Characterisation of Healthy Volunteers, Asthma and Chronic Obstructive Pulmonary Disease Patients for Inhalation Profile, Pharyngometry, Spirometric Indices and Lung Morphometry

Study Overview
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Brief Summary
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This is a clinical study, with no investigational product, to characterise the inhalation profiles of healthy volunteers, volunteers with mild, moderate and severe Asthma and volunteers with mild, moderate and severe Chronic Obstructive Pulmonary Disease (COPD), through the novel dry powder inhaler.

Official Title
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Characterisation of Healthy Volunteers, Asthma and Chronic Obstructive Pulmonary Disease Patients for Inhalation Profile, Pharyngometry, Spirometric Indices and Lung Morphometry

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Procedure: Inhalation Profiling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply. All volunteers must be aged between 21 to 70 years inclusive and be competent to understand and give informed consent. All female volunteers of child bearing potential must have provided a negative pregnancy test before inclusion and prior to any HRCT scan. Body weight < 120 kg and BMI within the range 18 - 35 kg/m2 (inclusive). Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Available to complete the study Subject will then be included only if they fulfil all criteria for the following relevant cohort Healthy: Cohort Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history and physical. A subject with a clinical abnormality or parameters outside the reference range for the population being studied may be included if the Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Non-smokers (never smoked or not smoking for >12 months with <1 pack year history) (Pack years = (cigarettes per day smoked/20) x number of years smoked)) No history of a chronic respiratory disorder. No history of acute respiratory disease within four weeks prior to inclusion. No history of breathing problems such as a history of asthma, unless the asthma was in childhood and has now completely resolved, no longer requiring maintenance or intermittent therapy. No other significant medical disorder that may affect the respiratory system or that causes significant disability. Asthmatic: Cohort Clinically diagnosed with asthma, for at least 6 months, stratified as either: mild, moderate or severe, based on current treatment, using the British Thoracic Society - - Guidelines on Asthma [BTS, 2009]. For inhaled steroid equivalence to budesonide please refer to the GINA guidelines [GINA, 2008] Mild, defined Step 1 or 2 by BTS Asthma Guidelines Moderate, defined as step 3 by BTS Asthma Guidelines Severe, defined as step 4 or 5 by BTS Asthma Guidelines Non-smokers (never smoked or not smoking for >12 months with <1 pack year history (Pack years = (cigarettes per day smoked/20) x number of years smoked)) Able to withhold from short acting bronchodilators for 6 hours and long acting bronchodilators for 12 hours before study assessments No history of acute respiratory disease within four weeks prior to inclusion. No history of any other inflammatory lung condition or carcinoma of the lung. No exacerbation of disease requiring hospitalisation within previous four weeks. COPD: Cohort - Clinically diagnosed COPD, for at least 6 months prior to screening, either: mild, moderate or severe/very severe (stage I, II, III/IV) COPD as defined by GOLD guidelines [GOLD 2008]. The following lung function criteria are post bronchodilator Stage I: Mild COPD. FEV1/FVC < 70%, FEV1 ≥ 80% predicted with or without chronic symptoms (cough, sputum production) Stage II Moderate COPD. FEV1/FVC < 70%. 50% ≤ FEV1 < 80% predicted with or without chronic symptoms (cough, sputum production) Stage III and IV Severe COPD. FEV1/FVC < 70%. 30% ≤ FEV1 < 50% predicted with or without chronic symptoms (cough, sputum production) Very Severe COPD.FEV1/FVC < 70%, FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (Pack years = (cigarettes per day smoked/20) x number of years smoked)). No history of acute respiratory disease within four weeks prior to inclusion No history of any other inflammatory lung condition or carcinoma of the lung. No exacerbation of disease requiring hospitalisation within previous four weeks. Able to withhold from short acting bronchodilators for 6 hours and long acting bronchodilators for 12 hours before study assessments Exclusion Criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: As a result of the medical interview, physical examination or screening investigations, the physician responsible considers the volunteer unfit for the study. Any pregnant female Volunteers who have a past or present disease, which as judged by the Investigator, may affect subject safety or influence the outcome of the study. The subject has received an investigational drug or participated in any other research trial within 30 days or five half-lives, or twice the duration of the biological effect of any drug (whichever is longer). The subject that has both asthma and COPD. Previous inclusion in a research and/or medical protocol involving nuclear medicine, Any Radiological investigations with significant radiation burden (a significant radiation burden being defined as ICRP category IIb or above: No more than 10 mSv in addition to natural background radiation, in the previous 3 years including the dose from this study). The subject has a history of alcohol or drug abuse. The subject has had a respiratory tract infection within four weeks of the start of the study. The subject has a history of claustrophobia. The subject is unable to perform the Multi Channel Recorder and/or Pharyngometry assessments correctly. The subject has a known allergy or hypersensitivity to milk protein. Unwillingness or inability to follow any of the procedures outlined in the protocol. Subject is kept under regulatory of judicial order in an institution. Subject is mentally or legally incapacitated.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Inhalation Profiling<br>All subjects have Inhaltion profiling, there are no other arms. | Procedure: Inhalation Profiling<br>* All subects recieve Inhaltion Profiling there are no interventions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhaltion Profile Recording (IPR): Measures will be Peak Pressure Drop (kPa), Peak Inspiratory Flow Rate (L/min), Inhaled Volume (L), Inhalation time (s) Average Inhalation flow rate (L/min) | To characterise the inhalation profiles of healthy volunteers, volunteers with mild, moderate and severe asthma and volunteers with mild, moderate and severe COPD, through the novel DPI, using the IPR | 24 hours | 
| Pharangometry: Measures will be, Distance (cm) Volume (cm3) Average cross sectional area (cm2) | To characterise the inhalation profiles of healthy volunteers, volunteers with mild, moderate and severe asthma and volunteers with mild, moderate and severe COPD, using pharangometry | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HRCT scans: Measures are Total Lung Capacity (TLC) and Functional Residual capacity (FRC) | Exploratory: To provide data from HRCT scans, spirometry and plethysmography measures which will enable further work in the mapping of the small and large airways and deliver 3D geometries of these airways. | 24 hours | 
| Lung function indices by spirometry: Measures, FEV1, Vmax25 and 50, PEFR, PIFR | Exploratory: To provide data from HRCT scans, spirometry and plethysmography measures which will enable further work in the mapping of the small and large airways and deliver 3D geometries of these airways. | 24 hours | 
| Whole body plethysmography: Measures include.Volume: total lung, residual volume, functional reserve volume, Impedance - generation 0 to 6, Resistance - generation 0 to 6 and Diffusion. | Exploratory: To provide data from HRCT scans, spirometry and plethysmography measures which will enable further work in the mapping of the small and large airways and deliver 3D geometries of these airways. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharyngometry, Novel Dry Powder Inhaler, HRCT, Inhalation Profiles