Inspiratory Muscle Training and COPD

Study Overview
=================
Brief Summary
-----------------
Subjects with chronic obstructive pulmonary disease (COPD) frequently develop considerable deterioration in exercise capacity in association with weakness and deconditioning of the respiratory muscles, which can be corrected with specific therapies. While pulmonary rehabilitation is a central component in the rather complex manangement of COPD, there is currently a lack of centers able to provide appropriate rehabilitation services in the Czech Republic. The main objective of this study will be to fully evaluate the utility of the Test of Incremental Respiratory Endurance (TIRE) as an at-home inspiratory muscle training method in subjects with COPD, while comparing the effectiveness of this novel training approach to the outcomes of more traditional ispiratory muscle training protocols. This prospective, randomized controlled trial will include 2 treatment groups and 1 sham intervention group in a 1:1:1 ratio. All participants will undergo a certain type of IMT regardless of group assignment, which will be perfomed via two different devices. The trial will comprise of an 8-week at-home training period with remote supervision followed by 4 months of unsupervised, independent inspiratory muscle training. Study outcomes will include measures of inspiratory muscle strength and endurance, pulmonary function, COPD-specific symptomatology, functional exercise capacity, surrogate markers of mortality risk, mental health status and health-related quality of life of participants. While investigators acknowledge the value of standard inspiratory muscle training protocols which use Threshold devices, investigators believe that the TIRE training has the potential to provide additional clinical benefits since it is able to modulate all aspects of muscular performance, including strength, endurance and work capacity. Investigators hypothesize that, as a home-based stand-alone rehabilitative therapy, TIRE will be superior to standard IMT in improving COPD-related measures.

Detailed Description
-----------------
Eligible participants will be randomly assigned to one of the following three distinct home-based IMT protocols: (1) TIRE, (2) Standard, and (3) Sham (i.e. Low Resistance). All subjects will undergo 8 weeks of daily unsupervised IMT using either a PrO2® device (Design Net, Smithfield, USA) or Threshold device at home. All training modalities require the subjects to be seated and wearing a nose clip while performing the required breaths. Subjects will be instructed on respective training procedures and complete first training session in the presence of a research team member upon enrollment. Regardless of training method, participants will be instructed to fill in diary cards at the end of each training session, in which participants document how many breaths were able to perform. This information will be later used for compliance assessment. Participants will be also provided with user guides developed by investigators research team with detailed instructions regarding equipment set-up, training protocol and contact information. In addition, subjects will receive weekly phone calls from week 0 to week 8 to encourage compliance and adherence to the study protocol, to address any subject questions or concerns, and to collect information regarding participants current symptomatology.

Official Title
-----------------
Novel Versus Traditional Inspiratory Muscle Training Regimens as Home-based, Stand-alone Therapies in COPD

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Device: Test of Incremental Respiratory Endurance - IMT
* Device: Threshold - IMT
* Device: Sham IMT (Low resistence)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: individuals over the age of 40 clinical and functional diagnosis of COPD Global Initiative of Chronic Obstructive Lung Disease (GOLD) - stages I to IV evidence of inspiratory muscle weakness, defined as a MIP ≤ 80 cmH2O and a SMIP ≤ 427 PTU ability to operate a computer, tablet or smartphone clinical stability with no history of infections or exacerbation of respiratory symptoms for at least two months prior to study enrollment non-participation in exercise programs in the past 12 months. Exclusion Criteria: subjects with history of lung surgery, lung cancer, any diagnosed cognitive (i.e. Mini Mental State Examination score < 24), orthopedic, neurological or neuromuscular disorders

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test of Incremental Respiratory Endurance - IMT<br>Training will consist of six levels (A-F) with six inspirations at each level for up to 36 breaths per session. TIRE data will be stored in the tablet and automatically synced to account on cloud-based online platform for subsequent interrogation and data retrieval. Before every training session, subjects will be required to complete one maximal and sustained inspiratory effort from which the training is based on for that day. | Device: Test of Incremental Respiratory Endurance - IMT<br>* The TIRE training regimen will involve the use of a tablet provided to assigned subjects with the training software installed and a PrO2® device through which they will train. The software allows subjects to track their inspiratory muscle performance via real-time graphic representations of their efforts as training progresses.<br>|
| Experimental: Threshold - IMT<br>Subjects assigned to the Standard training regimen will receive a commonly used Threshold inspiratory muscle trainer. This device features a one-way spring-loaded valve at one end and a mouthpiece on the other through which subjects will be required to breathe in hard enough to overcome the resistance provided by the spring-loaded valve, allowing correct inspiration to happen. In other words, air flow is blocked until subjects generate sufficient inspiratory pressure to exceed the device pre-set pressure in cmH2O. The resistance will be set using the device's adjustable pressure setting which is fixed at 50% of the subject's MIP at the time of enrollment. The resistance will be readjusted as needed at week 4 to still reflect 50% of their inspiratory muscle strength at that time. Subjects will be coached to perform up to 36 breaths daily using the device. They will be also instructed to complete the training session within a 30-minute period. | Device: Threshold - IMT<br>* The Threshold incorporates a flow-independent one-way valve to ensure consistent resistance and features an adjustable specific pressure setting to be set based on MIP values of each subject.<br>|
| Sham Comparator: Sham IMT (Low resistence)<br>The Sham (Low Resistance) training regimen will use the same methods described above for the Standard IMT, except for the amount of resistance applied within the device. Subjects will receive a Threshold which has been set to its minimal resistance, which is 9 cmH2O. Again, subjects will be instructed to perform up to 36 breaths daily using the device within a 30-minute period. | Device: Sham IMT (Low resistence)<br>* The Threshold incorporates a flow-independent one-way valve to ensure consistent resistance and features an adjustable specific pressure setting to be set based on MIP values of each subject.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Maximal Inspiratory Pressure (SMIP) | The primary outcome measure will be SMIP, which will be obtained along with MIP and ID in every subject using the PrO2® device, an electronic pressure manometer which utilizes wireless technology to connect to a tablet containing the software of the Test of Incremental Respiratory Endurance. | Change from baseline to 8 weeks and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Inspiratory Pressure (MIP) | MIP will be obtained from a maximal inspiratory effort from residual volume using the TIRE software and recorded in centimeters of water. | Change from baseline to 8 weeks and 24 weeks | 
| Inspiratory Duration (ID) | ID will be obtained from a maximal and sustained inspiratory effort using the TIRE software and recorded in seconds. | Change from baseline to 8 weeks and 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic obstructive pulmonary disease, Pulmonary rehabilitation, Telemedicine, Quality of life, Inspiratory muscle training, Test of incremental respiratory endurance