Brain Computer Interface - Functional Electrical Stimulation (BCI-FES) Therapy for Stroke Rehabilitation
Phase: NA
Conditions: Ischemic Stroke, Hemorrhagic Stroke
Sponsor: University of California, Irvine

#20194936 - BCI-FES therapy for stroke rehabilitation
Protocol Information
Protocol Renewal Form
Renewal Information
Protocol Type
Are you submitting a renewal for an IRB, sIRB, or hSCRO
protocol?
IRB (UCI is the IRB of Record)
IRB Renewal Instructions
Review Type
Full Board
Status
Expired
Time in Current
Status
Since October 18 –
a year
Submission Number
16
Approval Date
Oct 11, 2024
Continuing Review
Date
--
Expiration Date
Oct 10, 2025
Initial Approval Date
Jan 08, 2021
Initial Review Type
Full Board
PROTOCOLS

Timing of Submission
Exempt and Expedited IRB protocols must submit a short version of the renewal every three (3)
years unless determined otherwise by the IRB. Investigators should plan ahead and submit 60
days prior to the study's expiration date.
Full Committee IRB protocols must submit a renewal at least annually (not more than 365 days).
Investigators should plan ahead to meet required continuing review dates. For full committee
review protocols, please submit 90 days prior to the expiration date to guard against a lapse in
IRB approval.
Amendments at the Time of Renewal
Please refrain from making major changes during the renewal as this could result in a lapse of
IRB approval.
Protocol Closure
To close out an approved protocol at the time of renewal, the transaction must be submitted as
Request Close. If this option was not initially selected and closure is required, please Abandon
the draft and start again. For more information, visit Post-Review Responsibilities and select the
Protocol Renewal Tab.

Renewal Screener
Does any of the following apply to the currently approved
protocol:
• research involves Greater than Minimal Risk (Full
Committee)
• research is subject to Food and Drug Administration (FDA)
regulations
• Involves a drug
• A clinical investigation of a medical device
• ﻿research is funded/supported by the Department of Justice
(DOJ)
• current approval period is 1 year or less
Yes (Continuing Renewal Required)
Protocol Expiration
Protocol Expiration
Has approval for this protocol expired or will it expire within 3
weeks?
No
Confirmation of Protocol
Study Team
Review the Study Team Section and consider whether anyone
should be removed at this time via an Amendment.

RP Heat Map
Are RP tracked outside the approved protocol, in accordance
with the RP Heat Map?
Yes, RP are tracked on a Study Team Log or other comparable log
Financial Interests
Review the Study Team section and specify below if there have
been any changes in the study team's related financial
disclosable interests.
See Conflict of Interest Oversight Committee (COIOC) for more details.
No, there have been no changes to the study's teams related disclosable
financial interests
Relying Non-UCI Entity (as applicable)
When UCI is the IRB of Record for a non-UCI entity (i.e., site or
independent investigator), review the sIRB section and remove
any non-UCI entities (site or independent investigator) that are
no longer engaged in research via an Amendment.
Clinicaltrials.gov Status
ClinicalTrials.gov Registration
Does this research meet the definition of a clinical trial that
requires adherence to Clinicaltrials.gov (CT.gov)?
Yes

Confirm the accuracy of ClinicalTrials.gov section in the IRB
protocol (select one):
Please review the ClinicalTrials.gov section in the IRB protocol to verify that the information is
still accurate.
If any revisions are required, please submit an amendment to request a 'Change in
Clinicaltrials.gov' and update the the protocol accordingly.
As lead researcher, I confirm that the CT.gov information is accurate as
indicated in the protocol
Specify who is responsible for registering, maintaining, and
updating the CT.gov record:
UCI Investigator

Confirm the accuracy of the information on the
ClinicalTrials.gov Protocol Registration and Results System
(PRS):
IMPORTANT! Per federal requirements (42 CFR 11.64(a)(1)(ii)), clinical trial registration
information on PRS must be updated not less than once every 12 months.
Please review the information on PRS to verify that the following fields are accurate and up to
date:
• Study Status:
• Record Verification Date: Not less than every 12 months, enter the date on which
the responsible party last verified the clinical study information on PRS, even if no
additional or updated information was submitted.
• Overall Recruitment Status: 30 calendar days after a change in overall recruitment
status, enter the status for the clinical study as a whole, based upon the status of
the individual sites. If at least one facility in a multi-site clinical study has a status
of "Recruiting," then the overall status for the study must be "Recruiting."
• Primary Completion Date: 30 calendar days after the clinical trial reaches its actual
primary completion date, enter the date that the final participant was examined or
received an intervention for the purposes of final collection of data for the primary
outcome, whether the clinical study concluded according to the pre-specified
protocol or was terminated. In the case of clinical studies with more than one
primary outcome measure with different completion dates, this term refers to the
date on which data collection is completed for all of the primary outcomes.
IMPORTANT! This date cannot be in the past, please revise the date as necessary.
• Study Completion Date: 30 calendar days after the clinical trial reaches its actual
study completion date, enter the date the final participant was examined or received
an intervention for purposes of final collection of data for the primary and
secondary outcome measures and adverse events (for example, last participant’s
last visit), whether the clinical study concluded according to the pre-specified
protocol or was terminated. IMPORTANT! This date cannot be in the past, please
revise the date as necessary.
• Oversight:
• Human Subjects Review Board Status: 30 calendar days after a change in status,
ensure the status of IRB approval information is accurate.
• Contacts, Locations, and Investigator Information: 30 calendar days after a change, ensure
the information is accurate.

As leader researcher, I confirm that the clinical trial information (listed above)
on PRS is accurate and up to date.
Enrollment Status
Accruals
Please mark the option that represents the current status of
subject enrollments:
Enrollment closed - research procedures ongoing
Subject Enrollments
Please confirm the total number of subjects (i.e. individuals,
specimens, records) approved by the UCI IRB in the Subject
Populations section.
Indicate the number of new subjects enrolled since last IRB
review:
32
Indicate the total number of subjects (including the number
in the previous question) enrolled since initial UCI IRB
approval:
191
Did the total number of subjects enrolled to date exceeds the
total number approved by the IRB?
No
Indicate the total number of subjects enrolled per group
since initial IRB approval:

Man (total):
120
Woman (total):
71
Nonbinary (total):
0
Not Collected (total):
0
Adults (total):
191
Minor (total):
0
Multi-Center Studies: If known, indicate the total number of
subjects enrolled at ALL sites to date:
Not applicable
Subject Withdrawals
Early Termination(s)
Did the Lead Researcher or a Co-Researcher remove any
subject(s) from the study?
Yes
Please provide the reason(s) here (e.g., failed to follow
instructions, missed appointment, medical complications,
subject safety issue):
1 subject was removed from the study by the physician due to inability to
tolerate the treatment.
Voluntary Withdrawal(s)
Did any subject(s) voluntarily withdraw from the study?
Yes

Please describe the reason(s) here (e.g., relocation;
dissatisfaction):
1 subject withdrew from study due to inability to commit to the treatment
schedule.
Reportable Events
Reportable Events
Have there been any problems that required prompt reporting to
the UCI IRB?
No problems that require reporting
Complaints
Have there been any complaints from UCI participants or others
that required reporting to the UCI IRB?
No
Progress Report

UCI Progress
Please provide a detailed description of the progress of the
study, including a brief summary of any interim findings or
trends, and plans for the next approval period:
Our phase 2 clinical trial has concluded recruitment, enrollment and
treatment. The plan for the next approval period is to complete post treatment
assessments and data analysis. Interim data was reviewed confidentially by
the DSMB at their meeting in November 2023 and approved. The DSMB
Meeting report was uploaded to the attachment section. Subject status
breakdown: Aim 1: 168 assessed for eligibility; 106 were ineligible, 62 were
randomized to study; 54 received intervention per protocol and completed all
assessments, 1 withdrew from treatment but completed assessments, 4
withdrew consent from study, 2 were removed by physician; 1 is ongoing for
final assessment; Aim 3: 23 assessed for eligibility; 13 were ineligible, 10
were randomized to study; 8 received intervention per protocol and completed
all assessments, 0 withdrew from treatment but completed assessments, 0
withdrew consent from study, 0 were removed by physician; 2 are ongoing for
final assessment. Aims 1 and 3 were the only 2 aims that were enrolling
subjects and have closed enrollment. Clinicaltrials.gov has been updated to
reflect close of enrollment.
Relying Entity Progress (as applicable)
If UCI is the IRB of Record for a non-UCI entity, provide a
progress report for each relying entity (e.g., number of
participants enrolled at the sub-site; data analysis performed, if
any, etc):
Not applicable

Sponsor Multi-Center Progress (as applicable):
Is a multicenter progress report / newsletter is available from
the Sponsor?
Not Applicable
Informed Consent
Confirm that there is no new information that raises concerns
about the circumstances under which informed consent is being
obtained:
No new information
Confirm that any new findings that have developed since the
last continuing review, have been provided to enrolled subjects,
as appropriate:
No new findings
Confirm that the research team is using the most recently
approved version of the consent/assent document and that it
contains the most accurate, up-to-date information about the
research:
Yes
Confirm that all signed consent documents are on file and
available for inspection:
Yes
Specify if any subjects were enrolled using a non-English
consent document, information sheet, or script:
No

Given that some research studies have multiple consent/assent
forms, please indicate which approved consent/assent forms
should be reviewed by the IRB:
Review all consent/assent forms
Re-Consent Status
Since the last IRB Approval, did any Amendments require
subjects to be re-consented?
No
Internal and External Audits
Internal Audit(s)
Have any internal (UCI/UCI Health) audits occurred since last
IRB review?
No
External Audit(s)
Have any external (FDA/OHRP/Sponsor) audits occurred since
last IRB review?
No
Risk and Safety Assessments

Relevant Recent Literature
During the past year has there been anything in relevant
literature that the IRB should consider when reviewing this
application for continuing approval?
No
Current Risk/Benefit Assessment
Has there been a change in risk/benefit?
Take into account the information gathered during the past year such as interim results,
reportable events/problems, changes in scientific knowledge, and/or relevant regulatory actions
regarding study-wide safety and/or efficacy (e.g., product recall). This assessment should be
sufficiently detailed to assist the IRB in determining whether continuation of IRB approval is
appropriate.
No
Data Safety Monitoring Board (DSMB)
Has there been any new DSMB findings relating to subject
safety?
No new findings related to subject safety
Investigator's Brochure (IB)
For FDA regulated drug studies, enter the current version
number and date of the Investigator's Brochure in the
Supplemental Documents section.
End of renewal form!
IMPORTANT! Go to the next section to complete the amendment
form.

Protocol Amendment Form
Amendment Instructions
Specify the type of submission:
RENEWAL: This is a renewal that does not require changes to the approved
protocol
End of amendment form!
Project Details
Specify the study title (this title should not exceed more than 100 words):
BCI-FES therapy for stroke rehabilitation
Lead Researcher/Investigator:
An Hong Do
Enter the Lead Unit:
Project Screener
Submit a Human Subject Protocol for UCI Institutional Review Board (IRB)
Review
***IR-7455 - NEUROLOGY (Lead Unit)***

Will this protocol be reviewed under a sIRB process?
No, there is no reliance involved. UCI serves as the IRB of record
Are the research procedures limited to the use/analysis of identifiable private information and/or
identifiable biospecimens (no subject contact)?
No
Select the required level of review for this protocol:
Greater than Minimal Risk (Full Committee)
Check all sites where UCI investigator(s) will conduct research activities (e.g., recruitment,
informed consent, and research procedures including accessing identifiable, private information
about participants):
UCI Facilities or Sites (e.g. school, hospital or clinics, etc.)

Provide a non-technical summary of the project that can be understood by IRB/hSCRO members
with varied research backgrounds, including non-scientists and community members (this
summary should not exceed more than 250 words):
There are over 7 million stroke survivors in the US alone, with approximately
795,000 new cases annually. Despite the best available physiotherapy, 30-60%
of stroke survivors remain affected by difficulty walking, with foot weakness
often being the main cause. Given that post-stroke gait impairments remain
poorly addressed, new methods that can provide lasting improvements are
necessary. Brain-computer interface (BCI) technology may be one such novel
approach. BCI technology enables “direct brain control” of external devices
such as assistive devices and prostheses by translating brain waves into
control signals. When BCI systems are integrated with functional electrical
stimulation (FES) systems, they can be used to deliver a novel physical
therapy to improve movement after stroke. BCI-FES systems are hypothesized
to stimulate recovery after stroke beyond that of conventional physical
therapy. Preliminary research indicates that applying this technique to foot
weakness after stroke is safe and may improve walking function. Hence, this
warrants further investigation to: 1. determine if BCI-FES therapy can provide
lasting gains in walking in chronic stroke patients; 2. determine what factors
influence BCI-FES therapy; and 3. explicitly elucidate the underlying neural
repair mechanisms. First, a Phase II clinical trial in patients with foot drop due
to chronic stroke will compare the effect of BCIFES dorsiflexion therapy to
that of dose- and intensity-matched standard physical therapy (Aim 1).
Comparing the improvement in walking speed and other secondary outcome
measures between the two groups will test if BCI-FES therapy provides
functional and neurological gains beyond those of standard physical therapy.
The relationship between the patient baseline characteristics (walking speed,
ankle function, stimulated muscle responses, brain wave features, sensation)
and the outcomes will determine what features influence responsiveness to
BCI-FES dorsiflexion therapy (Aim 2). Finally, the underlying mechanism
driving the improvements of BCI-FES will be studied (Aim 3). Determining that
BCI-FES therapy can provide improvements beyond that of standard therapy
may lead to a new treatment for stroke patients. The underlying mechanism
can inform the design of future physical therapy techniques or improve
current ones. Finally, BCI-FES therapy may ultimately become a novel form of

physical therapy to reduce post-stroke disability, and in turn reduce the public
health burden of stroke.
Instructions
IRB Protocol Instructions
• For research with a Master Protocol or with a detailed project proposal, specify this in the
protocol and an abbreviated protocol will be generated.
• Submit all new and/or revised supporting documents in the Protocol Attachments section
near the end of the protocol.
• The Lead Researcher (LR) is responsible for maintaining all supplemental documentation
(as indicated in the form) in the research records. This documentation may be requested
by Human Research Protections for quality assurance review.
For regulatory or institutional guidance:
• Visit Human Research Protections
• Contact the Human Research Protections staff
For technical issues or questions:
• Visit the Kuali Research Protocols (KRP) User Guide
• Contact Electronic Research Administration (ERA)
Type of Research
The purpose, specific aims or objectives of the research is:
Biomedical
The research protocol is:
Investigator-Initiated
Does the investigator-initiated study have any industry support?
No

Does this study include a Master Protocol or detailed project proposal?
No
Is this study an extension of a UCI IRB approved study (e.g., resubmission of ongoing exempt
research; Open Label Extension) or is it otherwise related to a UCI IRB approved study?
No
Does this research meet the definition of a clinical trial that requires adherence to
Clinicaltrials.gov?
Yes
If currently available, provide the CT.gov registration NCT # (Enter 8-digit sequence of numbers
only):
04279067
Specify the rationale for Clinicaltrials.gov registration:
NIH-funded Clinical Trial
STOP! All clinical trials must be conducted under the auspices of an Organized Lead Unit (OLU).
Please update. Go to Project Details and choose the appropriate OLU for the trial.
Study Funding
Select the funding source(s) (check all that apply):
Grant/Contract
No Campus or Extramural funding
Select the sponsor type(s) (check all that apply):
Health and Human Services (HHS) (includes National Institutes of Health
(NIH)
List below all extramural proposals or awards that will support the study (if
applicable):
IMPORTANT! Skip this table if extramural funding is not available.

