Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000447156
Ethics application status
Approved
Date submitted
12/03/2019
Date registered
19/03/2019
Date last updated
19/03/2019
Date data sharing statement initially provided
19/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Characterisation of lung function in chronic obstructive pulmonary disease (COPD) and asthma patients using a new lung imaging technique.
Scientific title
The effect of bronchodilation and bronchoconstiction on airway closure, low ventilation and distribution of ventilation in COPD and asthma using SPECT.
Secondary ID [1] 297687 0
Nil known.
Universal Trial Number (UTN)
U1111-1229-6996
Trial acronym
COAST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 311928 0
Chronic Obstructive Pulmonary Disease 311929 0
Condition category
Condition code
Respiratory 310513 310513 0 0
Asthma
Respiratory 310514 310514 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will attend three visits, all of which will take place at the Royal North Shore Hospital. The three visits will be separated by at least 48 hours.

Visit 1 will take approximately 2 hours and will take place at the Department of Respiratory Medicine. Participants will complete a questionnaire to quantify their asthma/COPD symptoms and control, and will perform a series of simple breathing tests administered by a trained respiratory scientist:
o Spirometry: This test is to determine how quickly your lungs can breathe air in and squeeze air out. You will need to suck and blow air as fast as you can and as forcefully as you can.
o Body plethysmography: This test is used to calculate how big your lungs are. This test will involve sitting inside a glass box and taking panting breaths following by very big breaths.
o Lung diffusing capacity: This test measures how well the air that you breathe is transported into your blood. We will also ask you take a big, quick breath of air containing a very small amount of carbon monoxide and a very small amount of nitrogen oxide. We will ask you to hold your breath for 10 seconds and then gently breathe all the air out of your lungs.
o Forced oscillation technique (FOT): This test measures the stiffness of the airways. This machine sends different sound waves through the air, making the air feel ‘wobbly’. This test involves sitting and breathing normally on a mouthpiece.
o Multiple breath nitrogen washout test (MBNW): This test measure how evenly the air is distributed throughout your lungs. You will breathe into a mouthpiece, keeping the size of your breaths within a set range. During the test you will first breathe normal room air and then 100% oxygen for approximately 20 breaths. You will be asked to do this three times.
o Bronchodilator test: This is to see how well your lungs respond to an inhaled bronchodilator, which is a medication that relaxes the muscle around the airways and is increase the amount of airway you can breathe out. To determine whether your airways opened up after the bronchodilator, we will ask you to repeat the spirometry and FOT tests in the same way that you performed them earlier. We will administer a total of 4 puffs of salbutamol 100mcg per puff (400mcg in total).
o Methacholine challenge test: This is to test your airway sensitivity and involves inhalation of a stimulant (methacholine) that will result in airway narrowing, which closely controlled using lung testing (spirometry). Therefore, you may experience your usual symptoms of asthma or COPD. These symptoms are promptly reversed by inhalation of your usual reliever medication.

We will also perform an allergy test called a skin prick test. A small droplet of allergen will be placed on the subject's forearm and the skin will be pricked lightly through the droplet. If subject is allergic to any of the allergens you will develop a small itchy lump, like a mosquito bite.

In addition, after these tests we will take a standard blood sample at the Pathology Department, this will be done by a trained nurse. This test allows us to count inflammatory cells and measure inflammatory markers.

Visit 2 will take approximately 3 hours and will take place at the Department of Nuclear Medicine. During this visit you will have 2 SPECT scans to look at how the air moves within the lung. This involves breathing in a small amount of a radioactive aerosol, following by lying on a table for about 15 minutes during which the scan is undertaken. We will do 1 scan before, and 1 scan after inhalation of reliever medication (e.g. salbutamol) to see whether your ventilation has approved upon inhalation of your reliever medication.

You will also undergo a low-dose CT scan of the chest, which takes about 2 minutes to perform. These two tests will be done by a trained nuclear medicine scientist.

In addition, you will perform some of the same breathing tests as visit 1 (FOT and spirometry). These tests will be done by a trained respiratory scientist and will take place at the Department of Nuclear Medicine.

Visit 3 (final visit) will take approximately 1.5 hours and will take place at the Department of Nuclear Medicine. During this visit you will be given a methacholine challenge, followed by a SPECT scan, as described above to see how it affects your ventilation. In addition, you will perform some of the same breathing tests as visit 1 (FOT and spirometry).
Intervention code [1] 313888 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319406 0
Measurement of distribution of ventilation using SPECT.
Timepoint [1] 319406 0
This data will be collected during visit 1,2 and 3.
Primary outcome [2] 319407 0
Measurement of low ventilation using SPECT
Timepoint [2] 319407 0
This data will be collected during visit 1,2 and 3.
Primary outcome [3] 319451 0
Measurement of airway closure using SPECT
Timepoint [3] 319451 0
This data will be connected during visit 1, 2 and 3.
Secondary outcome [1] 368038 0
Symptom and clinical markers as measured by the asthma control test (ACT) and the COPD Assessment Test (CAT).
Timepoint [1] 368038 0
This data will be collected during visit 1
Secondary outcome [2] 368244 0
Measurement of lung function using spirometry, forced oscillation technique, body plethysmography, multiple breath nitrogen washout test and diffusing capacity test.
Timepoint [2] 368244 0
This data will be collected during visit 1, 2 and 3
Secondary outcome [3] 368245 0
Full blood count (FBC) in venous blood sample using standard analysis.
Timepoint [3] 368245 0
This data will be collected during visit 1

