteers, Healthy smokers |
| Cough questionnairesQuestionnaires designed to study cough. These include Leicester cough questionnaire, cough visual analogue score and cough quality of life questionnaire. | Other | Asthma, Chronic cough, Chronic obstructive pulmonary disease, Healthy Volunteers, Healthy smokers |
Primary outcome
Cough response to tussive agents
Time frame: 45 minutes
To measure cough responses to capsaicin, citric acid, prostaglandin E2 (PGE2) and Bradykinin (BK) in healthy volunteers, airway diseases (asthma and COPD) and chronic cough. To compare the ability of individual challenges and patterns of challenge response to discriminate between diagnostic groups.
Objective cough recording
Time frame: 24 Hours
To perform ambulatory cough recording over 24 hours to assess if there are any differences
1 secondary outcome
C2 to inhaled tussive agents
Time frame: 45 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2011.
- Derived from this study: PubMed 26741046Belvisi MG, Birrell MA, Khalid S, Wortley MA, Dockry R, Coote J, Holt K, Dubuis E, Kelsall A, Maher SA, Bonvini S, Woodcock A, Smith JA. Neurophenotypes in Airway Diseases. Insights from Translational Cough Studies. Am J Respir Crit Care Med. 2016 Jun 15;193(12):1364-72. doi: 10.1164/rccm.201508-1602OC.
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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.
Ashley A Woodcock, FRCP, MD principal investigator
University Hospital of South Manchester
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 Obstructive Airway Disease and Asthma, run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
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 21 inclusion and 1 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: finished, as of the sponsor's last update on 16 Sep 2011. 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 United Kingdom. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cough response to tussive agents (time frame: 45 minutes). The study lists 2 primary outcomes in all. 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 NCT01297790, which also lists 1 linked publication.
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 16 Sep 2011.