CHRONIC OBSTRUCTIVE PULMONARY DISEASEPhase 4NCT01721291
Inhaler Lung Deposition in Chronic Obstructive Pulmonary Disease (COPD)
A Phase 4 study testing SALBUTAMOL in people with CHRONIC OBSTRUCTIVE PULMONARY DISEASE and ASTHMA, run by Imperial College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- CHRONIC OBSTRUCTIVE PULMONARY DISEASE, ASTHMA, HEALTHY SUBJECTS
- What is being tested?
- SALBUTAMOL
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Oct 2012to 27 Nov 2017
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Oral corticosteroids taken within last month.
- Current involvement (or involvement in the last 4 weeks)in clinical trials assessing investigational medicinal products.
- Previous adverse reaction to short or long acting β2 agonist.
- 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.
- Those who have experienced an acute respiratory exacerbation requiring emergency room treatment and/ or hospitalisation within four weeks of visit 1 (screening visit).
- Pregnant or breastfeeding women.
- Subjects unable to give Informed Consent.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Brompton Hospital & Imperial College London
London, London, SW3 6LY
About this study
Official title: Improving Inhaler Treatment and Small Airways Assessment in Chronic Obstructive Pulmonary Disease (COPD)
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 the first part of the study, we will use an inhaler of 'fine-mist' drug-droplets, tagged with a radioactive tracer to track lung deposition in participants with COPD as well as Healthy participants. We will acquire images of the lungs with a gamma camera and calculate the Penetration Index (PI) to see if the fine-mist droplets reach the deep airways, and assess if this improves the breathing capacity in the COPD participants. Our research may allow the development of new, more efficient inhalers to improve treatment for patients with COPD.
Read the 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 have 7 randomized crossover treatments. A special aerosol generator called a Spinning Top Aerosol Generator (STAG), here referred to as a Research Nebuliser, is used to generate monodisperse aerosol droplets (aerosols that have a very narrow spread of particles sizes, such that they can be considered to be one size).
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, 12 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.
- Being tested
- SALBUTAMOL
- Keywords
- CHRONIC OBSTRUCTIVE PULMONARY DISEASE, ASTHMA, SALBUTAMOL, ALBUTEROL, VENTOLIN, LUNG PHYSIOLOGY, LUNG DEPOSITION, INHALERS, DRUG THERAPY
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SALBUTAMOLDrug
Also called ALBUTEROL; VENTOLIN; SALMOL
SALBUTAMOL is inhaled VIA the Spinning Top Aerosol Generator (STAG) at 3 particle size 1.5 microns, 3 microns and 6 microns.
In the LUNG DEPOSITION study radiolabeled salbutamol is given at slow and fast inhalations at a dosage of 30 micrograms, In addition , 200 MICROGRAMS of salbutamol will be inhaled via a standard metered dose inhaler (MDI). These are given in randomized order.
In the LUNG PHYSIOLOGY STUDY, unlabeled SALBUTAMOL is given at slow inhalation via the Spinning Top Aerosol Generator (STAG)at 2 different doses (30 micrograms and 15 micrograms)
| Study group | Role | What they receive |
|---|---|---|
| Lung Deposition study COPD 1 | Experimental | Subjects from COPD group 1 receive 6 radiolabeled treatments of 30mcg salbutamol of 1.5, 3.0 and 6.0 micron sized aerosols + 1 dose of 200mcg salbutamol from an MDI, in randomized crossover order. Receives: Drug: SALBUTAMOL |
| Lung Deposition study Healthy subjects | Experimental | Healthy subjects receive 6 radiolabeled treatments of 30mcg salbutamol of 1.5, 3.0 and 6.0 micron sized aerosols + 1 dose of 200mcg salbutamol from an MDI, in randomized crossover order. Receives: Drug: SALBUTAMOL |
| Lung Physiology study COPD 2 | Experimental | COPD subjects group 2 receive 6 treatments of 30mcg salbutamol of 1.5, 3.0 and 6.0 micron sized aerosols + 1 dose of 200mcg salbutamol from an MDI, in randomized crossover order. All does are non-radiolabeled. Receives: Drug: SALBUTAMOL |
| Lung Physiology study Asthmatics | Experimental | Asthmatic subjects group 2 receive 6 treatments of 30mcg salbutamol of 1.5, 3.0 and 6.0 micron sized aerosols + 1 dose of 200mcg salbutamol from an MDI, in randomized crossover order. All does are non-radiolabeled. Receives: Drug: SALBUTAMOL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Penetration Index (LUNG DEPOSITION STUDY)
Images of the lungs were acquired using gamma scintigraphy. Monodisperse salbutamol aerosols were radiolabeled with the radioisotope Technetium-99m (Tc99m). The images were processed using computer software and the lung images divided into central airways (C - region) and peripheral airways (P -region). We analyzed the amount of radiolabeled salbutamol in each region and calculated how deep into the lungs the inhaled salbutamol has reached by using the ratio C/P which is known as the Penetration Index. More precisely, the regional lung distribution was expressed as penetration index: the ratio of radioaerosol counts in the peripheral zone to the central lung zones divided by the same count ratio from a Krypton ventilation scan. No data is shown for the MDI metered dose inhaler (MDI) treatment as the drug inside the canister was not radiolabeled. This treatemnt was not undertaken by the COPD 2 and asthma groups.
