Comparing different responses of the cough reflex
| ISRCTN | ISRCTN96855098 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN96855098 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 288804 |
| Protocol serial number | 20-CAS-001 |
| Sponsor | University of Manchester |
| Funder | Manchester NIHR BRC charitable funds |
- Submission date
- 10/09/2021
- Registration date
- 16/09/2021
- Last edited
- 20/06/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Cough challenge testing is widely used to see how sensitive someone's cough reflex is. This can be very useful when studying treatments for cough or how cough affects people with different lung conditions. The challenge involves a person inhaling increasing doses of a substance which usually makes people want to cough by irritating the throat and activating nerves in the airways. There are different pieces of equipment used to deliver these substances. The aim of this study is to compare the performance of two pieces of equipment to see if they give the same cough responses in people.
Who can participate?
Healthy volunteers aged 18 years and over
What does the study involve?
The study involves two visits. The first visit will involve completing a consent form after talking through the study with a researcher. Participants will then be asked about their medical history and any medications they are taking. Their height and weight will be measured and their BMI calculated. They will then be asked to perform a blowing test (spirometry) so that the researcher can check that they meet the eligibility criteria for the study. Participants will then be asked to complete a cough challenge. They will be fitted with a recording device, a cough monitor, throughout the challenge to enable the researcher to listen back and count how many times they cough. Capsaicin or citric acid will be given to them to inhale using one of the pieces of equipment. The dose will increase and they will be asked to take four breaths of each dose. The test will end when either the participant has inhaled all of the doses or when they ask to stop because the feeling from inhaling the capsaicin or citric acid is too unpleasant. They will be asked to fill in a questionnaire about how they found the challenge and then the blowing test will be repeated to ensure that their airways have not tightened. Participants will be asked to return 3-7 days later to repeat the cough challenge with the other piece of equipment.
What are the potential benefits and risks of participating?
No benefits.
Spirometry can cause light-headedness in participants.
Capsaicin (naturally occurring extract of red chilli peppers) and citric acid inhalation can cause discomfort, including a temporary burning sensation in the throat, eye-watering, runny nose and coughing.
Cough challenge can cause bronchoconstriction, although this is rare in healthy volunteers.
Where is the study run from?
The NIHR Clinical Trials Facility and MFT Wythenshawe Hospital (UK)
When is the study starting and how long is it expected to run for?:
August 2021 to December 2024
Who is funding the study?
Manchester NIHR BRC charitable funds (UK)
Who is the main contact?
Joanne Mitchell
cough.research@manchester.ac.uk
Contact information
Scientific
2nd Floor ERC
Wythenshawe Hospital
Southmoor Road
Manchester
M23 9LT
United Kingdom
 ORCID ID |
0000-0001-8837-4928 |
|---|---|
| Phone | +44 (0)161 291 5031 |
| jacky.smith@manchester.ac.uk |
Public
North West Lung Research Centre
Wythenshawe Hospital
Southmoor Road
Manhester
M23 9LT
United Kingdom
| Phone | +44 (0)161 291 5921 |
|---|---|
| joanne.sale@manchester.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Single-centre randomized cross over trial |
| Secondary study design | Randomised cross over trial |
| Participant information sheet | 40403 PIS V1.2 10Sep21.pdf |
| Scientific title | A comparison and validation study of cough challenge responses evoked using two different bronchial provocation systems |
| Study acronym | CasCaDe |
| Study objectives | Current study hypothesis as of 21/06/2024: The aim of this study is to compare maximum cough responses to capsaicin and citric acid in healthy volunteers between two bronchial challenge systems: the Koko dosimeter and an alternative bronchial provocation system; ProvoX. Previous study hypothesis: The aim of this study is to compare maximum cough responses to capsaicin in healthy volunteers between two bronchial challenge systems: the Koko dosimeter and an alternative bronchial provocation system; ProvoX. |
| Ethics approval(s) | Approved 13/09/2021, University of Manchester Research Ethics Committee 1 (Research Governance, Ethics and Integrity, 2nd Floor Christie Building, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK; +44 (0)161 306 6000; research.ethics@manchester.ac.uk), ref: 2021-11272 |
| Health condition(s) or problem(s) studied | Cough challenge responses |
| Intervention | Current interventions as of 21/06/2024: Participants will be asked to attend two visits. At the first visit, informed consent will be taken, followed by a screening visit to ensure study eligibility. This will involve the recording of medical history and current medications; measurement of height and weight; and spirometry to measure the participant's FEV1 and FVC. Upon confirmation of eligibility, the participant will be asked to complete either a capsaicin cough challenge or a citric acid cough challenge. This is done by inhaling doubling doses of capsaicin or citric acid using one of the systems. The challenge will be continued until the participant reaches their maximum tolerated dose. The cough challenge will be recorded on a VitaloJAK audio cough monitoring device. Spirometry will be performed following the completion of the challenge. The participant will be asked to return for a second visit where they will repeat the spirometry and cough challenge using the other piece of equipment. The order of the equipment will be allocated in a randomised order created using Graphpad, a piece