Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT01812460 |
| Other study ID # |
H-1-2012-085 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
March 14, 2013 |
| Last updated |
October 25, 2013 |
| Start date |
December 2012 |
| Est. completion date |
November 2013 |
Study information
| Verified date |
October 2013 |
| Source |
Frederikssunds Hospital, Denmark |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Denmark: Ethics Committee |
| Study type |
Interventional
|
Clinical Trial Summary
We want to test the hypothesis, that resistance training by the use of weigth cuffs on the
angle can prevent loss or improve the strength of the quadriceps muscle in COPD patients
admitted to hospital due to an exacerbation. The training is started at day one of
admittance and the strength of the quadriceps is measured by a portable dynamometer.
Description:
Background Chronic obstructive pulmonary disease (COPD) is one of the most costly chronic
diseases (1). In Denmark it can be estimated that approximately 400.000 people suffers from
COPD amounting to about 15% of the adult population. COPD causes 10.000 visits to the
emergency room, approx. 25.000 acute admissions to hospital and 3.500 deaths a year. The
disease costs approx 2 billion Danish croners (400 million dollars) a year. Hospital
admissions due to exacerbations adds to the most costly part of the disease burden to
society. COPD is one of the few chronic diseases still on the rise (1).
COPD is characterized by an accelerated decline in lung function. Most of the patients with
severe degree of COPD suffer from recurrent acute deterioration named exacerbations. An
exacerbation is defined as a deterioration in symptoms including shortness of breath and
sputum production leading to a chance in medical treatment. Frequent exacerbations are
associated with an extra high rate of decline in lung function and a strongly negative
impact on the quality of life. The disease progression is followed by a gradual loss in
muscle mass and strength (3).
Admission to hospital has well known effects on maximal oxygen consumption and a reduction
in the physical condition leads to a more severe degree of shortness of breath during
physical activity (4). Just a few days in bed is followed by an important loss of muscle
mass and strength. Immobilization causes a decrease in metabolism and a loss of active motor
units and a reduced ability to activate the resting motor units. This has a greater negative
impact on the strength in the extensors that are engaged in maintaining the upright position
than other muscle groups. In keeping with this, the loss of muscle strength occurs at twice
as high a rate in muscles of the lower limb than in those of the upper limb (5). This leads
to an increased production of lactic acid and corresponding muscle fatique (6). Muscles
engaged in knee extension loose strength at the highest rate during immobilization. This
loss has great impact on the activities of daily life such as getting out of bed, rising
from a chair and climbing stairs. Even though the patients regain their premorbide lung
function and their symptoms improve to the "normal" level usually within 6 weeks, they do
not reach their habitual level of physical activity as expressed by the 6MWT (7). Admittance
due to exacerbations is followed by muscle wasting and prolonged inactivity, leading to an
increased risk of recurrent exacerbations.
Physical training of the muscles is the most efficient treatment to maintain or increase
muscle strength to prevent muscle wasting during immobilization. Since most of the decline
in muscle strength occurs during the first days of bed rest - 3-4% per day - and most
pronounced in the muscles of the lower limb, there is god reason for early intervention with
physical training of the extensors of the lower limb, the earlier after admittance, the
better.
There is solid evidence for a positive effect of training of clinically stable COPD
patients. Only two studies have investigated the effect of training during admittance for an
acute exacerbation (8) In the study by Troosters, the training consisted of 3 sets of 8
repetitions amounting to 70% of 1 repetition maximum (1RM: repetitions maximum: the maximal
weight that can be handled only one time). The subjects had an FEV1 of 40 ± 12 % of
predicted, and were trained by the use of a knee extension machine. We do not know the exact
exclusion criteria of the study - did they include patients who were unable to move from the
bed to the knee extension machine? Did the physiotherapists handled the most severely
diseased patients differently? Moreover, it would be more general applicable, if the
training could be performed with a less demanding and expensive equipment than a knee
extension machine. Accordingly, there is a need for at study with a more detailed
description of the training procedure, using a simple, low cost training device, that is
applicable to many centers and hospital units.
Most patients suffering from a severe degree of COPD (GOLD III and IV) (3)will experience
severe shortness of breath leading to exhaustion even after very low level activities.
Unilateral resistance training of the quadriceps by the use of wrist weights is low cost,
low technology.
The pilot study at our department of pulmonary medicine, Frederikssund Hospital, including 8
severely diseased COPD patients, trained by wrist weights on average for 5 days, showed that
all patients improved their muscle strength - amounting to an average of 50%.
The study showed that progressive lower limb muscle exercise was possible even in the most
severely disabled patients on home oxygen. We do not know if the surprisingly high degree of
improvement should be ascribed to the training or other factors. Accordingly, we want to
perform a randomized controlled single blinded study to clarify if progressive resistance
training with wrist weights can improve the strength of the large extensor muscle of the
lower limb to a degree that will translate into improved physical ability after discharge
from hospital.
Randomizing The investigation is designed as a randomized, controlled, single blinded study.
