Electrical Stimulation for Critically Ill Covid-19 Patients

Study Overview
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Brief Summary
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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
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Phase I: The purpose of this study is to test feasibility and proof-of-concept effectiveness of lower extremity electrical stimulation (EE) therapy to prevent muscular complications of COVID-19 including hospital-acquired weakness and neuropathy. This is a proof of concept randomized control trial (RCT) study for prevention. Eligible participants (n=19 anticipated) will be recruited from the Baylor St. Luke's' Medical Center (Houston, Texas). To be eligible participants should be hospitalized because of COVID-19 infection and suspected to be at risk for hospital acquired-weakness based on judgment of clinical intensivist investigators. Participants will be excluded if they are paralyzed. Other exclusion criteria include blow the knee amputation, those who have a demand-type cardiac pacemaker, implanted defibrillator or other implanted electronic device; those with wound infection, and other conditions that may interfere with outcomes or increase the risk of the use EE based on judgement of clinicians. The Investigators hypothesize that implementation of EE as means of regular activation of lower extremity muscle is feasible and acceptable for the target population and would help to retain lower extremity muscle mass, lower extremity tissue oxygen saturation and perfusion, and thus reducing the severity of hospital acquired weakness and potentially improve outcomes of treatment among COVID-19 patients. Participants will be randomized to intervention (IG) or control group (CG)). The entire cohort will receive daily EE in lower extremity (e.g. Gastronemius, tibial anterior muscle) up to 1 hour. 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. 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. Outcomes will be assessed at baseline, time of discharge or 2 weeks, whichever comes first.

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

Conditions
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Covid19, Muscle Atrophy, Muscle Weakness

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COVID-19 test positive critically ill patients in need of assisted ventilation requiring care in the intensive care unit COVID-19 test positive critically ill patients in need of assisted ventilation requiring prolonged care in the hospital Exclusion Criteria: Paralyzed patients (i.e., rocuronium, cisatracurium) at the moment of enrollment Patients under vasopressor therapy (i.e., norepinephrine, epinephrine, vasopressin) at the moment of enrollment Patients expected to be discharged in the next 24 hours 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
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Minimum Age: 18 Years
Maximum Age: 100 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: 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. Gastronemius muscle) for up to 1 hour. The EE device will be functional for IG and non-functional for CG. Phase I will include patients (n=19) admitted to the hospital due to severe COVID-19 infection. The time frame for therapy will be 2 weeks or until hospital discharge, whichever comes first.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active E-Stim<br>Subjects will receive an active electrical stimulation device to wear for 1 hour daily up to two weeks or until hospital discharge, whichever came first (phase I). | Device: Electrical Stimulation<br>* Subjects will receive an active electrical stimulation device to wear for 1 hour daily up to two weeks or until hospital discharge, whichever came first (phase I).<br>|
| Sham Comparator: sham E-Stim<br>Subjects will receive a sham electrical stimulation device to wear for 1 hour daily up to two weeks or until hospital discharge, whichever came first (phase I). | Device: Electrical Stimulation - Sham<br>* Subjects will receive a sham electrical stimulation device to wear for 1 hour daily up to two weeks or until hospital discharge, whichever came first (phase I).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 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 2 weeks (Phase I) | 
| Change in 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 2 weeks (Phase I) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plantar Tissue Oxygen Saturation/Consumption | Percentage of tissue oxygen saturation (SatO2) 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 SatO2 level in superficial tissue. The metatarsus area including the five toes will be traced. | an average of 2 weeks (Phase I) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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electrical stimulation, skin perfusion, Muscle dysfunction