Transcutaneous Electrical Nerve Stimulation for Lower Extremity in Patients With Neurogenic Pain - A Proof Concept Randomized Clinical Trial
Phase: NA
Conditions: Chemotherapy-induced Peripheral Neuropathy, Pain, Neuropathy
Sponsor: Baylor College of Medicine

 
 
Institutional Review Board for Baylor College of Medicine and Affiliated
Hospitals
 
Protocol Number:    H-50753
Status:                        Closed
Initial Submit Date:  10/27/2021
 
Section Aa:  Title & PI
A1.  Main Title
     TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION FOR LOWER EXTREMITY IN PATIENTS WITH
NEUROGENIC PAIN - A PROOF OF CONCEPT RANDOMIZED CLINICAL TRIAL
A2.  Principal Investigator
 
     Name:  
BIJAN NAJAFI
Phone:  
7137987536
     Id:  
191680
Fax:  
     Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
najafi@bcm.edu
     Center:  
Mail Stn:   BCM390
A3.  Administrative Contact
 
     Name:
MARIA NOUN
Phone:  
7137987537
     Id:  
204533
Fax:  
     
Email:   
noun@bcm.edu
     
Mail Stn:   BCM390
 
Section Ab:  General Information    
A4.  Co-Investigators
 
     Name:  
FIDAA SHAIB
Phone:  
7137988585
Id:  
130911
Fax:  
713 7983303
Department:   MEDICINE: PULMONARY
Email:   
shaib@bcm.edu
Center:  
Mail Stn:   BCM902
 
     Name:  
DIPABEN MODI
Phone:  
7137988929
Id:  
190680
Fax:  
713 7982688
Department:   MEDICINE: PULMONARY
Email:   
ddmodi@bcm.edu
Center:  
Mail Stn:   BCM902
 
     Name:  
NAIMA RODRIGUEZ
Phone:  
7137987537
Id:  
202557
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
naimar@bcm.edu
Center:  
Mail Stn:   BCM390
 
     Name:  
ANTHONY COSTALES
Phone:  
7137983495
Id:  
208504
Fax:  
Department:   OB-GYN: ADMINISTRATIVE
Email:   
costales@bcm.edu
Center:  
Mail Stn:   125084
 
     Name:  
ALEJANDRO ZULBARAN Y ROJAS
Phone:  
7137982556
Id:  
231680
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
231680@bcm.edu
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
1/12

Center:  
Mail Stn:  
 
     Name:  
SHALINI MAKAWITA
Phone:  
Id:  
240188
Fax:  
Department:   MEDICINE: HEMATOLOGY & ONCOLOGY
Email:   
u240188@bcm.edu
Center:  
Mail Stn:   BCM904
 
     Name:  
RASHA BARA
Phone:  
Id:  
240838
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
u240838@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
MYEOUNGGON LEE
Phone:  
Id:  
242415
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
u242415@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
SHALINI PATEL
Phone:  
7137987536
Id:  
247197
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
u247197@bcm.edu
Center:  
Mail Stn:   BCM390
 
     Name:  
MAARIA MUSTAFA
Phone:  
7137987640
Id:  
247330
Fax:  
Department:   MOLECULAR & CELLULAR BIOLOGY
Email:   
u247330@bcm.edu
Center:  
Mail Stn:   BCM215
 
     Name:  
SYED MURTAZA KAZMI
Phone:  
7137987536
Id:  
247356
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
u247356@bcm.edu
Center:  
Mail Stn:   BCM390
 
     Name:  
MIGUEL BARGAS OCHOA
Phone:  
Id:  
251804
Fax:  
Department:   SURGERY: VASCULAR SURGERY DIV.
Email:   
u251804@bcm.edu
Center:  
Mail Stn:  
 
     Name:  
BENJAMIN MUSHER
Phone:  
7137983750
Id:  
691891
Fax:  
7137983342
Department:   MEDICINE: HEMATOLOGY & ONCOLOGY
Email:   
blmusher@bcm.edu
Center:  
Mail Stn:   BCM904
A5.  Funding Source:
     Organization:  NATIONAL SCIENCE FOUNDATION (NSF);BAYLOR COLLEGE OF MEDICINE (BCM)
A5a. Associated ESP2 funding proposal linked to this protocol:
A6a.  Institution(s) where work will be performed:
     BCM: Baylor College of Medicine
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?
     Not set yet
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
2/12

