Chronic Obstructive Pulmonary Disease (COPD)NCT02221804
The Effect of Two Weeks of Voluntary Reduced Physical Activity in Chronic Obstructive Pulmonary Disease (COPD)
A study testing 14 days of voluntary step count reduction to no more than 1500 steps/day. in people with Chronic Obstructive Pulmonary Disease (COPD) and Muscle Atrophy, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease (COPD), Muscle Atrophy
- What is being tested?
- 14 days of voluntary step count reduction to no more than 1500 steps/day.
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2014to May 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Brompton & Harefield NHS Foundation Trust
London, SW3 6NP
Sara Kladidis, MB BS MRCP, 02073518029, s.kladidis@rbht.nhs.uk
Michael Polkey, FRCP PhD
About this study
Official title: 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.
Read more
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.
Read the detailed description
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.
- Being tested
- 14 days of voluntary step count reduction to no more than 1500 steps/day.
- Keywords
- Physical Inactivity, Skeletal Muscle, Cachexia
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Muscular Atrophy, Sedentary Behavior, Cachexia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
14 days of voluntary step count reduction to no more than 1500 steps/day.Behavioural
| Study group | Role | What they receive |
|---|---|---|
| COPD - reduced activity levels | Experimental | COPD patients who have voluntarily decreased their daily physical activity levels to no more than 1500 steps/day for 14 days. Receives: Behavioral: 14 days of voluntary step count reduction to no more than 1500 steps/day. |
| Healthy - reduced activity levels | Experimental | Healthy age-matched controls who have voluntarily decreased their daily physical activity levels to no more than 1500 steps/day for 14 days. Receives: Behavioral: 14 days of voluntary step count reduction to no more than 1500 steps/day. |
| COPD - unchanged activity levels | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Change from baseline in quadriceps muscle mass at 14 days.
Secondary outcomes (6)
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.
Measured: Before and after the 14 day intervention
Rectus Femoris Cross Sectional Area determined by Quadriceps Ultrasound (RFCSA US)
An ultrasound (US) scan is a painless test that uses sound waves to create images of organs and structures. We will use it to assess the thickness of the thigh muscles.
The patient rests in a reclined position for this test, and a lubricating jelly is applied to the thigh. The US probe is moved over the thigh area to produce a picture of the size of the thigh muscle. The leg to be scanned will be the same leg used for QMVC.
The units of measure for the RFCSA are cm2.
Measured: Before and after the 14 day intervention
6 minute walk distance (6MWD)
The 6MWD is a practical and simple test that measures the distance that a subject can walk quickly on a flat, hard surface in a period of 6 minutes. This will be performed by appropriately trained study site personnel.
The outcome of the 6MWD will the walking distance covered in meters. The test will be performed according to the ATS Guidelines, in a standardized manner.
Measured: Before and after the 14 day intervention
Short Physical Performance Battery (SPPB)
The SPPB is a brief performance test used to assess how well a subject can perform simple movements that represent the foundation of daily activities. The components that are assessed are 1) a Standing Balance Test, 2) a Four Meter Gait Speed and 3) a Sit to Stand Test. This collection of tests is routinely used in gerontology.
It is scored out of a total of 12 points (4 for each of the 3 parameters aforementioned).
Measured: Before and after the 14 day intervention
Blood and urinary biomarkers
Serum and plasma aliquots will be prepared from the blood samples for mediator analysis. Analysis will include full blood count, urea and electrolytes, d-dimers, and markers of systemic inflammation (C-reactive protein \& fibrinogen). Each donation of blood will not exceed 50mL per study visit.
Urine samples will be collected and frozen. These will be available for testing potentially relevant biomarkers which may come under investigation within our group.
Measured: Before and after the 14 day intervention
Atrophy signalling determined from muscle biopsies
Muscle biopsies will be taken from the leg quadriceps muscle. These will be assessed for the presence of atrophy and hypertrophy signalling changes. The exact signalling panel will be determined from the most current literature review but is likely to include atrophic markers including myostatin, atrogin and MURF-1, hypertrophic markers including GSK3b, p70S6K and 4E-BP1, together with related microRNAs currently under investigation in our group.
Measured: Before and after the 14 day intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2014 (estimated)
- Study startMay 2014
- Primary completionApr 2016 (estimated)
- Study completionMay 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Pulmonary Disease (COPD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Polkey, FRCP PhD, Principal investigator, Royal Brompton & Harefield NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02221804
- Sponsor's protocol ID
- 2014LF002B
- Status last verified
- Aug 2014
- First submitted
- 18 Aug 2014
- Last updated
- 22 Aug 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Two Weeks of Voluntary Reduced Physical Activity in COPD - A Novel Methodology for Anabolic Drug Development
- ClinicalTrials.gov ID
- NCT02221804
- Acronym / sponsor ID
- 2014LF002B
- Keywords
- Physical Inactivity, Skeletal Muscle, Cachexia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation TrustUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- Apr 2016 (estimated)
- Study completion
- May 2016 (estimated)
- First posted
- 20 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| COPD - reduced activity levels | Experimental | Behavioral: 14 days of voluntary step count reduction to no more than 1500 steps/day.COPD patients who have voluntarily decreased their daily physical activity levels to no more than 1500 steps/day for 14 days. |
| Healthy - reduced activity levels | Experimental | Behavioral: 14 days of voluntary step count reduction to no more than 1500 steps/day.Healthy age-matched controls who have voluntarily decreased their daily physical activity levels to no more than 1500 steps/day for 14 days. |
| COPD - unchanged activity levels | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 14 days of voluntary step count reduction to no more than 1500 steps/day. | Behavioural | COPD - reduced activity levels, Healthy - reduced activity levels |
Primary outcome
Quadriceps muscle mass as measured by dual-energy x-ray absorptiometry (DEXA) after two weeks of voluntary reduced physical activity.
Time frame: Change from baseline in quadriceps muscle mass at 14 days.
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).
6 secondary outcomes
Quadriceps strength determined as maximal voluntary contraction force (QMVC) and the force elicited by unpotentiated supramaximal stimulation of the femoral nerve (TwQ).
Time frame: Before and after the 14 day intervention
Rectus Femoris Cross Sectional Area determined by Quadriceps Ultrasound (RFCSA US)
Time frame: Before and after the 14 day intervention
6 minute walk distance (6MWD)
Time frame: Before and after the 14 day intervention
Short Physical Performance Battery (SPPB)
Time frame: Before and after the 14 day intervention
Blood and urinary biomarkers
Time frame: Before and after the 14 day intervention
Atrophy signalling determined from muscle biopsies
Time frame: Before and after the 14 day intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Polkey, FRCP PhD principal investigator
Royal Brompton & Harefield NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 14 days of voluntary step count reduction to no more than 1500 steps/day. in people with Chronic Obstructive Pulmonary Disease (COPD) and Muscle Atrophy, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sara Kladidis, MB BS MRCP (02073518029, s.kladidis@rbht.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quadriceps muscle mass as measured by dual-energy x-ray absorptiometry (DEXA) after two weeks of voluntary reduced physical activity. (time frame: Change from baseline in quadriceps muscle mass at 14 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2014.