Non-invasive Neustimulation and Respiratory Rehabilitation

Study Overview
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Brief Summary
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Introduction: Respiratory diseases are associated with high rate of morbidity and mortality in Brazil. Cardiopulmonary rehabilitation through respiratory muscle training, aerobic training and strengthening of upper and lower limbs emerges as one of the resources available for the treatment and monitoring of patients with respiratory diseases. To add in this perspective, the application of HD-tDCS induces significant neurophysiological and clinical effects in several body systems. Objective: To identify the chronic effects of non-invasive neurostimulation associated with the rehabilitation of patients with respiratory disorders. Material and methods: This is a pilot study, quantitative, clinical trial type, randomized and controlled, double blind. The sample will be composed by patients with respiratory diseases, aged above 18 years old. The study will consist of two groups: (1) HD-tDCS will be applied - anodic current + respiratory rehabilitation with respiratory muscle training (RMT) and (2) Sham - Only respiratory rehabilitation with RMT without any type of cortical stimulation. The chronic effects of neurostimulation by HD-tDCS associated with cardiopulmonary rehabilitation, with TMR, during 12 sessions will be evaluated. Patients will be evaluated, before and after the protocol, in relation to cortical activation function, pulmonary function, subjective perception of effort, respiratory muscle function, functional capacity, sensation of dyspnea and quality of life. For statistical analysis, intention-to-treat analysis will be used and groups will be compared using Student's t-test, for continuous variables, or chi-square, for categorical variables. ANOVA split-plot, repeated measures for primary outcomes. Analyzes of covariance to identify differences between groups using baseline scores as covariates. Effect sizes and confidence intervals will be calculated using eta squared (η²). Expected results: Neurostimulation would enhance the effects of respiratory rehabilitation and reduce the symptoms of patients with these diseases.

Official Title
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Non-invasive Neurostimulation and Rehabilitation in the Treatment of Patients With Respiratory Disorders: Randomized Controlled Clinical Trial

Conditions
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Lung Diseases

Intervention / Treatment
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* Other: Active non-invasive stimulation and inspiratory muscle training
* Other: Sham compatorator and inspiratory muscle training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: confirmed clinical diagnosis for respiratory disease; stable disease Exclusion Criteria: develop disabling condition that prevents the implementation of the protocol; join another rehabilitation program

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 experimental<br>group composed by patients with respiratory disorders, which will undergo 12 sessions of neurostimulation by HD-tDCS 4x1 (tDCS 1x1, developed by Soterix Medical Inc.). A current of 3 mA will be provided, positioning a central electrode (anode) on the left diaphragmatic primary motor cortex (4 cm lateral to the midline and 1 cm anterior to the binaural line) and the four return electrodes in a radius of 8 cm to the around. At the same time, inspiratory muscle training (IMT) will be performed by KH2; PowerBreathe International Ltd. UK with visual feedback, consisting of three series of two minutes of maximum and deep inspirations followed by two minutes of rest between them, totaling six minutes of TMI. The initial load will be through the maximum inspiratory pressure (MIP) achieved in the initial evaluation, using 40% of the total MIP in the first three weeks and 70% of the protocol will be used 40% of the MIP in the remaining three weeks and 70% in the remaining weeks. | Other: Active non-invasive stimulation and inspiratory muscle training<br>* Simultaneously with the current application, the patient will perform inspiratory muscle training (IMT) by KH2; PowerBreathe International Ltd. UK along with a feedback Breathelink, consisting of three series of two minutes of maximum and deep inspirations followed by two minutes of rest between them, totaling six minutes of TMI.<br>|
| Sham Comparator: Group 2 sham comparator<br>The participants allocated in the control group will receive the sham HD tDCS for 20 minutes associated with the IMT, following for this training the same load guidelines, duration and load increment used in the experimental group. | Other: Sham compatorator and inspiratory muscle training<br>* As for the patients allocated in the control group, they will receive the HD-tDCS sham for 20 minutes associated with IMT, following for the same training, duration and load increment used in the experimental group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung function | Spirometry will be performed following the American Thoracic criteria Society (ATS). All participants will undergo a minimum of three maneuvers, in a sitting position, with a nose clip and mouthpiece attached. It will be instructed to perform maximum inspiration, up to total lung capacity, followed by a maximal and continuous forced expiration for at least six seconds, until residual volume. | six weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum inspiratory pressure | To assess the maximum inspiratory pressure, a computerized electronic device (KH2; PowerBreathe International Ltd. United Kingdom) will be used. The participant will be seated, arms supported and nose clip to prevent air leaks. The maneuver consists of exhaling to the residual volume and performing a maximum inspiration maintained for as long as possible, being repeated 3 to 8 times to have a variation of less than 10%, based on the highest value. | six weeks | 
| functional capacity | Functional capacity will be assessed considering the distance covered in the six-minute walk test (6MWT). The 6MWT will be performed in a 30-meter corridor, checking heart rate (HR), peripheral oxygen saturation (SPO2), blood pressure (BP) and subjective perception of dyspnea by the Borg scale at the beginning and end of the test. HR and SpO2 will be observed throughout the test. For this porpuse, it will be used a stopwatch, a pulse oximeter to measure HR and SpO2, a sphygmomanometer to measure BP, a printed Borg scale that will be shown to the patient, a chair that can be moved to any area of the track and two cones to mark the return points that will be placed at the beginning and end of the test track. The test track will be marked in every 3 meters, in a closed environment and at a comfortable temperature. Instructions will be given for the patient to walk as fast as possible without running, in addition to warnings regarding the elapsed time of the test. | six weeks | 
| dyspnea sensation | For the evaluation of this outcome, it will be assessed by the dyspnea scale of the modified Medical Research Council (mMRC), which measures the degree of dyspnea in specific daily activities. The mMRC is divided into 4 grades, ranging from 0 (dyspnea on intense exercise) to 4 (dyspnea on minimal exertion) such as dressing or bathing). The scale is widely used in patients by its simplicity, easyness of use and correlation with quality of life, prognosis and distance covered in the six-minute walk test. | six weeks | 
| health-related quality of life | The assessment of health-related quality of life will be carried out through the application of a generic quality of life assessment questionnaire, the SF 36, which is a self-assessment instrument used to assess the quality of life of adults and is organized in eight dimensions: functionality (10 items), limitation caused by the physical problem (4 items), body pain (2 items), general health perception (5 items), vitality (4 items), social function (2 items), limitation caused by the emotional problem (3 items), mental health (5 items). A score is obtained through an algorithm (from 0 to 100), where 0 = lowest quality of life and 100 = better quality of life. | six weeks | 
| respiratory muscle resistance | To assess respiratory muscle resistance, a computerized electronic device (KH2; PowerBreathe International Ltd. United Kingdom) will be used. With the participant seated, arms supported and nose clip to prevent air leaks. The test consists of applying an incremental load, where the maximum number of breaths is performed for two minutes, starting with a load of 10 cmH2O and increasing this same value at each cycle, with a minute of rest. The highest value sustained for at least one minute will be considered. | six weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain Stimulation, Performance, Exercise