Agonist-Antagonist Myoneural Interface for Functional Limb Restoration After Transtibial Amputation
Phase: NA
Conditions: Amputation
Sponsor: Massachusetts Institute of Technology

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                                                         COUHES - STANDARD APPLICATION – ver. 3/31/2017 - 
 
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Massachusetts Institute of Technology 
Committee on the Use of 
Humans as Experimental Subjects 
Protocol # 
(assigned 
by 
COUHES) 
1812634918 
 
APPLICATION FOR USE OF HUMANS AS EXPERIMENTAL SUBJECTS  
(STANDARD FORM)  
 
Please answer every question. Positive answers should include details. N/A must be marked where the 
question does not pertain to your application. Any incomplete application will be rejected and returned 
for completion. This application must include the secondary personnel list form otherwise this 
application will be returned to you.  
I. BASIC INFORMATION 
1.  Title of Study 
NIH Study of Neural Control of a Bionic 2-DoF Ankle-Foot Prosthesis  
2.  Principal Investigator 
Name: Hugh Herr 
Building and Room #: E14-374 
Title: Professor 
Email: 
Department: Media Arts & Sciences 
Phone: (617) 258-6574 
3.  Funding. If the research is funded by an outside sponsor, please enclose one copy of the research 
proposal with your application.  A draft of the research proposal is acceptable. Do not leave this 
section blank. Check all that apply.  If your project is not funded, check No Funding. 
 
A.  Sponsored Project Funding: 
  Current Proposal  
Grant/Proposal #      
 
Sponsor         
 
Title         
 
 
 
 
Current Award 
Grant/Account # 1R01-HD097135 / 6940415  
Sponsor 
National Institutes of Health – National Institute for Child Health & Development  
Title  “Agonist-Antagonist Myoneural Interfaces for Functional Limb Restoration  
           after Transtibial Amputation” 
 
 
 
B.  Institutional Funding: 
  Gift                                   
  Departmental Resources                      
  Other (explain)         
C. No Funding 
  This protocol will not be funded 
4.   STATEMENT OF FINANCIAL INTEREST 
Does the investigator, study personnel involved in the study or their family have a financial interest in 
a company or other organization participating in or providing drugs, devices, biological agents, 
investigational medical devices, or any other tangible material or financial sponsorship for the 
research? 

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  Yes 
  No 
 
Does this study contemplate receiving/using any materials/data (data sets, confidential information) or 
making any purchases from or subawards to a company or other organizations in which you or a 
family member hold a Financial Interest? 
 
  Yes 
  No 
 
If yes was checked for any of the questions above, then attach a Supplement for Disclosure of 
Financial Interest for each individual with an interest. This supplement, together with detailed 
guidance on this subject and definitions of the highlighted terms, is available in the COUHES site 
under Policies & Procedures in the Financial Conflicts of Interest section. 
 
5. Anticipated Dates of Research 
Start Date: 03/01/2019 
Completion Date: 02/28/2025  
6. Collaborating Institutions. If you are collaborating with another institution(s) then you must obtain 
approval from that institution’s institutional review board, and forward copies of the approval to COUHES.  
 
 
Not Applicable 
7. Location of Research. If at MIT please indicate where on campus. If you plan to use the facilities of the 
Clinical Research Center you will need to obtain separate approval from the MIT Catalyst Clinical Research 
Center.  
 
MIT Media Laboratory E14-274, E15-463 
 
II. STUDY INFORMATION 
 
 
1.  Purpose of Study. Please provide a concise statement of the background, nature and reasons for 
the proposed study. Use non-technical language that can be understood by non-scientist members of 
COUHES. 
Loss of limb profoundly impacts the physical and emotional health of nearly two million Americans 
at an annual cost exceeding 250 million dollars. The vast majority of the people living with limb loss 
have affected lower limbs.  Outcomes of limb amputations are limited by prosthesis interfacing 
technologies.  Toward reinstating aspects of motor and sensory functions in persons with transtibial 
(TT) amputation, the Agonist-antagonist Myoneural Interface (AMI) was developed and first studied 
at the TT (i.e., below knee) amputation level through collaboration between MIT and the Brigham & 
Women’s Hospital (BWH). An AMI is comprised of two muscles – an agonist and an antagonist – 
that are surgically connected in series within the residual limb during an experimental BKA such that 
contraction of one muscle stretches the other.  Two AMI constructs are created in the residual limb: 
one AMI directly links the lateral gastrocnemius (LG) and the tibialis anterior (TA) muscles toward  
improving motor control and sensation of a virtual or prosthetic ankle joint, and the other AMI 

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directly links the peroneus longus (PL) and the tibialis posterior (TP) muscles toward improving 
motor control and sensation of a virtual or prosthetic subtalar joint. This surgical architecture is 
designed to preserve musculotendinous sensors and anatomical muscle relationships that evolved to 
provide bi-directional communication of neural signals post-amputation.  The TT AMI amputation is 
also anticipated to yield more isolated electromyography (EMG) signals resulting from residual limb 
muscle activations towards improved myoelectric control of a prosthetic device, and a myoneural 
interface for investigating proprioceptive sensations (i.e., perceptions of the position, movement, and 
torque) of the phantom limb. 
 
At the same time, next-generation wearable prostheses mimicking the physiological functions of the 
biological ankle-foot complex are under development in the MIT Biomechatronics group. One such 
system comprises flexible, socket-compatible EMG sensors, an embedded EMG data acquisition 
system, a mechatronic two degree-of-freedom (2-DoF) ankle-subtalar prosthesis with two on-board, 
high-torque motors to actuate ankle and subtalar joints, capability to measure joint state (i.e., position 
and speed) and sense joint torque, and an integrative electronics control platform. Beyond the intent to 
preserve range of motion after TT amputation in both the coronal and sagittal planes to allow more 
sophisticated balance control, clinical studies of TT amputation subjects that involve the 2-DoF 
prosthesis as data collection platform will yield novel EMG-modulated prosthetic control algorithms.  
The First human subject with a TT AMI amputation demonstrated a capacity for independent 
contraction of each AMI muscle, graded proprioceptive responses to controlled muscle activations, 
and a potential for closed-loop motor control of prosthesis in an experimental setting of force 
feedback [Clites, T.R. et al., Science Transl. Med. 2018,  and Clites,  TR et al., PRS- Global Open , 
2018]. 
 
This study protocol is linked to the clinicaltrials.gov registration NCT03913273 and NIH-NICHD-
NCMRR award R01-HD097135. The study has two arms and a prospective, non-randomized, non-
blinded design. There is an AMI interventional arm with amputee subjects drawn from the pool of 
patients who previously underwent a TT amputation with construction of AMIs in their residual limb. 
There is also a Non-AMI active comparator arm with amputee subjects who previously underwent TT 
amputations without AMI constructs incorporated. Each Non-AMI subject is prospectively matched 
to an AMI subject to the degree possible based on age at the time of testing, elapsed time since 
amputation, and body habitus, although there are no formal exclusion criteria in this regard. Best 
efforts are made to include a diverse subject population. The clinical trial rigorously evaluates the 
capabilities of all amputee subjects in the study population regardless of the type of amputation 
performed through computational analyses and experimental testing of a next-generation wearable 
prosthesis platform. If motor control for tasks relevant to daily life and sensory feedback can be 
successfully provided then the TT AMI procedure and/or the 2-DoF prosthesis platform have the 
potential to improve overall health. Additionally, we expect to collect an invaluable set of data that 
may inform system component designs as well as neuromuscular control paradigms for next-
generation lower extremity prostheses. 

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2.  Study Protocol. For biomedical, engineering and related research, please provide an outline of 
the actual experiments to be performed. Where applicable, provide a detailed description of the 
experimental devices or procedures to be used, detailed information on the exact dosages of drugs or 
chemicals to be used, total quantity of blood samples to be used, and descriptions of special diets. 
For applications in the social sciences, management and other non-biomedical disciplines please 
provide a detailed description of your proposed study. Where applicable, include copies of any 
questionnaires or standardized tests you plan to incorporate into your study. If your study involves 
interviews please submit an outline indicating the types of questions you will include. 
You should provide sufficient information for effective review by non-scientist members of COUHES. 
Define all abbreviations and use simple words. Unless justification is provided for additional length, 
this part of the application must not exceed 5 pages. Attaching sections of a grant application is not 
an acceptable substitute for a description of your study as requested here. 
Overview 
 
This study investigates the AMI TT amputation procedure and a prototype 2-DoF prosthesis with the 
intentions of evaluating motor control and proprioception in the residual limb in all amputee subjects 
as well as comparing AMI and Non-AMI subject outcomes. The study has three Specific Aims: 
Aim 1. Investigate if AMIs can improve voluntary free-space prosthetic control;   
Aim 2. Determine if AMIs improve voluntary and involuntary (reflexive) prosthetic terrain adaptations;  
Aim 3. Explore if AMIs can serve as a bi-directional human-device interface. 
 
Aim 1:  
 
Capacity for voluntary free-space prosthetic control is evaluated for AMI and Non-AMI amputee 
subjects through a combination of time-synchronized temporospatial EMG and goniometry data as 
well as real-time ultrasonography scans, collected from subjects’ residual limbs and biologically intact 
contralateral limbs.  Bony anatomical landmarks and target muscles are identified by palpation and 
their superficial projections are marked using a skin marker and reflective marker balls. For residual 
limb mapping, and ultimately for motor control, surface EMG electrodes are placed on the affected 
and unaffected limbs to assess muscle activations, and goniometers are secured to the posterior aspect 
of the unaffected limb. For the free-space performance tasks, subjects are initially positioned in a 
supine recumbent position, and then seated in a chair with lower limb support as needed to allow full 
foot mobility. To assess motor control capacity, subjects are asked to perform ankle joint plantar 
flexion and dorsiflexion (PF and DF) and subtalar joint eversion and inversion (EV and IN) while 
mirroring the intended phantom limb motions with actual joint motions of the contralateral, 
unaffected lower limb.  
 
Time-synchronized EMG and joint state data are simultaneously recorded during task performance to 
provide one-to-one temporospatial indicators of phantom limb efferent signaling and intended joint 
movement. As subjects demonstrate and mirror the range of motion (ROM) capacity for their 
phantom joint on their unaffected limb, time histories of PF and DF joint angles are measured using 
the 2-DoF goniometer attached across their biologically intact ankle joint. Residual limb muscle 
fascicle strains are recorded during PF, DF, EV, and IN motions for AMI and Non-AMI subjects 
using a high-definition ultrasound scanner at 60 fps. Positional discrimination tasks are used to assess 
subjects’ capabilities for precise, graded movements of their phantom limb. Subjects perform graded 

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movements of their phantom limb over their full ROM in each direction and corresponding muscle 
activation levels are measured.  Also, AMI construct muscle coupling is assessed for the AMI subjects 
by ultrasound tracking of opaque markers that were implanted within the constructs during the 
amputation surgery. Together, these data are used to create amputee-specific maps of the residual 
limbs and to develop neuromuscular models for more precise prosthetic joint motor control. 
 
For initial mapping and model development studies the EMG data are collected at high density using 
up to 128 H124SG Ag/AgCl electrodes (Covidien) positioned in a grid-like fashion on the residual 
limb, and using electrodes positioned over the anatomical locations of the LG, TA, TP, and PL of the 
unaffected lower limb. The EMG data are acquired and processed using a physiological amplifier 
(Refa136, TMSi), the goniometry data are collected using the 2-DoF goniometer (Bio-Metrics), and 
ultrasound data are collected using a high-definition, 60 fps scanner (LS128, Telemed).  
 
To assess free-space motor control in studies involving the 2-DoF prosthesis, AMI and Non-AMI 
subjects are seated in a chair and asked to follow position trajectories as presented on a graphical user 
interface (GUI). The 2-DoF prosthesis may either be located remotely or worn by the subject. In the 
latter case, thin flexible surface EMG electrodes are placed on the skin of the subject’s residual limb 
at locations informed by data obtained in Aim 1. The EMG leads are threaded between the skin and 
the liner to exit the liner and socket, if worn, proximally. Subjects are asked to perform specific 
target- tracking tasks designed to explore the motion spaces of the ankle and subtalar joints by moving 
the prosthetic foot to point to a target position specified on the GUI, stiffening the limb to hold that 
position for a specified time interval, and repeating for additional targets. Tasks are performed with 
and without visual feedback. EMG data and joint position, speed, and impedance data are all collected 
in real-time. The EMG data are collected from eight to sixteen custom-fabricated flexible EMG 
sensors that are fixed to the subject’s skin and under their own prosthetic liner, and in some tests the 
2-DoF prosthesis is attached to their own prosthetic socket. The EMG data are acquired using a 
custom-fabricated, portable embedded system and goniometry data are collected using the 2-DoF Bio-
Metrics system. 
 
