Study on Impact of Maximal Strength Training in Patients With COPD

Study Overview
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Brief Summary
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In the context of pulmonary rehabilitation of COPD patients, recent guidelines and metanalysis describe that Resistance Training (RT) can be successfully performed alone or in conjunction with Endurance Training (ET) without evidence of adverse events. Maximal Strength Training (MST) is a kind of RT typically performed at  85-90% of 1RM with maximal velocity to be developed in the concentric phase. Recent literature indicates a significant amelioration on the Rate of Force Development (RFD) after MST in healthy subjects, post-menopausal woman and older populations. When comparing to the conventional ET, MST generates a little change in muscle mass (no hypertrophy), but a much greater improvement in the RFD. It has been described that neural adjustments play a major role in the MST-induced adaptations. MST is also well documented to improve aerobic endurance by improving walking work efficiency. Only a small cohort study of COPD patients was conducted, describing that MST can meaningfully improve strength and RFD, with an increase of around 32% for mechanical efficiency and a decrease of the perceived effort during submaximal job. This improvement could determine best performances in daily activities and a best quality of life. The main aims of this physiological pilot randomized controlled trail will be to evaluate feasibility and efficacy of the MST compared to standard ET on strength, effort tolerance, fatigue, economy of walking, dyspnea and risk of falls in a populations of COPD patients, in a short and middle term (6 months).

Detailed Description
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Exercise intolerance is a cardinal problem existing in patients with Chronic Obstructive Pulmonary Disease (COPD). Moreover, skeletal muscle dysfunction is a common extra-pulmonary manifestation, leading to fatigue, decrease in activity of daily living (ADL) performance and quality of life and increase of risk of falls, mainly in older patients. In the context of pulmonary rehabilitation, recent guidelines and metanalysis describe that Resistance Training (RT) can be successfully performed alone or in conjunction with Endurance Training (ET) without evidence of adverse events. As concern the RT programs, metanalysis in COPD describe that training have been mainly performed with the lower limbs and the training intensities are heterogeneous, generally ranging from 40% to 70% of 1-Repetition Maximum (1-RM). Maximal Strength Training (MST) is a RT typically performed at  85-90% of 1RM with maximal velocity to be developed in the concentric phase. Recent literature indicates a significant amelioration on the Rate of Force Development (RFD) after MST in healthy subjects, post-menopausal woman and older populations. When comparing to the conventional ET, MST generates a little change in muscle mass (no hypertrophy), but a much greater improvement in the RFD. It has been described that neural adjustments play a major role in the MST-induced adaptations. MST is also well documented to improve aerobic endurance by improving walking work efficiency. Although the mechanisms at the base of MST effect on the mechanical efficiency have not been completely clarified, there is evidence that changes in the relationships between power and speed bring to a longer relaxation phase inside the cycle of job, improving the recovery between contractions. In this field, only a small cohort study of COPD patients was conducted describing that MST can meaningfully improve the strength and the RFD, with an increase of around 32% for mechanical efficiency and a decrease of the perceived effort during submaximal job. This improvement could determine best performances in daily activities and a best quality of life. Nevertheless, this study has been conducted only in a small cohort (twelve patients) of patients with COPD and further studies are necessary to define the impact on the different components that determine the effort intolerance. The main aim of this physiological pilot randomized controlled trail will be to test the feasibility and the efficacy of the MST compared to standard ET on strength, effort tolerance, fatigue, economy of walking, dyspnea and risk of falls in a populations of COPD patients, in a short and middle term (6 months).

Official Title
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Study on Impact of Maximal Strength Training in Patients With COPD: Physiological and Clinical Implications