Sponsor Name
NIH
Title of Proposal/Award (if different from study title):
Proposal or Award #:
Scientific/Scholarly Review
Is the research Sponsor-Initiated?
Yes
The proposed research qualifies as greater than minimal risk, sponsor-initiated biodmedical
research. It is assumed that scientific merit has been conducted. Available peer review
comments may be requested by the IRB for consideration.
Greater than Minimal Risk Non-Cancer, Sponsor Initiated Biomedical Research
- Received Peer Review
Data Safety Monitoring Plan
Does this protocol require a DSM plan?
Yes
Provide details of those individuals who will be responsible for the safety oversight of your
protocol, including the relevant experience/expertise of each individual (for UCI investigator
initiated studies conducted only at UCI, provide the names and titles as well):
- Dr. Gaby Thai, MD (Associate Professor, Department of Neurology, UCI - a
neurologist with over 10 years in clinical trial experience) - Dr. Kelli Sharp, DPT,
PhD (Professor, Department of Dance, UCI - a clinical research physical
therapist with extensive clinical trials experience for rehabilitation
technologies). - Dr. Luohua Jiang, PhD – a biostatistician with clinical trial
experience will analyze the data accrued so far and present the findings to the
DSMB

Indicate how frequently accumulated protocol data will be reviewed and evaluated for participant
safety, protocol conduct and progress, and, when appropriate, efficacy:
- DSMB will meet to review results after each time 26 subjects are recruited
(~one-third of the recruitment goal) during Aim 1. Note that Aim 2 relies on
the subjects from Aim 1. Aim 3 is not a clinical trial and hence will not be
subjected to this.
Describe the events that would trigger an unscheduled review. Also include stopping guidelines
and un-blinding rules if applicable:
- An unscheduled review can be triggered by an event in which a serious
adverse and unanticipated problem arose that was deemed related to the
study. This may include serious injury due to fall, or even death, that was
related to the study intervention. - The DSMB will be advised of the following
stopping criteria: 1. if the proportion of subjects experiencing falls in those
receiving BCI-FES therapy begins increases significantly (i.e. >10%) or if the
fall rate amongst subjects in the BCI-FES group increases significantly from
baseline; 2. More than 10% of subjects in the BCI-FES group experience a
decrement in gait velocity of >0.16 m/s. Additional specific stopping points
will not be prespecified, rather the judgment of the DSMB will be respected.
List who will be locally monitoring and collecting information on adverse events and/or
unanticipated problems (e.g., UCI Lead Researcher, Research Coordinator, etc.). Include the
name, title and experience of the individual(s) and further describe each individual’s role in the
oversight of subject/patient participating in the protocol:
- The lead researcher, Dr. An Do, and the study coordinator, Lucy Dodakian, will
be responsible for collecting information on adverse events and/or
unanticipated problems.
Describe the plan for annual reporting of the participants’ safety, and the protocol's conduct,
progress, and efficacy, when appropriate:
- All relevant clinical data will be presented to the IRB on a yearly basis,
including reports of the DSMB, including serial gait velocity, dorsiflexion range
of motion and torque, leg motor Fugl-Meyer score, gait endurance test, and
fall frequency. The investigative team will be blinded to these, so they will be
submitted directly from the DSMB to the IRB.
Potentially Hazardous Materials

If any of the following hazardous materials are involved in this research please check below:
N/A
Other UCI Committee Reviews
Check all ancillary committees that apply:
N/A
Study Team

Study Team:
• List only study team members who are engaged in human subjects research below.
• Administrative Contact (AC): Do not add ACs to the study team table. To add ACs,
navigate to the Permissions tab on top-right-hand-side of form. All ACs must
complete the requisite Human Research Protections CITI Training.
• Lead Researcher (LR): LRs must meet requirements specified on the Lead Researcher
Eligibility page for study to be approved.
• Select ‘Oversight of Research’ along with other applicable duties.
• Select 'Full Access'.
• Faculty Sponsor (FS): FSs are required when the person serving the LR role is not qualified
to serve as LR-- the FS must be eligible to be LR.
• Select ‘Oversight of Research’ along with other applicable duties.
• Select 'Full Access'. 
• Co-Researcher (CR): CRs are faculty, staff, students and other academic appointees who
the LR considers to be key personnel for conducting the research study. These individuals
work closely with the LR to design, conduct, and/or report on the research.
• Research Personnel (RP): List RP as required per the Research Personnel Heat Map. For
those RP who do not need to be listed on the protocol, they may be tracked by alternative
methods, see below.
• IMPORTANT! Do NOT list non-UCI researchers below, in the Permissions tab at top or on
the Study Team Tracking Log (or equivalent); instead, follow the Single IRB Reliance (sIRB)
process.
• Collaborative Institutional Training Initiative (CITI) Human Research Protections Training
Courses
• Confirm CITI training is complete and current for all study team members.
• Incomplete or expired CITI training will delay IRB approval.
• For more information, visit HRP Training and Education.
Researcher
An Hong Do

Training
To promote the objectivity of the research, all researchers are required to disclose their related
disclosable financial interests, per the IRB COI Policy. If you have any questions about the COI
process in general, contact the COI team.
Each member of the study team for this protocol must be asked the following question to
comply:
“Do you, your spouse/registered domestic partner, and dependent children have any
disclosable financial interests* (i) that would reasonably appear to be affected by this research
study; or (ii) in entities whose financial interests would reasonably appear to be affected by
this research study?"
No
Degree
MD
Degree Other
Position/Title
Assistant Professor
Department
GCP for Clinical Investigations of Devices -
Refresher Course
03/23/17 - 03/22/20
error Expired
GCP for Clinical Investigations of Devices - Basic
Course
11/10/22 - (no expiration)
GCP for Clinical Trials with Investigational Drugs
and Medical Devices (U.S. FDA focus) - Basic
Course
10/26/21 - 10/25/24
error Expired
GCP for Clinical Trials with Investigational Drugs
and Medical Devices (U.S. FDA focus) - Refresher
Course
03/23/17 - 03/22/20
error Expired
Biomedical Investigators - Refresher Course
11/10/22 - (no expiration)
***IR-7455 - NEUROLOGY (Lead Unit)***

Affiliation
UCI Faculty
Specify other UCI affiliation:
Researcher Role
Lead Researcher
Permissions
Full Access
Duties
Oversight of Research
Research Procedures
Screen/Recruit Subjects
Finalize Informed Consent
Access/Analyze Identifiable Information
Access/Analyze Identifiable Biospecimens
Describe additional research procedures below:
Will be involved in: - Subject screening, recruitment - Data analysis - BCI
procedures - Electrophysiological procedures (EEG, EMG) - Safety oversight
for participants in all groups of the study
Specify relevant training and experience for the referenced duties/responsibilities:
Medical degree, neurology, neurophysiology, clinical rehabilitation. He will
also be finalizing the consent as he has extensive experience, expertise and
training in clinical research and consenting patients and can answer any
questions the patients may have prior to deciding to participate, regarding
the risks/safety related to the devices used in this study, including medical-
related information.
Researcher
Steven c Cramer

Training
To promote the objectivity of the research, all researchers are required to disclose their related
disclosable financial interests, per the IRB COI Policy. If you have any questions about the COI
process in general, contact the COI team.
Each member of the study team for this protocol must be asked the following question to
comply:
“Do you, your spouse/registered domestic partner, and dependent children have any
disclosable financial interests* (i) that would reasonably appear to be affected by this research
study; or (ii) in entities whose financial interests would reasonably appear to be affected by
this research study?"
No
Degree
MD
Degree Other
Position/Title
Adjunct Professor, Neurology
Department
Affiliation
UCI Faculty
Specify other UCI affiliation:
Researcher Role
Co-Researcher
UCI Biomedical Research Investigators - Basic
Course
02/26/09 - (no expiration)
***IR-7455 - NEUROLOGY (Lead Unit)***

Permissions
Full Access
Duties
Research Procedures
Access/Analyze Identifiable Information
Access/Analyze Identifiable Biospecimens
Describe additional research procedures below:
Will be involved in: Overseeing design and implementation of study, data
analysis with access to de-identified data, overseeing design of
conventional physical therapy regimen, TMS procedures
Specify relevant training and experience for the referenced duties/responsibilities:
Medical degree, neurology, stroke, rehabilitation
Researcher
David J Reinkensmeyer
Training
GCP for Clinical Investigations of Devices -
Refresher Course
12/16/20 - 12/16/23
error Expired
GCP for Clinical Investigations of Devices - Basic
Course
12/15/23 - (no expiration)
Biomedical Investigators - Basic Course
03/23/22 - 03/22/27

To promote the objectivity of the research, all researchers are required to disclose their related
disclosable financial interests, per the IRB COI Policy. If you have any questions about the COI
process in general, contact the COI team.
Each member of the study team for this protocol must be asked the following question to
comply:
“Do you, your spouse/registered domestic partner, and dependent children have any
disclosable financial interests* (i) that would reasonably appear to be affected by this research
study; or (ii) in entities whose financial interests would reasonably appear to be affected by
this research study?"
No
Degree
PhD
Degree Other
Position/Title
Professor, Anatomy and Neurobiology
Department
Affiliation
UCI Faculty
Specify other UCI affiliation:
Researcher Role
Co-Researcher
Permissions
Full Access
IR-8095 - MECHANICAL ENGINEERING

Duties
Research Procedures
Screen/Recruit Subjects
Finalize Informed Consent
Access/Analyze Identifiable Information
Access/Analyze Identifiable Biospecimens
Describe additional research procedures below:
Will be involved in: - Subject screening, recruitment - Data analysis - BCI
procedures
Specify relevant training and experience for the referenced duties/responsibilities:
Mechanical engineering, rehabilitation engineering. He will also be finalizing
the consent as he has extensive experience, expertise and training in clinical
research and consenting patients and can answer any questions the
patients may have prior to deciding to participate, regarding the risks/safety
related to the devices used in this study, including medical-related
information.
Researcher
Zoran Nenadic

Training
To promote the objectivity of the research, all researchers are required to disclose their related
disclosable financial interests, per the IRB COI Policy. If you have any questions about the COI
process in general, contact the COI team.
Each member of the study team for this protocol must be asked the following question to
comply:
“Do you, your spouse/registered domestic partner, and dependent children have any
disclosable financial interests* (i) that would reasonably appear to be affected by this research
study; or (ii) in entities whose financial interests would reasonably appear to be affected by
this research study?"
No
Degree
Other
Degree Other
DSc
GCP for Clinical Investigations of Devices -
Refresher Course
08/10/22 - (no expiration)
GCP for Clinical Investigations of Devices - Basic
Course
03/08/19 - 03/07/22
error Expired
GCP - Social and Behavioral Research Best
Practices for Clinical Research - Basic Course
08/11/22 - (no expiration)
GCP for Clinical Trials with Investigational Drugs
and Medical Devices (U.S. FDA focus) - Basic
Course
03/08/19 - 03/07/22
error Expired
GCP for Clinical Trials with Investigational Drugs
and Medical Devices (U.S. FDA focus) - Refresher
Course
08/10/22 - (no expiration)
Biomedical Investigators - Basic Course
03/02/17 - 03/01/22
error Expired
Biomedical Investigators - Refresher Course
08/10/22 - (no expiration)

Position/Title
Professor, Biomedical Engineering
Department
Affiliation
UCI Faculty
Specify other UCI affiliation:
Researcher Role
Co-Researcher
Permissions
Full Access
Duties
Research Procedures
Screen/Recruit Subjects
Finalize Informed Consent
Access/Analyze Identifiable Information
Access/Analyze Identifiable Biospecimens
Describe additional research procedures below:
Will be involved in: - Subject screening, recruitment - Data analysis - BCI
procedures - Electrophysiological procedures (EEG, EMG)
Specify relevant training and experience for the referenced duties/responsibilities:
Biomedical engineering and signal analysis. He will also be finalizing the
consent as he has extensive experience, expertise and training in clinical
research and consenting patients and can answer any questions the
patients may have prior to deciding to participate, regarding the risks/safety
related to the devices used in this study, including medical-related
information.
IR-8098 - ENGINEERING/BIOMEDICAL ENGINEERING

Researcher
Danh Van Nguyen
Training
info Danh Nguyen has no training courses on file.
To promote the objectivity of the research, all researchers are required to disclose their related
disclosable financial interests, per the IRB COI Policy. If you have any questions about the COI
process in general, contact the COI team.
Each member of the study team for this protocol must be asked the following question to
comply:
“Do you, your spouse/registered domestic partner, and dependent children have any
disclosable financial interests* (i) that would reasonably appear to be affected by this research
study; or (ii) in entities whose financial interests would reasonably appear to be affected by
this research study?"
No
Degree
PhD
Degree Other
Position/Title
Professor, Internal Medicine
Department
Affiliation
UCI Faculty
Specify other UCI affiliation:
***IR-6101 - MEDICINE - DIVISION OF GENERAL INTERNAL MEDICINE & PRIMARY CARE (Lead
Unit)***

Researcher Role
Co-Researcher
Permissions
Full Access
Duties
Research Procedures
Access/Analyze Identifiable Information
Access/Analyze Identifiable Biospecimens
Describe additional research procedures below:
Data Analysis
Specify relevant training and experience for the referenced duties/responsibilities:
Biostatistics and clinical trial design
Researcher
Alison L Mckenzie
Training
info Alison Mckenzie has no training courses on file.
To promote the objectivity of the research, all researchers are required to disclose their related
disclosable financial interests, per the IRB COI Policy. If you have any questions about the COI
process in general, contact the COI team.
Each member of the study team for this protocol must be asked the following question to
comply:
“Do you, your spouse/registered domestic partner, and dependent children have any
disclosable financial interests* (i) that would reasonably appear to be affected by this research
study; or (ii) in entities whose financial interests would reasonably appear to be affected by
this research study?"
No

Degree
Other
Degree Other
PT, DPT, PhD
Position/Title
Project Scientist Department of Neurology
Department
Affiliation
UCI Faculty
Specify other UCI affiliation:
Researcher Role
Co-Researcher
Permissions
Full Access
Duties
Research Procedures
Screen/Recruit Subjects
Finalize Informed Consent
Access/Analyze Identifiable Information
Describe additional research procedures below:
see below
***IR-7455 - NEUROLOGY (Lead Unit)***

Specify relevant training and experience for the referenced duties/responsibilities:
Dr. Alison McKenzie is a collaborating physical therapist from Chapman
University. She has dual appointments at UC Irvine and Chapman University.
She will help with protocol development and implementation, recruitment,
data acquisition and analysis. She will also be involved in subject screening,
administer stroke outcome measures and assessments,
Electrophysiological procedures (EEG, EMG) and TMS procedures. She will
also be finalizing the consent as she has extensive experience, expertise
and training in clinical research and consenting patients and can answer
any questions the patients may have prior to deciding to participate,
regarding the risks/safety related to the devices used in this study, including
medical-related information.
Researcher
Lucy Dodakian
Training
UCI Biomedical Research Investigators - Refresher
Course
11/14/19 - 11/13/22
error Expired
GCP for Clinical Trials with Investigational Drugs
and Medical Devices (U.S. FDA focus) - Basic
Course
11/14/23 - (no expiration)
GCP for Clinical Trials with Investigational Drugs
and Medical Devices (U.S. FDA focus) - Refresher
Course
12/11/20 - 12/11/23
error Expired
Biomedical Investigators - Basic Course
10/07/22 - (no expiration)

To promote the objectivity of the research, all researchers are required to disclose their related
disclosable financial interests, per the IRB COI Policy. If you have any questions about the COI
process in general, contact the COI team.
Each member of the study team for this protocol must be asked the following question to
comply:
“Do you, your spouse/registered domestic partner, and dependent children have any
disclosable financial interests* (i) that would reasonably appear to be affected by this research
study; or (ii) in entities whose financial interests would reasonably appear to be affected by
this research study?"
No
Degree
MA
Degree Other
Position/Title
Research Occupational Therapist
Department
Affiliation
UCI Staff
Specify other UCI affiliation:
Researcher Role
Research Personnel
Permissions
Full Access
Physical Therapy - IP

Duties
Research Procedures
Screen/Recruit Subjects
Finalize Informed Consent
Access/Analyze Identifiable Information
Describe additional research procedures below:
- Study coordination - Subject recruitment - Administrative contact
Specify relevant training and experience for the referenced duties/responsibilities:
Training in clinical and research occupational therapy, extensive experience
in coordinating and conducting clinical studies and clinical trials. She will
also be finalizing the consent as she has extensive experience, expertise
and training in clinical research and consenting patients and can answer
any questions the patients may have prior to deciding to participate,
regarding the risks/safety related to the devices used in this study, including
medical-related information.
Researcher
WaiKi Vicky Chan
Training
GCP for Clinical Trials with Investigational Drugs
and Medical Devices (U.S. FDA focus) - Basic
Course
11/17/23 - (no expiration)
GCP for Clinical Trials with Investigational Drugs
and Medical Devices (U.S. FDA focus) - Refresher
Course
12/18/20 - 12/18/23
error Expired
Biomedical Investigators - Basic Course
09/30/24 - (no expiration)
Biomedical Investigators - Refresher Course
10/14/19 - 10/12/24
error Expired

To promote the objectivity of the research, all researchers are required to disclose their related
disclosable financial interests, per the IRB COI Policy. If you have any questions about the COI
process in general, contact the COI team.
Each member of the study team for this protocol must be asked the following question to
comply:
“Do you, your spouse/registered domestic partner, and dependent children have any
disclosable financial interests* (i) that would reasonably appear to be affected by this research
study; or (ii) in entities whose financial interests would reasonably appear to be affected by
this research study?"
No
Degree
Other
Degree Other
DPT
Position/Title
Research Physical Therapist
Department
Affiliation
UCI Staff
Specify other UCI affiliation:
Researcher Role
Research Personnel
Permissions
Full Access
Physical Therapy - IP

Duties
Research Procedures
Screen/Recruit Subjects
Finalize Informed Consent
Access/Analyze Identifiable Information
Describe additional research procedures below:
- Subject screening, recruitment - Administer stroke outcome measures and
assessments - Electrophysiological procedures (EEG, EMG) - TMS
procedures - will be finalizing consent for Groups 3&4 Consent Procedures
Specify relevant training and experience for the referenced duties/responsibilities:
Training in clinical and research physical therapy and assessments/devices
used in this study. She will also be finalizing the consent as she has
extensive experience, expertise and training in clinical research and
consenting patients and can answer any questions the patients may have
prior to deciding to participate, regarding the risks/safety related to the
devices used in this study, including medical-related information.
Researcher
Jill See
Training
GCP for Clinical Trials with Investigational Drugs
and Medical Devices (U.S. FDA focus) - Basic
Course
08/31/23 - 08/31/26
GCP for Clinical Trials with Investigational Drugs
and Medical Devices (U.S. FDA focus) - Refresher
Course
09/09/20 - 09/09/23
error Expired
IRB-Mandated Compliance - Biomedical
09/26/24 - 09/26/29