of statistical software with randomisation capabilities. Previous interventions: Participants will be asked to attend two visits. At the first visit, informed consent will be taken, followed by a screening visit to ensure study eligibility. This will involve the recording of medical history and current medications; measurement of height and weight; and spirometry to measure the participant's FEV1 and FVC. Upon confirmation of eligibility, the participant will be asked to complete a capsaicin cough challenge by inhaling doubling doses of capsaicin using one of the systems. The challenge will be continued until the participant reached their maximum tolerated dose. The cough challenge will be recorded on a VitaloJAK audio cough monitoring device. Spirometry will be performed following the completion of the challenge. The participant will be asked to return for a second visit where they will repeat the spirometry and cough challenge using the other piece of equipment. The order of the equipment will be allocated in a randomised order created using Graphpad, a piece of statistical software with randomisation capabilities. |
| Intervention type | Device |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | - |
| Primary outcome measure(s) |
Maximum cough response (Emax) is measured at visit 1 and visit 2 |
| Key secondary outcome measure(s) |
Current secondary outcome measures as of 21/06/2024: |
| Completion date | 04/12/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 24 |
| Total final enrolment | 26 |
| Key inclusion criteria | Current inclusion criteria as of 21/06/2024: 1. Aged ≥18 years 2. Normal spirometry (FEV1 and FVC %predicted of ≥80%) 3. No current or past history of chronic cough or any other respiratory disease 4. No current or history of chronic pain, irritable bowel syndrome, psychiatric illness or chronic headaches 5. No previous experience of performing cough challenges (capsaicin study arm only) 6. Must cough at least 2 times on a single inhalation of any dose of capsaicin/citric acid during the visit 1 cough challenge Previous inclusion criteria: 1. Aged ≥18 years 2. Normal spirometry (FEV1 and FVC %predicted of ≥80%) 3. No current or past history of chronic cough or any other respiratory disease 4. No current or history of chronic pain, irritable bowel syndrome, psychiatric illness or chronic headaches 5. No previous experience of performing cough challenges 6. Must cough at least 2 times on a single inhalation of any dose of capsaicin during the visit 1 cough challenge |
| Key exclusion criteria | Current exclusion criteria as of 21/06/2024: 1. Current smoker or ex-smoker with >20 pack-year history, and/or <6 months abstinence 2. Upper respiratory tract infection within the last 4 weeks 3. Use of ACE inhibitors 4. Use of anti-depressants 5. Use of centrally acting medications that may alter the cough reflex e.g. opiates 6. History of drug or alcohol abuse 7. Current pregnancy or breastfeeding 8. Concomitant conditions that may alter cough reflex sensitivity e.g. diabetes mellitus, Parkinson’s disease, cerebrovascular disease 9. Previous cough challenge experience (only applicable for capsaicin study arm) Previous exclusion criteria: 1. Current smoker or ex-smoker with >20 pack-year history, and/or <6 months abstinence 2. Upper respiratory tract infection within the last 4 weeks 3. Use of ACE inhibitors 4. Use of anti-depressants 5. Use of centrally acting medications that may alter the cough reflex e.g. opiates 6. History of drug or alcohol abuse 7. Current pregnancy or breastfeeding 8. Concomitant conditions that may alter cough reflex sensitivity e.g. diabetes mellitus, Parkinson’s disease, cerebrovascular disease 9. Previous cough challenge experience |
| Date of first enrolment | 12/09/2021 |
| Date of final enrolment | 27/11/2024 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Wythenshawe
Manchester
M23 9LT
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not expected to be made available |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available as the study is purely a validation study and we are doing this research because the current equipment being used for cough challenge testing is being withdrawn from use and it is important that we find an alternative which produces reliable results comparable with the previous research carried out. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1.2 | 10/09/2021 | 16/09/2021 | No | Yes |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Additional files
- 40403 PIS V1.2 10Sep21.pdf
- Participant information sheet
Editorial Notes
20/06/2025: The following changes were made to the study record:
1. The recruitment end date was changed from 06/12/2024 to 27/11/2024.
2. The overall study end date was changed from 30/06/2025 to 04/12/2024.
3. The intention to publish date was changed from 01/08/2025 to 31/07/2025.
17/01/2025: The recruitment end date was changed from 10/06/2025 to 06/12/2024. Total final enrolment added.
21/06/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 10/06/2024 to 10/06/2025.
2. The overall study end date was changed from 30/06/2024 to 30/06/2025.
3. The intention to publish date was changed from 01/08/2024 to 01/08/2025.
4. The study hypothesis, ethics approval, interventions, secondary outcome measures and inclusion/exclusion criteria were updated.
5. The target number of participants was changed from 12 to 24.
01/06/2023: The following changes were made to the study record:
1. The recruitment end date was changed from 16/06/2023 to 10/06/2024.
2. The overall study end date was changed from 30/06/2023 to 30/06/2024.
3. The intention to publish date was changed from 01/09/2023 to 01/08/2024.
04/01/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2022 to 16/06/2023.
2. The overall trial end date was changed from 12/09/2022 to 30/06/2023.
29/09/2022: The recruitment end date was changed from 12/09/2022 to 31/12/2022.
15/10/2021: The IRAS number has been added.
16/09/2021: Trial's existence confirmed by University of Manchester.
