Chronic obstructive pulmonary disease (COPD) Respiratory Other chronic obstructive pulmonary disease
Conditions
Interventions
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 registratio
Sponsors
Imperial College London (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
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).
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
United Kingdom
Outcome results
None listed