Overview

This trial is active, not recruiting.

Conditions chronic obstructive pulmonary disease, asthma, healthy subjects
Treatment salbutamol
Phase phase 4
Sponsor Imperial College London
Collaborator National Institute for Health Research, United Kingdom
Start date October 2012
End date April 2015
Trial size 50 participants
Trial identifier NCT01721291, NIHR-CDF-2011-04-053, NIHRCDF

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacokinetics/dynamics study
Intervention model crossover assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
DOSAGE FORM- SALBUTAMOL INHALED VIA RESEARCH NEBULISER;DOSAGE- 30 MICROGRAMS, ONCE SINGLE INHALATION ONLY; FREQUENCY- AT THREE VISITS (ONE VISIT INHALE SLOWY, ANOTHER VISIT INHALE FAST, ANOTHER VISIT INHALE SLOW AT 15 MICROGRAMS)
salbutamol ALBUTEROL; VENTOLIN; SALMOL
In the LUNG DEPOSITION STUDY; SALBUTAMOL INHALED VIA RESEARCH NEBULISER at 3 PARTICLES SIZES OF 1.5 MICRONS, 3 MICRONS AND 6 MICRONS WILL BE GIVEN AT SLOW INHLATION AND AGAIN AT FAST INHALTION;DOSAGE- 30 MICROGRAMS, ONE SINGLE INHALATION ONLY. IN ADDITION, SALBUTAMOL AT 200 MICROGRAMS INHALED VIA A STANDARD METERED DOSE INHALER WILL ALSO BE GIVEN AS A SINGLE INHALATION. In the LUNG PHYSIOLOGY STUDY; SALBUTAMOL INHALED VIA RESEARCH NEBULISER at 3 PARTICLES SIZES OF 1.5 MICRONS, 3 MICRONS AND 6 MICRONS WILL BE GIVEN AT TWO DOSAGES OF 30 MICROGRAMS AND AGAIN AT 15 MICROGRAMS, ONE SINGLE INHALATION ONLY. IN ADDITION, SALBUTAMOL AT 200 MICROGRAMS INHALED VIA A STANDARD METERED DOSE INHALER WILL ALSO BE GIVEN AS A SINGLE INHALATION. ALL INHALATIONS WIL BE AT SLOW INHALTION IN THIS PART OF THE STUDY.
(Experimental)
DOSAGE FORM- SALBUTAMOL INHALED VIA RESEARCH NEBULISER;DOSAGE- 30 MICROGRAMS, ONCE SINGLE INHALATION ONLY; FREQUENCY- AT THREE VISITS (ONE VISIT INHALE SLOWY, ANOTHER VISIT INHALE FAST, ANOTHER VISIT INHALE SLOW AT 15 MICROGRAMS)
salbutamol ALBUTEROL; VENTOLIN; SALMOL
In the LUNG DEPOSITION STUDY; SALBUTAMOL INHALED VIA RESEARCH NEBULISER at 3 PARTICLES SIZES OF 1.5 MICRONS, 3 MICRONS AND 6 MICRONS WILL BE GIVEN AT SLOW INHLATION AND AGAIN AT FAST INHALTION;DOSAGE- 30 MICROGRAMS, ONE SINGLE INHALATION ONLY. IN ADDITION, SALBUTAMOL AT 200 MICROGRAMS INHALED VIA A STANDARD METERED DOSE INHALER WILL ALSO BE GIVEN AS A SINGLE INHALATION. In the LUNG PHYSIOLOGY STUDY; SALBUTAMOL INHALED VIA RESEARCH NEBULISER at 3 PARTICLES SIZES OF 1.5 MICRONS, 3 MICRONS AND 6 MICRONS WILL BE GIVEN AT TWO DOSAGES OF 30 MICROGRAMS AND AGAIN AT 15 MICROGRAMS, ONE SINGLE INHALATION ONLY. IN ADDITION, SALBUTAMOL AT 200 MICROGRAMS INHALED VIA A STANDARD METERED DOSE INHALER WILL ALSO BE GIVEN AS A SINGLE INHALATION. ALL INHALATIONS WIL BE AT SLOW INHALTION IN THIS PART OF THE STUDY.
(Experimental)
