Clinical trial NCT02930421: Exercise Training in Patients With Mild COPD
Official title: Clinical and Physiological Effects of Exercise Training in Symptomatic Patients With Mild COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COPD
Keywords: mild COPD
Exercise training
Six minute walking distance
Quality of life
Saint George Respiratory Questionnaire (SGRQ)
Lead sponsor: Pontificia Universidad Catolica de Chile
Sponsor class: OTHER
First posted: 2016-10-12
Enrollment: 30
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary aim of this clinical study is to investigate if exercise training can improve exercise capacity and quality of life in dyspneic mild chronic obstructive pulmonary disease patients.

Detailed description: Peripheral muscle mass and function can be impaired in patients with mild chronic obstructive pulmonary disease (COPD). Quadriceps cross-sectional area is reduced in these patients compared to controls \[1\], particularly in those with dyspnea as compared to non-dyspneic counterparts and smoker controls \[2\]. Reduced physical activity is closely related to peripheral muscle mass in mild COPD \[1\], suggesting that early therapeutic interventions are needed in this group of patients. In addition, reduced quadriceps mass is strongly associated to quadriceps weakness \[3,4\] and a substantial proportion of patients with mild COPD (28%) had quadriceps weakness \[5\]. Reduced muscle mass and resultant muscle weakness contribute to limiting exercise in COPD \[6-8\] and to reduce physical activity, particularly in mild disease \[1\].

Exercise training (ET) is widely used in patients with moderate-to-very-severe COPD to improve peripheral muscle function and thus exercise capacity and quality of life \[9\]. Unfortunately, the effects of ET in mild COPD are currently unclear. A recent systematic review identified three low-quality studies with different designs (retrospective, one group pre-posttest, and one randomized controlled trial) \[10\]. The authors found significant improvements in exercise capacity (effect size 0.87-1.82) and quality of life (effect size 0.24-0.86) after comparing pretest-posttest data and ET with usual care. Although these results are inconclusive and indicate that additional and more robust studies should be conducted \[10\], current recommendations to initiate ET include even mild disease if dyspnea or exercise limitation are present \[11\]. Since peripheral muscle mass and function improve with ET \[9\], the investigators hypothesize that this statement is correct and consequently ET will increase exercise capacity in dyspneic patients with mild COPD in comparison to usual care.

Patients will enter an 8-week ET program of 3 days per week supervised exercise training at the Rehabilitation Physiotherapy Gymnasium. Exercise training will include high-intensity endurance training at 60-80% of baseline peak work rate and strength training of upper and lower limbs with 3 sets of 6 repetitions at 50% of one repetition maximum \[12,13\]. Each session will be 60 min duration, 30 min dedicated to cycle exercise. The UC group will receive usual outpatient care and follow-up.

The study will require 30 patients per arm to detect an effect size of 0.88 \[10\] at the 5% significance level and with 80% power, allowing a dropout rate of 30%.

Eligibility criteria: Inclusion Criteria:

* male or female subjects, aged 45-80 years
* baseline post-bronchodilator forced expiratory volume at one second (FEV1) ≥80% of predicted normal and baseline (post-bronchodilator) FEV1/forced vital capacity (FVC) ≤70%
* current or ex-smokers with a smoking history of at least 10 pack-years
* dyspnea during activities of daily life, defined as modified Medical Research Council (mMRC) scale \[0-4 points\] ≥1 point

Exclusion Criteria:

* history of asthma or other chronic lung disease (e.g.: interstitial lung disease; sarcoidosis; tuberculosis; cystic fibrosis; bronchiectasis; previous lung resection)
* comorbidities that would prevent the patient from performing an exercise test (including psychological or cognitive disorders): chronic congestive heart failure; recent myocardial infarction \[6 months or less\]; cardiac arrhythmia requiring drug therapy; neuromuscular and peripheral vascular diseases
* the presence of usual co-morbidities, such as essential hypertension, diabetes, osteoporosis, hypothyroidism, under proper medical control, and obesity, excluding extreme obesity, will not be considered an exclusion criterion.

Primary outcomes:
measure: Change in the six minute walking distance
timeFrame: Baseline and 8 weeks
Secondary outcomes:
measure: Change in disease specific quality of life (SGRQ)
timeFrame: Baseline and 8 weeks
measure: Change in exercise time during constant-load cycle exercise
timeFrame: Baseline and 8 weeks
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Respiratory Department; Hospital Clinico Universidad Catolica
Study officials:
affiliation: Departamento de Enfermedades Respiratorias
name: Orlando Díaz
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shrikrishna D, Patel M, Tanner RJ, Seymour JM, Connolly BA, Puthucheary ZA, Walsh SL, Bloch SA, Sidhu PS, Hart N, Kemp PR, Moxham J, Polkey MI, Hopkinson NS. Quadriceps wasting and physical inactivity in patients with COPD. Eur Respir J. 2012 Nov;40(5):1115-22. doi: 10.1183/09031936.00170111. Epub 2012 Feb 23.
citation: Diaz AA, Morales A, Diaz JC, Ramos C, Klaassen J, Saldias F, Aravena C, Diaz R, Lisboa C, Washko GR, Diaz O. CT and physiologic determinants of dyspnea and exercise capacity during the six-minute walk test in mild COPD. Respir Med. 2013 Apr;107(4):570-9. doi: 10.1016/j.rmed.2012.12.011. Epub 2013 Jan 9.
citation: Bernard S, LeBlanc P, Whittom F, Carrier G, Jobin J, Belleau R, Maltais F. Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 Aug;158(2):629-34. doi: 10.1164/ajrccm.158.2.9711023.
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citation: Seymour JM, Spruit MA, Hopkinson NS, Natanek SA, Man WD, Jackson A, Gosker HR, Schols AM, Moxham J, Polkey MI, Wouters EF. The prevalence of quadriceps weakness in COPD and the relationship with disease severity. Eur Respir J. 2010 Jul;36(1):81-8. doi: 10.1183/09031936.00104909. Epub 2009 Nov 6.
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