Neuromodulation for Prevention of Intensive Care Unit Acquired Weakness and Post Intensive Care Syndrome
Phase: NA
Conditions: Muscle Atrophy, Muscle Weakness, Blood Flow
Sponsor: Bijan Najafi, PhD

 
 
Institutional Review Board for Baylor College of Medicine and Affiliated
Hospitals
 
Protocol Number:    H-52968
Status:                        Draft
Initial Submit Date:  1/9/2023
 
Section Aa:  Title & PI
A1.  Main Title
     NEUROMODULATION FOR PREVENTION OF INTENSIVE CARE UNIT ACQUIRED WEAKNESS AND POST
INTENSIVE CARE SYNDROME - PROOF OF CONCEPT RANDOMIZED CONTROLLED TRIAL
A2.  Principal Investigator
 
     Name:  
ROBERT RIPLEY
Phone:  
7137982881
     Id:  
204713
Fax:  
     Department:   SURGERY: GENERAL THORACIC
Email:   
ripley@bcm.edu
     Center:  
Mail Stn:   BCM390
A3.  Administrative Contact
 
     Name:
MARIA NOUN
Phone:  
7137987537
     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:  
MUHAMMAD SIDDIQUE
Phone:  
7137982678
Id:  
174166
Fax:  
713 7982688
Department:   MEDICINE: PULMONARY
Email:   
siddique@bcm.edu
Center:  
Mail Stn:   BCM621
 
     Name:  
CHRISTOPHER HOWARD
Phone:  
7137985840
Id:  
177856
Fax:  
Department:   MEDICINE: PULMONARY
Email:   
ch5@bcm.edu
Center:  
Mail Stn:   BCM620
 
     Name:  
GABRIEL LOOR
Phone:  
8323553000
Id:  
196765
Fax:  
Department:   SURGERY
Email:   
loor@bcm.edu
Center:  
Mail Stn:   BCM390
 
     Name:  
NAIMA RODRIGUEZ
Phone:  
7137987537
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Id:  
202557
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
naimar@bcm.edu
Center:  
Mail Stn:   BCM390
 
     Name:  
ALEJANDRO ZULBARAN Y ROJAS
Phone:  
7137982375
Id:  
231680
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
231680@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
PUNEET GARCHA
Phone:  
Id:  
233350
Fax:  
Department:   MEDICINE: PULMONARY
Email:   
233350@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
RANDALL KIRBY
Phone:  
Id:  
239372
Fax:  
Department:   GRADUATE MEDICAL EDUCATION
Email:   
u239372@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
RASHA BARA
Phone:  
Id:  
240838
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
u240838@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
SCOTT LEIKIN
Phone:  
Id:  
242761
Fax:  
Department:   ANESTHESIOLOGY
Email:   
u242761@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
RAMIRO FERNANDEZ II
Phone:  
Id:  
246155
Fax:  
Department:   SURGERY: GENERAL THORACIC
Email:   
u246155@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
MOHAMMED MERCHANT
Phone:  
Id:  
247601
Fax:  
Department:   MEDICINE: PULMONARY
Email:   
u247601@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
MIGUEL BARGAS OCHOA
Phone:  
Id:  
251804
Fax:  
Department:   SURGERY: RESEARCH
Email:   
u251804@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
BERNARDO MARTINEZ LEAL
Phone:  
7137982715
Id:  
252946
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
u252946@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
JAMES HERLIHY
Phone:  
7137982400
Id:  
993122
Fax:  
713 7982791
Department:   MEDICINE: PULMONARY
Email:   
jherlihy@bcm.edu
Center:  
Mail Stn:   BCM621
 
     Name:  
DONAL PALENCIA
Phone:  
Id:  
Non-Baylor
Fax:  
Institution:  
CHI St Luke's Health
Email:   
donal.palencia@commonspirit.org
Address:  
1101 Bates Ave, Houston, TX 77030
 
     Name:  
JOHN SABO
Phone:  
Id:  
Non-Baylor
Fax:  
Institution:  
CHI St Luke's Health
Email:   
john.sabo@commonspirit.org
Address:  
1101 Bates Ave, Houston, TX 77030
 
     Name:  
LEONARD BRADLEY
Phone:  
Id:  
Non-Baylor
Fax:  
Institution:  
St Luke's Medical Center
Email:   
leonard.bradley@commonspirit.org
Address:  
6720 Bertner Ave, Houston, TX 77030
 
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     Name:  
BIANCA JENKINS
Phone:  
Id:  
Non-Baylor
Fax:  
Institution:  
St Luke's Medical Center
Email:   
bianca.jenkins@commonspirit.org
Address:  
6720 Bertner Ave, Houston, TX 77030
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. ClinicalTrials.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
     Not Applicable
 