To promote the objectivity of the research, all researchers are required to disclose their related
disclosable financial interests, per the IRB COI Policy. If you have any questions about the COI
process in general, contact the COI team.
Each member of the study team for this protocol must be asked the following question to
comply:
“Do you, your spouse/registered domestic partner, and dependent children have any
disclosable financial interests* (i) that would reasonably appear to be affected by this research
study; or (ii) in entities whose financial interests would reasonably appear to be affected by
this research study?"
No
Degree
Other
Degree Other
DPT
Position/Title
Research Physical Therapist
Department
Affiliation
UCI Staff
Specify other UCI affiliation:
Researcher Role
Research Personnel
Permissions
Full Access
Physical Therapy - IP

Duties
Research Procedures
Screen/Recruit Subjects
Finalize Informed Consent
Access/Analyze Identifiable Information
Describe additional research procedures below:
- Subject screening, recruitment - Administer stroke outcome measures and
assessments - Electrophysiological procedures (EEG, EMG) - TMS
procedures
Specify relevant training and experience for the referenced duties/responsibilities:
Training in clinical and research physical therapy and assessments/devices
used in this study. She will also be finalizing the consent as she has
extensive experience, expertise and training in clinical research and
consenting patients and can answer any questions the patients may have
prior to deciding to participate, regarding the risks/safety related to the
devices used in this study, including medical-related information.
Researcher
Sharada Sripathi Govindu
Training
GCP for Clinical Investigations of Devices - Basic
Course
02/15/22 - 02/14/25
error Expired
Biomedical Investigators - Basic Course
02/10/22 - 02/09/27
Research and HIPAA Privacy Protections
02/08/22 - 02/07/27

To promote the objectivity of the research, all researchers are required to disclose their related
disclosable financial interests, per the IRB COI Policy. If you have any questions about the COI
process in general, contact the COI team.
Each member of the study team for this protocol must be asked the following question to
comply:
“Do you, your spouse/registered domestic partner, and dependent children have any
disclosable financial interests* (i) that would reasonably appear to be affected by this research
study; or (ii) in entities whose financial interests would reasonably appear to be affected by
this research study?"
No
Degree
Other
Degree Other
DPT
Position/Title
Research Physical Therapist
Department
Affiliation
UCI Staff
Specify other UCI affiliation:
Researcher Role
Research Personnel
Permissions
Full Access
Physical Therapy - IP

Duties
Research Procedures
Screen/Recruit Subjects
Finalize Informed Consent
Access/Analyze Identifiable Information
Describe additional research procedures below:
Subject Screening, recruitment; Administer stroke outcome measures and
assessments; Electrophysiological procedures (EEG, EMG), will be finalizing
consent for the Screening and Groups 1&2 Consent Procedures.
Specify relevant training and experience for the referenced duties/responsibilities:
Training in clinical and research physical therapy and assessments/devices
used in this study. She will also be finalizing the consent as she has been
trained in clinical research and consenting patients and can answer any
questions the patients may have prior to deciding to participate, regarding
the risks/safety related to the devices used in the study.
Researcher
Heather B Carter
Training
GCP for Clinical Investigations of Devices - Basic
Course
06/14/23 - (no expiration)
Biomedical Investigators - Basic Course
06/13/23 - (no expiration)

To promote the objectivity of the research, all researchers are required to disclose their related
disclosable financial interests, per the IRB COI Policy. If you have any questions about the COI
process in general, contact the COI team.
Each member of the study team for this protocol must be asked the following question to
comply:
“Do you, your spouse/registered domestic partner, and dependent children have any
disclosable financial interests* (i) that would reasonably appear to be affected by this research
study; or (ii) in entities whose financial interests would reasonably appear to be affected by
this research study?"
No
Degree
Other
Degree Other
OT R/L (Masters); BA in Ecology
Position/Title
Research Occupational Therapist
Department
Affiliation
UCI Staff
Specify other UCI affiliation:
Researcher Role
Research Personnel
Permissions
Full Access
Physical Therapy - IP

Duties
Research Procedures
Screen/Recruit Subjects
Finalize Informed Consent
Access/Analyze Identifiable Information
Describe additional research procedures below:
Subject screening, recruitment; Administer stroke outcome measures and
assessments; Electrophysiological procedures (EEG, EMG), will be finalizing
consent for the Screening and Groups 3&4 Consent procedures.
Specify relevant training and experience for the referenced duties/responsibilities:
Training in clinical and research occupational therapy and
assessments/devices used in this study. She will also be finalizing the
consent as she has been trained in clinical research and consenting
patients and can answer any questions the patients may have prior to
deciding to participate, regarding the risks/safety related to the devices
used in the study.
Are RP tracked outside the approved protocol, in accordance with the RP Heat Map?
Yes, RP are tracked on a Study Team Log or other comparable log
Supplemental Documents
Does this study include supplemental documents?
No
Background & Purpose of the Research

Describe the purpose, specific aims or objectives and specify the hypotheses or research
questions to be studied:
Aim 1: Quantify the neurological and functional improvements due to BCI-FES
dorsiflexion therapy compared to dose- and intensity-matched conventional
therapy. Hypothesis: The neural repair mechanisms underlying BCI-FES
dorsiflexion therapy will lead to improvements in neurological and functional
outcomes that are greater and longer-lasting than those achieved by dose-
matched conventional therapy. Aim 2: Identify stroke features that are linked
to responsiveness to BCI-FES dorsiflexion therapy. Hypothesis: Based on
preliminary studies, baseline gait velocity, dorsiflexion AROM/torque, TA
muscle electromyogram (EMG) and motor evoked potentials, the magnitude
of EEG alpha- and beta-band ERD/ERS during attempted dorsiflexion, and
sensory function will influence the response to BCI-FES dorsiflexion therapy.
Aim 3: Investigate the mechanism of action of BCI-FES dorsiflexion therapy.
Hypothesis: BCI-FES therapy reinforces the connectivity between foot M1 and
the α-MN due to Hebbian plasticity. The study will have a significant impact in
rehabilitative neuroscience, clinical neurorehabilitation,

Provide the scientific or scholarly rationale for the research and describe the relevant
background information and the specific gaps in current knowledge that this study intends to
address:
There are >7 million stroke survivors in the US alone, with approximately
795,000 new cases annually. Despite spontaneous recovery and the best
available physiotherapy, between 30% and 60% of stroke survivors remain
affected by gait function impairments [2, 3], with foot-drop often being the
primary cause. Chronic poststroke gait impairments are: 1. associated with
significant disability and reduced physical activity; 2. directly linked to poor
social re-integration; and 3. ranked as the top rehabilitation priority among
stroke survivors. These problems lead to an increased risk of medical
complications and raise a major public health concern due to increased
healthcare, caregiving, and lost productivity costs. These costs are expected
to increase as the aging population grows and acute stroke survival rates
keep improving. Clinicians have for decades utilized biomechanical methods
such as ankle-foot orthoses (AFO) and functional electrical stimulation (FES)
orthoses to mitigate post-stroke gait impairment. However, these devices are
cumbersome, may cause discomfort, and their benefits disappear upon
removal. Consequently, post-stroke gait impairments remain suboptimally
addressed. Novel methods that are based on neurobiological principles and
can provide lasting neurological and functional improvements are therefore
necessary [9]. This is particularly needed for stroke survivors with the worst
neurological functions, whose impairments are too severe to participate in
most rehabilitative therapies. Such methods would improve the function of
the affected individuals to the point where they could participate in both
existing and novel physiotherapies. This outcome would improve the quality
of life and increase independence of the affected population. It would also
reduce the overall cost. Brain-computer interface (BCI) technology may be
one such novel approach to post-stroke rehabilitation. Noninvasive BCIs
perform real-time analysis of brain signals, e.g. electroencephalogram (EEG),
and translate these into control commands for assistive devices. For
example, when integrated with FES systems, BCIs could be used to deliver a
novel form of post-stroke physiotherapy. We hypothesize that such a therapy
can stimulate a Hebbian plasticity process (“neurons that fire together, wire
together”), and thereby improve poststroke plasticity and functional recovery
beyond those of conventional physiotherapy. Specifically, by modulating EEG,
a user can trigger FES of the impaired limb. This provides a co-incident
activation of the post-stroke motor cortex, M1, (detected by BCI) and the

corresponding spinal motor pools (via antidromic electrical stimulation of
peripheral motor neurons, alpha MN), which over time may reinforce their
connections. Since therapeutic gains in motor function are generally
accompanied by favorable forms of motor system plasticity, such
hypothesized changes due to BCI-FES therapy may translate into enduring
functional gains, possibly even in those who do not rehabilitate naturally. Early
feasibility studies of this BCI-FES concept in the upper and lower extremity
rehabilitation, suggest that this approach is safe and can significantly
improve post-stroke motor function. Using foot-drop as a post-stroke deficit
model, the applicants undertook four preliminary studies to engineer a
reliable BCI-FES system for foot dorsiflexion and demonstrate the BCI-FES
system’s safety and potential to promote neurological recovery after stroke.

Provide relevant preliminary data (animal and/or human):
We performed a long-term study to assess the safety and potential of BCI-FES
therapy. Nine chronic stroke subjects (>6 months post-ictus) with gait
impairment due to foot-drop underwent 12 sessions of BCI-FES therapy (3
sessions/week, for 4 weeks). The primary outcome measure was gait
velocity. Secondary outcomes were dorsiflexion active range of motion
(AROM), leg motor Fugl-Meyer score, gait endurance (6-min walk test), and
fall frequency. These outcomes were assessed before, on a weekly basis, and
1 month after completion of the BCI-FES therapy (Fig. 3). No subjects
experienced a significant decrement in any outcome measure and there were
no adverse events, indicating that BCI-FES therapy is safe. In post-hoc
analysis, 6 out of 9 (66.7%) subjects had a significant improvement in gait
velocity at 1 month post-therapy (average increase of 51%, or 0.21 +/- 0.15
m/s). While no spatial cortical reorganization was observed in any subject at
the end of therapy, the Cz channel (electrode over the foot motor area)
exhibited an increase in alpha- and beta-band event-related
desychronization/synchronization (ERD/ERS) magnitude in 5 of these 6
(83.3%) subjects. Conversely, these EEG changes did not occur in the 3
subjects with no gait velocity improvement. This suggests the existence of a
neural process underlying gait velocity improvements. Subjects with low gait
velocity (<0.4 m/s) and poor dorsiflexion AROM (<5 degrees) at baseline were
150% more likely than those with moderate-to-high gait velocity (>0.4 m/s) or
good-to-excellent AROM (>5 degree) to experience an increase in gait velocity.
This highlights a potential promise of BCI-FES therapy in that it may be
accessible and beneficial to stroke survivors whose baseline motor functions
are too low for current or emerging interventions.

Describe the primary outcome variable(s), secondary outcome variables, and predictors and/or
comparison groups as appropriate for the stated study objectives/specific aims:
The primary outcome measure will be gait velocity, which is directly linked to
disability and social re-integration after stroke. Gait velocity will be assessed
by measuring the time to traverse the middle 6 m of a 10-m walkway (5
repetitions/assessment). Secondary outcomes include: 1. Gait endurance:
The distance walked over 6 minutes. 2. Fall Frequency: Number of falls
experienced weekly. 3. Leg Motor Fugl-Meyer (FM) Score: Assessed
according to the FM rating system. 4. Dorsiflexion Active Range of Motion
(AROM) and torque: The paretic foot will be placed in an articulated brace
which maintains the ankle at neutral during idling, while fixing the tibia
perpendicular to the ground and the femur horizontal to the ground. The brace
will be instrumented with an electro-goniometer and torque meter to
automatically measure the maximum dorsiflexion AROM and torque (over 3
trials). 5. EEG Map: Subjects will undergo 64-channel EEG recording as they
engage in 100 alternating 10-s long epochs of idling and attempted
dorsiflexion. The EEG ERD/ERS, defined as the drop/rise in alpha (8-12 Hz)
and beta (13-30 Hz) band power during attempted dorsiflexion (compared to
idling), will be calculated and averaged over all epochs and across all
channels.

List up to ten relevant references/articles to support the rationale for the research:
• Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al.
Heart disease and stroke statistics–2012 update: a report from the American
Heart Association. Circulation. 2012;125(1):e2–e220. • Wolpaw JR, Birbaumer
N, McFarland DJ, Pfurtscheller G, Vaughan TM. Brain-computer interfaces for
communication and control. Clin Neurophysiol. 2002;113(6):767–791. •
McCrimmon CM, King CE, Wang PT, Cramer SC, Nenadic Z, Do AH. Brain-
controlled functional electrical stimulation therapy for gait rehabilitation after
stroke: a safety study. Journal of neuroengineering and rehabilitation.
2015;12(1):57. • Do AH, Wang PT, King CE, Abiri A, Nenadic Z. Brain-computer
interface controlled functional electrical stimulation system for ankle
movement. J Neuroeng Rehabil. 2011;8:49. Available from:
http://dx.doi.org/10.1186/1743-0003-8-49. • Do AH, Wang PT, King CE,
Schombs A, Cramer SC, Nenadic Z. Brain-computer interface controlled
functional electrical stimulation device for foot drop due to stroke. In: Proc
34th Ann Int Conf IEEE Eng Med Biol Soc; 2012. p. 6414–6417. • McCrimmon
C, Fu J, Wang M, Lopes LS, Wang P, Karimi-Bidhendi A, et al. Performance
Assessment of a Custom, Portable and Low-Cost Brain-Computer Interface
Platform. IEEE Transactions on Biomedical Engineering. 2017. • McCrimmon
CM, Wang PT, Nenadic Z, Do AH. BCI-Based Neuroprostheses and
Physiotherapies for Stroke Motor Rehabilitation. In: Neurorehabilitation
Technology. Springer; 2016. p. 617–627.
Subject Population(s) (Individuals/Records/Biospecimens)
Check all subject populations/data sources that apply to the research:
Adults Competent to Provide Informed Consent
Maximum and Expected Number of Persons/Records/Biospecimens to be Enrolled
1. Click "Add Line" button above Enrollment Table to add a Category/Group
a. To change visibility of columns, click "Columns" button above Enrollment Table and
select which Column rows to view.
2.  Specify the maximum and expected numbers of individual-level information and/or
biospecimens to be accessed/analyzed within each Category/Group

Category/Group
Adults (Aim 1 and 2)
Age Range
18-80
Maximum Number of Subjects, Subjects to be Consented or Reviewed/Collected
200
Number Expected to Complete the Study or Needed to Address the Research Question
80
Category/Group
Adults (Aim 3)
Age Range
18-80
Maximum Number of Subjects, Subjects to be Consented or Reviewed/Collected
40
Number Expected to Complete the Study or Needed to Address the Research Question
20
Will this study only take place at UCI and does not involve other sites?
Yes
Eligibility Factors (Inclusion/Exclusion Criteria)
1. Click "Add Line" button above Eligibility Factors Table to add a inclusion/exclusion criteria
a. To change visibility of columns, click "Columns" button above Eligibility Factors Chart
and select which Column rows to view.
2. Identify the factors for limited eligibility and provide a scientific rationale. Include additional
rows for factors, as needed.

