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

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01014338
• Other study ID #: P15099
• Secondary ID: ISRCTN05581879
• Status: Completed
• Phase: Phase 4
• First received: November 16, 2009
• Last updated: March 24, 2015
• Start date: October 2009
• Est. completion date: September 2012

Study information

• Verified date: June 2011
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Muscle Weakness
• Paresis
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Fosinopril
10mg od

Other:
• lactose
placebo

Locations

Country	Name	City	State
United Kingdom	Royal Brompton Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	Medical Research Council

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

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. — View 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. — View 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. Epub 2004 Apr 29. — View 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. Epub 2006 Nov 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in phosphorylation of components of the atrogene pathway		3 months	No
Secondary	Quadriceps endurance assessed non-volitionally		3 months	No
Secondary	Effect of ACE-I on quadriceps maximum voluntary contraction force		3 months	No
Secondary	Effect of ACE-I on quadriceps bulk (cross-sectional area)		3 months	No
Secondary	Effect of ACE-I on systemic inflammation and serum IGF-1		3 months	No