Clinical trial NCT01721291: Inhaler Lung Deposition in Chronic Obstructive Pulmonary Disease (COPD)
Official title: Improving Inhaler Treatment and Small Airways Assessment in Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: CHRONIC OBSTRUCTIVE PULMONARY DISEASE
ASTHMA
HEALTHY SUBJECTS
Keywords: CHRONIC OBSTRUCTIVE PULMONARY DISEASE
ASTHMA
SALBUTAMOL
ALBUTEROL
VENTOLIN
LUNG PHYSIOLOGY
LUNG DEPOSITION
INHALERS
DRUG THERAPY
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2012-11-04
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Patients with chronic obstructive pulmonary disease (COPD) experience breathing difficulties because the airways deep in their lungs become narrowed. COPD patients use inhaler drugs to provide relief from breathlessness. However, current inhalers are inefficient as they deliver a 'coarse-mist' of drug-droplets that do not reach the deep airways.

In our study, we will use an inhaler of 'fine-mist' drug-droplets, tagged with a radioactive tracer to track them. We will take images of the lungs to see if the fine-mist droplets reach the deep airways, and assess if this improves the breathing capacity in our patients. Our research may allow the development of new, more efficient inhalers to improve treatment for patients with COPD.

Detailed description: PURPOSE:

The purpose of the research (or "knowledge gap" this research is designed to fill) is to understand the fate of inhaled drug within the lungs of COPD patients. Current inhalers in use were developed to treat asthma, which is predominantly a disease of the large airways, and these inhalers may not be optimal in treating COPD patients (which is predominantly a disease of the small airways). Poor delivery of inhaled bronchodilators to the peripheral deep airways may be a major factor limiting the clinical benefit provided by existing devices. The key to successful treatment could be to accurately target inhaled drug to the diseased lung sites, which is the hypothesis that this protocol will test.

DESIGN \& FUNDING:

Dr Omar Usmani has developed the research protocol and the study has been funded by the UK Government Department of Health through the NIHR (National Institute for Health Research), which funds leading edge research in the NHS focussed on the needs of patients and the public and aims to improve the health and wealth of the nation through research. The study has been peer reviewed by International Experts in this field of research.

PROTOCOL:

This protocol has two studies: Lung DEPOSITION study (in COPD patients and Healthy subjects) and Lung PHYSIOLOGY study (in COPD patients and Asthmatics).

Each study (Lung DEPOSITION and Lung PHYSIOLOGY) will be a randomised, double-blind, crossover, (7 treatments,controlled against pMDI salbutamol), study. Treatments will be given as one off dose administration.

There will be an interval of at least 5 days between each study visit. The Lung DEPOSITION study will involve radiolabelled drug treatments.

All the treatments in the LUNG PHYSIOLOGY study will be non-radiolabelled. Salbutamol will be the drug aerosol administered to each subject at each visit. Subjects and investigators will be blinded to the 'fine-mist' aerosol particle sizes given (at 6 treatments). The control arm will be salbutamol drug aerosol delivered as a 'coarse mist' standard metered dose inhaler (7th treatment visit).

RECRUITMENT/SAMPLE SIZE; The study will recruit; Lung DEPOSITION study: 12 mild-moderate COPD patients, 12 healthy subjects Lung PHYSIOLOGY study: 26 mild-moderate COPD patients, 13 mild-moderate asthmatic patients

INCLUSION / EXCLUSION:

At the screening vist, no one will be unfairly excluded from the research, particularly as COPD is a disease of older age and those over 65 should not be discriminated against. This research will therefore reflect the 'real world' of COPD.

Eligibility criteria: Inclusion Criteria:

- COPD patients, either male or female, over the age of 40 with a clinical diagnosis of COPD with airflow obstruction(FEV1/FVC\<0.7) and post-bronchodilator FEV1\>50% predicted, gas trapping (on lung volume testing), and decreased carbon monoxide transfer factor.

Healthy subjects will be nonsmokers(or exsmokers stopped 5 years ago), will have no respiratory disease, normal spirometry and be age-matched to the COPD patients.

Asthmatic subjects, either male or female, over the age of 18 with a clinical diagnosis of Asthma with airflow obstruction (FEV1/FVC\<0.7).

All patients should be capable of giving informed consent.

Exclusion Criteria:

1. Oral corticosteroids taken within last month.
2. Current involvement (or involvement in the last 4 weeks)in clinical trials assessing investigational medicinal products.
3. Previous adverse reaction to short or long acting β2 agonist.
4. Any subject with a contraindication to taking inhaled beta2-adrenoceptor agonists (especially salbutamol) as listed in the British National Formulary will not be entered into this study.
5. Those who have experienced an acute respiratory exacerbation requiring emergency room treatment and/ or hospitalisation within four weeks of visit 1 (screening visit).
6. Pregnant or breastfeeding women.
7. Subjects unable to give Informed Consent.

Primary outcomes:
measure: ANALYSIS OF LUNG DEPOSITION - Penetration Index
timeFrame: 5 MINUTES AFTER INHALATION OF SALBUTAMOL
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton Hospital & Imperial College London
Study officials:
affiliation: Imperial College London
name: Omar S USMANI, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Usmani OS, Biddiscombe MF, Barnes PJ. Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size. Am J Respir Crit Care Med. 2005 Dec 15;172(12):1497-504. doi: 10.1164/rccm.200410-1414OC. Epub 2005 Sep 28.