Condition category
Respiratory
Date applied
26/06/2008
Date assigned
31/10/2008
Last edited
24/02/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

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 (0)20 7349 7775
n.hopkinson@ic.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MRC ref: G0701628; IC-DHTAX_P15099

Study information

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

Acronym

Study hypothesis

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

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)

Study design

A double-blind, randomised, placebo-controlled, parallel 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

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

Phase

Not Specified

Drug names

Angiotensin converting enzyme inhibitor (ACE-I) (Imidapril)

Primary outcome measures

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 trial start date

01/06/2009

Overall trial end date

01/05/2012

Reason abandoned

Eligibility

Participant 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).

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) 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

Recruitment start date

01/06/2009

Recruitment end date

01/05/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Brompton Hospital
London
SW3 6NP
United Kingdom

Sponsor information

Organisation

Imperial College London (UK)

Sponsor details

c/o Dr Gary Roper
GO2 Sir Alexander Fleming Building
South Kensington Campus
London
SW7 2AZ
United Kingdom
+44 (0)20 7594 1188
gary.roper@imperial.ac.uk

Sponsor type

University/education

Website

http://www3.imperial.ac.uk/

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) (UK) (ref: G0701628)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

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

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24556825

Publication citations

  1. Results

    Shrikrishna D, Tanner RJ, Lee JY, Natanek A, Lewis A, Murphy PB, Hart N, Moxham J, Montgomery HE, Kemp PR, Polkey MI, Hopkinson NS, A Randomized Controlled Trial of ACE-inhibition for Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease., Chest, 2014, doi: 10.1378/chest.13-2483.

Additional files

Editorial Notes