Category/Group Eligibility
Adults - all groups
Inclusion Criteria
1. Age18-80 years inclusively at time of consent; 2. Radiologically confirmed
stroke, ischemic or intracerebral hemorrhage (ICH) in etiology, with day of
onset at least 26 weeks prior to day of randomization 3. Gait velocity<0.8
m/s at screening and baseline visits. 4. Foot-drop in affected limb as
defined by dorsiflexion active range of motion (AROM) via goniometry in
seated position foot dangling is less than passive range of motion and less
than 15 degrees. 5. Plantarflexors spasticity<3 on modified Ashworth Scale;
6. Can walk >10 m (with or without ankle foot orthosis (AFO), and cane or
walker permitted) at a supervised level; 7. Can tolerate FES with pain no
more than 4 on pain analog scale and has adequate muscle response of
dorsiflexion ≥10 degrees; 8. Passive Range of Motion at least 0 degrees
ankle dorsiflexion in subtalar neutral or with FES

Exclusion Criteria
Exclusion Criteria: 1. A major, active, coexistent medical, neurological (apart
from stroke) or psychiatric disease (apart from stroke), including alcoholism
or dementia, orthopedic injuries, that substantially affects gait. **Because
old orthopedic injuries may or may not affect gait, at the discretion of the
site's study PI, exclusion criterion #2 related to orthopedic injuries can be
waived if the joint/muscles are back to normal motor and range of motion
function. 2. A major medical disorder that substantially reduces the
likelihood that a subject will be able to comply with all study procedures or
safely complete study procedures. This includes, but not limited to
documented serious cardiac conditions, serious pulmonary conditions, legal
blindness, end stage renal or liver disease, pulmonary embolism or deep
venous thrombosis. 3. Resting systolic blood pressure above 170, diastolic
blood pressure above 100 at screening and baseline evaluations 4.
Implanted electronic device (e.g. pacemaker) or skull metallic implants (e.g.
cranioplasty plate covering the leg motor area) with which study research
procedures are contraindicated or incompatible. 5. Deficits in
communication that interfere with reasonable study participation: language
or attention impairment (score>1 on NIH Stroke Scale items 9 and 11,
respectively) 6. Significant cognitive impairment, defined as Montreal
Cognitive Assessment score < 22 (For those with aphasia: **Because
Montreal Cognitive Assessment scores may be difficult to interpret for
patients with aphasia, at the discretion of the site's study PI, exclusion
criterion #5 (“MoCA score cannot be <22”) can be waived) 7. A new
symptomatic stroke occurs apart from the index stroke during the screening
process and prior to randomization 8. Life expectancy < 6 months 9. Skin
breakdown over electrical stimulation sites; 10. Received chemical
denervation (eg Botox) to legs in the preceding 6 months, or expectation
that chemical denervation will be administered to the leg prior to expected
completion of the study 11. Unable or unwilling to perform study
procedures/therapy, or expectation of non-compliance with study
procedures/therapy 12. Pregnancy; 13. Significant pain (visual analog scale
>4), chest pain, or shortness of breath with walking. 14. Receiving any
outside concurrent physical therapy involving the lower extremities after
enrollment in the study up to 1 month post treatment 15. Any general
medical condition and psychosocial situation that substantially interferes
with reasonable participate in study appointments 16. Non-English

speaking, such that subject does not speak sufficient English to comply with
study procedures 17. Concurrent enrollment in another investigational
interventional study 18. Severe depression, defined as Geriatric Depression
Scale Score >11: **Because Geriatric Depression scale scores may be
difficult to interpret for some patients, at the discretion of the site's study PI,
exclusion criterion #17 (“Geriatric Depression score cannot be >11”) can be
waived) 19. Concurrent use of FES orthosis for gait. 20. A new symptomatic
stroke occurs apart from the index stroke during the screening process and
prior to randomization If TMS Eligible (note that potential subjects who do
not qualify for TMS will not be excluded from the main study, they will only
be excluded from undergoing TMS procedures): 21. TMS: Metallic hardware
on the scalp (e.g. vascular clips or cranioplasty mesh) 22. TMS: Implanted
medication pumps, intracardiac line, or central venous catheter 23. TMS:
History of cortical stroke or other cortical lesion such as brain tumor 24.
TMS: Prior diagnosis of seizure or epilepsy 25. TMS: Any electrical,
mechanical, or magnetic implants 26. TMS: History of neurosurgery 27.
TMS: uncontrolled Migraine headaches 28. TMS: Any current medications
that affect seizure threshold such as tricyclic antidepressants and
neuroleptics 29. TMS: Unstable medical conditions
Is eligibility based on age, gender, pregnancy/childbearing potential, social/ethnic group, or
language spoken (e.g., English Speakers only)?
Yes
Limited Eligibility Factors (Special Populations)
1. Click "Add Line" button above Limited Eligibility Factors Table to add a special population
a. To change visibility of columns, click "Columns" button above Limited Eligibility Factors
Table and select which Column rows to view.
2. Identify the special populations and provide a scientific rationale. Add additional rows, as
needed.
Eligibility Limited to the Following Factors
Age

Specify the rationale for this group:
Only patients age 18-80 will be recruited. Children and minors have brains
that are still developing and will add additional unknown/variability to the
study. Adults over 80 years of age will be excluded because the aging
process produces deteriorations in motor control and motor learning, and
thus age is a confounding factor for identifying changes in motor ability due
to BCI training. English speaking only: The program for the BCI system is
only written in English. When other languages are available, the study can be
expanded.
Eligibility Limited to the Following Factors
Language Spoken (e.g., English speakers only)
Specify the rationale for this group:
The program for the BCI system is only written in English
Eligibility Limited to the Following Factors
Language Spoken (e.g., English speakers only)
Specify the rationale for this group:
non-English speakers are excluded because the program for the BCI system
is only written in English
Pre-Screening and Determining Eligibility without Informed Consent
Will Identifiable information be obtained for the purpose of screening, recruiting, or determining
eligibility of prospective subjects?
Yes
The 2018 Common Rule allows for Pre-Screening activities (i.e., determining if potential subjects
may be eligible to participate in research) performed without the written informed consent of the
prospective subject or legally authorized representative (LAR). This means that the IRB does not
need to grant a waiver of informed consent.

Provide a complete list of the data points, variables, and/or information that will be collected
during Pre-Screening (i.e. data abstraction form):
Or specify variables or information required for Pre-Screening:
radiologically confirm stroke through review of imaging, time of stroke
(greater than 6 months); age; presence of gait impairment due to stroke
Check all the Pre-Screening activities that apply:
Study team will screen medical records to determine subject eligibility
Select Medical Record Source (check all that apply):
Other medical record source
Study team will access their own UCI patients’ records and abstract data
directly from those records
Study team will request Non-UCI Health records and abstract data directly
from those records
Other Medical Record Source
Explain 'Other' medical record source:
The study team will request specific patient information/data from UCIMC
Health Information Management Services.
The Study Team Will Request Non-UCI Health Records and Abstract Data Directly
from those Records
Enter the name(s) of Non-UCI Entity/Entities:
other medical institutions where study participants have medical records
to be reviewed after subjects sign the HIPAA Authorization

How will the study team request Non-UCI Health records and abstract data directly from
those records?
Specify the non-UCI Health records that will be screened: History and
physical notes pertaining to stroke admission, neurology consult notes,
rehabilitation service notes, and MRI brain images Explain how the study
team has access to this clinical data: Potential subjects who are
interested who have passed initial screening and agree to sign HIPAA
waiver for release of information. Our research team will either screen
copies of the records provided to us by the potential subject or will
contact the appropriate medical institution to request a copy of the above
record types for review. Subjects will sign the HIPAA non-UCI provider
form and only after it’s signed will non-UCI records be released to study
team.
Will the study team screen stored identifiable biospecimens?
No
Will the study team contact subjects for eligibility or recruitment purposes?
No
Recruitment Methods
Will this study involve NO direct contact with participants (i.e., passive observation of public
behavior)?
No
Indicate all methods that will be used to recruit subjects for this study:
Recruitment Method
Flyers/Brochures

Specify Where Posted
Approved recruitment materials may be posted in local newspapers, on the
American Heart Association/American Stroke association and local stroke
support group websites. Recruitment materials may also be posted on
social media platforms such as Facebook, Twitter and Reddit. A Facebook
page for the study was created at:
https://www.facebook.com/legtherapystudy/
Type of Space
Private (i.e., site/media that allows control of access to content)
Confirm that applicable consent documents will include reference to the use of SONA
Confirm that the ClinicalTrials.gov statement is in all applicable consent documents
Confirm that the study from the Center for Clinical Research (CCR) Find a Trial web page
is registered on ClinicalTrials.gov
Specify how contact information will be obtained:
Specify how these individuals granted permission and enter HS#:
Examples:
• Individuals who are economically or educationally disadvantaged
• Individuals that have impaired decision-making capacity
• Physician's own inpatients and/or outpatients
• Students (undergraduate, graduate, and medical students)
• Employees of UCI (administrative, clerical, nursing, lab technicians, post-doctoral fellows
and house staff, etc.)
IRB requires that:
1. Subjects will be approached with an emphasis that participation is voluntary; and
2. Subject will be informed in a caring manner that no matter their decision, it will NOT
affect:
a. Their relationship with UCI
b. How their doctor cares for them as a patient or their care at UC Health in general
and/or
c. How their instructor grades their participation in the course; and
3. A statement attesting the information above in item b will be included in applicable
recruitment and/or consent documents.

Confirm that colleagues may provide a copy of the consent and other UCI IRB approved
materials but do not obtain subjects’ consent for the research or act as representatives of the
investigators
Confirm that:
1. The recruitment letter to be signed by the treating physician will be submitted in the
Attachments Section
2. Colleagues do not obtain subjects’ consent for the research or act as representatives of
the investigators
Specify 'Other' recruitment methods:
Specify the precautions taken to avoid compromised objectivity:
Recruitment Method
Online/Social Media
Specify Where Posted
Completely passive approach will be utilized where potential participants
are not presented with the info about study participation directly, whomever
is interest will contact study team first if interested, and no contact with be
made nor initiated from study team (e.g. general posting of study not linking
to each individual’s account, and where consideration for method of
approach has provisions in place to ensure patient/physician confidentiality
and/or subject privacy are not compromised).
Type of Space
Private (i.e., site/media that allows control of access to content)
Confirm that applicable consent documents will include reference to the use of SONA
Confirm that the ClinicalTrials.gov statement is in all applicable consent documents
Confirm that the study from the Center for Clinical Research (CCR) Find a Trial web page
is registered on ClinicalTrials.gov
Specify how contact information will be obtained:

Specify how these individuals granted permission and enter HS#:
Examples:
• Individuals who are economically or educationally disadvantaged
• Individuals that have impaired decision-making capacity
• Physician's own inpatients and/or outpatients
• Students (undergraduate, graduate, and medical students)
• Employees of UCI (administrative, clerical, nursing, lab technicians, post-doctoral fellows
and house staff, etc.)
IRB requires that:
1. Subjects will be approached with an emphasis that participation is voluntary; and
2. Subject will be informed in a caring manner that no matter their decision, it will NOT
affect:
a. Their relationship with UCI
b. How their doctor cares for them as a patient or their care at UC Health in general
and/or
c. How their instructor grades their participation in the course; and
3. A statement attesting the information above in item b will be included in applicable
recruitment and/or consent documents.
Confirm that colleagues may provide a copy of the consent and other UCI IRB approved
materials but do not obtain subjects’ consent for the research or act as representatives of the
investigators
Confirm that:
1. The recruitment letter to be signed by the treating physician will be submitted in the
Attachments Section
2. Colleagues do not obtain subjects’ consent for the research or act as representatives of
the investigators
Specify 'Other' recruitment methods:
Specify the precautions taken to avoid compromised objectivity:
Recruitment Method
Clinicaltrials.gov
Specify Where Posted
Type of Space

Confirm that applicable consent documents will include reference to the use of SONA
Confirm that the ClinicalTrials.gov statement is in all applicable consent documents
Confirm that the study from the Center for Clinical Research (CCR) Find a Trial web page
is registered on ClinicalTrials.gov
Specify how contact information will be obtained:
Specify how these individuals granted permission and enter HS#:
Examples:
• Individuals who are economically or educationally disadvantaged
• Individuals that have impaired decision-making capacity
• Physician's own inpatients and/or outpatients
• Students (undergraduate, graduate, and medical students)
• Employees of UCI (administrative, clerical, nursing, lab technicians, post-doctoral fellows
and house staff, etc.)
IRB requires that:
1. Subjects will be approached with an emphasis that participation is voluntary; and
2. Subject will be informed in a caring manner that no matter their decision, it will NOT
affect:
a. Their relationship with UCI
b. How their doctor cares for them as a patient or their care at UC Health in general
and/or
c. How their instructor grades their participation in the course; and
3. A statement attesting the information above in item b will be included in applicable
recruitment and/or consent documents.
Confirm that colleagues may provide a copy of the consent and other UCI IRB approved
materials but do not obtain subjects’ consent for the research or act as representatives of the
investigators
Confirm that:
1. The recruitment letter to be signed by the treating physician will be submitted in the
Attachments Section
2. Colleagues do not obtain subjects’ consent for the research or act as representatives of
the investigators
Specify 'Other' recruitment methods:
Specify the precautions taken to avoid compromised objectivity:

Recruitment Method
Other recruitment methods
Specify Where Posted
Type of Space
Confirm that applicable consent documents will include reference to the use of SONA
Confirm that the ClinicalTrials.gov statement is in all applicable consent documents
Confirm that the study from the Center for Clinical Research (CCR) Find a Trial web page
is registered on ClinicalTrials.gov
Specify how contact information will be obtained:
Specify how these individuals granted permission and enter HS#:
Examples:
• Individuals who are economically or educationally disadvantaged
• Individuals that have impaired decision-making capacity
• Physician's own inpatients and/or outpatients
• Students (undergraduate, graduate, and medical students)
• Employees of UCI (administrative, clerical, nursing, lab technicians, post-doctoral fellows
and house staff, etc.)
IRB requires that:
1. Subjects will be approached with an emphasis that participation is voluntary; and
2. Subject will be informed in a caring manner that no matter their decision, it will NOT
affect:
a. Their relationship with UCI
b. How their doctor cares for them as a patient or their care at UC Health in general
and/or
c. How their instructor grades their participation in the course; and
3. A statement attesting the information above in item b will be included in applicable
recruitment and/or consent documents.
Confirm that colleagues may provide a copy of the consent and other UCI IRB approved
materials but do not obtain subjects’ consent for the research or act as representatives of the
investigators

Confirm that:
1. The recruitment letter to be signed by the treating physician will be submitted in the
Attachments Section
2. Colleagues do not obtain subjects’ consent for the research or act as representatives of
the investigators
Specify 'Other' recruitment methods:
The study will be listed on the UC Irvine Health Clinical Trials web page.
Specify the precautions taken to avoid compromised objectivity:
Recruitment Method
Study team will approach subjects who are vulnerable to undue influence or
coercion (i.e. students, employees and patients)
Specify Where Posted
Type of Space
Confirm that applicable consent documents will include reference to the use of SONA
Confirm that the ClinicalTrials.gov statement is in all applicable consent documents
Confirm that the study from the Center for Clinical Research (CCR) Find a Trial web page
is registered on ClinicalTrials.gov
Specify how contact information will be obtained:
Specify how these individuals granted permission and enter HS#:

Examples:
• Individuals who are economically or educationally disadvantaged
• Individuals that have impaired decision-making capacity
• Physician's own inpatients and/or outpatients
• Students (undergraduate, graduate, and medical students)
• Employees of UCI (administrative, clerical, nursing, lab technicians, post-doctoral fellows
and house staff, etc.)
IRB requires that:
1. Subjects will be approached with an emphasis that participation is voluntary; and
2. Subject will be informed in a caring manner that no matter their decision, it will NOT
affect:
a. Their relationship with UCI
b. How their doctor cares for them as a patient or their care at UC Health in general
and/or
c. How their instructor grades their participation in the course; and
3. A statement attesting the information above in item b will be included in applicable
recruitment and/or consent documents.
Confirm that colleagues may provide a copy of the consent and other UCI IRB approved
materials but do not obtain subjects’ consent for the research or act as representatives of the
investigators
Confirm that:
1. The recruitment letter to be signed by the treating physician will be submitted in the
Attachments Section
2. Colleagues do not obtain subjects’ consent for the research or act as representatives of
the investigators
Specify 'Other' recruitment methods:
Specify the precautions taken to avoid compromised objectivity:
When enrolling researchers' own patients: Subjects will be approached with
an emphasis that participation is voluntary; and Subject will be informed in
a caring manner that no matter their decision, it will NOT affect: Their
relationship with UCI How their doctor cares for them as a patient or their
care at UC Health
Recruitment Method
Colleagues provide subjects with information about the research and how
to contact investigators

Specify Where Posted
Type of Space
Confirm that applicable consent documents will include reference to the use of SONA
Confirm that the ClinicalTrials.gov statement is in all applicable consent documents
Confirm that the study from the Center for Clinical Research (CCR) Find a Trial web page
is registered on ClinicalTrials.gov
Specify how contact information will be obtained:
Specify how these individuals granted permission and enter HS#:
Examples:
• Individuals who are economically or educationally disadvantaged
• Individuals that have impaired decision-making capacity
• Physician's own inpatients and/or outpatients
• Students (undergraduate, graduate, and medical students)
• Employees of UCI (administrative, clerical, nursing, lab technicians, post-doctoral fellows
and house staff, etc.)
IRB requires that:
1. Subjects will be approached with an emphasis that participation is voluntary; and
2. Subject will be informed in a caring manner that no matter their decision, it will NOT
affect:
a. Their relationship with UCI
b. How their doctor cares for them as a patient or their care at UC Health in general
and/or
c. How their instructor grades their participation in the course; and
3. A statement attesting the information above in item b will be included in applicable
recruitment and/or consent documents.
Confirm that colleagues may provide a copy of the consent and other UCI IRB approved
materials but do not obtain subjects’ consent for the research or act as representatives of the
investigators

Confirm that:
1. The recruitment letter to be signed by the treating physician will be submitted in the
Attachments Section
2. Colleagues do not obtain subjects’ consent for the research or act as representatives of
the investigators
Specify 'Other' recruitment methods:
Specify the precautions taken to avoid compromised objectivity:
Recruitment Method
Other recruitment methods
Specify Where Posted
Type of Space
Confirm that applicable consent documents will include reference to the use of SONA
Confirm that the ClinicalTrials.gov statement is in all applicable consent documents
Confirm that the study from the Center for Clinical Research (CCR) Find a Trial web page
is registered on ClinicalTrials.gov
Specify how contact information will be obtained:
Specify how these individuals granted permission and enter HS#:

Examples:
• Individuals who are economically or educationally disadvantaged
• Individuals that have impaired decision-making capacity
• Physician's own inpatients and/or outpatients
• Students (undergraduate, graduate, and medical students)
• Employees of UCI (administrative, clerical, nursing, lab technicians, post-doctoral fellows
and house staff, etc.)
IRB requires that:
1. Subjects will be approached with an emphasis that participation is voluntary; and
2. Subject will be informed in a caring manner that no matter their decision, it will NOT
affect:
a. Their relationship with UCI
b. How their doctor cares for them as a patient or their care at UC Health in general
and/or
c. How their instructor grades their participation in the course; and
3. A statement attesting the information above in item b will be included in applicable
recruitment and/or consent documents.
Confirm that colleagues may provide a copy of the consent and other UCI IRB approved
materials but do not obtain subjects’ consent for the research or act as representatives of the
investigators
Confirm that:
1. The recruitment letter to be signed by the treating physician will be submitted in the
Attachments Section
2. Colleagues do not obtain subjects’ consent for the research or act as representatives of
the investigators
Specify 'Other' recruitment methods:
mailings to local neurologists, rehab doctors, hospitals, and other health
professionals.
Specify the precautions taken to avoid compromised objectivity:
Informed Consent Process
Does this study involve the creation, use, or disclosure of Protected Health Information (PHI)?
Yes

Methods of Health Insurance Portability and Accountability Act (HIPAA) Authorization
Identify the HIPAA authorization process (Check all that apply):
Partial waiver of HIPAA authorization for screening/recruitment purposes
only. Signed authorization obtained prior to further access to PHI
Signed HIPAA authorization obtained
Methods of Informed Consent
Identify the consent or assent process as applicable for each participant population (check all
that apply):
Paper-based signed informed consent/assent
Paper-based Signed Informed Consent
Indicate the paper-based signed informed consent/assent (check all that apply):
Signed Informed Consent
REQUIRED! Submit the Adult Consent Form, Child Assent Form and/or Parental Permission
Form in the Attachments Section.
Circumstances of Consent
Indicate the location where the consent process will take place (check all that apply):
Private room
Specify how the research team will assure that subjects, their parents, or their legally authorized
representative (LAR) have sufficient time to consider whether to participate in the research:
Subjects or their LAR will be allowed to take home the unsigned consent form
for review prior to signing it
This study does NOT include Non-English Speaking Participants. Scientific justification/rationale
is required in the Eligibility Criteria Section for Subject Populations.