 
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:
     NCT05200858
 
Section B:  Exempt Request
B.  Exempt From IRB Review
     Not Applicable
 
Section C:  Background Information
     Neurogenic pain (NP) arises or is caused by central or peripheral nervous system dysfunction. The types of NP can be
derived from its origin including: 1) central, due to a lesion derived from the brain and/or spinal cord; 2) neuropathic, due to
injury to a peripheral nerve, or 3) deafferentation, due to stemming from loss or interruption of sensory nerve fiber
transmissions. Each of these types may manifest with different pain characteristics in relation to frequency, duration,
intensity, and severity. The most common NP are peripheral neuropathy or fibromyalgia. Standard of care treatment for
these conditions is pharmacologic-derived; however, other alternatives such as transcutaneous electrical nerve stimulation
(TENS) have demonstrated its ability to manage pain in patients with peripheral neuropathy (Najafi et al, JDST, 2017) and
fibromyalgia (Jamison et al, JPR, 2021).
In this matter, Neurometrix Inc. (Woburn, MA, USA) has created a wireless TENS device (Quell®) to address pain and its
associated symptoms (fatigue, reduced gait, sleep). This technology is a portable wireless non-invasive device placed in
the lower-extremity that works through the stimulation of nerves that carry non-painful sensations (A-beta fibers) by closing
a neurological "gate" in the spinal cord, thus, reducing transmission from pain nerves (A-delta and C fibers) to the brain.
This device utilizes a wireless technology manageable through a smart phone application (Quell App) that also tracks
symptom-status. Unlike other devices, it utilizes position and motion sensing to automatically adjust stimulation to the
patient both day and night. The device is practical by connecting via bluetooth to a smartphone/smartwatch apps that help
the patient personalize and control their treatment.
The Quell® device has been employed for treatment of various NP etiologies such as fibromyalgia, chemotherapy induced
peripheral neuropathy (CIPN), chronic back pain, post-acute sequelae of Sars-Cov-2 (PASC), neuromyelitis optica
spectrum disorder, restless leg syndrome, and painful diabetic neuropathy. Recently, Quell® has received FDA
breakthrough device designation for treatment of fibromyalgia and CIPN.
We purpose the use of Quell TENS device to explore its benefits in patients with NP derived by different etiologies.
Study #1: One population that has shown vast symptoms related to NP includes PASC. This is an emerging entity that has
been clearly recognized by musculoskeletal pain, fatigue, cognitive, and sleep disturbances, among other symptoms, in
patients who have recovered from severe Sars-CoV-2 infection. Hospitalized survivors have reported a significant excess
burden of many of these symptoms up to 8 months after discharge. Particularly in the lower extremity, NP and
musculoskeletal illness has been associated with prolonged immobilization, high-risk comorbidities, and the use of
glucocorticoids that is commonly administered to these patients. These manifestations are the cardinal symptoms of
fibromyalgia, a condition thought to be caused by hyperactive sensory signaling due to central sensitization as well as
deficient endogenous pain inhibition, triggered among others, by viral infections. Consequently, fibromyalgia sequelae are
one of the most common long-term complications seen in PASC. Thus, it is expected to impose a serious burden on
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
3/12