Section C:  Background Information
     Post-intensive care syndrome (PICS) is a collection of new or worsening physical, cognitive and psychiatric symptoms that
continue to persist after a patient leaves the intensive care unit (ICU). PICS is mainly triggered by serious conditions such
as respiratory failure, sepsis, multisystem organ failure, use of endotracheal tubes, mechanical ventilators, use of sedative
and intravenous corticosteroids, post-surgical complex procedures, and prolonged duration of the bed-restore. Previous
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studies have reported a 64%-84% prevalence of PICS up to 12 months in patients with at least 2 days of ICU length of
stay and/or mechanical ventilation. Therefore, patients do not return to their former level of function for weeks, months and
even years. This has led PICS to be recognized as a public health burden.
Particularly, the physical problems of PICS are of high concern because of its consequences regarding functional
impairment. This include neuromuscular weakness with no plausible cause other than critical illness described as flaccid
and symmetric paralysis provoked by polyneuropathy (axonal loss of motor and sensory fibers), myopathy (myosin loss) or
a combination of both. Ultimately, ending in joint and muscle contractures that worsens with malnutrition. Experts refer to
this condition as ICU-Acquired weakness (ICUAW), possibly seen in any extremity. However, the lower level attributes to
the worse consequences post-ICU discharge.
In ICUAW, affection to the lower extremity can be seen in 32.3%. Mainly due to prolonged periods of immobilization or
sedation, that lead to atrophy and dysfunction in the quadriceps and gastrocnemius muscles. The consequences are
reduced 6-minute walk test distance, reduced ability to perform activities of daily living, and reduced ability to return to
driving and paid employment. In healthy individuals, strict bed rest causes a 1% decrease in muscle strength per day.
Casting limbs such as in orthopedic injuries has been shown to result in 25% decrease in muscle strength in 7 days.
Therefore, in ICU patients, this problem should be approached as prompt as admission. A recent systematic review (Qin
ES et al) in 10 studies (n = 985) found that early mobilization decreased the incidence of ICUAW at hospital discharge,
increased the number of patients who were able to stand, and increased the number of ventilator-free days during
hospitalization. However, reduced hospital staff or increased burden can be a limitation for providing assisted mobilization.
A practical solution to address these limitations is the use of electrical stimulation (E-Stim). In this matter, AVAZZIA Inc.
(Dal, TX, USA) has created an E-Stim device (Tennant Biomodulator PRO) that works on a high voltage alternative pulsed
current (HVAPC) to address lower-extremity muscle weakness, endurance, pain, and neuropathy. This technology works
through a symmetric biphasic waveform that achieves deep stimulation of the muscle fibers. In our previous trial in ICU
COVID-19 patients (NCT04685213, H-47781-A), we demonstrated HVAPC improves gastrocnemius muscle endurance
without burnout of oxygen consumption. Other ICU studies (Nussbau et al.) have demonstrated E-Stim is feasible to
preserve strength and muscle mass, and reduce muscle degradation leading to maintenance of functional capacity. Its
benefit has seen to be higher when placed in hams and calf muscles bilaterally, in a supine position, and administered 5-7
days a week or until extubation or hospital discharge. Another benefit has been linked to neural adaptations.
Studies have 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. In our previously mentioned trial (NCT04685213, H-47781-A), dynamometer tests were difficult to obtain
due to patient sedation, medical paralyzation or intubation. Moreover, calf circumference was altered in patients with
present edema. Even though we did not assess MRC score or quality of life questionnaires, lack of feasibility also applies
for this measurements because it requires awareness of the patient. Therefore, objective measurements that do not
depend or interfere with the patient status are needed to evaluate the progress/effectiveness of E-Stim therapy.
Quantitative neuromuscular ultrasound is emerging as a potential research and diagnostic tool but is not a clinical standard
of care. Although creatinine kinase may be elevated in patients with ICUAW, there are no validated biomarkers used for
diagnosing ICUAW. In our previous trials (NCT04685213, H-47781-A; NCT05198466, H-47781-B), surface
electromyography (sEMG) has been able to detect muscle endurance in response to E-Stim. This parameter was
associated with a decreased likelihood to fall at the time of ICU discharge, and an increase in muscle perfusion of Post-
COVID-19 patients with neuromuscular sequelae. This suggests that sEMG can be an objective and feasible muscle
assessment for ICU patients regardless of awareness. Moreover, Moss et al. reported that sural sensory nerve conductive
assessment yielded a sensitivity of 100% with a specificity of 81% to diagnose neuromyopathy due to ICUAW. Therefore,
we purpose to utilize a nerve conductive/amplitude assessment tool of the sural nerve called DPN Check device
(Neurometrix Inc.).
Lastly, our institution has a high volume of intensive care units (N=10) (Baylor St Luke’s Medical Center, Houston, TX,
USA) supervised by specialists in critical, intensive, and post-surgical care. Therefore, we believe our institution is a
suitable place to perform this study.
 
Section D:  Purpose and Objectives
     
Aim 1. Acceptability: To examine feasibility and acceptability of lower extremity neuromodulation in patients at risk of
ICUAW. H1.1: The adherence to daily use of lower extremity neuromodulation is more than 80% among the IG. Adherence
is defined as the use of lower extremity neuromodulation at least one hour per day for at least 4 days per week. H1.2: The
perceived acceptability, and perceived benefit would be high among IG.
Aim 2. Proof of concept effectiveness: To examine effectiveness of lower extremity neuromodulation for intubated patients
at risk of ICUAW H1.1: E-Stim will improve motor function including muscle endurance and thickness, nerve conductivity
and amplitude, by utilizing objective assessments (surface electromyography, ultrasound, dynamometry), after 4 weeks of
application or hospital discharge, whichever comes first. H1.2: E-Stim will improve lower extremity nerve function and
tissue perfusion after 4 weeks of application or until hospital discharge, whichever comes first. The nerve function
parameters will be measured with assessed with a digital test (DPN Check) for peripheral neuropathy and the perfusion
parameters will be assessed using a near infrared spectroscopy using a validated imaging system (Kent Imaging System).
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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, Spanish
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 the cognitive impairment of intubated patients under ventilatory assistance, the consent will be obtained from the
patient legal authorized representative (LAR). The LAR is determined as an individual or judicial or other body authorized
under applicable law to make decisions on behalf of another individual. The LAR may provide consent on behalf of a
prospective subject to the subject’s participation in research. The terms surrogate decision maker or surrogate consent are
also sometimes used. The LAR may be a family member or caregiver who has the legal authority to grant consent on
behalf of another who has been invited to participate in research. The LAR will give consent by agreeing with the
procedures/ benefits/ risks and participation. All questions/doubts from the LAR about the study will be clarified. When the
patient regain consciousness or ability to consent, he/she will be fully informed about the study, and the research staff will
obtain their signature. In order to reconsent, the patient will need to be fully aware in time, space, and person. The signed
consent form will be maintained in research records.
The subject and/or LAR 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, LAR and by the Principal Investigator or Investigators. The original consent
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 future treatment. A signed copy of the consent form will be provided to the patient and LAR.
Informed consent will be obtained prior to performance of any study procedures. Specifically: 1. No minors will be
consented. 2. Subjects' LAR 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.
Sub-population: We will recruit patients undergoing surgery in need of post-surgical ICU admission at BSLMC. This
population is at risk of ICUAW. Patients will be consented either before surgery, or by a LAR on the day of surgery as
described above.
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.
     
We will prospectively recruit 40 patients at risk of ICUAW. Sample size is convenient and designed to explore acceptability
and feasibility of objective tools for measurement. Eligible participants will be screened at BSLMC. Those who satisfied the
inclusion and exclusion criteria and signed the informed consent form will be randomly assigned with ratio of 1:1 into two
groups. Consenting will be performed with a legal authorized representative (LAR) that is present. When the subject
regains consciousness and is aware in time, space, and person, he/she will be re-consented. If the subject decline to
continue participation in the study, the subject will be withdrawn. The informed consent will obtained from all participants
and their LAR.
Sub-population: Post-surgical patients that are admitted to the ICU will be consented either before surgery, or by a LAR on
the day of surgery as described above.
The study will be double-blinded (clinicians and patients) in intervention (IG) and control (CG) group. Both cohorts will be
followed-up and monitored at 3 days, and then weekly for a total period of 4 weeks or until hospital discharge, whichever
comes first. • Intervention group (IG). The IG (n=20) will be undergoing E-Stim therapy with an active device during the
hospitalization period until 4 weeks or discharge, whichever comes first. To deliver E-Stim, 2 electrodes will be placed in
each proximal gastrocnemius and Achilles tendons. • Control Group (CG). The CG (n=20) will be undergoing E-Stim
therapy with a placebo device (5-10% currents) as described in the IG.
Inclusion Criteria:
     
-Any patient older than 18 years old admitted to the ICU within two days. -Patient can be intubated with ventilatory
assistance or not.
Exclusion Criteria:
     
- Less than 48 hours of ICU stay - Major foot problems such as active lower extremity wounds, major foot deformity (e.g.,
Charcot Foot), and/or previous major amputations - Demand-type cardiac pacemaker, implanted defibrillator, or other
implanted electronic devices - Any conditions that may interfere with outcomes or increase the risk of the use
neuromodulation therapy based on the judgement of clinicians
F2.  Procedure
     Patients admitted to the ICU within 2 days will be eligible and enrolled in the study after obtaining consent form as
previously indicated.
Then, we will perform baseline measurements that include:
(Primary outcomes) Myopathy test: gastrocnemius muscle endurance (surface electromyogram, Trigno Delsys) in
response to 5 minutes of neuromodulation; and muscle thickness (gastrocnemius muscle ultrasound, Vscan Air).
(Secondary outcomes) Perfusion test: Plantar foot perfusion parameters (near infrared spectroscopy, Kent Imaging
System). The Snapshot NIR camera is a non-invasive imaging device that visualizes and maps tissue oxygen saturation,
oxyhemoglobin, and deoxyhemoglobin from the microvascular network of a particular area of the skin. The SnapShot NIR
camera is classified as an oximeter, tissue saturation device. As indicated in the 510 (k) summary by Kent Imaging, the
NIR SnapshotNIR is a class II device intended for use by healthcare professionals as a non-invasive tissue oxygenation
measurement system that reports an approximate value of: - oxygen saturation (St02), - relative oxyhemogoblin level
(Hb02), and - relative deoxyhemoglobin (Hb) level. SnapshotNIR is based on multispectral imaging technology and
performs spectral analysis at each point in a two-dimensional scanned area producing an image displaying information
derived from the analysis. In the present study, this device has no diagnostic, decision making, nor treatment intent, it is an
assessment camera for tissue perfusion status in real time. The camera is positioned 30-50 cm away from the desired skin
area, and a picture is taken. The pictures will be collected from the plantar foot of the patients as in our previous protocols
for electrical stimulation (H-47781, H-50753). The data collected will determine whether lower-extremity electrical electrical
stimulation improves perfusion to the distal foot by comparing each time point vs baseline and by group comparison
(placebo vs active device).
Neuropathy test: Sural nerve conduction/amplitude assessment (neuropathy, DPNCheck Device by Neurometrix Inc)
Biomarkers tests: Creatinine kinase, C-reactive protein, creatinine, potassium, myosin, serum lactate, arterial SpO2,
dupplex ultrasound for DVT will be collected from the electronic medical records. If biomarkers were not collected as a
standard/regular procedure in the ICU; data will not be extracted from the electronic medical records. Research staff will
not draw any blood samples.
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Then, the patients will receive an individually programmed device to deliver neuromodulation to both gastrocnemius
muscles simultaneously. The frequency of therapy will be 1 hour daily, and the duration will be up to 4 weeks or until
hospital discharge, whichever comes first.
The coordinator will provide the ICU staff with a weekly spreadsheet showing utilization (therapy sessions/day) so
compliance can be monitored. Also, the devices will monitor the time of usage to confirm hours of effective
neuromodulation therapy to the skin.
Follow-up assessments will be performed at 3 days, and then weekly until 4 weeks or until hospital discharge, whichever
comes first, by the research staff. The follow-up assessment will be identical to the baseline assessment.
In the final visit, we will assess muscle strength (ankle dynamometer, RoMech Digital Hanging Scale).
Additional measurements: - 1-month post-hospital discharge phone questionnaires: instrumental activity of daily living
scale (IADL), community engagement (the Life Space Questionnaire), independence in daily living activities (KATZ), and
anxiety (BAI).
 
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 neuromodulation therapy for 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?
     
Statistical Design: Independent t-test, U-test, or Chi-square (depends on type of variables) will be used to compare
between groups (IG, and CG for key baseline descriptors including demographics and relevant clinical characteristics).
Those descriptors which showed statistical significant difference will be considered as covariates for adjusting the results in
the following assessments. 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 or
secondary outcomes. Results will be adjusted by covariates as described above.
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, follow up 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 perfusion. The measured parameters (e.g.
sEMG, US, strength, Kent imaging, DPN Check, 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, US,
strength, Kent imaging, DPN Check, 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 at 1 month post-hospital discharge. 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.
 
