Contact information
Type
Scientific
Primary contact
Dr Michael Steiner
ORCID ID
Contact details
Consultant Respiratory Physician
University Hospitals of Leicester NHS Trust
Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom
+44 (0)116 256 3450
michael.steiner@uhl-tr.nhs.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
MRC ref: G0501985; UHL 10146
Study information
Scientific title
Molecular approaches to reversing skeletal muscle wasting in chronic obstructive pulmonary disease (COPD): the role of resistance training and protein supplementation - a double-blind randomised placebo-controlled trial
Acronym
Study hypothesis
This project will test the following principal hypotheses:
1. That muscle wasting in chronic obstructive pulmonary disease (COPD) is characterised by alterations in the expression of catabolic and anabolic genes (mRNA) and signalling pathways (protein and protein phosphorylation) that have been implicitly associated with the regulation of skeletal muscle protein degradation and synthesis when compared with non-wasted COPD patients, and similar aged healthy controls.
2. That a carefully controlled resistance training programme known to restore muscle mass in immobilised young healthy humans will have similar restorative effects in COPD patients and that these benefits will be mediated through changes in these candidate gene and signalling pathways. We will also determine how these effects differ between wasted and non wasted COPD patients and between patients and healthy controls.
3. That changes in the expression and activation of these regulatory pathways occurs early (within 24 hours) from the onset of rehabilitation as was seen following limb immobilisation in young healthy subjects.
4. That the positive effects of resistance training on skeletal muscle mass in COPD patients can be augmented when training is combined with dietary protein supplementation.
More details can be found at the following links:
UK Clinical Research Network Study Portfolio: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=4049
MRC research portfolio: http://www.mrc.ac.uk/ResearchPortfolio/Grant/Record.htm?GrantRef=G0501985&CaseId=6937
Ethics approval
1. Leicestershire, Northamptonshire & Rutland Research Ethics Committee 1, 26/09/2006, ref: 06/Q2501/138
2. University Hospitals of Leicester (UHL) NHS Trust R&D, 05/01/2007, ref: 10146
3. Leicester City Primary Care Trust (PCT), 12/02/2008, ref: LNR PCRA 0696
Study design
Double-blind randomised placebo-controlled single-centre trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Chronic obstructive pulmonary disease (COPD)
Intervention
1. Resistance training: The training programme will last 8 weeks and comprise three supervised half-hour lower limb resistance training sessions per week. Training will take place on an isokinetic dynamometer (Cybex II Norm: CSMi, USA). Subjects will perform 5 sets of 30 maximal knee extensions performed at 180 degrees/sec. Sets will be separated by 1 minute rest. Both legs will be trained.
2. Protein supplementation: COPD patients will be randomly allocated to receive a dietary protein (with carbohydrate) supplement or placebo throughout training. Healthy volunteers will receive a placebo. The supplement will contain 19 g protein and 49 g carbohydrate (Vitargo® Gainers Gold: Swecarb, Sweden) made up to 500 ml of water. The placebo will be an identical volume non-nutritive and non-caloric drink. Supplementation will take place immediately following each training session, as the timing of protein intake appears to be critical.
Intervention type
Mixed
Phase
Drug names
Primary outcome measures
Muscle gene and protein expression (vastus lateralis needle biopsy samples) at baseline, 24 hours, 4 weeks and 8 weeks.
Secondary outcome measures
1. Muscle strength (isometric and isokinetic quadriceps strength) at baseline, 4 weeks, 8 weeks and 6 months
2. Total body and quadriceps fat-free (muscle) mass (dual energy X-ray absorptiometry [DEXA]) at baseline, 4 weeks and 8 weeks
3. Circulating inflammatory cytokines (blood tests) at baseline, 24 hours, 4 weeks and 8 weeks
4. Whole-body exercise performance (incremental cycle ergometry test) at baseline and 8 weeks
5. Physical activity (questionnaire and activity monitor) at baseline and 8 weeks
6. Lung function and capillary blood gas tensions at baseline
Overall trial start date
14/02/2007
Overall trial end date
31/10/2010
Reason abandoned
Eligibility
Participant inclusion criteria
For both COPD subjects and healthy control subjects:
1. Both males and females, aged between 50-85 years
COPD subjects:
1. Moderate-severe airflow obstruction (Forced expiratory volume in one second [FEV1] <50% predicted, FEV1/forced vital capacity [FVC] ratio <70%)
2. Reduced exercise tolerance (MRC grades III-V)
3. Stable
4. Able to carry out lower-limb resistance training
Healthy age-matched control subjects:
1. No evidence of airflow obstruction (FEV1 >80% predicted)
2. Able to carry out lower-limb resistance training
Participant type
Mixed
Age group
Adult
Gender
Both
Target number of participants
120
Participant exclusion criteria
COPD subjects:
1. Long-term oral corticosteriods
2. Anticoagulant therapy or disorders
3. long term oxygen therapy (LTOT)
4. Diabetes
5. Co-morbid conditions preventing exercise training
6. Subects who have completed pulmonary rehabilitation in the previous 12-months
Healthy age-matched controls:
Same as for COPD subjects, also those who meet the criteria for fat-free mass depletion are excluded.
Recruitment start date
14/02/2007
Recruitment end date
31/10/2010
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Glenfield Hospital
Leicester
LE3 9QP
United Kingdom
Sponsor information
Organisation
University Hospitals of Leicester NHS Trust (UK)
Sponsor details
Research & Development Offices
Leicester General Hospital
Gwendolen Road
Leicester
LE5 4PW
United Kingdom
+44 (0)116 258 4109
carolyn.maloney@uhl-tr.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
Medical Research Council (ref: G0501985; grant ID: 77170)
Alternative name(s)
MRC
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2012 results (inflammatory and satellite cells in the quadriceps) in http://www.ncbi.nlm.nih.gov/pubmed/22459782
2012 results (ultrasound assessment of lower limb muscle mass) in http://www.ncbi.nlm.nih.gov/pubmed/23273255
2014 results (ventilatory requirements of quadriceps resistance training) in http://www.ncbi.nlm.nih.gov/pubmed/24940055
Publication citations
-
Menon MK, Houchen L, Singh SJ, Morgan MD, Bradding P, Steiner MC, Inflammatory and satellite cells in the quadriceps of patients with COPD and response to resistance training., Chest, 2012, 142, 5, 1134-1142, doi: 10.1378/chest.11-2144.
-
Menon MK, Houchen L, Harrison S, Singh SJ, Morgan MD, Steiner MC, Ultrasound assessment of lower limb muscle mass in response to resistance training in COPD., Respir. Res., 2012, 13, 119, doi: 10.1186/1465-9921-13-119.
-
Results
Houchen-Wolloff L, Sandland CJ, Harrison SL, Menon MK, Morgan MD, Steiner MC, Singh SJ, Ventilatory requirements of quadriceps resistance training in people with COPD and healthy controls, Int J Chron Obstruct Pulmon Dis, 2014, 9, 589-595, doi: 10.2147/COPD.S59164.