Waiver of HIPAA Authorization
You requested a Partial Waiver of HIPAA Authorization
When a partial waiver is requested, the Lead Researcher is requesting the HIPAA research
authorization be waived for a portion of the study, such as a waiver for subject identification or
recruitment purposes.
Please specify for what purpose the partial waiver is requested:
HIPAA waiver is needed to access medical records of UCI stroke patients for
study eligibility purposes.
Justification for a Waiver of HIPAA Authorization
Does the use or disclosure of personal health information involve more than minimal risk?
No
Would the granting of the waiver adversely affect privacy rights and welfare of the individuals
whose records will be used or disclosed?
No
Explain (justify) the answer:
Stroke subject medical records would be reviewed exclusively for study
eligibility information.
Could the research practicably be conducted without a waiver of HIPAA authorization?
No
Explain the answer:
Eligibility requirements are specific and can only be identified via a review of
stroke patient medical records.
Could the research practicably be conducted without access to, use or disclosure of the personal
identifiers listed in the PHI question?
No
Explain the answer:
Personal identifiers must be attained by study personnel in order to contact
potential study subjects for recruitment.

Are the privacy risks reasonable relative to the anticipated benefits of the research?
Yes
Describe the risk/benefit analysis performed to explain the answer above:
Review of medical records will allow stroke patients the opportunity to be part
of a study where there is a possibility that they will experience improved
walking ability, however this benefit is not guaranteed.
Describe the plan to protect the personal identifiers from improper use and disclosure (i.e.,
describe data security methods):
All information attained from medical records will be stored in a password
protected excel document stored on password protected computers in locked
UCI research offices.
Describe the plan to destroy the personal identifiers at the earliest opportunity, or provide a
health or research justification for retaining the identifiers:
All personal identifiers attained for subjects who do not meet eligibility
requirements will be destroyed as soon as ineligibility is determined.
Describe how potential subjects will be identified:
Potential subjects will be identified via by examining the neurology and acute
rehabilitation unit inpatient lists.
Research Procedures
Check all boxes that apply to the research:
Audio, Video, Digital or Image Recording and/or Photography for Collection of
Research Data
Clinical Investigation involving an Investigational Device
Other Non-invasive Physical Measurements (e.g., ECG, EEG, moderate
exercise, muscular strength testing, body composition assessment)
Will deception or incomplete disclosure be involved in the research?
No

Study Design
Include an explanation of the study design (e.g., randomized placebo-controlled, cross-over,
cross-sectional, longitudinal, etc.) and, if appropriate, describe stratification/
randomization/blinding scheme:
Aim 1 is a parallel, 2-arm randomized controlled Phase 2 clinical trial. Aim 3 is
a randomized, 2-arm randomized controlled study (not a clinical trial). They
will produce the following study groups 1. Aim 1 – randomization 1:1 between
2 groups as follows: a. Group 1 (40 subjects): undergoing multiple sessions
of 1 hour BCI-FES therapy followed by 1 hour of conventional physical therapy
b. Group 2(40 subjects): undergoing multiple sessions of 2 hour conventional
physical therapy sessions 2. Aim 3 – randomization 1:1 between 2 groups as
follows: a. Group 3 (10 subjects): BCI-FES therapy (no conventional physical
therapy) b. Group 4 (10 subjects): BCI-robotic orthosis therapy (no
conventional physical therapy) BCI-FES therapy: Group 1 subjects will undergo
placement of a 4-channel EEG cap using standard technique (Cz, Cpz, C1, C2)
and be connected to our custom BCI system (from Study 1a). Note that based
on Study 3, this electrode selection will likely capture brain areas subserving
dorsiflexion for all stroke subjects. Subjects will provide 5 min of training EEG
data as they engage in alternating epochs of idling and attempted foot
dorsiflexion (of the paretic side). The automated software will analyze the
data to generate and calibrate a BCI decoder (additional 5-10 mins). In the
online phase (involves actively operating the BCI system in real-time), the
subjects will perform 20-25 BCI-FES runs (total of 1 hour). In each run,
subjects will follow 10 alternating epochs of 10-s long idling/dorsiflexion
textual cues, and respond by either idling or attempting dorsiflexion to elicit
BCI-FES mediated contractions of the TA muscle. A total of 12 sessions will
be performed at a rate of 3x/week (over 4 weeks). Each BCI-FES therapy
session will be followed by 1 hour of conventional physiotherapy as described
below. Conventional Physical Therapy: This will consist of a standardized
regimen of activities typical of conventional post-stroke gait therapy, including
passive/active range of motion exercises (to reduce/prevent excessive
plantarflexor contractures), lower-extremity muscle strengthening, and a
progression from treadmill to overground walking exercises. A total of 12
sessions will be performed at 3x/week. For Group 1, conventional
physiotherapy will immediately follow each BCI-FES session and last for 1
hour. In the dose-matched control group (Group 2), it will be 2 hours/session.
Subjects will not be allowed to undergo outside physiotherapy for the entire

study. A commercial company will be used to assign patients a 30 minute
home exercise program to be completed 4 times a week with compliance
assessed via non-invasive sensors. For those without a mobile device, a pen
and paper version of the home exercise program will also be available. Aim 3:
The aim is designed as a randomized controlled study with two arms: BCI-FES
dorsiflexion therapy and BCI-robotic orthosis therapy. A total of 20 subjects
will be recruited and randomized with 1:1 ratio into the two arms. The primary
outcome is gait velocity, and the secondary outcomes are ankle torque and
active range of motion. The main interest is to evaluate if the correlation
between M1→EMG, w, (normalized range: 0-1), and gait velocity is different
between the two study groups averaged over time after treatment, adjusted
for baseline outcome measure. For example, with outcome gait velocity, the
analysis will be based on a regression model with group, we, and their
interaction, adjusted for baseline gait velocity. The relationship between both
w with secondary outcomes will be similarly analyzed. TR-NIRS parameters
will be measured at the TA muscle of stroke patients while they attempt
dorsiflexion while seated with the tibia perpendicular to the ground.
Measurements pertaining to oxygen metabolism at the TA muscle will be
acquired by placing the source and detector fibers on the skin surface
positioned over the muscle (using the adhesive pads). This setup allows for
the collection of metabolic data in real time while either the BCI-FES or BCI-
robotic orthosis systems are being used.

Provide precise definitions of the study endpoints and criteria for evaluation; if the primary
outcomes are derived from several measurements (i.e., composite variables) or if endpoints are
based composite variables, then describe precisely how the composite variables are derived:
Aim 1: The primary outcome measure will be gait velocity, which is directly
linked to disability and social re-integration after stroke. Gait velocity will be
assessed by measuring the time to traverse the middle 6 m of a 10-m
walkway (5 repetitions/assessment). Secondary outcomes include: 1. Gait
endurance: The distance walked over 6 minutes. 2. Fall Frequency: Number of
falls experienced weekly. 3. Leg Motor Fugl-Meyer (FM) Score: Assessed
according to the FM rating system. 4. Dorsiflexion Active Range of Motion
(AROM) and torque: The paretic foot will be placed in an articulated brace
which maintains the ankle at neutral during idling, while fixing the tibia
perpendicular to the ground and the femur horizontal to the ground. The brace
will be instrumented with an electro-goniometer and torque meter to
automatically measure the maximum dorsiflexion AROM and torque (over 3
trials). 5. EEG Map: Subjects will undergo 64-channel EEG recording as they
engage in 100 alternating 10-s long epochs of idling and attempted
dorsiflexion. The EEG ERD/ERS, defined as the drop/rise in alpha (8-12 Hz)
and beta (13-30 Hz) band power during attempted dorsiflexion (compared to
idling), will be calculated and averaged over all epochs and across all
channels. A pre-intervention baseline for each outcome will first be
established. Subsequently, measurements will be performed at 1 week
intervals during the intervention phase (total of 3), immediately after the
intervention phase, as well as 1 and 3 months after completion of
interventions. The primary efficacy outcome and endpoint will be gait velocity
immediately after the intervention phase. Aim 2 (subgroup analysis of Phase
II clinical trial) Since stroke is a heterogeneous disease, responsiveness to
rehabilitation therapy is not uniform across all subpopulations. Hence, it is
important to ensure that any new therapy, e.g. BCI-FES therapy, is matched to
subpopulations that will benefit the most. The following set of baseline
characteristics will be assessed during the pre-intervention phase (Fig. 6,
Phase 2) for Groups 1 and 2 to determine which features influence
responsiveness to BCI-FES therapy: 1. Baseline gait velocity, dorsiflexion
AROM and torque: Baseline gait velocity and dorsiflexion AROM and torque
will be taken from Aim 1. 2. TA volitional electromyogram (EMG): TA EMG will
be assessed by having subjects attempt dorsiflexion while seated with tibia
perpendicular to ground. EMG will be acquired by a bioamplifier with surface
electrodes placed over the TA muscle. Subjects will be categorized as either

having TA EMG or no response (no detectable EMG activity after 4 attempts).
3. EEG features: Movement induced EEG ERD/ERS and its spatial distribution
in µ (8-12 Hz) and β (13-30 Hz) bands may change after stroke. Since BCI-FES
therapy depends upon and possibly alters µ and β modulation, it is important
to understand how the baseline ERD/ERS magnitude affects response to the
therapy. EEG prior to the first BCI-FES session will be taken from Aim 1. 4.
Nottingham Sensory Score: Baseline sensory impairment, as assessed by the
Nottingham sensory system, can help determine if BCI-FES therapy can
circumvent this requirement or not. Note that subjects will be informed that
they are to refrain from starting any additional new physical therapies or other
studies in stroke recovery for the entire duration of the study (including post-
therapy visits). Subjects will be informed that those who become involved in
outside therapy will be removed from the study as this may confound the
scientific results. Aim 3 (Mechanism study, not a clinical trial): In order to
elucidate the plasticity mechanism underlying BCI-FES therapy, it is necessary
to compare BCI-FES therapy to a control. Hence, two new groups of chronic
stroke subjects with foot-drop will be recruited (10 subjects each, same
selection criteria as in Aim 1). The first group (Group 3), will undergo BCI-FES
therapy as in Aim 1 (no concurrent physiotherapy). The second group (Group
4), will undergo BCI-robotic orthosis therapy. This comparison will allow us to
determine if the mechanism of BCI-FES therapy is via enhanced sensory
feedback, or via co-incident activation of upper and lower motor neurons. BCI-
robotic orthosis therapy is similar to BCI-FES therapy, except that the FES
system is replaced by a robotic orthosis that dorsiflexes the foot when
attempted dorsiflexion is detected from EEG. The use of a BCI-robotic allows
us to test if sensory feedback is the primary driver of the neurological
improvements or if co-incident firing between the brain motor cortex and
muscles is the primary driver. It should be noted that BCI-FES and BCI-robot
therapies both provide sensory feedback, but only BCI-FES provides co-
incident firing between the brain motor cortex and the muscles. The primary
outcome examined here will also be gait velocity. Other secondary outcomes
include gait endurance and TA volitional EMG, as described above.
Assessments are on done on the same schedule as in Aim 1. This device will
be used because, unlike EMG, NIRS systems are optically based. This allows
for continuous monitoring at the muscle while the FES system is in use. EMG
systems do not allow for continuous measurements when using FES, given
that EMG systems measure electrical activity at the muscle that cannot be
separated from the electrical activity of the FES system. TR-NIRS data will

provide insight into the metabolic changes at the TA muscle that can be
compared between patients in the BCI-FES and BCI-robotic orthosis groups.
This data will not only aid the stroke research community but will also aid the
rehabilitation field in understanding healing dynamics post injury. The
coherence between the Cz EEG electrode and the TA EMG will be calculated,
known as w. The correlation between gait velocity and w will be calculated
across the entire duration of study for all subjects. This will be repeated for
both BCI-FES groups and BCI-robotic orthosis groups. Comparing the
correlation between these 2 groups can provide insight into which of the
above mechanisms is primarily driving plasticity.
Statistical Considerations
Is a statistical analysis plan appropriate for this qualitative study design?
Yes

Describe the statistical methods for the stated specific aims and hypotheses. Your analysis
plans should match the stated study specific aims and hypotheses:
Aim 1: The study design is a parallel randomized controlled trial with two
arms: BCI-FES dorsiflexion therapy and dose-matched conventional physical
therapy. A total of 80 subjects (which includes 10% attrition) will be
randomized with 1:1 ratio into the two study arms. The primary outcome is
gait velocity and the secondary outcomes are gait endurance, fall frequency,
leg motor FM score, and dorsiflexion AROM and torque. Outcomes measures
will be evaluated at baseline, weekly during therapy, immediately post-
intervention, and 1- month and 3-months post-therapy. The primary efficacy
analysis (with intent-to-treat analysis with respect to treatment randomized)
will be based on a linear mixed model (LMM) with gait velocity measured at
baseline weeks 1-4 (time 0, 1, 2, 3, and 4) with time, treatment group and
group by time interaction assess the difference in the rates of change
(improvement) in gait velocity between treatment groups. Model estimation
will be based on restricted maximum likelihood (REML) with unstructured
covariance among repeated measurements over time. The LMM will also be
applied to evaluate group difference for secondary outcomes and secondary
endpoints at 1- and 3-months post-therapy. In order to determine if µ and β
ERD/ERS significantly changes over the 4 weeks of therapy, the ERD and ERS
magnitude will be calculated for each EEG channel across all attempted
dorsiflexion epochs, and for each assessment. The Mann-Whitney U test will
be used to determine if any significant changes in the magnitude of ERD/ERS
at each assessment with respect to the baseline. Based on the findings, each
subject will be categorized as demonstrating significant changes in ERD/ERS
or not. Next, all subjects will also be categorized on whether they experienced
a detectable increase in gait velocity (defined as an increase in gait velocity of
>0.16 m/s with respect to baseline). A Chi-square test will be used to assess
if there is a difference between the proportion of those with changes in
ERD/ERS magnitude in those who had gait improvement within the BCI- FES
therapy group. This will also be repeated for the control group. In addition, to
determine if the presence of significant ERD/ERS changes was affected by
group, the Chi-square test will be repeated by using BCI-FES group as the
observation and the control group as the expected values. Aim 2: Data from
Aim 1 will be used for analysis in this aim. The primary outcome is gait
velocity immediately post-BCI-FES therapy, and the secondary outcomes are
the same as in Aim 1. To test whether specific stroke features (e.g. baseline
gait velocity, dorsiflexion AROM, etc.) modify response to treatment over

treatment duration, a LMM model with three-way interaction (group, time,
modifying factor) will be used to test whether the slope of the three-factor
interaction is zero (specific stroke feature does not modify response to
treatment). Aim 3: The aim is designed as a randomized controlled study with
two arms: BCI-FES dorsiflexion therapy and BCI-robotic orthosis therapy. A
total of 20 subjects will be recruited and randomized with 1:1 ratio into the
two arms. The primary outcome is gait velocity, and the secondary outcomes
are ankle torque and active range of motion. The main interest is to evaluate if
the correlation between M1→EMG, w, (normalized range: 0-1), and gait
velocity is different between the two study groups averaged over time after
treatment, adjusted for baseline outcome measure. For example, with
outcome gait velocity, the analysis will be based on a regression model with
group, we, and their interaction, adjusted for baseline gait velocity. The
relationship between both w with secondary outcomes will be similarly
analyzed.
Describe the statistical method(s) that will be used to analyze the primary outcome(s) or
endpoints:
The primary statistical methods for primary outcome, gait velocity, is already
described in Aim 1 above.
If appropriate describe secondary or post hoc analyses of primary outcome(s) or other
exploratory analysis and if necessary, provide a breakdown of the methods used per outcome or
endpoint:
The statistical method for secondary outcome measures is similar to the
primary outcome, and is already described in Aim 1 and 2 above.

Sample Size Determination: Explain how the overall target sample size was determined (e.g.,
power analysis; precision estimation), providing justification of the effect size for the primary
outcome based on preliminary data, current knowledge/literature and/or cost consideration; if
appropriate, provide sample size justification for secondary outcomes. Power analysis should (at
least) match the primary outcome/endpoint:
Power Analysis: For Aims 1 and 2, the power analysis was based on a LMM
with two treatment groups and 5 repeated measures (baseline and after
weeks 1-4) with a significance level of 0.05. Previous studies have examined
the clinically meaningful gait improvement (minimal clinically important
difference) of 0.16 m/s, including a multicenter randomized clinical trial that
includes conventional physical therapy. Thus, to ensure clinically meaningful
effect size, we assume conventional therapy will have an improvement of
0.25 m/s after 4 weeks of treatment. Data from prior studies as well as our
own preliminary data (n=9) found that the between-subject variance in gait
velocity of about 0.16 m/s and the within-subject correlation of about 0.95.
Table 1 below shows the power to detect improvement of BCI-FES over
conventional therapy of 30% - 40%. Thus, for the proposed study with n=80
patients (40 per arm) has 92% to 94% power to detect an effect
size/improvement of 35% for various between-subject variance (0.15 m/s to
0.17 m/s) in determining treatment efficacy (Aim 1). We note that n=80 total
has been intentionally inflated in order to accommodate the objectives of aim
2 to examine modifying factors, such as TA MEP (primary modifying factor),
on treatment. That is, for n=30 per arm the power to determine efficacy (aim
1) is 85% for detecting an effect size/improvement of 35% (between-subject
variance 0.16 m/s); thus, increasing to n=40 allows for detecting modifying
factor on treatment (aim 2) when the interaction effect smaller (effect size
28% can be detected with 79% power). Table 1: Power to detect improvement
in gait velocity due to BCI-FES over conventional therapy for n=80 with various
between-subject variance (aim 1). Between-Subject Variance Effect Size
(Improvement) 0.15 0.16 0.17 30% 87.3% 85.2 % 83.0% 35% 94.5% 93.5%
92.1% 40% 98.3% 97.7% 97.0% Aim 3: Total sample size of n=20 will have 82%
power to detect an R-square of 0.16 (attributed to the effect of interest, e.g., w
x group) adjusted for baseline measurement and main effects whose total
contribution R-square is 0.5 (for 3 independent variables) in a multiple
regression model.

Research Procedures
Provide a detailed chronological description of the clinical or treatment plan:
See attachment "ResearchProcsTable"
List all procedures involving the use and/or collection of photographs, or audio/video recording:
Photographs, video, audio may be taken for purposes of publication, and may
include facial images. Any identifier, e.g. facial images, will be removed prior
publication. Subject’s participation in study does not depend on if they agree
to have photos, videos, or audio taken.
Specify the total duration of a subject’s participation in the study and clearly outline the duration
of participation for each study visit and sub-study, as applicable:
Groups 1 and 2: Participation will last approximately 40 hours over 4 months
and will include 17 visits. Groups 3 and 4: Participation will last approximately
30 hours over 4 months and will include 17 visits.
List data collection tools (e.g., measures, questionnaires, observational tool) below by clicking the
'Add Line' button. Include additional rows for study instruments, as needed:
The 'Columns' button allows you to display or hide columns in the Study Instrument List.
Name of Tool:
see ResearchProcsTable attachment to view the list of data collection
instruments.
Is the data collection tool standardized or validated?
Yes

Please provide data collection tool citation:
Citations for validated assessments: 1)Fugl-Meyer: See J, Dodakian L, Chou
C, Chan V, McKenzie A, Reinkensmeyer DJ, et al. A standardized approach to
the fugl-meyer assessment and its implications for clinical trials.
Neurorehabilitation and neural repair. 2013;27:732-741 2) NIH Stroke Scale:
Schlegel D, Kolb SJ, Luciano JM, Tovar JM, Cucchiara BL, Liebeskind DS,
Kasner SE. Utility of the NIH Stroke Scale as a predictor of hospital
disposition. Stroke. 2003 Jan;34(1):134-7. 3) Modified Ashworth Scale: Lee
G, An S, Lee Y, Lee D, Park DS. Predictive factors of hypertonia in the upper
extremity of chronic stroke survivors. J Phys Ther Sci. 2015 Aug;27(8):2545-
9. 4) Nottingham Sensory: Scalha TB, Miyasaki E, Lima NM, Borges G.
Correlations between motor and sensory functions in upper limb chronic
hemiparetics after stroke. Arq Neuropsiquiatr. 2011 Aug;69(4):624-9 5)
Geriatric Depression Scale: Sivrioglu EY, Sivrioglu K, Ertan T, Ertan FS,
Cankurtaran E, Aki O, Uluduz D, Ince B, Kirli S. Reliability and validity of the
Geriatric Depression Scale in detection of poststroke minor depression. J
Clin Exp Neuropsychol. 2009 Nov;31(8):999-1006 6) Modified Rankin Scale:
Dennis M, Mead G, Doubal F, Graham C. Determining the modified Rankin
score after stroke by postal and telephone questionnaires. Stroke. 2012
Mar;43(3):851-3. 7) Neuro QoL: Carlozzi NE, Tulsky DS, Kisala PA. Traumatic
brain injury patient-reported outcome measure: identification of health-
related quality-of-life issues relevant to individuals with traumatic brain
injury. Arch Phys Med Rehabil. 2011 Oct;92(10 Suppl):S52-60 8) Gait
Velocity: Tyson S, Connell L. The psychometric properties and clinical utility
of measures of walking and mobility in neurological conditions: a
systematic review. Clin Rehabil. 2009 Nov;23(11):1018-33. 9) Gait
Endurance: Flansbjer UB, Holmbäck AM, Downham D, Patten C, Lexell J.
Reliability of gait performance tests in men and women with hemiparesis
after stroke. J Rehabil Med. 2005 Mar;37(2):75-82
Will this study require clinical items/ services from UC Irvine Health?
No
Does the research involve the use of identifiable private information?
Yes

Use of Identifiable Private Information as Part of the Main Study
Indicate the types/sources of identifiable private information (Check all that apply):
Identifiable photographs, images, or digital/audio/video recordings
Non-UCI Health Medical Records
UCI Health Medical Records
Identifiable Media
Specify identifiable photographs, images, or digital/audio/video recording source:
Photographs, video, audio may be taken for purposes of publication, and
may include facial images. Any identifier, e.g. facial images, will be
removed prior publication. Subject’s participation in study does not
depend on if they agree to have photos, videos, or audio taken.
Indicate whether the information was
originally collected for research purposes:
Not originally collected for research
Explain how the information were originally
collected (e.g., clinical care):
clinical care
Provide a complete list of the data points, variables, and/or information that will be collected (i.e.
data abstraction form):
Or specify variables or information required here:
photo, video, audio
Specify the time-frame of the data to be accessed (e.g. January 2002 to 2024):
Any identifier, e.g. facial images, will be removed prior publication. Subject’s
participation in study does not depend on if they agree to have photos, videos,
or audio taken. De-identified version will be maintained indefinitely in case of
need for future research/publication

This study will use medical records, indicate the source:
Study team will access their own UCI patients’ records and abstract data
directly from those records
Study team will request non-UCI Health records and abstract data directly
from those records
UCI IRB approved protocol
The Study Team Will Request Non-UCI Health Records and Abstract Data Directly
from those Records
Specify Non-UCI Entity:
History and physical notes
pertaining to stroke admission,
neurology consult notes,
rehabilitation service notes, and
MRI brain images
Explain how the study team will request
non-UCI Health records and abstract data
directly from those records:
Potential subjects who are
interested who have passed initial
screening and agree to sign HIPAA
waiver for release of information.
Our research team will either
screen copies of the records
provided to us by the potential
subject or will contact the
appropriate medical institution to
request a copy of the above record
types for review. Subjects will sign
the HIPAA non-UCI provider form
and only after it’s signed will non-
UCI records be released to study
team.
UCI IRB Approved Protocol
Provide the HS number for the UCI IRB Approved Protocol study (enter multiple HS numbers
if appropriate):
2004-3852, 2014-1607, 2017-4067

Does the research involve the use of identifiable biospecimens?
No
Sharing Results with Subjects
Will Individual results be shared with subjects?
No
Will overall study results will be shared with subjects?
The overall study results will be listed on Clinicaltrials.gov
Medical Devices
Name of Device or Product
Brain-computer interface controlled functional electrical stimulation device
Device Manufacturer
UC Irvine
Description of the device:
The device consists of a circuit board which contains electronics necessary
to acquire EEG signals, process the signals, and to control an electrical
stimulator (TENS unit) to deliver FES to muscles. The device has a touch
screen which is used by the operator to interact with it, and has connectors
to attach an EEG cap. The entire circuit board is enclosed within a plastic
case. A photo of the device is shown below (taken out of case).

Specify the proposed use of the device for this study:
The BCI-FES system will be used to deliver a form of BCI-based
physiotherapy to stroke patients participating in the study. BCI-FES therapy:
Group 1 subjects will undergo placement of a 4-channel EEG cap using
standard technique (Cz, Cpz, C1, C2) and be connected to our custom BCI
system (from Study 1a). Note that based on Study 3, this electrode
selection will likely capture brain areas subserving dorsiflexion for all stroke
subjects. Subjects will provide 5 min of training EEG data as they engage in
alternating epochs of idling and attempted foot dorsiflexion (of the paretic
side). The automated software will analyze the data to generate and
calibrate a BCI decoder (additional 5-10 mins). In the online phase (involves
actively operating the BCI system in real-time), the subjects will perform 20-
25 BCI-FES runs (total of 1 hour). In each run, subjects will follow 10
alternating epochs of 10-s long idling/dorsiflexion textual cues, and respond
by either idling or attempting dorsiflexion to elicit BCI-FES mediated
contractions of the TA muscle. Further details of the procedure are provided
in the study narrative.
Does this device have an Instructions for Use/User Manual/Product Brochure?
No
REQUIRED! Submit the Instructions for Use, User Manual or Product Brochure in the
Attachments Section
Include information to describe how it works and the foreseeable risks associated with its use:
The BCI-FES system should not be considered a significant risk device. It is
non-invasive, does not make any diagnoses, and does not sustain life. Its
components, namely EEG and FES are both independently considered safe.
Prior studies have demonstrated safe use of EEG and FES in combination.
Risks and side effects related to the BCI-FES therapy include those which
are: - Discomfort with wearing EEG electrodes (unlikely) - Increased falls
(highly unlikely) - Fatigue (unlikely) - Skin breakdown due to electrical
stimulation (highly unlikely)
Is the device a medical device?
Yes, this device is a medical device

If “no”, for minimal risk studies and the device is intended to be used in a clinical setting,
provide justification for selecting “no”, citing any regulatory guidance as applicable:
Are you testing the safety and/or efficacy of this device?
Yes, we are assessing the safety and/or efficacy of this medical device; this
is a clinical investigation
If “no”, for minimal risk research and if the device is the object of the investigation, provide
justification for selecting “no”, citing any regulatory guidance as applicable:
Is the device approved for marketing in the United States?
No
How is the device approved in the United States?
REQUIRED! Submit FDA Documentation in the Attachments Section
Select one of the following:
Is the device authorized for use under an FDA Emergency Use Authorization (EUA)?
N/A
Is the device being used in this study according to its approved indication?
No, this device is not being used in this study according to its approved
indication
Is the Device Exempt from the Investigational Device Regulations (21 CFR 812)?
No
Select the device exemption that meets one of the following categories:
Clarify how the device meets the category selected:
Is this device a Significant Risk (SR) device?
No, this device is not a significant risk device. This device is also not
exempt; it is not a HUD/HDE

Has the investigator or sponsor of this research obtained an Investigational Device Exemption
(IDE) from the FDA for the use of this device for this research?
REQUIRED! Submit the IDE Authorization Letter in the Attachments Section
IDE Number
Holder of the IDE (check all that apply):
Specify Lead Researcher:
Specify 'Other' IDE Holder:
Does the IDE allow billing of subjects?
Does the IDE cover a combination use (e.g., combination of an investigational drug and
device)?
Specify the combination use:
Specify why an IDE has not been obtained yet:
Specify 'Other' reason:

Based on the criteria for a significant risk device listed in the link below, explain why the device
as it is used in this study, qualifies as Non-Significant Risk (NSR) device:
According to the FDA criteria for significant risk determination
(https://www.fda.gov/media/75459/download), the BCI-FES system is not a
significant risk device as follows: -Is the device implanted?: No, this device
is entirely non-invasive. -Does the device perform life sustaining functions?:
No, this device does not perform any life sustaining functions -Is the device
use of any substantial importance in diagnosis or treatment of disease?:
No, this system does not perform any important diagnostic function.
Although it is being tested for its potential efficacy in mitigating stroke
related weakness and gait impairment, it does not pose any potential
serious risk for health, safety, and welfare of a subject. The individual
components, which include an EEG and an non-invasive FES device, are
both independently non-invasive devices that are widely known to be safe.
In fact, according to the FDA document above, both EEG and non-invasive
FES is specifically listed as examples NSR devices. It is not expected that
their combination should any potential for serious safety risk. -Otherwise
being used in any way that presents a serious risk to health, safety, or
welfare of a subject?: As indicated above, the individual components of the
BCI-FES system include an EEG system and a non-invasive FES system.
These devices are already examples of NSR devices as indicated by the
FDA, and their use of them in combination is not expected to result in any
serious safety risk. One example of a comparable combination use of EEG
and FES is in non-invasive somatosensory evoked potentials, which is
considered a safe, routine, outpatient procedure.
Has the FDA or another IRB determined the device to be non-significant risk as it is used in
this study?
No
Indicate who will be responsible for the management of the device during the study:
Dr An Do and Dr Po Wang

Explain the plan to ensure that the investigational device is used only in accordance with the
UCI IRB approved protocol:
Research team members will receive training on how the device is to be
used, and will informed that it will only be used for the current study. A
standard operating procedure will be provided to guide how the device
should be operated each time it is used to deliver BCI-FES therapy.
Indicate who will have access to the device and how access will be controlled to secure the
device (or device stock):
Dr An Do, Dr Po Wang and Dr Zoran Nenadic
Specify how records for control of the device (or device stock) will be recorded:
The sample Device Accountability Log on the HRPP website will be used
REQUIRED! Submit the Sponsor Device Log in the Attachment Section
Specify why no log will be used:
Indicate whether the investigational device is manufactured in a UCI facility:
Yes
Identify the lab and location:
UCI BCI Lab Gross Hall 1022
You have completed the form for this medical device. Click the 'Done' button. If you need to
add more devices, click on the + Add Line button above the table to enter additional devices.
Name of Device or Product
Brain-computer interface controlled robotic orthosis
Device Manufacturer
UC Irvine

Description of the device:
The device consists of a circuit board which contains electronics necessary
to acquire EEG signals, process the signals, and to control an robotic
orthosis that moves the foot. The device has a touch screen which is used
by the operator to interact with it, and has connectors to attach an EEG cap.
The entire circuit board is enclosed within a plastic case. A photo of the
device is shown below (taken out of case).
Specify the proposed use of the device for this study:
The BCI-FES system will be used to deliver a form of BCI-based
physiotherapy to stroke patients participating in the study. Robotic
exoskeleton sensory task: The robotic exoskeleton (same as used in already
part of the study for Group 3 and 4) will be used for a foot position matching
task. The subject will bear one robotic exoskeleton placed on each foot for
the sensory testing. The foot position will be randomly moved by the
exoskeleton and the subject will indicate when the ankle positions overlap.
This will be repeated for a total of 25 times. BCI-robotic orthosis therapy is
similar to BCI-FES therapy, except that the FES system is replaced by a
robotic orthosis that dorsiflexes the foot when attempted dorsiflexion is
detected from EEG. The use of a BCI-robotic allows us to test if sensory
feedback is the primary driver of the neurological improvements or if co-
incident firing between the brain motor cortex and muscles is the primary
driver. It should be noted that BCI-FES and BCI-robot therapies both provide
sensory feedback, but only BCI-FES provides co-incident firing between the
brain motor cortex and the muscles.
Does this device have an Instructions for Use/User Manual/Product Brochure?
No
REQUIRED! Submit the Instructions for Use, User Manual or Product Brochure in the
Attachments Section
Include information to describe how it works and the foreseeable risks associated with its use:
Risks and side effects related to the BCI-Robot operation include those
which are: - Discomfort with wearing EEG electrodes (unlikely) - Increased
falls (highly unlikely) - Fatigue (unlikely)