different medical specialties in a near future. In a population that has persistent lack of symptom resolution such as
fibromyalgia, adherence to therapy could be challenging. Patients with constant pain, fatigue, and sleep disturbances, are
difficult to keep motivated, especially those pain-medication dependents that often present low quality of life. Therefore, we
purpose the use of TENS to address pain management and its accompanied symptoms. Since this technology is dose-
dependent, we propose a practical daily-basis therapy that patients with persistent associated fibromyalgia due to previous
COVID-19 infection could apply at home, thus, addressing PASC without relying only on medication.
Our institution has created the Post-COVID-19 Clinic (McNair Campus, BCM St Luke's, Houston, TX, USA) supervised by
specialists in critical and pulmonary care. This Clinic has a high volume of patients that present with PACS, particularly
those with associated fibromyalgia (i.e., persistent muscle pain, fatigue, weakness, atrophy, sleep problems, and/or
anxiety). Therefore, we believe our institution is a suitable place to perform this pilot study.
Study #2: Chemotherapy and other cancer treatments can cause damage to the peripheral nerves mainly reflected in
severe pain in the upper and/or lower extremities. Additional to pain, cancer treatment may cause loss of balance which
affects motor capacity and is a major cause of poor quality of life. There are only minimally effective treatments for CIPN
despite over 20 years of research. Few recent studies including ours have suggested that exercise intervention could be
effective to restore numbness and motor capacity loss because of CIPN. Unfortunately, conventional rehabilitation
programs however suffer from poor adherence and those programs for supervised settings have limitation of access for
those who live in the remote areas (e.g., rural area), or could be too frail to travel after chemotherapy. This raised a
significant disparity for delivering an effective therapy for those who are living in remote areas or those who are too frail to
travel. Therefore, we believe the user-friendly design, and wireless practicality of Quell® is a suitable option for our CIPN
population at BCM.
Our institution's Duncan Cancer Center (McNair Campus, BCM St Luke's, Houston, TX, USA) supervised by specialists in
clinical and surgical oncology, has a high volume of patients that present with CIPN. Therefore, we believe our institution is
a suitable place to perform this sub-study. The premise of this sub-study is that daily basis of TENS therapy could be
effective to reduce pain, reduce numbness and improve both motor-capacity and mobility performance leading to improve
quality of life in those who suffer from CIPN and have limited access to health care.
 
Section D:  Purpose and Objectives
     
The purpose of the pilot study is to examine acceptability and proof of concept effectiveness of a wireless TENS
technology to address NP due to different etiologies.Sample size (n=60) is convenient and designed to explore
acceptability and feasibility.
Study #1: PASC associated FM. Eligible participants (N=30) will be screened at the BCM Post-COVID-19 Clinic for
inclusion criteria.
Study #2: Patients with CIPN (N=30). Eligibility will be screened at the Duncan Cancer Center at BCM.
Participants, who satisfy the inclusion and exclusion criteria and sign the informed consent form will be randomly assigned
with ratio of 1:1 into two groups. One group will utilize TENS functional devices (Active group, AG); the other group will
utilize TENS non-functional devices (Placebo group, PG). The baseline measurements will be performed, and the patients
will take the programmed device home for a duration of 4 weeks. Then, the patients will come back after four weeks (4W).
At this 4th week visit, both groups will be unblinded and the AG will keep their functional device and the PG group will
receive a functional device. Both groups will continue to deliver 3-5 hour of stimulation daily, until their final 8th week follow
up visit (8W). The primary outcomes will be pain symptoms, sleep and fatigue. Secondary outcomes include limb strength
and perfusion, gait assessment (gait speed, stride length, double stance, and gait steadiness), balance, pulse oximetry,
and quality of life. The coordinator will utilize a weekly spreadsheet showing utilization (therapy sessions/day, logged in the
Quell health Cloud) so compliance can be monitored and those that are not using the device can be encouraged.
 
Section E:  Protocol Risks/Subjects
E1.  Risk Category
     Category 1: Research not involving greater than minimum risk.
E2.  Subjects
Gender:
     Both
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
4/12

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?
     
Vulnerable populations require special protections.  How will you obtain informed consent, protect subject confidentiality, and
prevent undue coercion?
     