Aim 2: 
 
Capacities for walking on level ground and performing real-life terrain adaptations are evaluated for 
AMI and Non-AMI amputee subjects through the use of techniques as already described for the Aim 
1 (surface EMG acquired from within the subject’s worn socket and goniometry) as well as a set of 
reflective markers to enable tracking of anatomical landmarks (e.g., hip, knee, ankle, foot). Subjects 
don the 2-DoF prosthesis and are given time to practice standing, balancing, and walking on a 
walkway equipped with handrails. The subjects then carry out and repeat specific ambulatory 
performance tasks.  In one task, the subject performs a terrain obstacle maneuver involving everting 
the prosthetic subtalar joint such that the lateral edge of the prosthetic foot contacts the vertically 
offset block during the swing phase of the step while the medial edge of the prosthetic foot remains at 
the base height. In a second task, the subject ascends stairs in sequential steps. In a third task, the 
subject descends stairs in sequential steps.  
 
To assess voluntary and involuntary (reflexive) motor control during the performance tasks, EMG 
data, kinematic, and kinetic data are collected in real-time. Kinetic data are collected from on-board 
prosthesis sensors. Also, the following force or motion sensors may be used to collect data: (i) 

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pressure-sensitive insoles inserted into one or both shoes worn by the subject along with associated 
electronics,  (ii) force-measuring load-cell between the socket and prosthesis,  and (iii) inertial 
measurement units (small motion sensors). Additionally, data are collected from force platforms 
embedded in the terrain equipment (a force platform is like a sophisticated bathroom scale that can 
sense the forces applied to the ground by the subject). Kinematic data are collected wirelessly using a 
12-camera motion capture system (MX-T40S, Vicon Motion Systems). Photographs are taken to 
enable visualization of anatomical landmarks as subjects perform tasks in a motion-capture space. 
Biometric data, including subject weight, height, limb-segment lengths and circumference are also 
collected to help interpret the aforementioned kinematic and kinetic data. 
 
Aim 3:  
 
To explore whether AMIs can serve as a bi-directional human-device interface and provide data that 
can advance science and enable precise prosthetic motor control, functional electrical stimulation 
(FES) is tested as a force feedback modality in an experimental setting. Only the AMI subjects and 
not the Non-AMI subjects participate in Aim 3. The experimental set-up involves the same pedal-
pushing task and FES paradigm implemented under COUHES protocol 1609692618 (Herr) with 
promising results and without any adverse effects.  
 
The pedal-pushing task involves instructing the subject to voluntary contract their AMI agonist 
muscles (in this case the LG, an ankle joint plantar flexor) and, based on the resulting prosthetic joint 
torque, applying FES to the AMI antagonist muscle (in this case the TA, an ankle joint dorsiflexor). 
Fine-wire electrode FES is selected for this task because the electrical current amplitude necessary for 
surface FES to elicit a meaningful muscle contraction is sufficiently high that crosstalk would 
interfere with the EMG electrodes that are required to implement prosthetic joint control. We default 
to electrodes affixed to the subjects’ skin as the primary mode of collecting EMG data. In the event 
that the surface EMG is not sufficiently robust to carry out the trials, we will move to fine-wire 
electrodes. Several factors will be used to evaluate surface EMG signal robustness, including the 
signal-to-noise ratio, the degree of inter-muscular crosstalk, signal quality degradation, and 
consistency of electrode placement. (Final implementation of AMIs for torque feedback will likely 
leverage implanted electrodes, which are being used in clinical trials but are not yet FDA-approved 
devices).  
 
Experienced clinicians (Matthew Carty and other IRB-approved clinicians) are involved in this 
research study and will contribute their clinical experience through locating target muscles within the 
subjects’ residual limbs, placing the surface and fine-wire electrodes for EMG and FES, and 
collecting clinical research data such as ultrasound images. Their involvements in this study are 
limited to their MIT roles as Visiting Scientists and other MIT Affiliations. They will NOT provide 
any medical advice or treatment within the scope of this study.  
 
Two single-use electrodes are provided pre-assembled with one 27-gauge needle in a sterile medical 
kit  (Motion Lab Systems part 000318-130-30). The kit comprises two electrodes threaded through the 
lumen of one needle with the electrodes’ tips crimped and bent backward at needle tip. The fine-wire 
electrodes are extremely fine, with a diameter of only 0.051 mm, and are acutely placed in the lower 
limb by an experienced clinician (Dr. Matthew Carty or another IRB-approved clinician). The subject 
volitionally moves the phantom or biological foot through DF, PF, EV, and IN motions, while the 