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Other: Maximal strenght training (MST) plus endurance training (ET)
* Other: Endurance training (ET)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD clinical definition according to GOLD guidelines with forced expiratory volume (FEV1)/ forced vital capacity (FVC) < 70%, and FEV1 < 50% of predicted stable clinical condition Exclusion Criteria: pulmonary diseases other than COPD type II diabetes or other metabolic diseases malign disease a respiratory tract infection within the last 4 wks long oxygen therapy use.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pilot randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Maximal strenght training (MST) plus endurance training (ET) | Other: Maximal strenght training (MST) plus endurance training (ET)<br>* Patients will perform an addictive out-patients rehabilitative treatment of 8 weeks (3 times/week, ≥20 training sessions) consisting of: MST- It will consist of four sets of five repetitions on a leg-press with a focus on the rate of force development during the concentric contraction of the quadriceps from a 90° to legs complete extension. The load will be 85-90% of 1RM. When a patient will be able to perform more than five repetitions in a set, the load will be increased. All strength training will be performed on a seated horizontal leg press. ET - A cycling session will follow the MST and last 40 minutes at constant-load, starting from a load intensity corresponding to patient specific AT. The intensity will be gradually increased with a symptom-based progression.<br>|
| Active Comparator: Control group<br>Endurance training (ET) | Other: Endurance training (ET)<br>* Patients will perform a usual out-patients rehabilitative treatment of 8 weeks (3 times/week, ≥20 training sessions). They will perform ET by cycling sessions that will last 40 minutes/each at constant-load, starting from a load intensity corresponding to patient specific AT, assessed during the baseline incremental test. The intensity will be gradually increased during the sessions with a symptom-based progression, according to the protocol by Maltais and coworkers. A 3-min warm-up and cool-down will be provided. Heart rate (HR), blood pressure, oxygen pulsoxymetry, and symptoms by Borg CR10 scale will be monitored at the beginning and end of each session. Out of the training-days, both groups will continue their normal daily living with modest regular activity, as recommended by their physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in walking efficiency | The text will be executed using a portable metabolimeter detecting oxygen consumption (VO2). After a 10 min of warm up on a treadmill, the patient will walk 5 min at submaximal steady state walking at 4.5 km/h at 5% incline. Using the average of VO2 of the last minute of walking, the walking efficiency will be defined as percentage of change as follows: external work accomplished/ energy expenditure x 100. | baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Leg Strength by 1-Repetition Maximum on leg press | 1-Repetition Maximum (1RM) will be evaluated. 1RM will be measured on a horizontal leg press at a knee angle of 90°. 1RM will be recorded as the heaviest lifted load achieved, applying rest periods of  4 min between test lifts and increments of 5 kg between each trial until failure. | baseline and 8 weeks | 
| Change in maximal Rate of Force Development (RFD) | Immediately after the maximal test 1-RM (see above), using the same apparatus, maximal rate of Force Development (RFD) will be assessed using a force platform and applying a load corresponding to 75% of the participant's pre-test 1RM. The subjects will be instructed to execute the lift as rapidly as possible in the concentric phase. RFD will be analyzed as the time difference between 10% and 90% of Peak force. | baseline and 8 weeks | 
| Change in maximal effort tolerance | It will be evaluated by VO2 consumption on maximal cardiopulmonary exercise test (CPET) on cycloergometer | baseline and 8 weeks | 
| Change in Constant Load Effort tolerance | It will be evaluated by evaluated by time of execution of Cardiopulmonary Constant-Load Endurance Test | baseline and 8 weeks | 
| Change in Fatigue (physiological evaluation) | To define peripheral and central component of fatigue, before and after CLET, the investigators will test the difference on force produced during a single twitch superimposed on the Maximal Voluntary Contraction (MVC) and the force produced by the electrically evoked Resting Twitch (RT) produced, at rest, 5 seconds after the MVC. | baseline and 8 weeks | 
| Change in Fatigue (qualitative evaluation) | Fatigue Severity Scale (scale measuring fatigue, 9-item scale ranging from 7 = absence of fatigue to 63= maximal presence of fatigue) | baseline and 8 weeks | 
| Change in Muscle volume | Sagittal ultrasound images of the Vastus Lateralis (VL) muscle will be recorded with an 8-12 MHz linear transducer. Images will be obtained with a 90° flexion of hip and knee, at 50% of femur length. The pennation angle (hp) of the VL fascicles will be measured as the angle between the VL muscle fascicles and the deep aponeurosis of the insertion. | baseline and 8 weeks | 
| Change in Dyspnea | Barthel Index Dyspnea (scale measuring dyspnea during basal ADL, 10-item scale ranging from 0 = absence of dyspnea to 100 = maximal dyspnea) | baseline and 8 weeks | 
| Concentration of CRP | C reactive protein [CRP] (mg/dl) | baseline and 8 weeks | 
| Change in Low grade Inflammation | Evaluation of neutrophils/ lymphocytes ratio | baseline and 8 weeks | 
| Concentration of Tumor necrosis factor alpha | TNF-alpha (pg/ml) | baseline and 8 weeks | 
| Concentration of Interleukin-6 | IL6 (pg/ml) | baseline and 8 weeks | 
| Muscular proteolyses by 3-MeH concentration | Evaluation of urinary 3 Methyl-Histine (3-MeH) (micromol/ml) | baseline and 8 weeks | 
| Change in Balance (qualitative measure) | BERG scale ( scale measuring balance, composed by 14 balance related tasks, ranging from 0 = worse balance to 56= best balance) | baseline and 8 weeks | 
| Change in quality of life | EuroQol 5-D (scale measuring quality of life, composed by 2 sessions: one of 5 questions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) with multiple choice ranging from 0 = no problem to 25= very low quality of life and one using Visual Analogic Scale (VAS) to quantify the health status ranging from 0 = worst health condition to 100 = best health condition. The two scale sessions are considered separately. | baseline and 8 weeks | 
| Patient Satisfaction: Likert Scale | Likert Scale 0-4 ( 0=completely unsatisfied, 4= very satisfied). | at 8 weeks | 
| Change in Falls | Evaluation of the rate of falls | baseline and 8 months | 
| Hospitalizations | Evaluation of the rate of hospitalizations | baseline and 8 months | 
| Mortality | Evaluation of deaths (number) | baseline and 8 months | 
| Change in Balance (quantitative measure) | The fall risk (FR) assessment will be evaluated by Balance Board. | baseline and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rehabilitation, resistive training, exercise