Electrical Stimulation for Critically Ill Post-Covid-19 Patients

Study Overview
=================
Brief Summary
-----------------
Unfortunately, hospital-acquired weakness is highly prevalent among COVID-19 hospitalized patients, who often require prolonged bed-rest or paralytics for an extended period of time in order to maintain oxygenation. Prolonged bed rest has been associated with pronounced loss of muscle mass that can exceed 10% over the 1st week, which leads to functional impairment and complications post-hospital discharge. Physical therapy and in-hospital mobility program may reduce the incident of hospital-acquired weakness, but they are often impractical for COVID-19 patients. In particular, conventional mobility programs are challenging for those who are being treated in an intensive Care Unit. The purpose of this study is to test feasibility and proof-of-concept effectiveness of daily use of lower extremity electrical stimulation (EE) therapy, as a practical solution to address lower extremity muscle deconditioning, to address chronic consequences of COVID-19 including hospital-acquired weakness.

Detailed Description
-----------------
20 subjects that were hospitalized due to severe COVID-19 infection and present neuromuscular complications (i.e., hospital acquired weakness due to neuromyopathy) will be recruited after the first phase of this study is completed. Unlike Phase I (study for prevention), this is a proof of concept randomized control trial (RCT) study for recovery. The patients will be recruited from the COVID-19 Clinic at Baylor College of Medicine and will begin the study after being diagnosed with neuromyopathy due to prolonged hospitalization for COVID-19. This will be performed by a critical care and pulmonary specialist at the BCM COVID-19 Clinic. The entire cohort will receive daily electrical stimulation in lower extremity (e.g. Gastrocnemius, tibial anterior muscle) up to 1 hour to recover from Neuromyopathy complications and prolonged hospital stay. Participants will be randomized to intervention (IG) or control group (CG)). EE therapy will be provided using a bio-electric stimulation technology (BEST) platform (Tennant Biomodulator PRO®, AVAZZIA, Inc.). The EE device will be functional for IG and non-functional for CG. In addition to taking the device home to deliver electrical stimulation themselves, the patients will attend a weekly assessment at the McNair Campus for up to 4 weeks. The primary outcomes include between group difference and change from the baseline in muscle endurance, muscle strength, lower extremity tissue oxygen saturation, neuropathy, and muscle atrophy.

Official Title
-----------------
Electrical Stimulation Therapy for Recovery of Hospital-acquired Weakness in Critically Ill COVID-19 Patients - A Proof of Concept Randomized Controlled Trial

Conditions
-----------------
COVID-19, Muscle Atrophy, Muscle Weakness

Intervention / Treatment
-----------------
* Device: Electrical Stimulation
* Device: Electrical Stimulation - Sham


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Post-COVID-19 patients who required hospitalization due to COVID-19 severe infection. Post-COVID-19 patients who required hospitalization and present neuromuscular sequelae due to COVID-19 severe infection. Exclusion Criteria: Patient has a demand-type cardiac pacemaker, implanted defibrillator or other implanted electronic device. Active wound infection. Below the knee amputations. Based on the clinicians decision whether the patient is eligible for the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

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

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

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

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to intervention (IG) or control group (CG) with ratio of 1:1. The entire cohort will receive daily electrical stimulation (EE) in lower extremity (e.g. Gastrocnemius muscle) for up to 1 hour. The EE device will be functional for IG and non-functional for CG. Phase II will include previously hospitalized patients (n=20) who had recover from severe COVID-19 infection, but present persistent neuromuscular sequelae. This will be performed in an outpatient clinic. The time frame will be 4 weeks.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active E-Stim<br>Subjects will receive a sham electrical stimulation device to wear for 1 hour daily for 4 weeks (phase II). | Device: Electrical Stimulation<br>* Subjects will receive an active electrical stimulation device to wear for 1 hour daily for 4 weeks (phase II).<br>|
| Sham Comparator: Electrical Stimulation - Sham<br>Subjects will receive a sham electrical stimulation device to wear for 1 hour daily for 4 weeks (phase II). | Device: Electrical Stimulation - Sham<br>* Subjects will receive a sham electrical stimulation device to wear for 1 hour daily for 4 weeks (phase II).<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation | Gastrocnemius muscle endurance in response to 5 minutes of electrical stimulation therapy will be assessed with surface electromyography using a validated non-invasive device (Delsys Trino Wireless EMG System, MA, US). | an average of 4 weeks (Phase II) | 
| Ankle Strength | Ankle strength will be measured in response to the average of three 5-second dorsiflexion maximum voluntary isometric contractions per 30 seconds of relaxation in-between using a dynamometer (RoMech Digital Hanging Scale). | an average of 4 weeks (phase II). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plantar Oxyhemoglobin | Percentage of oxyhemoglobin (OxyHb) will be measured using a validated near-infrared (NIR) camera (Snapshot NIR, KENT Imaging Inc., Calgary, AB, Can) that detects an approximate value of real-time OxyHb level in superficial tissue. The metatarsus area including the five toes will be traced. Data reported includes plantar oxyhemoglobin after 10 minutes of stopping 1 hour of electrical stimulation therapy. | an average of 4 weeks (phase II) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Electrical Stimulation, Skin perfusion, Muscle dysfunction