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

Condition(s) targeted: Chronic Obstructive Pulmonary Disease

Intervention: Fosinopril (Drug); lactose (Other)

Phase: Phase 4

Status: Recruiting

Sponsored by: Imperial College London

Official(s) and/or principal investigator(s):
Nicholas S Hopkinson, MRCP, PhD, Principal Investigator, Affiliation: Imperial College London

Overall contact:
Dinesh Shrikrishna, BSc, MRCP, Phone: 0207 351 8029, Email: d.shrikrishna@ic.ac.uk

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.

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

Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Changes in phosphorylation of components of the atrogene pathway

Secondary outcome:

Quadriceps endurance assessed non-volitionally

Effect of ACE-I on quadriceps maximum voluntary contraction force

Effect of ACE-I on quadriceps bulk (cross-sectional area)

Effect of ACE-I on systemic inflammation and serum IGF-1

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Dinesh Shrikrishna, BSc, MRCP, Phone: 0207 351 8029, Email: d.shrikrishna@ic.ac.uk

Royal Brompton Hospital, London SW3 6NP, United Kingdom; Recruiting
Dinesh Shrikrishna, BSc, MRCP, Phone: 0207 351 8029
Nicholas S Hopkinson, MRCP, PhD, Principal Investigator
Dinesh Shrikrishna, BSc, MRCP, Sub-Investigator

Related publications:

Hopkinson NS, Nickol AH, Payne J, Hawe E, Man WD, Moxham J, Montgomery H, Polkey MI. Angiotensin converting enzyme genotype and strength in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004 Aug 15;170(4):395-9. Epub 2004 Apr 29.

Swallow EB, Reyes D, Hopkinson NS, Man WD, Porcher R, Cetti EJ, Moore AJ, Moxham J, Polkey MI. Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary disease. Thorax. 2007 Feb;62(2):115-20. Epub 2006 Nov 7.

Hopkinson NS, Eleftheriou KI, Payne J, Nickol AH, Hawe E, Moxham J, Montgomery H, Polkey MI. +9/+9 Homozygosity of the bradykinin receptor gene polymorphism is associated with reduced fat-free mass in chronic obstructive pulmonary disease. Am J Clin Nutr. 2006 Apr;83(4):912-7.

Andreas S, Herrmann-Lingen C, Raupach T, Lüthje L, Fabricius JA, Hruska N, Körber W, Büchner B, Criée CP, Hasenfuss G, Calverley P. Angiotensin II blockers in obstructive pulmonary disease: a randomised controlled trial. Eur Respir J. 2006 May;27(5):972-9. Epub 2006 Jan 30.

Starting date: October 2009
Last updated: June 22, 2011