Angiotensin converting enzyme (ACE) inhibition and mechanisms of skeletal muscle weakness in chronic obstructive pulmonary disease (COPD)

ISRCTN	ISRCTN05581879
DOI	https://doi.org/10.1186/ISRCTN05581879
ClinicalTrials.gov number	NCT01014338
Secondary identifying numbers	MRC ref: G0701628; IC-DHTAX_P15099

Submission date: 26/06/2008
Registration date: 31/10/2008
Last edited: 13/02/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Nicholas Hopkinson
Scientific

Royal Brompton Hospital
Fulham Road
London
SW3 6NP
United Kingdom

Phone	+44 (0)20 7349 7775
Email	n.hopkinson@ic.ac.uk

Study information

Study design	A double-blind, randomised, placebo-controlled, parallel trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Angiotensin converting enzyme (ACE) inhibition and mechanisms of skeletal muscle weakness in chronic obstructive pulmonary disease (COPD): a double-blind, randomised, placebo-controlled, parallel trial
Study objectives	That angiotensin converting enzyme (ACE) inhibition will improve muscle function in patients with chronic obstructive pulmonary disease (COPD) who have leg weakness. Muscle function will be assessed in terms of strength and endurance. Changes in muscle function (strength and endurance) will be related to changes in the molecular pathways which are thought to be involved in muscle wasting in COPD. As of 17/02/2009 this record was updated to include a change to the ACE-I drug used. more details of this can be found in the interventions section. At this time, the anticipated trial dates were also updated; the initial trial dates at the time of registration were: Initial anticipated start date: 01/10/2008 initial anticipated end date: 30/09/2011
Ethics approval(s)	The study has been approved by the Joint UCL/UCLH Committees on the Ethics of Human Research Committee Alpha on the 2nd October 2008 (ref: 08/H0715/90)
Health condition(s) or problem(s) studied	Chronic obstructive pulmonary disease (COPD)
Intervention	Amended as of 17/02/2009: 10 or 20 mg of fosinopril per day for three months, versus placebo on same administrative routine. Initial information at time of registration: Imidapril tablets (ACE-I) up to 20 mg per day for three months, versus placebo on same administrative routine.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Angiotensin converting enzyme inhibitor (ACE-I) (Imidapril)
Primary outcome measure	Primary analysis will focus on the activity of the insulin-like growth factor-1 (IGF-1) Akt pathways controlling muscle catabolism and anabolism assessed in muscle biopsies. Measurements will include phosphorylated and non-phosphorylated Akt and mammalian target of rapamycin (mTOR) as well as myogenic differentiation factor (MyoD), muscle-specific RING-finger protein (MuRF) and atrogin-1 messenger ribonucleic acid (mRNA) and protein levels. Changes in these pathways will be related to changes in muscle phenotype. These measurements will be made in muscle biopsies taken at baseline and after three months of treatment.
Secondary outcome measures	The following will be assessed in muscle biopsies taken at baseline and after three months of treatment: 1. Effect of ACE-I on quadriceps maximum voluntary contraction force 2. Effect of ACE-I on quadriceps endurance: T80 Time for force output in response to stimulation 3. Effect of ACE-I on quadriceps bulk (cross-sectional area) 4. Effect of ACE-I on systemic inflammation and serum IGF-1 At the initial screening assessment patients biopsies will have been obtained from patients who are not weak and therefore ineligible for this trial. Data from these patients will be compared cross-sectionally with the weaker patients to compare activity of the molecular pathways mentioned above and related to muscle phenotype.
Overall study start date	01/06/2009
Completion date	01/05/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	80
Key inclusion criteria	Adult patients (greater than 18 years, either sex) with COPD diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Only patients with quadriceps weakness will be enrolled into this randomised controlled trial (RCT).
Key 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) less than 50 ml/min 5. Hypotension 6. Use of anticoagulants (contraindication to biopsy) or angiotensin converting enzyme inhibitor (ACE-I) or angiotensin II (ATII) receptor antagonists 7. Allergy to ACE-I 8. Pregnancy 9. Patients who have participated in a pulmonary rehabilitation programme within the past three months
Date of first enrolment	01/06/2009
Date of final enrolment	01/05/2012

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Royal Brompton Hospital

London
SW3 6NP
United Kingdom

Sponsor information

Imperial College London (UK)
University/education

c/o Dr Gary Roper
GO2 Sir Alexander Fleming Building
South Kensington Campus
London
SW7 2AZ
England
United Kingdom

Phone	+44 (0)20 7594 1188
Email	gary.roper@imperial.ac.uk
Website	http://www3.imperial.ac.uk/
"ROR"	https://ror.org/041kmwe10

Funders

Funder type

Research council

Medical Research Council (MRC) (UK) (ref: G0701628)
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/10/2014		Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

13/02/2020: ClinicalTrials.gov number added.