Is the device a medical device?
Yes, this device is a medical device
If “no”, for minimal risk studies and the device is intended to be used in a clinical setting,
provide justification for selecting “no”, citing any regulatory guidance as applicable:
Are you testing the safety and/or efficacy of this device?
Yes, we are assessing the safety and/or efficacy of this medical device; this
is a clinical investigation
If “no”, for minimal risk research and if the device is the object of the investigation, provide
justification for selecting “no”, citing any regulatory guidance as applicable:
Is the device approved for marketing in the United States?
No
How is the device approved in the United States?
REQUIRED! Submit FDA Documentation in the Attachments Section
Select one of the following:
Is the device authorized for use under an FDA Emergency Use Authorization (EUA)?
N/A
Is the device being used in this study according to its approved indication?
No, this device is not being used in this study according to its approved
indication
Is the Device Exempt from the Investigational Device Regulations (21 CFR 812)?
No
Select the device exemption that meets one of the following categories:
Clarify how the device meets the category selected:

Is this device a Significant Risk (SR) device?
No, this device is not a significant risk device. This device is also not
exempt; it is not a HUD/HDE
Has the investigator or sponsor of this research obtained an Investigational Device Exemption
(IDE) from the FDA for the use of this device for this research?
REQUIRED! Submit the IDE Authorization Letter in the Attachments Section
IDE Number
Holder of the IDE (check all that apply):
Specify Lead Researcher:
Specify 'Other' IDE Holder:
Does the IDE allow billing of subjects?
Does the IDE cover a combination use (e.g., combination of an investigational drug and
device)?
Specify the combination use:
Specify why an IDE has not been obtained yet:
Specify 'Other' reason:

Based on the criteria for a significant risk device listed in the link below, explain why the device
as it is used in this study, qualifies as Non-Significant Risk (NSR) device:
According to the FDA criteria for significant risk determination
(https://www.fda.gov/media/75459/download), the BCI-robotic exoskeleton
system is not a significant risk device as follows: -Is the device implanted?:
No, this device is entirely non-invasive. -Does the device perform life
sustaining functions?: No, this device does not perform any life sustaining
functions -Is the device use of any substantial importance in diagnosis or
treatment of disease?: No, this system does not perform any important
diagnostic function. In Aim 3 of this study, the BCI controlled robotic ankle
exoskeleton is being used as a tool to elucidate the potential mechanism of
how BCI systems may elicit neuroplasticity. It is not being used to provide
treatment for stroke rehabilitation. -Otherwise being used in any way that
presents a serious risk to health, safety, or welfare of a subject?: This device
is a non-invasive, wearable exoskeleton that has the capacity to passively
measure movement trajectories and also actively manipulate the user’s
ankle as controlled via a BCI. The exoskeleton itself is similar to a category
of devices called powered exercise equipment, which is designated as an
exempt category per the FDA. Our specific exoskeleton is a seated system
which is calibrated to the user’s range of motion, with emergency cut off
buttons and extensive training and well documented protocol/manual. It
can provide robotically assisted dorsiflexion movement to the subject upon
their intent to dorsiflexion attempt, uses a low amount of torque, and only
operates within the subjects available range of motion. As such, it is not
expected to pose any serious risk of orthopedic injury or other
safety/welfare concerns to the subjects.
Has the FDA or another IRB determined the device to be non-significant risk as it is used in
this study?
No
Indicate who will be responsible for the management of the device during the study:
Dr. Do and Dr. Reinkensmeyer

Explain the plan to ensure that the investigational device is used only in accordance with the
UCI IRB approved protocol:
Research team members will receive training on how the device is to be
used, and will informed that it will only be used for the current study. A
standard operating procedure will be provided to guide how the device
should be operated each time it is used to deliver BCI-robotic orthosis
therapy.
Indicate who will have access to the device and how access will be controlled to secure the
device (or device stock):
Dr. Reinkensmeyer, Jill See, and Vicky Chan
Specify how records for control of the device (or device stock) will be recorded:
The sample Device Accountability Log on the HRPP website will be used
REQUIRED! Submit the Sponsor Device Log in the Attachment Section
Specify why no log will be used:
Indicate whether the investigational device is manufactured in a UCI facility:
Yes
Identify the lab and location:
Hewitt Hall Room 1341
You have completed the form for this medical device. Click the 'Done' button. If you need to
add more devices, click on the + Add Line button above the table to enter additional devices.
Name of Device or Product
MP150 bioamplifier with EMG100 attachment
Device Manufacturer
Biopac
Description of the device:
This is a standard research bioamplifier system that is used to record
electromyogram or other peripheral nerve activity

Specify the proposed use of the device for this study:
This will be used to record the motor evoked potential from the tibialis
anterior muscle, which is stimulated by the transcranial magnetic
stimulation delivered to the brain. Manual links:
https://www.biopac.com/wp-content/uploads/MP150-Systems.pdf
EMG100C attachment: https://www.biopac.com/product/electromyogram-
amplifier/
Does this device have an Instructions for Use/User Manual/Product Brochure?
Yes
REQUIRED! Submit the Instructions for Use, User Manual or Product Brochure in the
Attachments Section
Include information to describe how it works and the foreseeable risks associated with its use:
Is the device a medical device?
Yes, this device is a medical device
If “no”, for minimal risk studies and the device is intended to be used in a clinical setting,
provide justification for selecting “no”, citing any regulatory guidance as applicable:
Are you testing the safety and/or efficacy of this device?
No, the safety and/or efficacy of this medical device is not being assessed
If “no”, for minimal risk research and if the device is the object of the investigation, provide
justification for selecting “no”, citing any regulatory guidance as applicable:
please complete this question
Is the device approved for marketing in the United States?
How is the device approved in the United States?
REQUIRED! Submit FDA Documentation in the Attachments Section
Select one of the following:
Is the device authorized for use under an FDA Emergency Use Authorization (EUA)?

Is the device being used in this study according to its approved indication?
Is the Device Exempt from the Investigational Device Regulations (21 CFR 812)?
Select the device exemption that meets one of the following categories:
Clarify how the device meets the category selected:
Is this device a Significant Risk (SR) device?
Has the investigator or sponsor of this research obtained an Investigational Device Exemption
(IDE) from the FDA for the use of this device for this research?
REQUIRED! Submit the IDE Authorization Letter in the Attachments Section
IDE Number
Holder of the IDE (check all that apply):
Specify Lead Researcher:
Specify 'Other' IDE Holder:
Does the IDE allow billing of subjects?
Does the IDE cover a combination use (e.g., combination of an investigational drug and
device)?
Specify the combination use:
Specify why an IDE has not been obtained yet:
Specify 'Other' reason:
Based on the criteria for a significant risk device listed in the link below, explain why the device
as it is used in this study, qualifies as Non-Significant Risk (NSR) device:

Has the FDA or another IRB determined the device to be non-significant risk as it is used in
this study?
Indicate who will be responsible for the management of the device during the study:
Explain the plan to ensure that the investigational device is used only in accordance with the
UCI IRB approved protocol:
Indicate who will have access to the device and how access will be controlled to secure the
device (or device stock):
Specify how records for control of the device (or device stock) will be recorded:
REQUIRED! Submit the Sponsor Device Log in the Attachment Section
Specify why no log will be used:
Indicate whether the investigational device is manufactured in a UCI facility:
Identify the lab and location:
You have completed the form for this medical device. Click the 'Done' button. If you need to
add more devices, click on the + Add Line button above the table to enter additional devices.
Name of Device or Product
Magstim 200/220 Transcranial Magnetic Stimulator
Device Manufacturer
Magstim
Description of the device:
This is a TMS device that delivers magnetic impulse to the brain to trigger a
neural response.
Specify the proposed use of the device for this study:
The purpose of this device is to identify if the subjects in the study have a
connection between the brain motor cortex and the tibialis anterior muscle.

Does this device have an Instructions for Use/User Manual/Product Brochure?
Yes
REQUIRED! Submit the Instructions for Use, User Manual or Product Brochure in the
Attachments Section
Include information to describe how it works and the foreseeable risks associated with its use:
Is the device a medical device?
Yes, this device is a medical device
If “no”, for minimal risk studies and the device is intended to be used in a clinical setting,
provide justification for selecting “no”, citing any regulatory guidance as applicable:
Are you testing the safety and/or efficacy of this device?
No, the safety and/or efficacy of this medical device is not being assessed
If “no”, for minimal risk research and if the device is the object of the investigation, provide
justification for selecting “no”, citing any regulatory guidance as applicable:
please complete this question
Is the device approved for marketing in the United States?
How is the device approved in the United States?
REQUIRED! Submit FDA Documentation in the Attachments Section
Select one of the following:
Is the device authorized for use under an FDA Emergency Use Authorization (EUA)?
Is the device being used in this study according to its approved indication?
Is the Device Exempt from the Investigational Device Regulations (21 CFR 812)?
Select the device exemption that meets one of the following categories:
Clarify how the device meets the category selected:

Is this device a Significant Risk (SR) device?
Has the investigator or sponsor of this research obtained an Investigational Device Exemption
(IDE) from the FDA for the use of this device for this research?
REQUIRED! Submit the IDE Authorization Letter in the Attachments Section
IDE Number
Holder of the IDE (check all that apply):
Specify Lead Researcher:
Specify 'Other' IDE Holder:
Does the IDE allow billing of subjects?
Does the IDE cover a combination use (e.g., combination of an investigational drug and
device)?
Specify the combination use:
Specify why an IDE has not been obtained yet:
Specify 'Other' reason:
Based on the criteria for a significant risk device listed in the link below, explain why the device
as it is used in this study, qualifies as Non-Significant Risk (NSR) device:
Has the FDA or another IRB determined the device to be non-significant risk as it is used in
this study?
Indicate who will be responsible for the management of the device during the study:
Explain the plan to ensure that the investigational device is used only in accordance with the
UCI IRB approved protocol:
Indicate who will have access to the device and how access will be controlled to secure the
device (or device stock):

Specify how records for control of the device (or device stock) will be recorded:
REQUIRED! Submit the Sponsor Device Log in the Attachment Section
Specify why no log will be used:
Indicate whether the investigational device is manufactured in a UCI facility:
Identify the lab and location:
You have completed the form for this medical device. Click the 'Done' button. If you need to
add more devices, click on the + Add Line button above the table to enter additional devices.
Name of Device or Product
A time-resolved near infrared spectroscopy (TR-NIRS) device
Device Manufacturer
TRS-21; Hamamatsu Photonics
Description of the device:
A time-resolved near infrared spectroscopy (TR-NIRS) device (TRS-21;
Hamamatsu Photonics) will be used to acquire metabolic measurements
(e.g., tissue hemoglobin concentration and oxygenation) at the TA muscle.
This device is noninvasive, consisting of two source fibers connected to
light sources in the visible to near infrared wavelength range, and two
detector fibers to collect backscattered photons and direct them to a
photodetector. The output is connected to a computer to provide data
acquisition and handling. The source and detector fibers are mounted within
tethered pads that adhere to the surface of the skin.

Specify the proposed use of the device for this study:
TR-NIRS parameters will be measured at the TA muscle of stroke patients
while they attempt dorsiflexion while seated with the tibia perpendicular to
the ground. Measurements pertaining to oxygen metabolism at the TA
muscle will be acquired by placing the source and detector fibers on the
skin surface positioned over the muscle (using the adhesive pads). This
setup allows for the collection of metabolic data in real time while either the
BCI-FES or BCI-robotic orthosis systems are being used.
Does this device have an Instructions for Use/User Manual/Product Brochure?
Yes
REQUIRED! Submit the Instructions for Use, User Manual or Product Brochure in the
Attachments Section
Include information to describe how it works and the foreseeable risks associated with its use:
Is the device a medical device?
No, this is not a medical device
If “no”, for minimal risk studies and the device is intended to be used in a clinical setting,
provide justification for selecting “no”, citing any regulatory guidance as applicable:
The device is not intended for use in the diagnosis of disease or other
conditions, or in the cure, mitigation, treatment, or prevention of disease, in
man or other animals, or intended to affect the structure or any function of
the body of man or other animals. The device is approved for clinical
research and it has been used in clinical research settings as an
investigational device. So we will not be testing it's saftey as it has already
been proven to be safe. We are not testing the efficacy of the device. It is a
monitoring device that does not provide any treatment or intervention. This
device will report changes in subject's: oxy-hemoglobin, deoxy-hemoglobin,
total hemoglobin and oxygen saturation.
Are you testing the safety and/or efficacy of this device?
If “no”, for minimal risk research and if the device is the object of the investigation, provide
justification for selecting “no”, citing any regulatory guidance as applicable:

Is the device approved for marketing in the United States?
How is the device approved in the United States?
REQUIRED! Submit FDA Documentation in the Attachments Section
Select one of the following:
Is the device authorized for use under an FDA Emergency Use Authorization (EUA)?
Is the device being used in this study according to its approved indication?
Is the Device Exempt from the Investigational Device Regulations (21 CFR 812)?
Select the device exemption that meets one of the following categories:
Clarify how the device meets the category selected:
Is this device a Significant Risk (SR) device?
Has the investigator or sponsor of this research obtained an Investigational Device Exemption
(IDE) from the FDA for the use of this device for this research?
REQUIRED! Submit the IDE Authorization Letter in the Attachments Section
IDE Number
Holder of the IDE (check all that apply):
Specify Lead Researcher:
Specify 'Other' IDE Holder:
Does the IDE allow billing of subjects?
Does the IDE cover a combination use (e.g., combination of an investigational drug and
device)?

Specify the combination use:
Specify why an IDE has not been obtained yet:
Specify 'Other' reason:
Based on the criteria for a significant risk device listed in the link below, explain why the device
as it is used in this study, qualifies as Non-Significant Risk (NSR) device:
Has the FDA or another IRB determined the device to be non-significant risk as it is used in
this study?
Indicate who will be responsible for the management of the device during the study:
Explain the plan to ensure that the investigational device is used only in accordance with the
UCI IRB approved protocol:
Indicate who will have access to the device and how access will be controlled to secure the
device (or device stock):
Specify how records for control of the device (or device stock) will be recorded:
REQUIRED! Submit the Sponsor Device Log in the Attachment Section
Specify why no log will be used:
Indicate whether the investigational device is manufactured in a UCI facility:
Identify the lab and location:
You have completed the form for this medical device. Click the 'Done' button. If you need to
add more devices, click on the + Add Line button above the table to enter additional devices.
Risk Assessment

Risks and Discomforts
1. Describe and assess any reasonably foreseeable risks and discomforts associated with each
procedure for each subject population — physical, psychological, social, legal or other:
2. If this study will involve the collection of identifiable private information, even temporarily, for
which the disclosure of the data outside of the research could reasonably place the subjects at
risk, include the risk of a potential breach of confidentiality:
As listed in the 3 Consents for this study (Screening Consent, Full Study Group 1 and 2 Consent, Full
Study Group 3 and 4 Consent).
Risk in Screening
No long-term side effects are anticipated as part of the screening examinations. There is a low risk
of fatigue associated with undergoing the examination. The test of electrical stimulation on your leg
muscles may lead to some temporary discomfort, although this risk is very low. There is also a low
risk of falling when asked to walk without leg prostheses during the physical exam.
Risk in Aim 1 and 2 (Groups 1 and 2)
Risks and side effects related to the BCI-FES therapy include those which are:
-      Discomfort with wearing EEG electrodes (unlikely)
-      Increased falls (highly unlikely)
-      Fatigue (unlikely)
-      Skin breakdown due to electrical stimulation (highly unlikely)
Risks and side effects related to physical therapy include:
-      Falls during therapy (highly unlikely)
-      Physical injury during therapy (highly unlikely)
-      Fatigue (unlikely)
Risks and side effects related to detailed physical examinations:
-      Discomfort due to performing tasks (unlikely)
-      Falls due to walking during exams (highly unlikely)
Risk in Aim 3 (Group 3 and 4)
Risks and side effects related to the BCI-FES operation include those which are:
-      Discomfort with wearing EEG electrodes (unlikely)
-      Increased falls (highly unlikely)
-      Fatigue (unlikely)
-      Skin breakdown due to electrical stimulation (highly unlikely)
Risks and side effects related to the BCI-Robot operation include those which are:
-      Discomfort with wearing EEG electrodes (unlikely)
-      Increased falls (highly unlikely)
-      Fatigue (unlikely)

Discuss what steps have been taken and/or will be taken to prevent and minimize any
risks/potential discomforts to subjects:
Subjects who are enrolled in the study will have been screened to ensure that
they meet the study criteria above. Meeting these criteria will minimize the
risks associated with participation. Additional measures will be taken to
minimize the risks described above. More specifically, the physical risk of fall
and injury resulting from the fall will be minimized given that the gait
assessments and physiotherapies are performed with standard techniques
and by qualified practitioners. Furthermore, any discomfort resulting from
stimulation techniques (FES, TMS) will addressed by reducing the stimulation
intensity until discomfort is eliminated. Dr. Do (lead researcher), and Lucy
Dodakian (study coordinator), will be responsible for safety oversight of the
study.
Certificate of Confidentiality
Is the research partially or wholly funded by NIH (including NIH Institutes and Centers), or does
the research involve identifiable sensitive information that require CoC protections?
Yes
Indicate whether the research is protected by a NIH Certificate of Confidentiality (CoC):
This research is partially or wholly funded by NIH, including NIH Institutes and
Centers. A CoC is automatically issued
Indicate in what situations identifiable private information protected by a CoC will be disclosed
(check all that apply):
As required by Federal, State, or local laws, excluding instances of disclosure
in any Federal, State, or local civil, criminal, administrative, legislative, or other
proceeding. Some examples are laws that require reporting of child or elder
abuse, some communicable diseases, and threats to harm yourself or others
Risks and side effects related to detailed physical examinations:
-      Discomfort due to performing tasks (unlikely)
-      Falls due to walking during exams (highly unlikely) 
-      Skin irritation due to TR-INR device (highly unlikely)

