Aridol Challenge as a Tool to Predict Treatment Response to Inhaled Corticosteroids in COPD

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the Aridol (mannitol) challenge test can predict response to treatment with inhaled corticosteroids in COPD subjects. Subjects will undergo an Aridol test and then 3 months of treatment with inhaled corticosteroids. The effect on lung function and quality of life will then be measured and correlated with the Aridol test result.

Official Title
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A Phase II Study to Investigate Mannitol Challenge as a Tool to Predict Treatment Response to Inhaled Corticosteroids in COPD

Conditions
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Lung Diseases, Obstructive

Intervention / Treatment
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* Drug: Dry powder mannitol
* Drug: Budesonide 400mcg administered via turbuhaler
* Drug: Ipratropium bromide 80mcg
* Drug: Salbutamol 400mcg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of COPD (history, spirometry, symptoms including chronic cough and/or shortness of breath that is worse on exertion and/or excess sputum production) Aged 45 - 80 years Have pre-bronchodilator FEV1 > 1.4 litres and at least 60% of predicted for height, age and gender and a post-bronchodilator FEV1 <80% of predicted for height, age and gender Post-bronchodilator FEV1/FVC < 70 % ≥ 10 pack years smoking history As determined by the investigator, are capable and willing to: perform all of the techniques necessary to measure lung function; administer the dry powder mannitol. Are capable of, and have given informed consent to, participating in this study in accordance with local regulations. The subject must be in stable clinical condition at the time of, and for a period of 14 days prior to, their recruitment into the study. Stable clinical condition is defined as lack of: change in sputum production (volume, colour, consistency); increased cough; worsening dyspnoea; increased malaise, fatigue or lethargy; reduction in exercise tolerance; fever; antibiotic treatment (for respiratory infection). Exclusion Criteria: Investigators, site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biologically or legally adopted. Subjects receiving treatment with inhaled corticosteroids (including combination therapies, e.g. Seretide®, Symbicort®) or oral corticosteroids within the last 6 weeks. Subjects who have had an exacerbation or a chest infection within the 2 weeks prior to the study. Subjects receiving antibiotic treatment for respiratory infection. Known diagnosis of asthma or allergic rhinitis. Myocardial infarction in the six months prior to enrolment. Cerebral vascular accident in the six months prior to enrolment. Ocular surgery in the three months prior to enrolment. Abdominal surgery in the three months prior to enrolment. Active tuberculosis (TB). Lung cancer or any other malignancies, which are considered by the investigator as a contraindication to participating in the study. Lung disease other than COPD (e.g. bronchiectasis). Uncontrolled insulin-dependant or non-insulin dependant diabetes, i.e. >10% HbA1c. Female subjects of reproductive capability, not using a reliable form of contraception Inability to obtain informed consent from the subject or subject's authorised representative. Subjects who have participated in another investigative drug study parallel to, or within 4 weeks of, study entry. Known intolerance to mannitol. Uncontrolled hypertension - systolic blood pressure (BP) > 200 mmHg and or diastolic BP > 100 mmHg. Planned pulmonary rehabilitation. Have had major abdominal, chest or brain surgery in the three months prior to enrolment. Have known cerebral, aortic or abdominal aneurysm.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Dry powder mannitol|nan|
|Drug: Budesonide 400mcg administered via turbuhaler|nan|
|Drug: Ipratropium bromide 80mcg|nan|
|Drug: Salbutamol 400mcg|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced expiratory volume in one second (FEV1) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response dose ratio (RDR) |  |  | 
| Dose of provoking stimulus causing a 15%, 12% or 10% fall in FEV1 (PD15, PD12, PD10) |  |  | 
| Lung function values |  |  | 
| Quality of life assessed by St. George's Respiratory Questionnaire (SGRQ)- total score |  |  | 
| COPD clinical control scores (CCQ) |  |  | 
| Exacerbation frequency |  |  | 
| Days on antibiotics |  |  | 
| Days off work or days unable to carry out normal activities |  |  | 
| Reversibility of airflow obstruction |  |  |