Angiotensin-converting Enzyme (ACE)-Inhibition and Mechanisms of Skeletal Muscle Weakness in Chronic Obstructive Pulmonary Disease (COPD)

Sponsor

Imperial College London (Other)

Overall Status

Completed

CT.gov ID

NCT01014338

Collaborator

Medical Research Council (Other)

Enrollment

Location

Arms

Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A double blind randomised placebo controlled parallel trial of the effect of fosinopril, an angiotensin converting enzyme inhibitor, on the quadriceps muscle in 80 COPD patients who have quadriceps weakness. Patients will have a baseline assessment including measures of quadriceps strength and endurance and a quadriceps biopsy. Patients with weakness will be randomised to ACE inhibitor or placebo and re-assessed after three months of treatment.

The investigators aim to show that ACE-inhibition will alter the IGF-1/AKT/FoXO/atrogene pathways involved in muscle wasting in COPD.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Fosinopril Other: lactose	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

ACE-inhibition and Mechanisms of Skeletal Muscle Weakness in Chronic Obstructive Pulmonary Disease

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Sep 1, 2012

Actual Study Completion Date :

Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ACE-inhibitor	Drug: Fosinopril 10mg od
Placebo Comparator: Sugar Pill	Other: lactose placebo

Arm

Intervention/Treatment

Active Comparator: ACE-inhibitor

Drug: Fosinopril

10mg od

Placebo Comparator: Sugar Pill

Other: lactose

placebo

Outcome Measures

Primary Outcome Measures

Changes in phosphorylation of components of the atrogene pathway [3 months]

Secondary Outcome Measures

Quadriceps endurance assessed non-volitionally [3 months]
Effect of ACE-I on quadriceps maximum voluntary contraction force [3 months]
Effect of ACE-I on quadriceps bulk (cross-sectional area) [3 months]
Effect of ACE-I on systemic inflammation and serum IGF-1 [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patient with COPD diagnosed according to GOLD criteria.

Exclusion Criteria:

Clinically unstable patients (within one month of exacerbation), those with a permanent pacemaker (which is a contraindication to magnetic stimulation), or significant co-morbidity, patients with an accepted indication for ACE inhibition (left ventricular dysfunction, diabetes) or a contraindication such as renovascular disease; creatinine clearance (estimated) <50); hypotension; use of anticoagulants (contra-indication to biopsy) or ACE-I or ATII receptor antagonists.
Allergy to ACE-inhibitors.
Pregnancy.

Patients will not be enrolled within three months of participation in a pulmonary rehabilitation program.