Potential Benefits
Is there the prospect of a direct benefit anticipated for subjects?
Yes
Describe the potential benefits subjects may expect to receive from participation in this study:
Undertaking BCI-FES therapy may provide improvement in gait velocity to the
subjects. Undertaking the conventional physiotherapy components of the
study may also provide improvement in gait function. Given the low risks
associated with the study and the potential benefits of improvement in gait
function, the risk-benefit ratio for participation is considered to be reasonable.
Specify the expected potential societal/scientific benefit(s) of this study:
If the BCI-FES therapy technique is found to be potentially efficacious, this
may in the future benefit other stroke patients and society by providing a
novel therapy to help reduce stroke-related disabilities and the associated
public health burden.
Alternatives to Participation
Describe the alternatives to participation in the study available to prospective subjects. Include
routine (standard of care) options as well as other experimental options, as applicable (check all
that apply):
Routine standard of care available
Specify the routine standard of care:
physical therapy or at home exercise
Participant Compensation
Will subjects be compensated?
Yes

Specify whether compensation is applicable and, if so, the method, amount and schedule of
compensation (Check all that apply):
Cash
Check
Gift Card
Cash Compensation
Specify cash amount:
Total compensation for participation in the entire study is $100.
Cash schedule:
Other
Specify 'Other' cash schedule:
Compensation is provided at the
end of study participation. If
subjects decide to withdraw from
the study or are withdrawn by the
research team, they will receive
compensation for the visits that
they have completed
Will the cash compensation method include all subjects?
Yes
Specify check amount:
Compensation will be provided to subjects in the form of a check issued
to the subjects through the UCI Accounting Office. The subject’s name,
address, and social security number, will be released to the UCI
Accounting Office for the purpose of payment and for tax reporting to the
Internal Revenue Service (IRS). Total compensation for participation in the
entire study is $100.
Check schedule:
Other

Specify 'Other' check schedule:
Compensation is provided at the end of study participation. If subjects
decide to withdraw from the study or are withdrawn by the research team,
they will receive compensation for the visits that they have completed
Will the check compensation method include all subjects?
Yes
Specify gift card type and amount:
Total compensation for participation in the entire study is $100.
Gift Card schedule:
Other
Specify 'Other' gift card schedule:
Compensation is provided at the end of study participation. If subjects
decide to withdraw from the study or are withdrawn by the research team,
they will receive compensation for the visits that they have completed
Will the gift card compensation method include all subjects?
Yes
Will subjects be reimbursed for out-of-pocket expenses?
No
Participant Costs
Will subjects or their insurers be charged for study procedures?
No
Confidentiality of Research Data

Information and/or Biospecimens Storage
Indicate how information and/or biospecimens (including signed consent forms) will be stored
(check all that apply):
Information will be maintained electronically. Information will be password
protected and maintained in an encrypted format
Encrypted Format
Specify where the information will be maintained electronically:
Secure data server will be kept in Engineering Gateway 3121.
Will subject/patient identifiers be collected or retained?
Yes
Subject/Patient Identifiers
Will any subject/patient identifiers be collected or retained for data analysis, recruitment,
consenting and/or compensation (check all that apply)?
All elements of dates (except year) for dates that are directly related to an
individual: birth date, admission date, discharge date, death date, and all ages
over 89
Email addresses
Full-face photographs and any comparable images
Medical record numbers
Names
Telephone numbers
Will a code be used to link subject/patient identifiers with the information and/or biospecimens?
A code will be used. Subject/Patient identifiers will be kept separately from
the information and/or biospecimens. The code key will be destroyed at the
earliest opportunity, consistent with the conduct of this research
Will research data/biospecimens be transported or maintained on portable devices (e.g., laptop,
smartphone, external hard drive, etc.)?
No

Specify who will have access to subject/patient identifiable information/biospecimens as part of
this protocol (check all that apply):
Authorized UCI personnel (such as the research team) and appropriate
institutional officials: such as the Office of Human Research Protections
(OHRP) Regulatory entities such as the Food and Drug Administration (FDA),
the National Institutes of Health (NIH)
Specify whether subject/patient identifiers be disclosed in presentations and/or publications:
Subject/Patient identifiers will not be disclosed
Specify how long all subject/patient identifiers
will be retained. This includes identifiers
stored in paper format, stored electronically as
well as video recordings, audio recordings,
photographs, etc.:
Other
Specify 'Other' time frame and provide
rationale:
The researchers intend to keep the
research data indefinitely. The
researchers may continue to use and
share the information and
information obtained from analyses
of the information indefinitely
Will any identifiable photos or audio/video recordings be collected or used?
Yes
Collection of Photographs, or Audio/Video Retention & Recording
Will identifiable audio recordings be collected?
Yes
How will the audio recordings be transcribed?
Identifiable audio recordings
transcribed by the study team
Specify timeframe for the audio transcription:
Identifiable audio recordings will be
transcribed by the study team within
1 week.
Will the identifiable audio recordings be de-identified?
Yes

Specify timeframe for the audio recordings de-identification and how will the recordings be de-
identified:
De-identified version will be maintained indefinitely in case of need for future
research/publication
Will identifiable video recordings be collected?
Yes
How will the video recordings be transcribed?
Identifiable video recordings
transcribed by the study team
Specify timeframe for the video transcription:
within 7-14 days
Will the identifiable video recordings be de-identified?
Yes
Specify timeframe for the video recordings de-identification and how will the recordings be de-
identified:
De-identified version will be maintained indefinitely in case of need for future
research/publication
Will identifiable photographs be collected?
Yes
Will the identifiable photographs be de-
identified?
Yes
Specify timeframe for the photographs de-
identification and how will the photographs be
de-identified:
De-identified version will be
maintained indefinitely in case of
need for future research/publication
Research Information and/or Biospecimens Retention
Indicate how long research information/biospecimens will be retained:
In addition, if the research involves the investigation of FDA regulated
products, information/biospecimens will be retained for two years after an
approved marketing application. If approval is not received, the
information/biospecimens will be kept for 2 years after the investigation is
discontinued and the FDA is notified per FDA sponsor requirements

Will research information and/or biospecimens be shared?
No
Attachments
If required documentation is not provided, the submission is incomplete and your Application will be
returned to you. Be sure to upload each document as required. If changes are needed, go back to
the sub-section to revise your selections.
Maximum file size is 30MB
All UCI templates are available on the Human Research Protections Applications & Forms page or
Human Stem Cell Research Applications & Forms page.
To access approval documents where UCI will rely on another IRB, including commercial IRBs, visit
their respective online portals. Frequently used commercial IRB portals include:
• WIRB Copernicus Group's WCG IRB Connexus
• Advarra’s CIRBI
• SMART Online Reliance System (ORS)
Attachment
Attachment Type
File Comments
File Name
Status (IRB/hSCRO Use Only)
Attachment
2019-4936 email to confirm no COIOC review is required_normal_352530.pdf
2019-4936 Neuro-QOL Item Bank v1.0 - Lower Extremity Function (Mobility) v02-27-
18_normal_372029.pdf

Attachment Type
Data Collection Tool/Instrument
File Comments
File Name
Status (IRB/hSCRO Use Only)
Attachment
Attachment Type
HIPAA Research Authorization Form
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
Attachment
Attachment Type
Recruitment Material
File Comments
20194936 HIPAA Authorization_11-09-22.docx
2019-4936 Facebook Ad 12-02-20_normal_400073.pdf

File Name
Status (IRB/hSCRO Use Only)
Approved
Attachment
Attachment Type
Recruitment Material
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
Attachment
Attachment Type
Consent Form
File Comments
File Name
2019-4936 Facebook Ad 12-02-20_approved_400073.pdf
20194936 Screening Consent 10-11-24.docx

Status (IRB/hSCRO Use Only)
Approved
Add
Attachment
Attachment Type
Consent Form
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
Attachment
Attachment Type
Consent Form
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
20194936 Screening Consent and HIPAA 10-11-24.pdf
20194936 Groups 1 & 2 Consent 10-11-24.docx

Add
Attachment
Attachment Type
Consent Form
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
Attachment
Attachment Type
Recruitment Material
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
20194936 Groups 1 & 2 Consent and HIPAA 10-11-24.pdf
2019-4936 UCIMC Clinic Trials Web Page Ad 12-02-20_normal_400076.docx

Attachment
Attachment Type
Recruitment Material
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
Attachment
Attachment Type
Recruitment Material
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
Attachment
2019-4936 UCIMC Clinic Trials Web Page Ad 12-02-20_approved_400076.pdf
2019-4936 Recruitment Flyer 12-02-20_normal_400078.doc
2019-4936 Recruitment Flyer 12-02-20_approved_400078.pdf

Attachment Type
Recruitment Material
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
Attachment
Attachment Type
Recruitment Material
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
Attachment
Attachment Type
Other
2019-4936 Recruitment Letter to Referring HealthCare Professional 12-02-20 (NO
STAMPING)_normal_400080.docx
20194936 Procedure Table 06-22-2023.docx

File Comments
File Name
Status (IRB/hSCRO Use Only)
Attachment
Attachment Type
Medical Device Instructions (User Manual/Product Brochure)
File Comments
File Name
Status (IRB/hSCRO Use Only)
Add
Attachment
Attachment Type
Data Safety Monitoring Plan Documentation
File Comments
Revised
File Name
TMS_Magstim 200_262 Operating Manual 3001-23-04.doc.pdf
DSMB Charter_20231017.pdf

Status (IRB/hSCRO Use Only)
Attachment
Attachment Type
Medical Device Picture
File Comments
Ankle Measuring Proprioception Device (AMPD) Manual
File Name
Status (IRB/hSCRO Use Only)
Add
Attachment
Attachment Type
Medical Device Instructions (User Manual/Product Brochure)
File Comments
File Name
Status (IRB/hSCRO Use Only)
Add
AMPD SOP_V6.docx
BCI-FES Protocol.docx

Attachment
Attachment Type
Medical Device Instructions (User Manual/Product Brochure)
File Comments
File Name
Status (IRB/hSCRO Use Only)
Add
Attachment
Attachment Type
HIPAA Research Authorization Form
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
Attachment
TR-NIRS device_Manual.pdf
20194936 HIPAA Authorization_11-09-22.pdf
20194936 Groups 3 & 4 Consent 10-11-24 .docx

Attachment Type
Consent Form
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
Add
Attachment
Attachment Type
Consent Form
File Comments
File Name
Status (IRB/hSCRO Use Only)
Approved
Attachment
Attachment Type
Data Safety Monitoring Plan Documentation
20194936 Groups 3 & 4 Consent and HIPAA 10-11-24.pdf
DSMB_interrim_report_BCI_20230917_dvn.pdf

File Comments
File Name
Status (IRB/hSCRO Use Only)
Add
Attachment
Attachment Type
Data Safety Monitoring Plan Documentation
File Comments
File Name
Status (IRB/hSCRO Use Only)
Add
Attachment
Attachment Type
UCI IRB Approval Letter
File Comments
File Name
DSMB_Approval_2023.pdf
20194936 Renewal Approval Letter 10-11-24.pdf

Status (IRB/hSCRO Use Only)
Approved
Lead Researcher Certification

Investigator's Assurance
As Lead Researcher, I have ultimate responsibility for the performance of this study, the
protection of the rights and welfare of the human subjects, and strict adherence by all co-
investigators and research personnel to all Institutional Review Board (IRB) requirements, federal
regulations, and state statutes for research involving human subjects.
I hereby assure the following:
1. The information provided in this application is accurate to the best of my knowledge.
2. The information provided in this application has been discussed and shared with my
Department Chair. Any requests for changes based on this discussion are included in this
application upon submission or will be initiated by the research team either during the IRB
review process or via an amendment.
3. All named individuals on this project have read and understand the procedures outlined in
the protocol and their role on the study.
4. All named individuals on this project have completed the required Educational research
tutorials and have been made aware of the "Common Rule" (45 CFR Part 46), applicable
Food and Drug Administration (FDA) regulations (21 CFR Parts 50, 56, 312 and 812), have
read the Belmont Report, and UCI's Federalwide Assurance (FWA) that are available on the
Human Research Protections Program (HRP) website.
5. All experiments and procedures involving human subjects will be performed under my
supervision or that of another qualified professional listed on this protocol.
6. I understand that, if the study described in this IRB application is supported by a federal
award or used as a basis for a proposal for funding, it is my responsibility to ensure that
the description of human subjects activities in the proposal/award is identical in principle
to that contained in this application. I will submit modifications and/or changes to the IRB
as necessary to assure the proposal/award and application are identical in principle.
I and all co-investigators and research personnel agree to comply with all applicable
requirements for the protection of human subjects in research including, but not limited to, the
following:
1. Obtaining the legally effective informed consent of all human subjects or their legally
authorized representatives (unless waived) and using only the currently approved, stamped
consent form (if applicable).
2. Per federal regulations, once a human research study has received IRB approval, any
subsequent changes to the study must be reviewed and approved by the IRB prior to
implementation except when necessary to avoid an immediate, apparent hazard to a
subject. See Reporting of Unanticipated Problems.
3. Reporting any unanticipated problems involving risk to subjects or others, including
protocol violations per UCI IRB policy. In addition, HIPAA privacy violations must be
PROMPTLY disclosed to the UCI Privacy Officer. There are time requirements for reporting
these breaches of confidentiality, which, if not met, may result in monetary damages to the
researcher and the institution.
4. Responding appropriately to subjects' complaints or requests for information about the
study; and reporting to the IRB any subject complaints that are not resolvable by the study

team.
5. Promptly providing the IRB with any information requested relative to the project.
6. Assuring the appropriate administration and control of investigational test articles (i.e.,
investigational drugs, biologics or devices) by a qualified investigator or other appropriate
individual or entity (e.g., UCI Health pharmacy), and assuring use and maintenance of an
Investigational Drug/Biologic Accountability Log or Device Accountability Log.
7. Registering applicable clinical trials with clinicaltrials.gov. For more information about this
topic, visit the ClinicalTrials.gov web page or the HRP webpage. The consequences of not
meeting the registration and reporting requirements include monetary damages to the
researcher and the institution.
8. Obtaining continuing review prior to study expiration (I understand if I fail to apply for
continuing review, approval for the study will automatically expire, and all human research
activities must cease until IRB approval is obtained).
9. Promptly and completely complying with an IRB decision to suspend or terminate its
approval for some or all research activities.
10
. Submitting to a routine review of human subject research records. The Compliance &
Privacy Office at UCI Health performs ongoing routine reviews of open biomedical research
protocols, in an effort to ensure in part that human subject research activities are
conducted in accordance with regulations, laws and institutional policies regarding the
protection of human subjects. In addition, the HRP unit of the Office of Research has
developed the Education Quality and Improvement Program (EQUIP). Through EQUIP, HRP
staff conduct periodic quality improvement monitoring and educational outreach.
11
. For clinical trials initially approved by the IRB on or after January 21, 2019, posting one (1)
IRB-approved clinical trial consent form at a publicly available federal website. The consent
form must be posted after recruitment closes, and no later than 60 days after the last study
visit. For additional guidance, refer to the OHRP FAQs on Informed Consent.
12
. Filing a final report with UCI HRP at the conclusion of this project.
As the Lead Researcher, I assure all of the above

Financial Disclosure
Investigators' Disclosure of Financial Interest
In order to inform research subjects of circumstances that may affect their decision to
participate in this study, all researchers are required to disclose their financial interests with
outside institutions.  
The Lead Researcher of the protocol must ask the following question of all study team
members:     
“Do you, your spouse/registered domestic partner, and dependent children together have any
disclosable financial interests (i) that would reasonably appear to be affected by the research;
or (ii) in entities whose financial interests would reasonably appear to be affected by the
research?"
A member of the study team who answers in the affirmative will be contacted by the Conflict of
Interest Oversight Committee (COIOC) to obtain additional information regarding their specific
financial interest(s). 
IMPORTANT! If there has been a change in the financial disclosures of the LR or the study team,
please also request a 'Change in Financial Interests'.
As Lead Researcher, I certify that the disclosures for all study team members
are accurate
End of form. Please review responses for accuracy and
completeness.
Please ignore the Admin Details Section below. This section is for
IRB/hSCRO use only.

Administrative Details Form
Project Status
Committee:
IRB B
Project Status:﻿
Approved
Date of Project Determination:
October 11, 2024
Amendment Status:
Approved
Date of Amendment Determination:
June 22, 2023
Date of ERA Transcription:
November 11, 2021
Pre-2018 Common Rule:
No
Date of Transition to 2018 Common Rule:
No date entered