Electrical Stimulation Therapy for Preventing Hospital-acquired Weakness in Critically Ill COVID-19 Patients - A Proof of Concept Randomized Controlled Trial
Phase: PHASE1
Conditions: Covid19, Muscle Atrophy, Muscle Weakness
Sponsor: Baylor College of Medicine

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Institutional Review Board for Baylor College of Medicine and Affiliated
Hospitals
 
Protocol Number:    H-47781
Status:                        Approved
Initial Submit Date:  5/13/2020
Approval Period:       5/21/2021 - 4/27/2022
 
Section Aa:  Title & PI
A1.  Main Title
     EFFECTIVENESS OF LOWER EXTREMITY ELECTRICAL STIMULATION THERAPY IN THE TREATMENT OF LOWER
EXTREMITY CRITICAL ILLNESS MYOPATHY AND NEUROPATHY IN PATIENTS WITH SEVERE COVID-19
A2.  Principal Investigator
 
     Name:  
BIJAN NAJAFI
Phone:  
713 7987536
     Id:  
191680
Fax:  
     Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
najafi@bcm.edu
     Center:  
Mail Stn:   BCM390
A3.  Administrative Contact
 
     Name:
MARIA NOUN
Phone:  
713 7987537
     Id:  
204533
Fax:  
     
Email:   
noun@bcm.edu
     
Mail Stn:   BCM390
A3a.  Financial Conflict of Interest
Does any member of study personnel (Investigator (including investigator’s spouse and/or dependent children)) that are
involved in the design, conduct, or reporting of the research have a Significant Financial Interest (SFI) that would reasonably
appear to be affected by the research for which funding is sought and/or associated with an entity/business that would
reasonably appear to be affected by the research?
          No
 
Section Ab:  General Information    
A4.  Co-Investigators
 
     Name:  
ROBERT SOUTHARD
Phone:  
713 7988051
Id:  
134040
Fax:  
Department:   SURGERY: GENERAL SURGERY DIV.
Email:   
southard@bcm.edu
Center:  
Mail Stn:   BCM390
 
     Name:  
GALINA TONEVA
Phone:  
Id:  
157483
Fax:  
Department:   SURGERY: GENERAL SURGERY DIV.
Email:   
toneva@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
MICHELE LOOR
Phone:  
713 7982067
Id:  
199599
Fax:  
Department:   SURGERY: GENERAL SURGERY DIV.
Email:   
mloor@bcm.edu
Center:  
Mail Stn:   BCM390
 
     Name:  
NAIMA RODRIGUEZ
Phone:  
713 7985700

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Id:  
202557
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
naimar@bcm.edu
Center:  
Mail Stn:   BCM390
 
     Name:  
YESENIA ROJAS-KHALIL
Phone:  
713 7987348
Id:  
231322
Fax:  
Department:   SURGERY: GENERAL SURGERY DIV.
Email:   
231322@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
ALEJANDRO ZULBARAN Y ROJAS
Phone:  
(1) 713 7982
Id:  
231680
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
231680@bcm.edu
Center:  
Mail Stn:  
A5.  Funding Source:
     Baylor College of Medicine (Internal Funding Only)
A6a.  Institution(s) where work will be performed:
     BCM: Baylor College of Medicine

Baylor St. Luke's Medical Center (BSLMC)
A6b.  Research conducted outside of the United States:
     
Country:  

Facility/Institution:  

Contact/Investigator:  

Phone Number:  

If documentation of assurances has not been sent to the Office of Research, please explain:

A7.  Research Category:
     
A8. Therapeutic Intent
Does this trial have therapeutic intent?
     Yes
 
A9. ClinicalTrails.gov Registration
Does this protocol/trial require registration on ClinicalTrials.gov due to it: meeting the definition of an Applicable Clinical Trial,
being required under the terms and conditions of an award, or being proposed to be published in ICMJE journals?
     Yes
 
Who will be responsible for registering and maintaining the registration of this Applicable Clinical Trial?
     The BCM PI will register the trial because either:
     -   the trial is BCM PI-initiated,
     -   BCM is the lead site of this multicenter trial, or,
     -   the industry sponsor has instructed the BCM PI to register the trial, or,
     -   registration of this trail is required as a term and condition of the reward by the funding agency.
 
ClinicalTrials.gov Identifier:
     NCT
 
Section B:  Exempt Request
B.  Exempt From IRB Review

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     Not Applicable
 
Section C:  Background Information
     
Critically ill patients often suffer from hospital acquired weakness. This condition may originate from Neurogenic (critical
illness Polyneuropathy or CIP) or Myogenic (critical illness Myopathy or CIM) disturbances, or a combination of both
(critical illness Neuro-Myopathy or CINM). Moreover, prolonged hospital stay 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. Prevalence of hospital-acquired weakness varies widely depending on patient population and risk
factors, assessment period, diagnosis method, and patients pre-hospital functional status (age-related frailty).

Unfortunately, hospital-acquired weakness is highly prevalent among COVID-19 patients, who require paralytics for an
extended period of time in order to maintain oxygenation. The prolonged use of these agents lead to long-term inhibition of
the Acetylcholine receptors of Neuromuscular junctions. All COVID-19 ventilated patients at our institution have been on
paralytics for at least 48 hours, and most of these patients receive concomitant Glucocorticoid therapy. Together
Glucocorticoids and paralytics, lead to Myosin depletion and muscle atrophy. This combination has shown to be a risk
factor for CINM. In a recent JAMA study on 5700 COVID-19 patients performed in NYC, 72% of the ventilated patients
remained in the hospital, and only 3% of this population have been discharged. We believe that the major reason for this is
the inability to wean from the ventilator and to rehabilitate due to Neuro-Myopathy.

A recent systematic review suggested the major pathways involved in CINM. These major pathways include muscle disuse
due to prolonged immobilization, inflammation, impaired perfusion and oxygen delivery, and hyperglycemia. All these
factors might be magnified among COVID-19 patients. Additional to muscle atrophy, a hyper-inflammatory systemic state
and coagulation disorders induced by the COVID-19 virus, poor blood oxygen saturation, and poor perfusion to lower
extremities are other important risk factors to be aware in these patients. As described above, this type of work may allow
physicians to provide more personalized care and evaluate their interventions with a practical test.

Muscle weakness and fatigue impede patients¿ capacity to exercise, and are known to delay extubation, extend length of
stay in hospital, and delay patients to achieve independent mobility. The goal of E-stim in advanced disease states is to
prevent or reverse skeletal muscle wasting for persons who are not able to exercise. Conditions include advanced periods
of mechanical ventilation.

A recent review including 27 papers regarding E-Stim for critical illness in hospital patients revealed a summary of E-stim
characteristics which have shown to benefit this specific population. Characteristics include: a) electrode placement in
lower extremity muscle groups bilaterally, hams and calf muscles; b) position for E-stim in hospital patients should be
supine; and c) session frequency is effective at 5¿7 d/wk or daily until extubation or D/C from hospital. In this summary,
Nussbau, et al reported a series of measurements to demonstrate the efficacy of E-stim therapy such as: thigh
circumference, strength of lower extremity muscles (isometric or isotonic dynamometry, MRC score), and quality of life
questionnaires. The majority of these studies selected parameters to minimize muscle fatigue. They concluded that E-stim
preserves muscle strength and muscle mass, and reduces rate of muscle degradation. Also, it facilitates maintenance of
functional capacity. Others have suggested that the benefit of E-stim was related to neural adaptations. 

Additionally, our previous studies demonstrated that daily use of EE therapy effectively improves limb perfusion, oxygen
delivery, Neuropathy, motor capacity (e.g., gait and balance), and mobility (e.g., daily number of steps). Armed with these
preliminary studies, we proposed this current study to examine the effect of daily use EE therapy in critically ill COVID-19
patient. Our fundamental hypothesis is that EE therapy is effective to maintain the activation of lower extremity muscles
and improve perfusion and oxygen delivery, thus preventing or reversing CINM due to prolonged hospital stay. The
electrical stimulation was not performed on COVID-19 patients, it was performed as a recovery measure not in the hospital
but after surgeries, duration of electrical stimulation was done for about an hour. There is no limit on the duration, patients
at home use the electrical stimulation up to three times a day. 

This is the previous study that our protocol mentions:

Thakral G, Lafontaine J, Najafi B, et al. Electrical stimulation to accelerate wound healing. Diabetic foot & ankle. 2013;4.
More references below: Reid B, Zhao M. The Electrical Response to Injury: Molecular Mechanisms and Wound Healing.
Advances in wound care. 2014;3(2):184-201
Ud-Din S, Bayat A. Electrical Stimulation and Cutaneous Wound Healing: A
Review of Clinical Evidence. Healthcare. 2014;2(4):445-467
Ashrafi M, Alonso-Rasgado T, Baguneid M, et al. The efficacy
of electrical stimulation in lower extremity cutaneous wound healing: A systematic review. Experimental dermatology.
2017;26(2):171-178.
Rachel L-C Kwan GL-YC, Sinfia K-S Vong & Sing K Lo. Electrophysical therapy for managing
diabetic foot ulcers: a systematic review. 10. 2013(121-131).
Bai H, McCaig CD, Forrester JV, et al. DC electric fields
induce distinct Preangiogenic responses in Microvascular and macrovascular cells. Arteriosclerosis, thrombosis, and
vascular biology. 2004;24(7):1234-1239.
Kloth LC. Electrical stimulation for wound healing: a review of evidence from in
vitro studies, animal experiments, and clinical trials. The international journal of lower extremity wounds. 2005;4(1):23-44.

Electrical stimulation device is used for pain management, for this study it will be used as an investigational device to test
the treatment/ prevention of Myopathy an Neuropathy in the hospital (inpatient setting).
 

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Section D:  Purpose and Objectives
     
COVID-19 status are in need of a rigorous physical therapy (PT) program for treatment of hospital-acquired weakness.
Thus far,hospital COVID-19 patients at our hospital are getting limited PT because of the lack of an established protocol
and the associated risk from interaction with the medical staff. To address this gap, we suggest daily use of lower extremity
electrical stimulation (EE) therapy, as an alternative therapy. We hypothesize that implementation of Electrical Stimulation
as means of improving Myopathy, would be crucial to reduce hospital length of stay and improve outcomes of treatment
among COVID-19 patients.
The purpose of this pilot study is to examine the effectiveness of daily use of electrical
stimulation therapy to address side effects of long hospital stay in patients with COVID-19. These effects include lower
extremity critical illness Myopathy and Neuropathy due to prolonged hospital stay. Lengthened hospital stay decreases
activity and muscle activation provoking atrophy, weakness and pain. We believe that electrical stimulation will maintain
muscle activity and improve venous return flow to prevent these side effects.
 
Section E:  Protocol Risks/Subjects
E1.  Risk Category
     Category 1: Research not involving greater than minimum risk.
E2.  Subjects
Gender:
     Both
Age:
     Adult (18-64 yrs), Geriatric (65+ yrs)
Ethnicity:
     All Ethnicities
Primary Language:
     English
Groups to be recruited will include:
     Patients
Which if any of the following vulnerable populations will be recruited as subjects?
     Cognitively impaired
Vulnerable populations require special protections.  How will you obtain informed consent, protect subject confidentiality, and
prevent undue coercion?
     
Due to no visitation, the consent will be done over the phone by the physician with a legal representative of the patient.
Two nurses will be present during the call and the consenting will be done by the physician following current consenting
procedures with other ongoing studies in the hospital. This study has minimal risks for the patient, all notes will be added
to the consent form based on the call. If patient is able to give verbal consent will be singed physically. 

For patients who lack the capacity to consent, the investigator/designee may explain the study to the legally authorized
representative by phone. The discussion will be documented in the subject's medical record or research chart. Two copies
of the unsigned consent form will be sent to the subject/legal representative with instructions for completion of the
signature page and assent (if applicable). Signatures will be obtained according to standard Baylor IRB regulations. The
subject will be told to keep one form and returned the other to the investigator by mail, email, or fax. The Baylor
Investigator/designee will sign the consent form when returned from the subject. The signed consent form will be
maintained in research records.
E3.  Pregnant woman/fetus
Will pregnant women and/or fetuses (as described in 45 CFR 46 Subpart B) be enrolled in the research?
     No
E4.  Neonates
Will neonates of uncertain viability or nonviable neonates (as described in 45 CFR 46 Subpart B) be enrolled in the research?
     No
E5.  Children
Will children be enrolled in the research?
     No
 

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Section F:  Design/Procedure
F1.  Design
Select one category that most adequately describes your research:
     c) Pilot
Discuss the research design including but not limited to such issues as: probability of group assignment, potential for subject
to be randomized to placebo group, use of control subjects, etc.
     
Phase I:
20 subjects with COVID-19 infection that are being treated in the hospital. This means that this patient population
is positive to COVID-19, are hospitalized, or develop severe symptomatology, but they have been admitted with no more
than 48 hours to the hospital. Also,in some cases the patients will not able to consent at the time of enrollment determines
a high grade of severity of illness. The entire cohort will receive daily electrical stimulation in lower extremity (e.g.
Gastronemius, tibial anterior muscle) up to 1 hour to decrease Neuromyopathy complications and prolonged hospital stay.
Due to the condition of the patient we are looking to reduce the interaction with staff, the device will be placed with no
additional requirements. Physical therapy targets other physical performances, this device is aimed to improve blood flow,
tissue perfusion and muscle activation while the patient is non-responsive to physical activities. 
Phase II: 20 additional subjects with post-COVID-19 infection coming to the COVID-19 clinic at Baylor College of Medicine
for treatment of complications (i.e., hospital acquired weakness due to neuromyopathy). Patients 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. Gastronemius, tibial anterior muscle) up to 1 hour to recover from Neuromyopathy complications and
prolonged hospital stay. The patients will take the device home up to 4 weeks and will be screened once a week at the
COVID-19 clinic for neuromuscular evaluation.
Inclusion Criteria:
     
Age: Adults age 18 years or older
Disease status: COVID-19 test positive Critically ill requiring care in the hospital.

Patients must have been previously hospitalized due to COVID-19 infection and diagnosed with hospital acquired
weakness by pulmonary care specialists. Patients will have to be alert and conscious to sign the consent form. 

Exclusion Criteria:
     Subject 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.
F2.  Procedure
     Phase I:

Aim1 (to understand mechanism of action): Examine immediate benefit of lower extremity EE to improve venous return
flow, tissue oxygenation, and muscle activation (short term benefit). In this study, we will recruit a convenient sample of 20
hospital patients diagnosed with COVID-19 (short-term benefit). 

Optional:
Subjects will be assessed using Doppler ultrasound and near infrared imaging (Kent Imaging System) at pre-,
30min, 60min, and 30min post-treatment (after stopping of EE device). Lower extremity muscle activation will be assessed
by using sEMG (electromyography).

Patients will begin the study after being admitted to the hospital no more than 48 hours. 

Aim 2 (to examine effectiveness): Examine effectiveness of daily use of EE to treat CINM, and other associated major
adverse events (MAE) including deep vein thrombosis (DVT), cardiovascular events, and death. Participants will receive
standard of care plus adjunctive daily EE therapy using an FDA approved bio-electric stimulation technology (BEST)
platform (Tennant Biomodulator® PRO, AVAZZI A, Inc) during the entire length of stay in hospital. The device will be
provided by the research staff. 

We will assess incidence of neuropathy and myopathy during hospital discharge or 4 weeks, whichever comes first.
Neuropathy severity will be quantified using vibratory perception threshold (VPT) test. Myopathy will be assessed by
measuring changes in calf muscle circumstance, weight change from pre-hospital admission, and sEMG. In addition, we
will determine weakness using foot dynamometer and a validated frailty meter. Length of hospital stay and MAE
(documented via electronic health record) will be tracked for planning of future studies. Both extremities will have all
measurements and 1 hour electrical stimulation therapy at baseline. Daily treatment will performed up to 3 times per day,
but no more than 1 hour in total. 

Daily electrical stimulation will be administered by a nurse/staff involved in the hospital care. A chart will be signed to
register each therapy performed and will include a log of day and time of device application. 
Both electrical stimulation and EMG devices will have disposable pads, after usage they will be discarded. For the Devices

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they will be placed inside a plastic bag that will be disposed inside the room before exiting and sanitized (wipes) based
upon hospital protocols. 
The researchers will take digital photographs /videos throughout the study. This is done using a special camera for tissue
oxygen detection and visual images. This method is non invasive and does not cause any harm to the patient. **We will
blur the face out in the photographs/videos. We will only use videos and photos for scientific presentations or scientific
publications.
Phase II:
Patients 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 protocol will consist of 4 weeks of lower-extremity electrical stimulation. Opposite to our initial study, this modality will
consist of home-based therapy, meaning that the patient will take the device home and attend the clinic once a week for
screening and assessment of therapy. 
The protocol will be performed as the following description:
This trial will have 20 patients divided in two groups. Group 1
(intervention, n=10): Will receive an active Tennant Biomodulator
Group 2 (control, n=10): Will receive an inactive Tennant
Biomodulator
This study will consist of 5 visits total and one phone interview 12 weeks after baseline for both groups. The
patient will be compensated $50 per visit (total $250), with free parking.
Payment will only be available for subjects who
participate in Part II.
During the first and last visit, the research staff will turn the Tennant Biomodulator PRO® on for one hour and measure any
changes in muscle strength, endurance, and blood flow after the therapy. Once the first visit is over, the patient will take
the Tennat Biomodulator® home and will be instructed to turn it on for one hour every day for four weeks. 
The visits in-between will be performed in the following order:
1) Questionnaires (pain, weakness, sleep, quality of life,
frailty, depression, life and space, beck anxiety scale, Katz-daily living)
2) Musculoskeletal assessments (non-invasive
surface electromyography, vibration perception threshold)
3) Vascular assessments (non-invasive Near infra-red
spectroscopy)
After 4 weeks, the patients will turn back the device to the research staff. 
The supervision of this study will be by pulmonary care specialists, and the location will be at the recently open COVID-19
clinic at Baylor College of Medicine. 
 
Section G:  Sample Size/Data Analysis
G1.  Sample Size
How many subjects (or specimens, or charts) will be used in this study?
     Local: 40              Worldwide: 40
Please indicate why you chose the sample size proposed:
     
Sample size is convenient and selected based on available resources to demonstrate feasibility and the proof of concept
effectiveness of EE therapy for COVID-19 patients admitted to ICU and post-ICU. We plan to recruit 40 eligible subjects. 

G2.  Data Analysis
Provide a description of your plan for data analysis. State the types of comparisons you plan (e.g. comparison of means,
comparison of proportions, regressions, analysis of variance). Which is the PRIMARY comparison/analysis? How will the
analyses proposed relate to the primary purposes of your study?
     P-values of 0.05 or less will be considered statistically significant based on a two-sided test unless otherwise noted. All
variables will be tabulated descriptively at each scheduled time point (baseline and discharge date). For each continuous
variable, the analyses will include the mean, standard deviation, minimum and maximum. For each categorical variable,
the summary will include frequencies and percentages. Each variable will be analyzed using all available data. Baseline
variables will be summarized using descriptive statistics. We assume that a successful intervention is also helpful to
maintain subjects muscle mass, reduce neuromyopathy signs and increase venous return flow. The measured parameters
(e.g. muscle circumference, sEMG, kent imaging, doppler, etc.) should change substantially from baseline to the end of the
intervention. For example, the EMG amplitude values should show increased voltages. Next, for all continuous variables,
pre-treatment scores will be regressed on post-treatment scores to form residualized change scores (e.g. sEMG, VPT,
dynamometer, etc). Correlations will then be generated among these scores to determine whether changes in sEMG
factors are related appropriately with increases in (clinically assessed) functional capacities and self-report measures of
activities. ANOVA test will be used to examine significant difference between patients with severe risk factors for prolonged
ICU stage (e.g. age, BMI, cardiovascular morbidities). Moderator effects will also be examined for exploratory purposes.
Using gender as an example, mixed design ANOVAs will be conducted to determine whether mobility factors change over

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the course of treatment at different rates or with different patterns for men and women. Additional analyses will test
whether changes in muscle strenght and neuropathy (e.g. VPT and dynamometer assessement at time of discharge).
 
Section H:  Potential Risks/Discomforts
H1.  Potential Risks/Discomforts
Describe and assess any potential risks/discomforts; (physical, psychological, social, legal, or other) and assess the likelihood
and seriousness of such risks:
     
The risk to participants of this study is considered to be minimal in a controlled environment with an attendant present.
This research routine will not place subjects at higher risk than normal activities of daily living, and no more risk of harm or
discomfort is associated with these tests than the discomfort normally incurred while performing normal muscle stretching.
Subjects will be allowed rest time between trials as needed. The EMG device will detect level of fatigue and based on that
we will determine the lenght of the sessions. 

The devices and technology is completely non-¬invasive, safe, non-¬toxic and non- ionizing. The potential risks to subject
are minimal. However, like any battery powered systems, there is a minimum risk of sensor malfunctioning. In addition, the
study devices are not waterproof, and although they use a low powered battery (similar to a cellphone battery), in order to
avoid any risk of shock the monitor should not be submerged or saturated with fluids during operations or cleaning. It does
not emit any radiation to the human body, and does not offer any significant risk to the subject.

Subjects may experience mild discomfort from the sensor on their legs. We will inform the subject to please notify the
investigators if the sensor is uncomfortable.

All information we will collect about the subject will be stored in a secure location and coded in a way to maintain
confidentiality. Only study personnel will have access to their records. Data collected during the study may be published
and made publicly available. Data may also be shared with other research groups. However, data that could in any way
identify them will not be made public or shared.

Some of potential risks of using TENS therapy could be: * Skin related discomfort, such as tingling * Skin reaction to
adhesive patch.

If the tingling sensation is too intense for the participant, they have the ability to reduce the intensity for their best level of
comfort.

H2.  Data and safety monitoring plan
     Do the study activities impart greater than minimal risk to subjects?
          No
H3.  Coordination of information among sites for multi-site research
Is the BCM Principal Investigator acting as the SPONSOR-INVESTIGATOR for this multi-site research?
          No or Not Applicable
Is BCM the COORDINATING CENTER for this multi-site research?
          No or Not Applicable
 
Section I:  Potential Benefits
Describe potential benefit(s) to be gained by the individual subject as a result of participating in the planned work.
     There is potential benefit of prevention or improvement of hospital acquired weakness due to prolonged hospital stay for
participants, based on previous studies the electrical stimulation will improve blood flow, tissue perfusion and muscle
activation. The device is used to reduce pain. However, the proposed treatment may assist in preventing or improving
hospital-acquired Weakness because of prolonged hospital stay . In addition, the participation in this study may help the
investigators better understand how COVID19 may impact cause myopathy and neuropathy and how to best help these
patients to recover from prolonged hospital-stay .

Primary outcomes include neuropathy (assessed using VPT test); muscle function (assessed using sEMG), and tissue
oxygenation (assessed using Kent Imaging). Secondary outcomes include weakness (assessed using dynamometer);
muscle atrophy (assessed by weight loss as well as measuring ankle, calf, and thigh circumference); venous return flow
(Doppler US [optional]); frailty (frailtymeter [optiona]); hospital length of stay (patient medical record); and major adverse
events (patient health record). The primary and secondary outcomes will be assessed at baseline (if feasible) and on
biweekly basis up to 4 weeks or hospital discharge, whichever came first. Appropriate mixed models (linear for continuous
or Generalized Estimating Equations (GEEs) for non-continuous or non-parametric variables) will be used to test the
intervention effect for each of the primary (e.g., tissue perfusion, tissue oxygen delivery, neuropathy severity, and

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myopathy incident) or secondary (e.g., frailty, weight loss, MAE, etc) outcomes.
Also, participation may help the investigators design a practical assessing method to identify the impact of neuromyopathy
in the hospital setting. This may allow physicians to provide personalized care by monitoring muscle loss and limb
complications caused by prolonged hospital length of stay.
Describe potential benefit(s) to society of the planned work.
     
As described above, this type of work may allow physicians to provide more personalized care for hospitalized patients in
need of physical therapy for continuous and prolonged periods, specially when having a severe illness that includes
medical staff risk contact. 

Do anticipated benefits outweigh potential risks? Discuss the risk-to-benefit ratio.
     
This study brings no more than minimal risk to subjects as it only involves a non-invasive device. There are some risks
associated with lack of comfort from EE, skin allergy to the EE sticky patches that are used for delivering EE therapy, risk
associated with electrical mal-function of EE, and other unknown risks. All EE devices will be checked before any use to
minimize the risk associated with electrical malfunction. All EE devices are FDA approved for the purpose of pain
reduction. However, these devices have not been used before for purpose of managing COVID-19 side effects like the
purpose of this study.Although there is no direct benefit for participating in the study, their participation may help the
investigators design a practical assessing method to identify the impact of Neuromyopathy in the hospital(inpatient)
setting.
 
Section J:  Consent Procedures
J1.  Waiver of Consent
Will any portion of this research require a waiver of consent and authorization?
     No
 
J1a.  Waiver of requirement for written documentation of Consent
Will this research require a waiver of the requirement for written documentation of informed consent?
     No
J2.  Consent Procedures
Who will recruit subjects for this study?
     PI

PI's staff
Describe how research population will be identified, recruitment procedures, any waiting period between informing the
prospective participant and obtaining consent, steps taken to minimize the possibility of coercion or undue influence and
consent procedures in detail.
     Subjects will be recruited from the hospital. They may get some referrals from other collaborators. In order to recruit or
identify subjects, we will screen our patient charts for eligible subjects. The CO­I will identify eligible subjects and alert the
coordinator. The coordinator will review all the details of the study with the subject and/or their family. If the subject agrees
to participate in the study, they will be screened and then enrolled into the study.

We will be conducting the study during the first days of their stay in the hospital, in case the patient is not able to consent
we will ask for consent from their legal authorized representative. The legal representative will be consented the same way
the patient would but over the phone by stating the procedures/ benefits/ risks and ask questions. 

For patients who lack the capacity to consent, the investigator/designee may explain the study to the legally authorized
representative by phone. The discussion will be documented in the subject's medical record or research chart. Two copies
of the unsigned consent form will be sent to the subject/legal representative with instructions for completion of the
signature page and assent (if applicable). Signatures will be obtained according to standard Baylor IRB regulations. The
subject will be told to keep one form and returned the other to the investigator by mail, email, or fax. The Baylor
Investigator/designee will sign the consent form when returned from the subject. The signed consent form will be
maintained in research records.

When they regain consciousness the subject will be fully informed about the study, and will verbalize understanding and
voluntarily agree to participate with the guidelines as stipulated in the informed consent. The subject will be informed if
he/she can withdraw from the study at any time without loss of benefits. Consent forms will be signed and dated by the
subject and by the Principal Investigator or Investigators. The original (with patient's signature) will be maintained per IRB
policy. Any critical information will be sent for inclusion in the medical records, if it affects patient¿s well-being and any

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future treatment. A signed copy of the consent form will be provided to the patient. Informed consent will be obtained prior
to performance of any study procedures. Specifically: 1. No minors will be consented. 2. Subjects are given as much time
as needed to ask questions and read over the consent. They are will be given a copy of the consent and can return at a
later date if they need to discuss it with family members, etc.
There will be an attachment in section S for the waiver of consent the form was retrieved from Section J- Adult assent. 
Phase II:
Subjects will be recruited from the COVID-19 clinic. They may get some referrals from other collaborators. In order to
recruit or identify subjects, we will screen our patient charts for eligible subjects. The CO­I will identify eligible subjects and
alert the coordinator. The coordinator will review all the details of the study with the subject and/or their family. If the
subject agrees to participate in the study, they will be screened and then enrolled into the study.
We will be conducting the study from the first visit to the COVID-19 clinic until 4 weeks. The patients enrolled will have to
be alert and aware, there will not be patients with loss of consciousness enrolled in this phase.
Are foreign language consent forms required for this protocol?
     No
J3.  Privacy and Intrusiveness
Will the research involve observation or intrusion in situations where the subjects would normally have an expectation of
privacy?
     No
J4.  Children
Will children be enrolled in the research?
     No
J5.  Neonates
Will non-viable neonates or neonates of uncertain viability be involved in research?
     No
J6.  Consent Capacity - Adults who lack capacity
Will Adult subjects who lack the capacity to give informed consent be enrolled in the research?
     Yes
J7.  Prisoners
Will Prisoners be enrolled in the research?
     No
 
Section K:  Research Related Health Information and Confidentiality
Will research data include identifiable subject information?
     Yes
Information from health records such as diagnoses, progress notes, medications, lab or radiology findings, etc.
     Yes
Specific information concerning alcohol abuse:
     Yes
Specific information concerning drug abuse:
     Yes
Specific information concerning sickle cell anemia:
     No
Specific information concerning HIV:
     No
Specific information concerning psychiatry notes:
     No

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Demographic information (name, D.O.B., age, gender, race, etc.):
     Yes
Full Social Security #:
     No
Partial Social Security # (Last four digits):
     No
Billing or financial records:
     Yes
Photographs, videotapes, and/or audiotapes of you:
     Yes
Identifiable biospecimens
     No
Other:
     No
At what institution will the physical research data be kept?
     The physical research will be kept in our BCM offices housed in the Mcnair Building room B10.401.
How will such physical research data be secured?
     Data will be kept in locked file cabinets that only the research team has access to.
At what institution will the electronic research data be kept?
     
Data will be kept locked on network computers in our BCM offices, under the password protected server.

Address:\\discovery1.ad.bcm.edu\bcm-dept-icamp
Such electronic research data will be secured via BCM IT Services- provided secured network storage of electronic research
data (Non-Portable devices only):
     Yes
Such electronic research data will be secured via Other:
     No
Will there be anyone besides the PI, the study staff, the IRB and the sponsor, who will have access to identifiable research
data?
     
Yes, identify the classes of the persons:

People who ensure quality from the institutions where the research is being done, federal and other regulatory agencies
will have access to all of the research data.
Please describe the methods of transmission of any research data (including PHI, sensitive, and non-sensitive data) to
sponsors and/or collaborators.
     Transmissions, if any, will only happen via secure emails.
 
Will you obtain a Certificate of Confidentiality for this study?
     No
Please further discuss any potential confidentiality issues related to this study.
     NA
 
Section L:  Cost/Payment
Delineate clinical procedures from research procedures. Will subject's insurance (or subject) be responsible for research
related costs? If so state for which items subject's insurance (or subject) will be responsible (surgery, device, drugs, etc). If
appropriate, discuss the availability of financial counseling.
     
All clinical/standard procedures will be billed to the subject's insurance. These include, physician visits, debridement,
medications prescribed by physician.

There will be no research procedures charged to the subject or their insurance. This includes, the research device,
materials provided by the research team, visits with the research team.

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If subjects will be paid (money, gift certificates, coupons, etc.) to participate in this research project, please note the total
dollar amount (or dollar value amount) and distribution plan (one payment, pro-rated payment, paid upon completion, etc) of
the payment.
Dollar Amount:
     250
Distribution Plan:
     
For taking part in this research, the subject may be paid a total of $250. Their compensation will be broken down as
follows:
Subjects will be paid $50 for every visit completed visit. There are a total of 5 visits. Payments will be done using the
ClinCard method. Their SSN will be requested for the research team to issue the payments. The research study will also
cover the subject's parking or transportation expenses to go to their research visits.
 
Section M:  Genetics
How would you classify your genetic study?
     
Discuss the potential for psychological, social, and/or physical harm subsequent to participation in this research. Please
discuss, considering the following areas: risks to privacy, confidentiality, insurability, employability, immigration status,
paternity status, educational opportunities, or social stigma.
     
Will subjects be offered any type of genetic education or counseling, and if so, who will provide the education or counseling
and under what conditions will it be provided? If there is the possibility that a family's pedigree will be presented or published,
please describe how you will protect family member's confidentiality?
     
 
Section N:  Sample Collection
None
 
Section O:  Drug Studies
Does the research involve the use of ANY drug* or biologic? (*A drug is defined as any substance that is used to elicit a
pharmacologic or physiologic response whether it is for treatment or diagnostic purposes)
     No
Does the research involve the use of ANY gene transfer agent for human gene transfer research?
     No
O1.  Current Drugs
 
Is this study placebo-controlled?
     No
Will the research involve a radioactive drug?
     No
 
Section P:  Device Studies
     Does this research study involve the use of ANY device?
          Yes
Device 1:  Trigno Wireless EMG System
Device 2:  Tennat Biomodulator
 
Section Q:  Consent Form(s)

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Effectiveness of lower extremity electrical stimulation therapy in patients with COVID-19
 
Section R:  Advertisements
None