Back to resultsAngiotensin-converting Enzyme (ACE)-Inhibition and Mechanisms of Skeletal Muscle Weakness in Chronic Obstructive Pulmonary Disease (COPD)
Primary Purpose
Chronic Obstructive Pulmonary Disease
Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Fosinopril
lactose
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease
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.
Sites / Locations
- Royal Brompton Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
ACE-inhibitor
Sugar Pill
Arm Description
Outcomes
Primary Outcome Measures
Changes in phosphorylation of components of the atrogene pathway
Secondary Outcome Measures
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
Full Information
NCT ID
NCT01014338
First Posted
November 16, 2009
Last Updated
March 24, 2015
Sponsor
Imperial College London
Collaborators
Medical Research Council
1. Study Identification
Unique Protocol Identification Number
NCT01014338
Brief Title
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
2. Study Status
Record Verification Date
June 2011
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
September 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
Collaborators
Medical Research Council
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ACE-inhibitor
Arm Type
Active Comparator
Arm Title
Sugar Pill
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Fosinopril
Intervention Description
10mg od
Intervention Type
Other
Intervention Name(s)
lactose
Intervention Description
placebo
Primary Outcome Measure Information:
Title
Changes in phosphorylation of components of the atrogene pathway
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Quadriceps endurance assessed non-volitionally
Time Frame
3 months
Title
Effect of ACE-I on quadriceps maximum voluntary contraction force
Time Frame
3 months
Title
Effect of ACE-I on quadriceps bulk (cross-sectional area)
Time Frame
3 months
Title
Effect of ACE-I on systemic inflammation and serum IGF-1
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicholas S Hopkinson, MRCP, PhD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Brompton Hospital
City
London
ZIP/Postal Code
SW3 6NP
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
15117739
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.
Results Reference
background
PubMed Identifier
17090575
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.
Results Reference
background
PubMed Identifier
16600946
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.
Results Reference
background
PubMed Identifier
16446313
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.
Results Reference
background
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Angiotensin-converting Enzyme (ACE)-Inhibition and Mechanisms of Skeletal Muscle Weakness in Chronic Obstructive Pulmonary Disease (COPD)
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