Measured: 5 MINUTES AFTER INHALATION OF SALBUTAMOL
Scond - MBNW (LUNG PHYSIOLOGY STUDY)
This section is reporting data only for the Lung Physiology Study (the results for the Lung Deposition Study have been reported in the previous sections).
Measure of ventilation heterogeneity in conducting airways (measures relate to the peripheral lung compartment conducting airways, which are non-gas-exchanging i.e. Scond). For the COPD 2 group, the measurements are made 30 minutes after the participant has inhaled either 15mcg or 30 mcg of salbutamol inhaled slowly at 1.5um, 3um, or 6um aerosol particle size and 200 mcg from MDI. For the Asthma group measures are made after inhaling only 30mcg of salbutamol inhaled slowly at 1.5um, 3um, or 6um aerosol particle size and 200mcg from MDI. The asthma group was not given the 15mcg dose.
MBNW stands for Multiple Breath Nitrogen Washout.
Measured: 30 minutes after salbutamol
Sacin - MBNW (LUNG PHYSIOLOGY STUDY)
This section is reporting data only for the Lung Physiology Study (the results for the Lung Deposition Study have been reported in the following section). Measure of ventilation heterogeneity in conducting airways (measures relate to the peripheral lung acinar compartment conducting airways, which are gas-exchanging i.e. Sacin). COPD 2 - The measurements are made 30 minutes after the participant has inhaled either 15mcg or 30 mcg of salbutamol inhaled slowly at 1.5um, 3um, or 6um aerosol particle size and 200 mcg from MDI. For the Asthma group measures are made 30 minutes after inhaling only 30mcg of salbutamol inhaled slowly at 1.5um, 3um, or 6um aerosol particle size and 200mcg from MDI. The 15mcg dose is not given, as outlined in the protocol.
MBNW stands for Multiple Breath Nitrogen Washout
Measured: 30 minutes after inhaling salbutamol
Secondary outcomes (2)
Scond - MBNW (LUNG DEPOSITION STUDY)
This section is reporting data only for the Lung Deposition Study (the results for the Lung Physiology Study have been reported in the previous sections). Here Scond is a seconadry measure. Scond is a measure of Ventilation heterogeneity in the conducting airways (measures relate to the peripheral lung compartment conducting airways, which are non-gas-exchanging i.e. Scond). No MBNW measurements were made for the Healthy subjects Multiple Breath Nitrogen analysis (MBNW).
Measured: 30 minutes after inhaling salbutamol
Sacin (MBNW) (LUNG DEPOSITION STUDY)
This section is reporting data only for the Lung Deposition Study (the results for the Lung Physiology Study have been reported in the previous sections). Here Sacin is a seconadry measure. Sacin is a measure of Ventilation heterogeneity in the acinar airways (measures relate to the peripheral lung compartment conducting airways). No MBNW measurements were made for the Healthy subjects Multiple Breath Nitrogen analysis (MBNW).
Measured: 30 minutes after inhaling salbutamol
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2012 (estimated)
- Study start1 Oct 2012
- Primary completion27 Nov 2017
- Study completion27 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CHRONIC OBSTRUCTIVE PULMONARY DISEASEStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Crossover is within each of the groups., ie COPD1, Healthy, COPD2, Asthma ( 6 interventions each)
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Omar S USMANI, MD, PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01721291
- Sponsor's protocol ID
- NIHRCDF
- Other IDs
- NIHR-CDF-2011-04-053, 2011-005544-10
- Status last verified
- Sep 2026
- First submitted
- 16 Oct 2012
- Last updated
- 3 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 16192448