Condition category
Respiratory
Date applied
21/10/2009
Date assigned
09/12/2009
Last edited
25/02/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.uhl-tr.nhs.uk

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

  1. 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.

  2. 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.

  3. 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.

Additional files

Editorial Notes