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
 
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 60 patients with NP derived from different etiologies (study #1: PASC, study #2: CIPN).
Randomization will be done through a computer‐generated list followed by sequential allocation.
Patients will be followed-up and monitored for up to 8 weeks. The study will be double-blinded (clinicians and patients) until
the 4th week, where study participants will be told of their group assignment.
The following characteristics will be included: 1. Frequency: 3+ hours daily. 2. Patient reported outcomes: Fibromyalgia
Diagnostic Criteria (FMS), Symptom Impact Questionnaire (SIQR), Patients Global Impression of Change (PGIC), Brief
pain inventory (BPI), Medical Outcome Study Sleep Scale (MOS) questionnaires, and Multidimensional Assessment of
Fatigue (MAF), common terminology criteria for adverse events (CTCAE) v5., EORTC-CIPN20, UENS, EORTC-QLQC30
3. Perfusion test: Lower limb calf tissue oxygen saturation (Kent Imaging System) 4. Other measurements: pulse oximetry,
muscle calf activation in response to TENS (surface electromyography [sEMG] assessment), muscle calf activation in
response to ankle maximum voluntary contraction (sEMG assessment), ankle strength (measured using ankle
dynamometer), peripheral neuropathy (DPNCheck), vibration perception threshold (VPT test). 5. Time points: The outcome
measures will be obtained at baseline and four weeks. 6. Optional questionnaires collected at each time point: instrumental
activity of daily living scale (IADL), daily living independence (KATZ), depression (CES-D), fatigue (FACIT), cognitive
assessment (MOCA), pain and mobility, global health (PROMIS), sleep (PSQI), frailty (TSFI), anxiety (BAI), and user
acceptability (TAM). 7. Optional assessments of the 6-minute walk test, gait speed, balance, frailty and physical monitoring
will be conducted at both study visits using wearable sensors. 8. Optional: Patients keep the device after the study ends
(those who wore sham will get an active device).
The cohorts (per sub-study) will be randomized in two arms: Active group (AG). The AG (n=15) will be undergoing TENS
therapy with an active device during 4 weeks. To deliver TENS, a band strap with hydrogel pads will be placed around the
calf muscle of one lower-extremity alternating to the other side in a weekly basis. We hypothesize that a high dose nerve
stimulation has a widespread effect on pain and other symptoms, not just at the location of stimulation. To get localized
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
5/12

effects in both limbs the subjects will alternate limbs. We also recommend this in any case to minimize the risk of skin
irritation from the hydrogel pads. According to previous studies, perceived afferent stimulation by the brain from only one
limb is able to send efferent signals to both limbs. Therefore, both limbs will be assessed for therapy outcomes.
Placebo Group (PG). The PG (n=15) will be undergoing TENS therapy with a sham device as described in the AG. The
sham device is identical to the active device in all respects except that it stimulates for 6 minutes during each therapy
session instead of 60 minutes, and is therefore 10% of the dose.
Both groups will receive their respective devices at the initial visit (BL) and will be asked to return in 4 weeks for follow-up
assessment (4W visit). At this 4 week visit, study participants will be unblinded and the active group will keep their active
device, while the placebo group will receive a placebo device. Study participants will return for a final in-person visit at the
8th week (8W), which will include the assessments described above. Throughout this 8-week period the participants may
receive follow-up phone calls assessing their compliance. All subjects will keep their active device after completion of the
8-week study.
Inclusion Criteria:
     
Study #1: Previous COVID-19 infection Persistent symptoms for lower extremity pain, fatigue, weakness, or poor gait and
balance after infection assessed by critical care clinicians on the initial consultation Willing to attend clinic for assessments
Study #2: Patients with chemotherapy induced peripheral neuropathy in current active or having finished treatment for any
type of cancer that requires chemotherapy regardless of dosage. Willing to attend clinic for assessments
Exclusion Criteria:
     
