Inhaler Lung Deposition in Chronic Obstructive Pulmonary Disease (COPD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by Imperial College London
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01721291
First received: October 16, 2012
Last updated: November 1, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
ASTHMA
HEALTHY SUBJECTS
Drug: SALBUTAMOL
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Improving Inhaler Treatment and Small Airways Assessment in Chronic Obstructive Pulmonary Disease (COPD)

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • ANALYSIS OF LUNG DEPOSITION - Penetration Index [ Time Frame: 5 MINUTES AFTER INHALATION OF SALBUTAMOL ] [ Designated as safety issue: No ]
    Images of the lungs will be taken for radiolabelled salbutamol treatment. The images will be processed using computer software and the lungs divided into central airways (C - region) and peripheral airways (P -region). We will analyse the amount of radiolabelled salbutamol in each region and calculate how deep into the lungs the inhaled salbutamol has reached by using the ratio C/P which is known as the Penetration Index.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    We will undertake simple blowing physiology lung tests that tell us about the large airways and also the small airways. The small airway tests (Impulse oscillometry R5 and X5; S-acin and S-cond) will be analysed to determine if the inhaled salbutamol has a greater effect on these small airway tests or on the traditional large airway tests (FEV1).


Estimated Enrollment: 63
Study Start Date: October 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SALBUTAMOL 1.5 MICRONS
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)
Drug: SALBUTAMOL

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.

Other Name: ALBUTEROL; VENTOLIN; SALMOL
Experimental: SALBUTAMOL 3 MICRONS
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)
Drug: SALBUTAMOL

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.

Other Name: ALBUTEROL; VENTOLIN; SALMOL
Experimental: SALBUTAMOL 6 MICRONS
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)
Drug: SALBUTAMOL

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.

Other Name: ALBUTEROL; VENTOLIN; SALMOL
Active Comparator: SALBUTAMOL 200 MICROGRAMS
DOSAGE FORM- SALBUTAMOL INHALED VIA METERED DOSE INHLAER;DOSAGE- 200 MICROGRAMS, ONCE SINGLE INHALATION ONLY; FREQUENCY- AT ONE VISIT INHALE SLOWY)
Drug: SALBUTAMOL

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.

Other Name: ALBUTEROL; VENTOLIN; SALMOL

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01721291

Contacts
Contact: Omar S USMANI, MD, PhD 0044 207 351 8051 o.usmani@imperial.ac.uk
Contact: Sally MEAH, RGN 0044 207 351 8051 sally.meah@imperial.ac.uk

Locations
United Kingdom
Royal Brompton Hospital & Imperial College London Recruiting
London, United Kingdom, SW3 6LY
Contact: Omar S USMANI, MD, PhD    0044 207 351 8051    o.usmani@imperial.ac.uk   
Contact: Sally MEAH, RGN    0044 207 351 8051    sally.meah@imperial.ac.uk   
Principal Investigator: Omar S USMANI, MD, PhD         
Sponsors and Collaborators
Imperial College London
National Institute for Health Research, United Kingdom
Investigators
Principal Investigator: Omar S USMANI, MD, PhD Imperial College London
  More Information

Additional Information:
Publications:
Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01721291     History of Changes
Other Study ID Numbers: NIHRCDF, NIHR-CDF-2011-04-053
Study First Received: October 16, 2012
Last Updated: November 1, 2012
Health Authority: United Kingdom: National Institute for Health Research
United Kingdom: Medicines and Healthcare Products Regulatory Agency
UNITED KINGDOM: ADMINISTRATION OF RADIOACTIVE MEDICINAL PRODUCTS (ARSAC)

Keywords provided by Imperial College London:
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
ASTHMA
SALBUTAMOL
ALBUTEROL
VENTOLIN
LUNG PHYSIOLOGY
LUNG DEPOSITION
INHALERS
DRUG THERAPY

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Albuterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014