ACE inhibition and mechanisms of skeletal muscle weakness in COPD

• Research type

  Research Study

• Full title

  ACE inhibition and mechanisms of skeletal muscle weakness in COPD

• IRAS ID

  4420

• Sponsor organisation

  Imperial College, Faculty of Medicine

• Eudract number

  2008-004431-38

• ISRCTN Number

  n/a

• Research summary

  Lay Summary: Chronicobstructive pulmonary disease (COPD) is a major public health problem in the UK andworldwide. As well as being a lung disease COPD has well-recognised andimportant consequences for other parts of the body, and these contribute tothe enormous burden of disabilityassociated with the condition. Muscle weakness is one of these consequences,and is associated with reduced exercise capacity, reduced quality of life andincreased mortality. Since efforts to treat the lung disease have to date hadlimited impact it is important to address the systemic complications of thedisease directly. The molecular pathways involved in muscle wasting aregradually becoming understood. An important signalling pathway in muscle linksthe hormone insulin-like growth factor with the production of ??atrogenes?? whichare substances that mark muscle proteins for breakdown. There is evidence inanimal models that this could be influenced by drugs called angiotensinconverting enzyme inhibitors (ACE-I). This class of drugs are widely used forthe treatment of high blood pressure and heart failure, and in fact patientsprescribed these drugs for that reason have better preservation of limb musclethan those who receive another class of drug. We are testing this possibilityin humans by performing a placebo controlled study of an ACE inhibitor in 70patients with COPD who have leg muscle weakness. We will measure quadricepsmuscle endurance using a repetitive magnetic stimulator before treatment andthen after three months on either treatment or placebo. A small sample ofmuscle will be taken before and after treatment to allow us to study themolecular mechanisms involved. We hypothesise that ACE inhibitors will cause areduction in atrogene levels and that this will occur in tandem with anincrease in quadriceps strength and endurance. If this is the case it wouldopen the way for a much larger study tosee if use of ACE inhibitors could improve exercise capacity and quality oflife in people with COPD.

• REC name

  London - Harrow Research Ethics Committee

• REC reference

  08/H0715/90

• Date of REC Opinion

  14 Oct 2008

• REC opinion

  Further Information Favourable Opinion