Effect and Feasibility of Non-linear Periodized Resistance Training in People With COPD

Study Overview
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Brief Summary
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This study aims at improving the knowledge about resistance training for people with COPD. Resistance training is an important part of pulmonary rehabilitation when the goal is to improve muscular endurance and strength. The study will evaluate the effects and the feasibility of two resistance training programs for people with COPD using a parallel group design. One program will include a larger day-to-day variation (i.e. non-linear periodization) and the progression will be guided by ratings of dyspnea, muscle fatigue, and exertion. The other program will follow the established guidelines for resistance training for people with COPD. The programs will be evaluated for effects regarding muscular endurance, strength, intramuscular adaptions, functional preformance, dyspnea, and health related quality of life. The programs will also be evaluated for feasibility regarding the duration of training sessions, attendance rates, adverse events, and participant satisfaction. The hypothesis is that the non-linear periodization group will have superior effects and that feasibility aspects will be similar between groups.

Official Title
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Effect and Feasibility of Non-linear Periodized Resistance Training in People With Chronic Obstructive Pulmonary Disease: a Randomized Controlled Multicenter Trial

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Other: Non-linear Periodized Resistance Training
* Other: Resistance training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: FEV1/FVC ratio < 70% postbronchodilator FEV1 <80% of the predicted normal value postbronchodilator Exclusion Criteria: Clinical evidence of asthma, cardiovascular diseases, and/or neuromuscular diseases that are unstable and/or that may contribute to exercise limitation Other contraindications to exercise Currently participating in a structured exercise or pulmonary rehabilitation program or been involved in pulmonary rehabilitation in the past 6 months Experienced a COPD exacerbation and/or change in medication dosage/frequency in the past 6 weeks

