Condition category
Respiratory
Date applied
12/03/2015
Date assigned
18/03/2015
Last edited
18/03/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Asthma is a common disorder of the small tubes that carry air in and out of the lungs (airways). The main problem in asthma is that these tubes can become inflamed, tight and narrowed. Patients with asthma occasionally have symptoms of wheeze, cough, shortness of breath, and chest tightness during attacks of asthma. We are currently unsure how narrowing of the tubes actually causes these symptoms. In our previous study the participants inhaled a chill pepper extract called capsaicin to induce coughing. We found that people with asthma coughed more than healthy volunteers. This suggests that the nerves that cause cough might not be working properly. The majority of the patients in the study had good lung function, i.e. the airways were not narrowed. Our next aim is to find out whether people with asthma cough more to capsaicin if their airways are narrowed slightly. This will help us to understand if narrowing of the airways causes coughing. Likewise, we also want to understand if excessive coughing makes it easier for your airways to become narrowed.

Who can participate?
People with asthma, aged 18 or over, who have taken part in the “Studying Cough in Asthma Phenotypes” (CoAst ) study.

What does the study involve?
The study involves six visits in total. Visit 1 involves taking consent and taking a medical history to ensure participants meet the eligibility criteria for the study. Thereafter all participants will inhale capsaicin to induce coughing. This has been used extensively over the last 15 years to assess coughing. Visit 2 will entail inhaling methacholine, which is a substance known cause narrowing of the airways. This is a commonly used test for the diagnosis of asthma. During all the visits, lung volumes will be measured using a spirometer. Visits 3, 4, 5, and 6 will involve inhaling a combination of capsaicin and methacholine along with a placebo (dummy) in different orders to assess how much coughing occurs after the airway become narrowed and vice versa. All participants will be given salbutamol at the end of each visit to ensure that their lung function is normal.

What are the possible benefits and risks of participating?
Participants will undergo a range of clinical tests to review their asthma symptoms and control and also have detailed physiological assessments of their lung function. As well as helping to advance our understanding of the mechanisms causing cough in asthma and to develop improved treatments, the subject will benefit from being reviewed by a chest specialist. It is possible that participants may experience an increase in their asthma symptoms during the withdrawal of asthma medication before the methacholine and capsaicin challenge tests. Should this happen, patients will be advised to re-start their medication and inform the chief investigator. There will be an on-call study doctor who is contactable outside of working hours should advice be needed. The main risk of performing a methacholine challenge is that of wheezing due to narrowing of the airways, but many patients do not develop any symptoms at all. Precautions will be taken for patient safety such as the availability of monitoring equipment and short-acting bronchodilators (salbutamol and ipratropium via inhaler/nebuliser), oxygen, and resuscitation equipment. Capsaicin can cause a burning/hot sensation at the back of the throat when inhaled. This can cause temporary discomfort, but wears off quickly. Capsaicin also makes people cough several times at the highest doses and this may be uncomfortable. Capsaicin can very rarely cause wheezing and this is easily treated. To minimise this risk, lung function will be measured before and after all cough challenges. If necessary, participants will receive rescue medications including oxygen and/or salbutamol inhalers. All participants will be warned of these possible risks before they agree to take part and a medical doctor will be available during all visits.

Where is the study run from?
NIHR Clinical Research Facility, South Manchester and NIHR/Wellcome Central Manchester Clinical Research Facility (UK).

When is the study starting and how long is it expected to run for?
From January 2015 to September 2015.

Who is funding the study?
University of Manchester (UK).

Who is the main contact?
Dr Imran Satia

Trial website

Contact information

Type

Public

Primary contact

Dr Imran Satia

ORCID ID

Contact details

University Hospital of South Manchester
Level 2 ERC
Manchester
M23 9LT
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

14/BEA/003

Study information

Scientific title

A randomised, single-blind, cross-over study investigating the interactions between bronchoconstriction and cough in asthma

Acronym

BEACH

Study hypothesis

The interaction between methacholine-induced bronchoconstriction and capsaicin-evoked coughing is unclear. Methacholine directly activates muscarinic receptors found on smooth muscle and capsaicin activates TRPV1 receptors found characteristically on vagal c-fibres. This study aims to investigate whether there is an interaction between neuronal activation via TRPV1 on vagal C-fibres and muscarinic receptors on airway smooth muscle. Our hypothesis is that capsaicin-evoked coughing will be independent of airway calibre (the degree of bronchoconstriction). Secondly, if capsaicin-evoked coughing is truly independent then we would predict it would have no influence on airway hyper-responsiveness.

Ethics approval

Liverpool East, North West, 28/01/2015, ref: 15/NW/0052

Study design

Randomised single-blinded cross-over study involving two centres

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Mild atopic asthma

Intervention

VISIT 1: Consent, screening, and full dose capsaicin cough challenge

After taking consent and checking eligibility, a focused medical history and examination will take place to ensure the patient’s asthma is currently stable. Participants will then undergo a full dose response capsaicin cough challenge. Spirometry will be performed pre and post challenge to detect any bronchoconstriction. If participants demonstrate a reduction of 20% in FEV1 or experience chest tightness or wheezing, then four puffs of 100 mcg of salbutamol (bronchodilator medication) will be administered via a spacer. Spirometry will be repeated to ensure values return to baseline.

VISIT 2: Methacholine challenge

Visit 2 will take place between 2-7 days after visit 1 and will involve an assessment of airway hyper-responsiveness (AHR) using a methacholine challenge test. The provocative concentration that causes a 20% drop in FEV1 (PC20) will be calculated. Four puffs of 100 mcg of salbutamol will be administered via a spacer after the last dose of methacholine.