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 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
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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 neuromodulation therapy could be: * Skin related discomfort, such as tingling * Skin
reaction to adhesive patch.
Some of potential risks of using DPN Check could be: * Skin related discomfort, such as tingling *
If the tingling sensation is too intense for the participant, they have the ability to reduce the intensity for their best level of
comfort.
The risk to participants due to the optional assessments and surveys is considered minimal because all that is required is
simple walking and balance movements 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.
Potential risk to the subject due to the pulse oximeter optional test is considered minimal; this device is non-invasive, non-
toxic, and non-ionizing. The device will be placed on the subject's finger, and monitor their oxygen levels.
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 ICU stay, based on previous
studies the neuromodulation therapy will improve blood flow, tissue perfusion and muscle activation. In addition, the
participation in this study may help the investigators better understand the prevention of ICU-acquired weakness and post-
ICU syndrome and may determine if this therapy has an impact in daily leaving and activities after getting discharged from
the hospital.
Primary outcomes include myopathy (sEMG) and neuropathy (DPN Check) assessment. Secondary outcomes include
perfusion (Kent Imaging), and biomarkers. This therapy will also help to determine if hospital length of stay, and time for
extubating can be reduced (patient health record). The primary and secondary outcomes will be assessed at baseline, 3
days, and then weekly after completing 4 weeks or until hospital discharge, whichever comes 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 or secondary outcomes.
Also, participation may help the investigators design a practical assessing method to identify the impact of neuromyopathy
in the hospital setting and the prevention or reduction of post-ICU syndrome. 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 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.
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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 neuromodulation, skin allergy to the neuromodulation sticky patches/electrode pads
that are used for delivering neuromodulation therapy, risk associated with electrical mal-function of neuromodulation, and
other unknown risks. All neuromodulation devices will be checked before any use to minimize the risk associated with
electrical malfunction. All neuromodulation devices are FDA approved for the purpose of pain reduction and have been
used for lower extremity muscle weakness prevention in our previous trial for ICU COVID-19 patients (Zulbaran-Rojas et
al, Frontiers in Medicine, 2022). However, these devices have not been used before for purpose of reducing or preventing
post-ICU syndrome. 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 (ICU) 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. The recruitment process will be the same
for English and Spanish patients, we are only adding the Spanish consent in the event a subject who's primary language is
not English can be consented. We have a bilingual Research Coordinator who will explain the consent and conduct the
visit in the subjects primary language.
We will be conducting the study during the first 48 hours of intubation at the ICU. Consent will be obtained from the patient
legal authorized representative (LAR). The LAR is determined as an individual or judicial or other body authorized under
applicable law to make decisions on behalf of another individual. The LAR may provide consent on behalf of a prospective
subject to the subject’s participation in research. The terms surrogate decision maker or surrogate consent are also
sometimes used. The LAR may be a family member or caregiver who has the legal authority to grant consent on behalf of
another who has been invited to participate in research. The LAR will give consent by agreeing with the procedures/
benefits/ risks and participation. All questions/doubts from the LAR about the study will be clarified. When the patient
regain consciousness or ability to consent, he/she will be fully informed about the study, and will the research staff will
obtain their signature. In order to reconsent, the patient will need to be fully awake in time, space, and person. The signed
consent form will be maintained in research records.
The subject and/or LAR 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, LAR and by the Principal Investigator or Investigators. The original consent
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 future treatment. A signed copy of the consent form will be provided to the patient and LAR.
Informed consent will be obtained prior to performance of any study procedures. Specifically: 1. No minors will be
consented. 2. Subjects' LAR 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.
Are foreign language consent forms required for this protocol?
     Yes
Which of the following ways will you document informed consent in languages other than English?
     A full-length informed consent document
J3.  Privacy and Intrusiveness
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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:
     No
Specific information concerning drug abuse:
     No
Specific information concerning sickle cell anemia:
     No
Specific information concerning HIV:
     No
Specific information concerning psychiatry notes:
     No
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:
     No
Photographs, videotapes, and/or audiotapes of you:
     Yes
Identifiable biospecimens
     No
Other:
     No
At what institution will the physical research data be kept?
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     The physical research will be kept in our BCM offices housed in the McNair Building room B01.529.
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
Additional electronic data may be stored on REDCap. REDCap is hosted by Baylor College of Medicine - Institute for
Clinical & Translational Research.
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:
     
Yes, (describe below):
Electronic data will be stored using the REDCap (Research Electronic Data Capture) software. This software is used to
electronically collect and manage research data. REDCap is a secure, web-based platform.
Electronic data will also be stored and secured under the password protected server provided by BCM IT Services.
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.
     N/A
 
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.
     
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.
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:
     0
Distribution Plan:
     N/A
 
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.
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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
Device 3:  Snapshot NIR
Device 4:  DPNCheck
Device 5:  Vscan Air
 
Section Q:  Consent Form(s)
Neuromodulation Therapy for Lower Extremity in ICU Patients
 
Section R:  Advertisements
None
 
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