Plain English Summary
Background and study aims
Chronic obstructive pulmonary disease (COPD) is a combination of chronic bronchitis (infection of the main airways of the lungs) and emphysema (destruction of lung tissue) usually caused by smoking. It is very common, affecting up to 2.4 million people in the UK. Because breathing capacity is reduced, patients get breathless with exercise and become less active. This in turn causes a loss of fitness which leads to worse breathlessness. This vicious spiral of inactivity can be helped by a supervised exercise program known as pulmonary rehabilitation. Muscle weakness occurs in about one third of people with COPD and is associated with a reduced ability to do daily activities and with a greater risk of death. Because COPD is so common it is only possible to provide short exercise programs and these are only available to a small proportion of patients. An additional problem is that the muscles of people with lung disease do not necessarily respond to exercise in the same way as healthy people. There is an excessive stress response in the muscle and this blocks some of the beneficial effects of exercise. Researchers have been trying to find ways to increase the response to exercise training especially because of the limited resources available. Laboratory experiments and some work in humans suggest that a class of medication called ACE inhibitors would provide a more 'oxidative' type of muscle which would have greater endurance properties, to enable people to do daily activities more easily. ACE inhibitors are commonly used as a treatment for high blood pressure.
Who can participate?
Patients with COPD who are limited in their daily activities.
What does the study involve?
Patients will take part in an 8-week pulmonary rehabilitation study. Half of them will take an ACE inhibitor daily and half will take a placebo (dummy) tablet daily. We will measure their exercise capacity on an exercise bike before and after the program to see if the ACE inhibitor group show more improvement. We will also take small samples of muscle and blood before and after so that we can study the molecular mechanisms involved and how these relate to changes in exercise capacity.
What are the possible benefits and risks of participating?
Because ACE inhibitors are an established (and relatively cheap) class of drug, if the study is positive it would be possible to start using them for this purpose in the clinic quickly, potentially benefiting a large number of people.
Where is the study run from?
Royal Brompton Hospital, London (UK)
When is the study starting and how long is it expected to run for?
December 2012 to March 2015
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Dr Nicholas Hopkinson
n.hopkinson@ic.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Nicholas Hopkinson
ORCID ID
Contact details
Royal Brompton Hospital
Fulham Road
London
SW3 6NP
United Kingdom
+44 20 7349 7775
n.hopkinson@ic.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
V1 16th January 2012
Study information
Scientific title
ACE inhibitors to augment the effects of pulmonary rehabilitation in COPD
Acronym
ACE-EPIC
Study hypothesis
The objective of the study is to establish whether enalapril can augment the effects of pulmonary rehabilitation on patients with COPD. This will focus on exercise capacity measured using cycle ergometry but data will also be collected on strength, body composition, physical activity level and health related quality of life.
Ethics approval
London Bloomsbury Research Ethics Committee, 21/03/2012, ref: 12/LO/0331
Study design
Single centre double blind placebo controlled parallel group study
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
COPD
Intervention
Treatment will with 10mg enalapril or matched placebo once daily. Drug and placebo will be encapsulated by Royal Free Pharmacy. Drug will be dispensed from the pharmacy at Royal Brompton and Harefield NHS Foundation Trust.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
Increase in peak workload achieved on a cycle ergometer following a rehabilitation program compared between enalapril and placebo treated patients.
Secondary outcome measures
1. Quadriceps strength
2. Six minute walk distance
3. HRQOL (CAT score)
4. Physical activity level (SenseWear armband)
Overall trial start date
01/12/2012
Overall trial end date
31/03/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Adults with GOLD stage II-IV COPD and a clinical indication for pulmonary rehabilitation (MRC score of 3 or more or functionally limited)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
80
Participant exclusion criteria
1. Clinically unstable patients (within one month of exacerbation)
2. Those with a permanent pacemaker (which is a contraindication to magnetic stimulation), or significant co-morbidity
3. Patients with an accepted indication for ACE inhibition (left ventricular dysfunction, diabetes) or a contraindication such as renovascular disease
4. Creatinine clearance (estimated) <50)
5. Hypotension
6. Use of anticoagulants (contra-indication to biopsy) or ACE-I or ATII receptor antagonists
7. Allergy to ACE-inhibitors
8. Pregnancy
Recruitment start date
01/12/2012
Recruitment end date
31/03/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal Brompton Hospital
Sydney Street
Chelsea
London
SW3 6NP
United Kingdom
Sponsor information
Organisation
Imperial College London (UK)
Sponsor details
Imperial College Healthcare NHS Trust
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
+44 (0)203 311 0206
lucy.parker@imperial.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Research council
Funder name
Medical Research Council [MRC] (UK) ref: MR/J000620/1
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication of results in a peer reviewed journal.
Intention to publish date
01/06/2016
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/27248440