Clinical trial NCT01014338: Angiotensin-converting Enzyme (ACE)-Inhibition and Mechanisms of Skeletal Muscle Weakness in Chronic Obstructive Pulmonary Disease (COPD)
Official title: ACE-inhibition and Mechanisms of Skeletal Muscle Weakness in Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Medical Research Council
First posted: 2009-11-17
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Changes in phosphorylation of components of the atrogene pathway
timeFrame: 3 months
Secondary outcomes:
measure: Quadriceps endurance assessed non-volitionally
timeFrame: 3 months
measure: Effect of ACE-I on quadriceps maximum voluntary contraction force
timeFrame: 3 months
measure: Effect of ACE-I on quadriceps bulk (cross-sectional area)
timeFrame: 3 months
measure: Effect of ACE-I on systemic inflammation and serum IGF-1
timeFrame: 3 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
affiliation: Imperial College London
name: Nicholas S Hopkinson, MRCP, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1164/rccm.200304-578OC. Epub 2004 Apr 29.
citation: 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. doi: 10.1136/thx.2006.062026. Epub 2006 Nov 7.
citation: 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. doi: 10.1093/ajcn/83.4.912.
citation: Andreas S, Herrmann-Lingen C, Raupach T, Luthje L, Fabricius JA, Hruska N, Korber W, Buchner B, Criee 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. doi: 10.1183/09031936.06.00098105. Epub 2006 Jan 30.