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, assessor-blind, parallel-group randomized controlled multicenter trial with a pre- and post-intervention design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-linear Periodized Resistance Training<br>The objective of the Non-linear Periodized Resistance Training (NLPRT) program is to increase muscle strength as well as muscle endurance. The NLPRT program will over the 8 week intervention period target several different aspects of limb muscle function, by alternating the intensity and volume of the exercises. Progression of exercise is symptom dependent and will be based on Borg CR-10 ratings (dyspnea, muscle fatigue and exertion). All exercises will be performed using exercise equipment that are available at each included center. All sessions are supervised and conducted by local professionals using a group format, with approximately 2-4 participants per group. | Other: Non-linear Periodized Resistance Training<br>* 8 week non-linear periodized resistance training intervention, 3 sessions per week, 60 minutes per session<br>|
| Active Comparator: Resistance Training<br>The primary objective of the Resistance training (RT) group is to increase muscular strength. The RT program will be performed in line with current guidelines that are recommended for increasing muscular strength in patients with COPD. Progression of exercise is performance dependent and will be based on the previous 2 sessions. All exercises will be performed using exercise equipment that are available at each included center. All sessions are supervised and conducted by local professionals using a group format, with approximately 2-4 participants per group. | Other: Resistance training<br>* 8 week resistance training intervention, 3 sessions per week, 60 minutes per session<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline dynamic maximal endurance at week 9 | Maximal limb muscle endurance measured using resistance training machines or free weights. Reported as the number of repetitions at 45% of the baseline one repetition maximum. | Baseline and week 9 | 
| Change from baseline dynamic maximal strength at week 9 | Maximal limb muscle strength measured using resistance training machines or free weights. Reported as one repetition max in kg. | Baseline and week 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline static maximal endurance at week 9 | Maximal limb muscle endurance measured using a computerized dynamometer or strain gauge. Reported in seconds maintaining 60% of the isometric maximal voluntary contraction. | Baseline and week 9 | 
| Change from baseline static maximal strength at week 9 | Maximal limb muscle strength measured using a computerized dynamometer or strain gauge. Reported in Nm | Baseline and week 9 | 
| Change from baseline unsupported upper limb test (UULEX) at week 9 | The UULEX is a progressive test where the participants will be asked to a raise plastic bar from the hip to the UULEX eight-level chart with a cadence of 30 movements per minute. If a patient reaches the highest level, the plastic bar will be replaced by a heavier one every minute. There are five different bar weights (0.2, 0.5, 1, 1.5, 2 Kg) and participants will continue on the highest level until symptom limitation. Results are reported in seconds. | Baseline and week 9 | 
| Change from baseline endurance shuttle walk test (ESWT) at week 9 | The ESWT is a derivative of the Incremental shuttle walk test (ISWT), where patients walk for as long as possible at a predetermined percentage of maximum walking performance as assessed by the ISWT on a 10 meter course. Reported in seconds to termination of the test or total meters walked. | Baseline and week 9 | 
| Change from baseline 60 seconds sit to stand test (60STS) at week 9 | During the 60STS, participants will be instructed to fully stand up and sit down as fast as possible, as many times as possible within 60 seconds. Arms will be held fold across the chest with feet remaining in full contact with the floor. Reported as the number of repetitions performed within 60 seconds. | Baseline and week 9 | 
| Change From Baseline Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Total Scores at week 9 | The CRQ-SAS is a self-administered questionnaire which consist of 20 items across four domains: dyspnea (5 items), fatigue (4 items), emotional function (7 items), and mastery (4 items). Participants rates their experience on a 7-point scale in response to each item ranging from 1 (maximum impairment) to 7 (no impairment). Individual items are equally weighted, and total score ranges from 20 to 140 (20 maximum impairment, 140 no impairment). | Baseline and week 9 | 
| Change From Baseline Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) dyspnea Domain Scores at week 9 | Domain scores are calculated as the mean of all items (5) within the dyspnea domain. Participants rates their experience on a 7-point scale in response to each item ranging from 1 (maximum impairment) to 7 (no impairment). Individual items are equally weighted, and total score ranges from 7 to 35 (7 maximum dyspnea, 35 no dyspnea). | Baseline and week 9 | 
| Number of responders | The total amount of responders i.e. defined as a response over the known minimal detectable change/or minimal important difference for included test(s) will be determined and compared. | Week 9 | 
| Attendance rate | Attendance rate will be evaluated by calculating the number of attended sessions divided by total number of sessions for each participant | Week 1 up to 8 | 
| Duration of exercise sessions | Mean time in minutes of exercise sessions | Week 1 up to 8 | 
| Satisfaction rate | Participant satisfaction with the exercise regimens will be recorded by adapting an existing patient satisfaction questionnaire. Participants rate their satisfaction on 7 items each with a 5 point likert scale. Results using the total score (0-35, higher score indicating higher satisfaction). | Week 9 | 
| Proportion of drop-outs | Proportion of participants that don't complete the intervention | Week 9 | 
| Adverse Events rate | Occurrence of any adverse events. An adverse event rate will be calculated for each patient as the total number of sessions during which any adverse events occurred divided by the total number of attended sessions. | Week 1 up to 8 | 
| Adverse Events stratified by severity | The severity of the adverse events will be assessed and rated into four different categories: 1) minor and temporary, 2) serious symptoms (potential risk of severe injury or life threatening), 3) manifest injury or disease, and 4) death. Presented in factual numbers for each group. | Week 1 up to 8 | 
| Change from baseline muscle fiber size at week 9 | The tissue sample obtained from the vastus lateralis muscle will be examined with morphometric analyses to determine cross-sectional fiber area. Reported in square micrometers. | Baseline and week 9 | 
| Change from baseline proportion of slow and fast subtypes of contractile myosin heavy chain isoforms in fibers at week 9 | The tissue sample obtained from the vastus lateralis muscle will be examined with immunohistochemistry techniques to categorize fiber types. | Baseline and week 9 | 
| Change from baseline oxidative (citrate synthase (CS), EC 4.1.3.7) enzyme activities at week 9 | The tissue sample obtained from the vastus lateralis muscle will be examined to demonstrate enzyme activities. Reported in micromol/min/g tissue. [Time Frame: Baseline and week 9] The tissue sample obtained from the vastus lateralis muscle will be examined by histochemistry to demonstrate enzyme activities. Reported in micromol/min/g tissue. | Baseline and week 9 | 
| Change from baseline glycolytic (lactate dehydrogenase (LDH), EC 1.1.1.27) enzyme activities at week 9 | The tissue sample obtained from the vastus lateralis muscle will be examined to demonstrate enzyme activities. Reported in micromol/min/g tissue. | Baseline and week 9 | 
| Change from baseline capillarization (capillary density) at week 9 | The tissue sample obtained from the vastus lateralis muscle will be examined with morphometric analysis to determine capillary density, estimated as the total number of capillaries per millimeter squared muscle cross-section. | Baseline and week 9 | 
| Change from baseline capillarization (capillaries to fiber) at week 9 | The tissue sample obtained from the vastus lateralis muscle will be examined with morphometric analysis to determine the number of capillaries around fibers including all capillaries in contact with each muscle fiber. | Baseline and week 9 | 
| Change from baseline capillarization (capillaries relative to fiber area) at week 9 | The tissue sample obtained from the vastus lateralis muscle will be examined with morphometric analysis to determine the number of capillaries around each fiber relative to its cross-sectional area. | Baseline and week 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscle dysfunction