DOSAGE FORM- SALBUTAMOL INHALED VIA RESEARCH NEBULISER;DOSAGE- 30 MICROGRAMS, ONCE SINGLE INHALATION ONLY; FREQUENCY- AT THREE VISITS (ONE VISIT INHALE SLOWY, ANOTHER VISIT INHALE FAST, ANOTHER VISIT INHALE SLOW AT 15 MICROGRAMS)
salbutamol ALBUTEROL; VENTOLIN; SALMOL
In the LUNG DEPOSITION STUDY; SALBUTAMOL INHALED VIA RESEARCH NEBULISER at 3 PARTICLES SIZES OF 1.5 MICRONS, 3 MICRONS AND 6 MICRONS WILL BE GIVEN AT SLOW INHLATION AND AGAIN AT FAST INHALTION;DOSAGE- 30 MICROGRAMS, ONE SINGLE INHALATION ONLY. IN ADDITION, SALBUTAMOL AT 200 MICROGRAMS INHALED VIA A STANDARD METERED DOSE INHALER WILL ALSO BE GIVEN AS A SINGLE INHALATION. In the LUNG PHYSIOLOGY STUDY; SALBUTAMOL INHALED VIA RESEARCH NEBULISER at 3 PARTICLES SIZES OF 1.5 MICRONS, 3 MICRONS AND 6 MICRONS WILL BE GIVEN AT TWO DOSAGES OF 30 MICROGRAMS AND AGAIN AT 15 MICROGRAMS, ONE SINGLE INHALATION ONLY. IN ADDITION, SALBUTAMOL AT 200 MICROGRAMS INHALED VIA A STANDARD METERED DOSE INHALER WILL ALSO BE GIVEN AS A SINGLE INHALATION. ALL INHALATIONS WIL BE AT SLOW INHALTION IN THIS PART OF THE STUDY.
(Active Comparator)
DOSAGE FORM- SALBUTAMOL INHALED VIA METERED DOSE INHLAER;DOSAGE- 200 MICROGRAMS, ONCE SINGLE INHALATION ONLY; FREQUENCY- AT ONE VISIT INHALE SLOWY)
salbutamol ALBUTEROL; VENTOLIN; SALMOL
In the LUNG DEPOSITION STUDY; SALBUTAMOL INHALED VIA RESEARCH NEBULISER at 3 PARTICLES SIZES OF 1.5 MICRONS, 3 MICRONS AND 6 MICRONS WILL BE GIVEN AT SLOW INHLATION AND AGAIN AT FAST INHALTION;DOSAGE- 30 MICROGRAMS, ONE SINGLE INHALATION ONLY. IN ADDITION, SALBUTAMOL AT 200 MICROGRAMS INHALED VIA A STANDARD METERED DOSE INHALER WILL ALSO BE GIVEN AS A SINGLE INHALATION. In the LUNG PHYSIOLOGY STUDY; SALBUTAMOL INHALED VIA RESEARCH NEBULISER at 3 PARTICLES SIZES OF 1.5 MICRONS, 3 MICRONS AND 6 MICRONS WILL BE GIVEN AT TWO DOSAGES OF 30 MICROGRAMS AND AGAIN AT 15 MICROGRAMS, ONE SINGLE INHALATION ONLY. IN ADDITION, SALBUTAMOL AT 200 MICROGRAMS INHALED VIA A STANDARD METERED DOSE INHALER WILL ALSO BE GIVEN AS A SINGLE INHALATION. ALL INHALATIONS WIL BE AT SLOW INHALTION IN THIS PART OF THE STUDY.

Primary Outcomes

Measure
ANALYSIS OF LUNG DEPOSITION - Penetration Index
time frame: 5 MINUTES AFTER INHALATION OF SALBUTAMOL

Secondary Outcomes

Measure
ANALYSIS OF LUNG PHYSIOLOGY TESTS - Impulse Oscillometry R5 & X5 and Multi-breath Washout tests of S-acin and S-cond
time frame: LUNG PHYSIOLOGY: 30 MINUTE INTERVALS AFTER INHALATION OF SALBUTAMOL UP TO 2 HOURS

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

Official title Improving Inhaler Treatment and Small Airways Assessment in Chronic Obstructive Pulmonary Disease (COPD)
Principal investigator Omar S USMANI, MD, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Imperial College London.