Muscle wasting in chronic obstructive pulmonary disease (COPD): the role of resistance training and protein supplementation

ISRCTN ISRCTN22764439
DOI https://doi.org/10.1186/ISRCTN22764439
Protocol serial number MRC ref: G0501985; UHL 10146
Sponsor University Hospitals of Leicester NHS Trust (UK)
Funder Medical Research Council (ref: G0501985; grant ID: 77170)
Submission date
21/10/2009
Registration date
09/12/2009
Last edited
25/02/2015
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Michael Steiner
Scientific

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

Study information

Primary study designInterventional
Study designDouble-blind randomised placebo-controlled single-centre trial
Secondary study designRandomised controlled trial
Study type Participant information sheet
Scientific titleMolecular 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
Study objectivesThis 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(s)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
Health condition(s) or problem(s) studiedChronic obstructive pulmonary disease (COPD)
Intervention1. 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 typeMixed
Primary outcome measure(s)

Muscle gene and protein expression (vastus lateralis needle biopsy samples) at baseline, 24 hours, 4 weeks and 8 weeks.

Key secondary outcome measure(s)

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

Completion date31/10/2010

Eligibility

Participant type(s)Mixed
Age groupAdult
SexAll
Target sample size at registration120
Key inclusion criteriaFor 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
Key exclusion criteriaCOPD 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.
Date of first enrolment14/02/2007
Date of final enrolment31/10/2010

Locations

Countries of recruitment

  • United Kingdom
  • England

Study participating centre

Glenfield Hospital
Leicester
LE3 9QP
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results (inflammatory and satellite cells in the quadriceps) 01/11/2012 Yes No
Results article results (ultrasound assessment of lower limb muscle mass) 28/12/2012 Yes No
Results article results (ventilatory requirements of quadriceps resistance training) 05/06/2014 Yes No
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes
BMC - Part of Springer Nature Springer Nature