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

This study has been completed.
Sponsor:
Collaborator:
Medical Research Council
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01014338
First received: November 16, 2009
Last updated: March 24, 2015
Last verified: June 2011
  Purpose

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 Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Fosinopril
Other: lactose
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: ACE-inhibition and Mechanisms of Skeletal Muscle Weakness in Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Changes in phosphorylation of components of the atrogene pathway [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Quadriceps endurance assessed non-volitionally [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Effect of ACE-I on quadriceps maximum voluntary contraction force [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Effect of ACE-I on quadriceps bulk (cross-sectional area) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Effect of ACE-I on systemic inflammation and serum IGF-1 [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: October 2009
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ACE-inhibitor Drug: Fosinopril
10mg od
Placebo Comparator: Sugar Pill Other: lactose
placebo

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01014338

Locations
United Kingdom
Royal Brompton Hospital
London, United Kingdom, SW3 6NP
Sponsors and Collaborators
Imperial College London
Medical Research Council
Investigators
Principal Investigator: Nicholas S Hopkinson, MRCP, PhD Imperial College London
  More Information

Publications:
Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01014338     History of Changes
Other Study ID Numbers: P15099  ISRCTN05581879 
Study First Received: November 16, 2009
Last Updated: March 24, 2015
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Muscle Weakness
Paresis
Respiratory Tract Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathologic Processes
Signs and Symptoms
Fosinopril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents

ClinicalTrials.gov processed this record on December 02, 2016