The Effect of Two Weeks of Voluntary Reduced Physical Activity in COPD - A Novel Methodology for Anabolic Drug Development
The Effect of Two Weeks of Voluntary Reduced Physical Activity in COPD - A Novel Methodology for Anabolic Drug Development
Chronic Obstructive Pulmonary Disease (COPD) is the most common pulmonary disease, responsible for considerable morbidity and mortality and is the third leading cause of death worldwide. As well as its consequences in the lungs, COPD is well recognized to be associated with a range of important systemic consequences and co-morbidities. Interestingly, skeletal muscle dysfunction is noted in both early and advanced disease, suggesting its origins may not be wholly pulmonary.
Treatment strategies targeting lung function are, unfortunately, of limited value. Given the burden of disease, it is becoming increasingly important that investigative and therapeutic work now focuses on other systemic characteristics and sequelae which define the disease phenotype.
This is a randomized controlled trial of the effect of 14 days of voluntary reduced activity on muscle mass, muscle strength, body composition, and atrophy signalling in patients with COPD and age-matched controls.
The primary hypothesis upon which this study is based is that a short reduction in ambulation will induce a transient reduction in quadriceps muscle mass, quadriceps strength and physical performance in patients with COPD compared to matched COPD patients whose mobility has not been restricted.
The secondary hypothesis is that the magnitude of the above changes will be greater in physically inactive COPD patients compared to physically inactive age-matched controls.
The overall aim of this research is to use an in vivo human model of 14 days of voluntary reduced physical activity to test the above hypotheses. If the model proves feasible, this will allow for earlier proof of concept studies of novel therapeutic agents.
This is a non-commercial randomized controlled trial. 15 patients with COPD and 15 age-matched controls will voluntarily reduce their daily step-count to no more than 1500 steps/day, from a baseline of > 3500 steps/day.
Before and after 14 days of reduced daily step-count, these 30 participants will undergo measures of appendicular mass, quadriceps strength, exercise tolerance and blood and urinary biomarkers. Quadriceps muscle biopsies will also be taken before and after the 14-day intervention.
15 patients with COPD will be studied 14 days apart but will not undergo the intervention.
Inclusion Criteria:
Exclusion Criteria:
s.kladidis@rbht.nhs.uk02073518029