Eligibility
Key inclusion criteria
1. Willing and able to give written informed consent
2. Have a physician-diagnosed COPD or asthma
3. For asthma only:
- no history of smoking or smoking history of less that 10 pack years
4. For COPD only:
- history of current or past smoking, with total exposure of greater than 10
pack years.
- FEV1/FVC ratio of less the 95th percentile of the normal range (according to subject
age, gender and height); AND
- FEV1 less the 95th percentile of the normal range predicted for subject age, gender and
height; or FEV1 within the normal range, in the presence of symptoms consistent with
COPD; AND
- FEV1 greater than or equal to 40% of the predicted value.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Significant cardiac disease (ischemic heart disease or arrhythmia) deemed by the investigators or the subject’s treating cardiologist to make it unsafe for the subject to undertake a supervised near-maximal exercise test.
2. Documented hypersensitivity to, or intolerance of anti-cholinergic therapies.
3. Significant respiratory infection or documented exacerbation of Asthma or COPD within the previous 6 weeks.
4. Intensive Care Unit admission in the last 12 months.
5. Other active or chronic respiratory pathologies (for example, interstitial lung disease, asthma, chest wall pathology causing ventilatory restriction).
6. Past history of lung surgery (including lobectomy or pneumonectomy, but not lung biopsy) or thoracic radiation therapy (excluding isolated mediastinal radiation therapy with no evidence of subsequent pulmonary fibrosis).
7. Any major comorbidities deemed to impact on respiratory physiology or symptoms, including severe on uncontrolled heart failure, morbid obesity (BMI >40), muscular or neurological disorders causing respiratory muscle weakness or dysfunctional swallowing.
8. History of chronic kidney disease (creatine greater than the upper limit of normal).
9. Unable to perform lung function testing.
10. Dependence on domiciliary supplemental oxygen, unable to go without for at least 1 hour.
11. Women who are breast feeding, pregnant, or unwilling to avoid pregnancy during the study period.
12. Unable to provide informed consent
13. Current enrolment in other trials

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2019
Actual
Date of last participant enrolment
Anticipated
1/04/2021
Actual
Date of last data collection
Anticipated
1/10/2021
Actual
Sample size
Target
70
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 13355 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 13359 0
Woolcock Institute of Medical Research - Glebe
Recruitment postcode(s) [1] 25954 0
2065 - St Leonards
Recruitment postcode(s) [2] 25959 0
2037 - Glebe

Funding & Sponsors
Funding source category [1] 302186 0
Other
Name [1] 302186 0
Woolcock Institute of Medical Research
Country [1] 302186 0
Australia
Primary sponsor type
Other
Name
Woolcock Institute of Medical Research
Address
431 Glebe point Road, 2037, NSW, Glebe
Country
Australia
Secondary sponsor category [1] 302027 0
Commercial sector/Industry
Name [1] 302027 0
Cyclopharm
Address [1] 302027 0
Unit 4/1 The Crescent, Kingsgrove NSW 2208
Country [1] 302027 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302866 0
The Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 302866 0
NSLHD Research Office
Level 13, Kolling Building
Royal North Shore Hospital
St Leonards NSW 2065
Ethics committee country [1] 302866 0
Australia
Date submitted for ethics approval [1] 302866 0
31/07/2018
Approval date [1] 302866 0
12/11/2018
Ethics approval number [1] 302866 0
RESP/18/198

Summary
Brief summary
The purpose of this research study is to determine the changes in lung ventilation using a new imaging technique before and after inhalation of a bronchodilator that opens the airways, and before and after inhalation of a stimulant that narrows the airways in asthma and COPD patients.
In this study you will perform several standard lung function tests and you will undergo lung imaging to assess lung ventilation during a total of 3 visits. We predict that the outcomes of this study will contribute to further characterisation of asthma and COPD and will support the use of this imaging technique as a new clinical tool to measure responses to new treatments.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91658 0
Prof Gregory King
Address 91658 0
Department of Respiratory Medicine
Royal North Shore Hospital
Pacific Highway
St Leonards, NSW 2065
Australia
Country 91658 0
Australia
Phone 91658 0
+61 2 9463 2935
Fax 91658 0
+61 2 9463 2099
Email 91658 0
[email protected]
Contact person for public queries
Name 91659 0
Prof Gregory King
Address 91659 0
Department of Respiratory Medicine
Royal North Shore Hospital
Pacific Highway
St Leonards, NSW 2065
Australia
Country 91659 0
Australia
Phone 91659 0
+61 2 9463 2935
Fax 91659 0
+61 2 9463 2099
Email 91659 0
[email protected]
Contact person for scientific queries
Name 91660 0
Prof Gregory King
Address 91660 0
Department of Respiratory Medicine
Royal North Shore Hospital
Pacific Highway
St Leonards, NSW 2065
Australia
Country 91660 0
Australia
Phone 91660 0
+61 2 9463 2935
Fax 91660 0
+61 2 9463 2099
Email 91660 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.