Patients who fulfill the inclusion criteria and none of the exclusion criteria are invited
to participate in the study. After an initial evaluation and testing the patients are
randomized to either standard pulmonary physiotherapy and physical training (intervention
group) or standard physiotherapy without training (control group). The list of randomization
is based on a computer program. Numbers of randomization are kept in 70 closed envelopes.
The content of the envelope is disclosed only after inclusion, initial evaluation and
testing. The envelopes are numbered on the outside (a consecutive line of numbers different
from the numbers of randomization) and kept by a secretary and released in the order of
outside number.
Tests at inclusion and after 6 weeks will be performed by physiotherapists blinded to the
randomization. It is impossible to blind the physicians, nurses and physiotherapists at the
pulmonary ward.
Security and Ethics Based on the current evidence, the patients are not exposed to any kind
of risk, except that a slight degree of muscle soreness may occur following the first few
days of physical training. The study is not blinded to the physiotherapists who perform the
training, and if any problem related to training should occur, it will be easily addressed.
The present study aims at progressive physical training with cheap equipment which is easy
to handle for both the physiotherapists and the patients with minimal risk to the patients.
This adds to the importance of the study.
The control group will be treated according to usual therapeutic guidelines. The study is
reported to the local ethical committee. The patients are covered by patient insurance of
Frederikssund Hospital.
Registration of data and informed consent Data evaluation agrees to the technical demands
made by the Danish Data Protection Agency The patients are familiar with all collected data,
and information about this included in the informed consent.
All data of the study will be kept in a separate locked container in a locked room. Only the
principal investigator has access to the room and container. Data will be stores in excel,
where every patient has a unique number and all date from that particular patient is stored
under this number. The security container is obtained for the specific purpose of the study
and is in accordance with the procedures of the local region regarding login on the
internet.
The patients will be contacted by the principal investigator or another member of the staff
adequately trained for the study within 24 hours of admittance to the pulmonary ward of
Frederikssund Hospital.
The patients will receive oral information and information in writing about the study the
day of admittance, about their rights as voluntaries in a scientific study in the field of
health science. The patient will be informed about the nature of the study according to the
guidelines of The Danish Council of Ethics. The oral information is guided by the
information in writing, where every aspect of the study is explained in detail to the
patient. Informed consent is obtained the day after information after a minimum of 24 hours
of reconsideration. The patient can decide to withdraw from the study at any time during the
investigation. The investigators can also decide that a patient should be withdrawn from the
study and the reason for exclusion should be documented in the research files.
Statistics The primary aim of the study is to compare the strength of the extensor of the
thigh of the intervention group with that of the control group by an isometric contraction
test.
Calculations have showed that the need for 35 subjects in each group to be able to reveal a
difference in strength of at least 30%, with a limit of statistical significance of 5% and a
power of 80%. The power calculation is based on the expected change in extension strength
from the start of the study to discharge where it is not expected that the control group
will improve in strength. .
The applied statistical analyses (by SPSS) will be repeated measures (ANOVA) to determine a
systematic difference between muscle strenght with or without quadriceps training.
Measurements All participants are tested latest on day one after admittance, at discharge
from hospital and on an outpatient basis 6 weeks later. The day of admittance is denoted as
day 0. The 6 weeks follow up are chosen due to the belief that most COPD patients are
clinically stable 6 weeks after an exacerbation.
Economy and Time schedule The study is started up by the persons responsible for the
investigation. The study is not yet fully financed. We are planning to apply for additional
finalcial support. None of the foundations will have any connection to the drug industry and
none of the possible supporters will have any impact on the results, their interpretation or
publication.
The study will start in autumn 2012 and finished when all 70 COPD patients are included and
followed up, hopefully finished autumn 2013.
The results of the study both positive, negative and inconclusive will be reported in an
international journal of pulmonary medicine. The results will be presented at relevant
congresses both in Denmark and abroad
References
(1) Juel K, Døssing M. KOL i Danmark: sygdommen der hver dag koster 10 danskere livet. Kbh.:
Statens Institut for Folkesundhed; 2003.
(3) GOLD- Guidelines. Global Strategy for the Diagnosis, Management and Prevention of COPD,
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011.. Available at:
www.goldcopd.org. Accessed 26.06.12.
(4) Bernard S, LeBlanc P, Whittom F, Carrier G, Jobin J, Belleau R, et al. Peripheral muscle
weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med
1998 Aug;158(2):629-634.
(5) Bloomfield SA. Changes in musculoskeletal structure and function with prolonged bed
rest. Med Sci Sports Exerc 1997 Feb;29(2):197-206.
(6) Steiner MC, Evans R, Deacon SJ, Singh SJ, Patel P, Fox J, et al. Adenine nucleotide loss
in the skeletal muscles during exercise in chronic obstructive pulmonary disease. Thorax
2005 Nov;60(11):932-936.
(7) Pitta F, Troosters T, Probst VS, Spruit MA, Decramer M, Gosselink R. Physical activity
and hospitalization for exacerbation of COPD. Chest 2006 Mar;129(3):536-544.
(8) Troosters T, Probst VS, Crul T, Pitta F, Gayan-Ramirez G, Decramer M, et al. Resistance
training prevents deterioration in quadriceps muscle function during acute exacerbations of
chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010 May
15;181(10):1072-1077
