Contact information
Type
Scientific
Primary contact
Dr David Singh
ORCID ID
Contact details
Medicines Evaluation Unit
Ledson Road
Wythenshawe
Manchester
M23 9GP
United Kingdom
+44 (0)161 291 2672
dsingh@meu.org.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N0226156349
Study information
Scientific title
Acronym
Study hypothesis
To investigate the effect of withdrawal of inhaled seretide on airway inflammation and airflow limitation in Chronic Obstructive Pulmonary Disease (COPD) patients using non-invasive measurement methods and lung function tests.
Please note that this record was extensively updated on the 9th November 2007. Updates were performed to the ethics, inclusion criteria, interventions and secondary outcome measures, as some of this information was not provided in the original record. Where changes have been made, the update date (09/11/2007) has been mentioned. Also please note that previous to this update, the anticipated end date of this trial was 03/07/2006.
Ethics approval
Added on 09/11/2007: Ethics approval received from the Central Manchester Local Research Ethics Committee on 25/02/2005.
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Chronic Obstructive Pulmonary Disease (COPD)
Intervention
1. Seretide withdrawal group (withdrawal of Seretide dose for six weeks)
2. Continuation group
Added on 09/11/2007:
Patients will undergo spirometry, impulse oscillometry, body plethysmography, exhaled breath condensate, exhaled nitric oxide, induced sputum and questionaires at two occasions 2 weeks apart prior to randomisation and then at 2 weekly intervals for 6 weeks.
Intervention type
Drug
Phase
Not Specified
Drug names
Seretide
Primary outcome measures
Induced sputum inflammatory cell counts
Secondary outcome measures
Added on 09/11/2007:
1. Exhaled breath condensate pH
2. Exhaled breath condensate Leukotriene B4, 8-isoprostane and other metabolites
3. Exhaled breath condensate and serum metabolite profiling by mass spectrometry
4. Exhaled nitric oxide in parts per billion (at 50 mls/sec, Caw, Calvin and Diffusing Capacity)
5. Induced sputum messenger Ribonucleic Acid (RNA) and protein for inflammatory mediators (e.g., Interleukin-8 [IL-8], Interleukin-6 [IL-6])
6. Sputum and blood gene expression (e.g., glucocorticoid receptor)
7. FEV1, Maximal Expiratory Flow (MEF), FVC (measured by spirometry)
8. Total Lung Capacity (TLC), Residual Volume (RV), Functional Residual Capacity (FRC), Inspiratory Capacity (IC), specific airways conductance (sGaw), airway flow resistance (Raw) (measured by body plethysmography)
9. Resonant Frequency (RF), Respiratory resistance at 5 Hz (R5), reactance at 5 Hz (X5) (measured by impulse oscillometry)
Overall trial start date
01/03/2005
Overall trial end date
31/07/2007
Reason abandoned
Eligibility
Participant inclusion criteria
12 in withdrawal group and 12 in continuation group, patients aged 40 - 75 years
Added on 09/11/2007:
1. Males or females aged 40 - 75 years inclusive
2. Ex smokers or current smokers with a cigarette smoking history of pack years (1 pack-year = 20 cigarettes smoked per day for 1 year or the equivalent)
3. Subjects with Forced Expiratory Volume in one second (FEV1) 50 - 80% of predicted normal for height, age and sex at screening visit
4. Subjects with FEV1/Forced Vital Capacity (FVC) ratio less than 70% at screening visit
5. Patients taking inhaled seretide or combined fluticasone/salmeterol at a dose of 200 - 1000 µg fluticasone and 50 - 100 µg serevent per day
6. Subjects on a stable dose of all COPD treatment over the 4 weeks prior to starting the study
7. Subjects capable of providing signed written consent to participate
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
24
Participant exclusion criteria
1. Subjects taking regular oral leukotriene receptor antagonists, oral cortiscosteroids, inhaled nasal corticosteroids, oral theophylline or inhaled tiotropium for 4 weeks prior to the study start
2. Subjects having one or more exacerbations of COPD in the past 12 months requiring treatment with oral corticosteroids
3. Subjects who have had a previous admission for exacerbation of COPD requiring non-invasive or endo-tracheal intubation or admission to the Intensive Care Unit (ICU)
4. History of asthma or significant atopy/rhinitis (requiring medication)
5. Subjects with uncontrolled angina, myocardial infarction within the last 12 months or congestive cardiac failure
6. Subjects with other significant pulmonary, cardiovascular, neurological, hepatic, renal, endocrine or haematological diseases
7. Female subjects who intend to become pregnant
8. Subjects who have experienced cold or flu-like symptoms or a respiratory infection within 4 weeks of the study start
9. Subjects who have received an investigational drug within 30 days or within 5 drug half-lives of the drug
10. Subjects with a history (or suspected history) of alcohol misuse or any other recreational substance abuse
Recruitment start date
01/03/2005
Recruitment end date
31/07/2007
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Medicines Evaluation Unit
Manchester
M23 9GP
United Kingdom
Sponsor information
Organisation
Department of Health
Sponsor details
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)20 7307 2622
dhmail@doh.gsi.org.uk
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
South Manchester University Hospitals NHS Trust (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
NHS R&D Support Funding (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19603154
Publication citations
-
Results
Borrill Z, Roy K, Kolsum U, Southworth T, Vestbo J, Singh D, Seretide withdrawal increases airway inflammation in moderate COPD patients., Eur. J. Clin. Pharmacol., 2009, 65, 11, 1165-1166, doi: 10.1007/s00228-009-0697-5.