Inspiratory Muscle Strength Training in Post-Covid Syndrome

Study Overview
=================
Brief Summary
-----------------
Patients with post-Covid-19 syndrome are at high risk of developing cardiovascular diseases 12 months after acute infection of COVID-19. We recently revealed that these patients have elevated muscular sympathetic nerve activity (MSNA), vascular dysfunction, impaired cardiac diastolic function, and reduced functional capacity. Considering that these outcomes are independent predictors of cardiovascular mortality, it is urgent to restore the cardiovascular health of these patients. High resistance inspiratory muscle strength training (IMST) at 75% of pressure inspiratory (PImax) performed at home (5 min/session, 5-7 times/week per 6 weeks) reduces the MSNA, improves the endothelial function and lowers blood pressure in different populations. Based on these findings, IMST (75% PImax) is an excellent therapeutic option for patients with post-COVID-19 syndrome. Therefore, the aim of the present proposal is to test whether IMST (75% PImax) reduces sympathetic activity, improves vascular function, and restores cardiac function, evoking an increase in functional capacity in patients with post-COVID-19 syndrome. To test these hypotheses we will conduct a randomized, double-blind, sham-controlled clinical trial to test these hypotheses.

Official Title
-----------------
The Effects of Based-home High-resistance Inspiratory Muscle Training on Neurovascular Control, Blood Pressure, and Exercise Capacity in Patients With Post-COVID-19 Syndrome

Conditions
-----------------
Cardiovascular Abnormalities, Post-COVID-19 Syndrome, Physical Exercise

Intervention / Treatment
-----------------
* Other: Inspiratory muscle strength training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Post-COVID-19 syndrome Have been diagnosed with COVID-19 by RT-PCR Have oxygen saturation ≤ 93% in room air during the acute phase of the COVID-19 Have received oxygen supply from any device during the acute phase of the COVID-19 Hospitalization to treat the Covid-19 Participants in cardiopulmonary rehabilitation or physical conditioning programs Exclusion Criteria: Pregnant History of chronic obstructive pulmonary disease or dependence on oxygen support History of cardiovascular and renal diseases and cancer prior to the COVID-19 diagnosis Difficulties in moving to the laboratory for assessments

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inspiratory Muscle Strength Training<br>Using a handheld device, participants will perform 30 breaths a day at 75% of maximal inspiratory pressure, six days a week, for 6 weeks. | Other: Inspiratory muscle strength training<br>* Using a handheld device, participants will perform 30 breaths per day at 75% of maximal inspiratory pressure, six days a week, during 6 weeks.<br>|
| Sham Comparator: Sham- Inspiratory Muscle Training<br>Using a handheld device, participants will perform 30 breaths a day at 15% of maximal inspiratory pressure, six days a week, for 6 weeks. | Other: Inspiratory muscle strength training<br>* Using a handheld device, participants will perform 30 breaths per day at 75% of maximal inspiratory pressure, six days a week, during 6 weeks.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle sympathetic nerve activity | Microneurography | Baseline and 6 weeks after ISMT and Sham | 
| Endothelial function | Doppler Ultrasound | Baseline and 6 weeks after ISMT and Sham | 
| Arterial stiffness | Applanation tonometry | Baseline and 6 weeks after ISMT and Sham | 
| Blood pressure | Sphygmomanometry | Baseline and 6 weeks after ISMT and Sham | 
| Exercise Capacity | Cardiopulmonary exercise testing | Baseline and 6 weeks after ISMT and Sham | 
| Maximum inspiratory pressure | Manovacuometry | Baseline and 6 weeks after ISMT and Sham | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative stress | Blood samples | Baseline and 6 weeks after ISMT and Sham | 
| Nitric oxide | Blood samples | Baseline and 6 weeks after ISMT and Sham | 
| Inflammatory profile | Blood samples | Baseline and 6 weeks after ISMT and Sham |