Study #1: Severe cognitive decline reduces their ability to interact with the TENS mobile app Major visual or hearing
weakness reduces the ability to interact with TENS mobile app Unable to walk independently for a distance of 10 meter
Major foot problems such as active lower extremity wounds, major foot deformity (e.g., Charcot Foot), previous major
amputations, and claudication Demand-type cardiac pacemaker, implanted defibrillator, or other implanted electronic
devices; and any conditions that may interfere with outcomes or increase the risk of the use TENS based on the judgement
of clinicians
Study #2: Severe cognitive decline reduces their ability to interact with the TENS mobile app Major visual or hearing
weakness reduces the ability to interact with TENS mobile app Unable to walk independently for a distance of 10 meter
Major foot problems such as active lower extremity wounds, major foot deformity (e.g., Charcot Foot), previous major
amputations, and claudication Demand-type cardiac pacemaker, implanted defibrillator, or other implanted electronic
devices; and any conditions that may interfere with outcomes or increase the risk of the use TENS based on the judgement
of clinicians. Patients with metastatic or terminal cancer disease that are receiving recurrent chemotherapy.
F2.  Procedure
     30 subjects per sub-study (study #1: 30 subjects, study#2: 30 subjects):
Aim 1 (acceptability): To examine feasibility and acceptability of TENS in patients with NP.
At the baseline visit and each of the follow-up visits (at four weeks, 4W; and eight weeks, 8W), electrical stimulation using
the TENS device, will be administered by the coordinator. Daily electrical stimulation, between the baseline and follow-up
visit, will be administered by the patient at their convenience. They will be asked to use the device at least 3 hours per day
for at least 4 days per week. At follow-up study visits (4W and 8W), a Technology Acceptance Model (TAM) survey adopted
for tele-health and smart wearables applications perception of benefit, technological anxiety, technology acceptance, trust,
facilitation conditions, risk, and attitude of use will be obtained for each subject.
Aim 2 (proof of concept effectiveness): To examine effectiveness of TENS for NP.
At the baseline visit (BL) and each of the follow-up visits (at four weeks, 4W; and eight weeks, 8W), electrical stimulation
using the TENS device, will be administered by the coordinator. This trial will have 30 subjects divided into two groups.
Group 1 (Active group, n=15) will receive a functional Neurometrix Quell Relief Device; Group 2 (Placebo group, n=15) will
receive a non-functional Neurometrix Quell Relief Device that will administer 6 minutes of stimulation per hour of
stimulation. Lower extremity muscle activation will be assessed by using sEMG (electromyography) at each study visit
during the delivery of stimulation. At the 4th week (4W), both groups from study #1 will be unblinded and the AG will keep
their functional device, the PG will return their non-functional device and receive a functional device.
The subjects will be monitored for another 4 weeks with a final follow-up visit at 8 weeks (8W), both groups from study #2
will be unblinded at eight weeks (8W visit), On this last visit, the AG will have the option to keep their functional device, the
PG will return their non-functional device and have the option to receive a functional device to take home.
Tissue Oxygen Saturation: near infrared imaging (Kent Imaging System) at pre-, 30min, 60min, and 30min post-treatment
(after stopping of EE device) at each study visit.
Patient reported outcomes: Fibromyalgia Diagnostic Criteria (FMS), Symptom Impact Questionnaire (SIQR), Patients
Global Impression of Change (PGIC), Brief pain inventory (BPI), Medical Outcome Study Sleep Scale (MOS)
questionnaires, and Multidimensional Assessment of Fatigue (MAF), Common Terminology Criteria for Adverse Events
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
6/12

(CTCAE) v5., European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-
item scale (EORTC-CIPN20), Utah Early Neuropathy Scale (UENS), European Organization for Research and Treatment
Core Quality of Life questionnaire (EORTC-QLQC30).
Peripheral Neuropathy: Peripheral neuropathy will be assessed at BL, 4W, and 8W using DPNCheck (Neurometrix,
Woburn, MA, USA). This is a noninvasive device which will measure conduction velocity and amplitude. Vibration
perception threshold (VPT) will also be used to assess sensitivity of patients' lower extremity.
Optional assessments: Oxygen Level Assessment: Oxygen saturation will be measured using a pulse oximeter.
Gait assessment: Gait performance will be assessed using a validated body worn sensors (LegSys, Biosensics LLC, USA).
The device uses five sensor modules respectively attached to right and left anterior shins, right and left anterior thighs, and
posteriorly to the lower back. Based on the subject's height and using a two-link inverse pendulum model the following
spatio-temporal gait parameters will be estimated: velocity, stride length, stride time, double support, single support, stride-
to-stride variability, and gait initiation. In addition, the center of mass (COM) range of motion during walking will be
calculated by using the data from the sensor attached to lower-back. Gait will be assessed over a distance of 20 meters
under 2 conditions: (1) walking at habitual speed (2) walking at maximum speed (fast walking).
Balance assessment: Balance will be quantified using validated body worn sensors (BalanSens, Biosensics LLC, USA).
The system measures ankle and hip motion in three dimensions (3D), 2D COM sway as well as RCI in ML and AP
directions. Balance will be assessed according to Romberg protocol during eyes-open and eyes-closed condition during
double, semi-tandem, and full tandem stances. For those patients who may not be able to do gait and balance test, we will
use alternative upper extremity test, which according to our previous studies provide similar results as gait bit do not
require subject to walk. (See Attachment)
Upper Extremity Frailty Test: Investigators will measure arm motion from each participant by implementing validated
wearable inertial sensors (e.g. accelerometer, gyroscope) such as LegSys (Biosensics LLC, MA, USA), Frailty Meter
(Biosensics LLC, MA, USA), or BioStamp (MC10, MA, USA). These inertial sensors will assess respectively kinematic of
upper extremities (e.g., arm and shoulder) motion as well as joint coordination. We will be used at least 1 sensor attached
on wrist to capture arm motion.
Physical Activity and Health Monitoring: The subject will be given a wearable device (PAMSys) and/or a smart watch
(Vivosmart 4) that will be measuring several parameters including number of steps taken, duration of sitting, standing,
walking and lying, time taken and number of transitions from sit to stand, and walking speed for a minimum of 48 hours. At
the end of the specific visit, the subject will be given the device, if they are given PAMSys it will be attached to pendant to
wear around the neck, otherwise they may wear the smart device on their wrist. Investigators will ask the subject to return
the wearable device at study completion. Subjects will either return the device at their next research visit or be given a
prepaid package to mail the device back.
Optional Questionnaires at each study visit: pain, weakness, sleep, quality of life, frailty, depression, life and space, beck
anxiety scale, Katz-daily living, fatigue, and user acceptability.
The supervision of this study will be by pulmonary care specialists (Study #1), and cancer care specialists (study #2) and
the location will be at Baylor College of Medicine McNair Campus.
 