VISIT 3: Methacholine inhalation followed by capsaicin inhalation

The objective of this visit is to assess cough responses to four inhalations of the ED50 capsaicin dose following a 15-25% induced fall in FEV1. The following will be performed:

1. Spirometry (FEV1)
2. Modified methacholine challenge
3. Spirometry (FEV1) at 30 seconds and 90 seconds thereafter
4. Four inhalations of a single dose of capsaicin (ED50 dose)
5. Spirometry (FEV1)
6. Four puffs of 100 mcg of salbutamol will be administered via a spacer
7. Spirometry (FEV1)

VISIT 4: Saline (placebo) inhalation followed by capsaicin inhalation

Visit 4 will last up to 45 minutes and will include:
1. Spirometry (FEV1)
2. Saline (0.9%) inhalation (2 minutes tidal breathing)
3. Spirometry (FEV1) at 30 seconds and 90 seconds thereafter
4. Four inhalations of a single dose of capsaicin (ED50 dose)
5. Spirometry (FEV1)
6. Four puffs of 100 mcg of salbutamol will be administered via a spacer
7. Spirometry (FEV1)

VISIT 5: Capsaicin inhalation followed by methacholine inhalation

This visit will last up to 45 minutes. The objective of this visit is to evoke coughing by inhaling capsaicin and then administer either one/two doses (for determination of these doses, see procedures section 5.6.4) of the methacholine concentrations for 2 minutes. This visit will involve:
1. Spirometry (FEV1)
2. Four inhalations of a single dose of capsaicin (ED50 dose)
3. Spirometry (FEV1) at 30 seconds after inhalation
4. Modified methacholine challenge
5. Spirometry (FEV1) at 30 seconds and 90 seconds thereafter
6. Four puffs of 100 mcg of salbutamol will be administered via a spacer
7. Spirometry (FEV1)

Visit 6: Saline (placebo) inhalation followed by methacholine inhalation

This visit will last up to 45 minutes and the following will take place:
1. Spirometry (FEV1)
2. Four inhalations of saline (0.9%)
3. Spirometry (FEV1) 30 seconds after inhalation
4. Modified methacholine challenge
5. Spirometry (FEV1) at 30 seconds and 90 seconds thereafter
6. Four puffs of 100 mcg of salbutamol will be administered via a spacer
7. Spirometry (FEV1)

A telephone call will be made within 48 hours after completing visit 6 to ensure participants are safe and no adverse events have occurred after completing the study.

Intervention type

Other

Phase

Drug names

Primary outcome measures

1. The number of coughs evoked by an ED50 dose of capsaicin after methacholine-induced bronchoconstriction compared with saline inhalation
2. The % drop in FEV1 after inhaling methacholine immediately after coughing evoked by an ED50 dose of capsaicin compared to saline (0.9%)

Secondary outcome measures

The secondary outcome will be to explore the number of coughs throughout the duration of each visit, and in particular during methacholine challenges and the recovery periods after salbutamol is given

Overall trial start date

01/01/2015

Overall trial end date

01/09/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged ≥18
2. Have taken part in “Studying Cough in Asthma Phenotypes” (CoAst ) study
3. Person with a diagnosis of atopic asthma (based on a positive skin prick test)
4. The subject is treated with:
4.1. Short acting Beta 2 Agonist PRN AND/OR
4.2. Inhaled corticosteroid (≤250 mcg fluticasone propionate daily or equivalent)
5. Controlled or has partial asthma control according to GINA classification

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

15

Participant exclusion criteria

1. Subjects who have previously coughed less than a total of four coughs in one dose at the ED50 dose of capsaicin inhalation (assess after visit 1)
2. Subjects who bronchoconstrict by more than 10% at the end of the full dose capsaicin cough challenge (assess after visit 1)
3. Subjects who do not display evidence of airway hyper-responsiveness (PC20 >8 mg/ml) (assess after visit 2)
4. Symptoms of upper respiratory tract infection (URTI) in the last 1 month which have not resolved
5. Lower respiratory tract infection or pneumonia in the last 6 weeks
6. Current smoker or ex-smoker with ≥10 pack-year smoking history and abstinence of ≤6 months
7. Asthma exacerbation in the previous month requiring an increase or start of an ICS or OCS
8. Asthma medication which include theophylline or anti-cholinergic drugs
9. Subject has changed asthma medication within the past 4 weeks prior to screening
10. A previous asthma exacerbation requiring Intensive Care Unit (ICU) admission
11. Significant other primary pulmonary disorders, in particular: pulmonary embolism, pulmonary hypertension, interstitial lung disease, lung cancer, cystic fibrosis, emphysema or bronchiectasis
12. Pregnancy or breastfeeding
13. Use of ACE inhibitors
14. Any centrally acting medication which in the view of the investigator could alter the sensitivity of the cough reflex*
15. History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial
*Any participant who is taking tricyclic anti-depressants, pregabalin, gabapentin or opioids will not be eligible to take part in this study unless they are willing and medically able to withdraw from such medication for the duration of the study. The reason for this is that centrally acting medications may alter the sensitivity of the cough reflex

Recruitment start date

12/04/2015

Recruitment end date

01/09/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

NIHR Clinical Research Facility, South Manchester
University Hospital of South Manchester
Manchester
M23 9LT
United Kingdom

Trial participating centre

NIHR/Wellcome Central Manchester Clinical Research Facility
Grafton Street
Manchester
M13 9WL
United Kingdom

Sponsor information

Organisation

University Hospital of South Manchester

Sponsor details

R&D Department
Manchester
M23 9LT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

University/education

Funder name

University Of Manchester

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

academic

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Intention to publish date

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes