The Effect of Two Weeks of Voluntary Reduced Physical Activity in Chronic Obstructive Pulmonary Disease (COPD)

Royal Brompton & Harefield NHS Foundation Trust45 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Non-smoking adult patients with COPD (GOLD stage II-IV) * Non-smoking, healthy, age-matched controls * Baseline step count \> 3500 steps/day * Baseline 6 minute walk distance \> 140m Exclusion Criteria: * Inability to provide written, informed consent * Significant co-morbidity limiting exercise tolerance * Within 1 month of acute exacerbation of COPD * Within 1 month of pulmonary rehabilitation * History of venous thrombo-embolism or known increased risk of thrombotic disease

Outcomes

Primary Outcomes

Quadriceps muscle mass as measured by dual-energy x-ray absorptiometry (DEXA) after two weeks of voluntary reduced physical activity.

Dual-energy X-ray absorptiometry (DEXA) scanning will be used to assess body composition. Two X-ray beams with different energy levels are used during this technique. It is a widely used scanning modality and is entirely painless. The radiation received by the patient during the scan is less than that of an airline flight from California to New York and back. Specifically, appendicular lean composition will be measured (g).

Time frame: Change from baseline in quadriceps muscle mass at 14 days.

Secondary Outcomes

Quadriceps strength determined as maximal voluntary contraction force (QMVC) and the force elicited by unpotentiated supramaximal stimulation of the femoral nerve (TwQ).

Subjects sit on a specially designed chair keeping the knee flexed at 90 degrees over the end. Force is measured via an inextensible strap placed around the ankle and connected to a strain gauge. Subjects are asked to extend their knee maximally against the strap with visual feedback and verbal encouragement from the investigator, until no further increased in QMVC occurs. QMVC is reported in kg and is the highest single value obtained. In addition, the strength and endurance of the quadriceps will be measured using magnetic femoral nerve stimulation (TwQ). This is used to determine muscle strength in a non-volitional manner. The nerve to be studied is depolarised by the application of a rapidly changing magnetic field produced by a coil positioned on the overlying skin surface. The magnetic field is relatively unimpeded by skin, fat and bone, and thus has the ability to stimulate deep nerves easily and with little discomfort.