Section G:  Sample Size/Data Analysis
G1.  Sample Size
How many subjects (or specimens, or charts) will be used in this study?
     Local: 60              Worldwide: 60
Please indicate why you chose the sample size proposed:
     
Convenient and selected based on available resources to demonstrate feasibility and the proof of concept effectiveness of
TENS therapy for patients with NP. We plan to recruit 60 eligible subjects.
Study #1: 30 subjects Study #2: 30 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?
     Independent t-test, U-test, or Chi-square (depends on type of variables) to compare between groups (AG, and PG for key
baseline descriptors including demographics and relevant clinical characteristics. Those descriptors which show statistical
significant difference, baseline value of the outcomes measured in the model, and other variables that are deemed to be
prognostic, 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)
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
7/12

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.
 
Section H:  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 length of the sessions.
The devices and technologies are 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 band or hydrogel pads on their legs. We will inform the subject to please
notify the investigators if the band or hydrogel pads are 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: (1) Skin related discomfort, such as tingling or (2) Skin reaction to
hydrogel pads (irritation, rash).
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 peripheral neuropathy device (DPNCheck) has minimal risks to the subjects as it is non-invasive, safe, non-toxic, and
non-ionizing. The subjects may feel a tingling sensation during its use, and if it is too intense, the research staff will stop
the test.
 
Section I:  Potential Benefits
Describe potential benefit(s) to be gained by the individual subject as a result of participating in the planned work.
     
Study #1: We cannot promise any benefit to you or to others from you joining this research. However, the proposed
treatment may assist in reducing symptoms of PACS associated FM. In addition, the participation in this study may help
the investigators better understand how COVID-19 may impact cause neuropathy and how to best help these patients to
recover from NP. This may allow physicians to provide personalized care by monitoring chronic pain caused by PASC.
Study #2: We cannot promise any benefit to you or to others from you joining this research. However, the proposed
treatment may assist in reducing symptoms of pain associated to your chemotherapy. In addition, the participation in this
study may help the investigators better understand how TENS help patients with CIPN. This may allow physicians to
provide personalized care by monitoring chronic pain caused by CIPN.
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 patients with NP.
Do anticipated benefits outweigh potential risks? Discuss the risk-to-benefit ratio.
     Study #1:
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 TENS, skin allergy to the TENS band, risk associated with electrical mal-function of
the TENS device, and other unknown risks. All TENS devices will be checked before any use to minimize the risk
associated with electrical malfunction. All TENS devices are FDA approved for the purpose of temporary relief of pain.
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 COVID-19. The peripheral neuropathy device (DPNCheck) has
minimal risks to the subjects as it is non-invasive, safe, non-toxic, and non-ionizing. The subjects may feel a tingling
sensation during its use, and if it is too intense, the research staff will stop the test.
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
8/12

Study #2:
The risk to participants of this study is considered to be minimal because all that is required is simple walking in a
controlled environment with a research staff present (all subjects will be mobile, and walking as a regular part of their
activities of daily living this research routine will not place them at higher risk than normal activities of daily living). No more
risk of harm or discomfort is associated with these tests than the discomfort normally incurred while walking or during
normal muscle stretching. The peripheral neuropathy device (DPNCheck) has minimal risks to the subjects as it is non-
invasive, safe, non-toxic, and non-ionizing. The subjects may feel a tingling sensation during its use, and if it is too intense,
the research staff will stop the test.
 
Section J:  Consent Procedures
J1.  Waiver of Consent
Will any portion of this research require a waiver of consent and authorization?
     NA
 
J1a.  Waiver of requirement for written documentation of Consent
Will this research require a waiver of the requirement for written documentation of informed consent?
     NA
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.
     
Study #1 Subjects will be recruited from the Post-COVID-19 Clinic (McNair Campus, BCM St Luke's, Houston, TX, USA).
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.
Study #2: Subjects will be recruited from the Duncan Cancer Center (McNair Campus, BCM St Luke's, Houston, TX, USA).
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.
Informed Consent Form signatures will be obtained according to standard Baylor IRB regulations. The PI/research staff will
review the study and consent document with the participant, asking questions to gauge comprehension, and answering the
subject's questions and concerns. Once the subject completes reviewing the consent and all questions are addressed, the
subject and the PI/designee will sign the ICF. The subject will receive a paper copy of the ICF to review. The signed
consent form will be stored in the research facility to which only authorized personnel have access.
Reconsent plan (if needed): Currently enrolled subjects will be reconsented at their next in-person, follow up visit. The
consent form will be explained and all questions will be answered.
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
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
9/12

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?
     No
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?
     NA
Information from health records such as diagnoses, progress notes, medications, lab or radiology findings, etc.
     NA
Specific information concerning alcohol abuse:
     NA
Specific information concerning drug abuse:
     NA
Specific information concerning sickle cell anemia:
     NA
Specific information concerning HIV:
     NA
Specific information concerning psychiatry notes:
     NA
Demographic information (name, D.O.B., age, gender, race, etc.):
     NA
Full Social Security #:
     NA
Partial Social Security # (Last four digits):
     NA
Billing or financial records:
     NA
Photographs, videotapes, and/or audiotapes of you:
     NA
Identifiable biospecimens
     NA
Other:
     NA
At what institution will the physical research data be kept?
     NA
How will such physical research data be secured?
     NA
At what institution will the electronic research data be kept?
     NA
Such electronic research data will be secured via BCM IT Services- provided secured network storage of electronic research
data (Non-Portable devices only):
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
10/12

     NA
Such electronic research data will be secured via Other:
     NA
Will there be anyone besides the PI, the study staff, the IRB and the sponsor, who will have access to identifiable research
data?
     NA
Please describe the methods of transmission of any research data (including PHI, sensitive, and non-sensitive data) to
sponsors and/or collaborators.
     NA
 
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.
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:
     150
Distribution Plan:
     
For taking part in this research, the subject may be paid a total of $150. Their compensation will be broken down as
follows:
Subjects will be paid $50 for every visit completed visit. There are a total of up to 3 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
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
11/12

 
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 study need an IDE?
     No
Regarding your device study, could potential harm to subjects be life-threatening?
     No
Regarding your device study, could potential harm to subjects result in permanent impairment of a body function?
     No
Regarding your device study, could potential harm to subjects result in permanent damage to a body structure?
     No
 
Section Q.  Consent Form(s)
Transcutaneous Electrical Nerve Stimulation for Lower Extremity in Patients with Post Acute COVID-19 Syndrome
Transcutaneous Electrical Nerve Stimulation for Lower Extremity in Patients with Chemotherapy Induced Peripheral
Neuropathy
 
Section R:  Advertisements
Mode of Advertising:  Other: Flyer
Exact language of Advertisement:
     Has been attached to Section S - Attachments
 
8/7/24, 11:29 AM
Human Protocol Report
https://brain.bcm.edu/esp1/reports/Human/Protocol.asp?protocol=487013
12/12