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clinician palpates the limb to identify the corresponding muscle of interest. Fine-wire electrodes are 
then inserted into each target muscle. Placement is verified electromyographically and via direct 
muscle stimulation; poorly-placed electrodes are removed and replaced. The needle is removed 
immediately after insertion, thereby placing the electrode tip in the muscle for the test session and 
allowing easy removal of the electrode as needed. In the event of two sequential trial days, the fine-
wire electrodes may remain in place overnight. If this is to happen, the clinician will apply local 
antibiotic to the area of each electrode insertion site and will bandage the limb. The subject will be 
instructed not remove the bandage, not to use the socket overnight, and not to bear weight on the 
residual limb while it is bandaged. The subject will also be instructed to avoid any circumstance in 
which the bandage would become wet (i.e. showering, swimming, etc.) and is provided with either 
crutches or a wheelchair to use for the overnight period. If a problem or concern should arise during 
the overnight period, the clinician will be available by telephone. In this scenario, the electrodes are 
removed at the end of the second day and are left in place for a maximum of two trial days, or one 
overnight period. 
 
The FES protocol involves delivering a periodic stream of mono- or bi-phasic electrical pulses to the 
muscle, causing it to contract. The FES protocol uses frequency-, current-, and pulse-width controlled 
medical grade equipment (DS-5, Digitimer) that is fully equipped with hard-stop settings. All 
stimulation settings will be maintained within historically safe limits and will be tuned to prevent 
subject discomfort. Relevant literature indicates that, for the fine-wire electrodes, average current 
densities not exceeding 10 microamperes/mm2 show no increased tissue trauma over that incurred by 
passive electrodes. Current densities will be kept well within this safe range. The safe range for 
transcutaneous stimulation (through the surface electrodes) is much larger: commercially available 
transcutaneous muscle stimulation systems deliver stimulation with parameters in the following 
ranges: 0-to-100 milliamperes, 1-to-100 Hz, and a pulse width of 30-to 300 microseconds. To find 
subject-specific comfort limits, we begin at low stimulation amplitude and pulse width, and slowly 
increase intensity until the subject reports reaching a limit of comfortable stimulation or until safe 
limits are reached, whichever happens first. The lower of this value and the historically safe limits 
described above will provide a hard-stop reference for stimulation settings.   
 
In one task, subjects are instructed to move their phantom ankle joint through a series of joint 
positions and stiffnesses (e.g. “move to 80% plantar flexion and stiffen to 50%”) in the absence of 
FES while EMG and ultrasound data are collected. In a second task, EMG and ultrasound data are 
collected from both the LG and the TA as FES is applied at various intensities to the TA, and the 
subject is asked to report the perceived phantom joint position and torque. In a third task, subjects are 
instructed to plantar flex the prosthetic ankle, thereby applying torque to a sensorized foot pedal. The 
prosthesis is mounted to an assembly that holds it in contact with the foot pedal, remote from the 
subject. Subjects are blindfolded and isolated from auditory input as they are asked to produce torque 
at varying levels of percent effort (i.e., 25, 50, 75, 100%), both with and without FES feedback. 
During task performance, EMG, goniometry, and ultrasongraphy data are collected from subjects’ 
affected and unaffected limbs.  
 
Additional information  
 
Subjects in the AMI intervention group will participate in 5 or 6 experimental sessions during the 
study, with 4 of these sessions requiring approximately 4 hours and the other 1 or 2 sessions requiring 

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up to 8 hours; Subjects in the Non-AMI control group will participate in 4 of the aforementioned 
sessions requiring approximately 4 hours each. Within a given session, individual performance tasks 
typically last for less than 5 minutes. The subject will be given rest breaks between trials. In addition, 
subjects may ask to rest or stop at any time. There is no time limitation between sessions.  
 
Subjects will use a prototype powered, 2-DoF ankle-foot prosthesis in place of their customary ankle-
foot prosthesis for the trial. The prosthesis has the capability of providing active neural control of both 
ankle and subtalar joints, and its controller can be adjusted through a wireless link. Prosthesis control 
settings may be modified by the researchers between trials or during a trial as the subject is walking. 
Subjects are given as much time as necessary to practice using the prosthesis before the data 
collection begins.  
 
3. Drugs and Devices. If the study involves the administration of an investigational drug that is not 
approved by the Food and Drug Administration (FDA) for the use outlined in the protocol, then the 
principal investigator (or sponsor) must obtain an Investigational New Drug (IND) number from the 
FDA. If the study involves the use of an approved drug in an unapproved way the investigator (or 
sponsor) must submit an application for an IND number. Please attach a copy of the IND approval 
(new drug), or application (new use.). 
If the study involves the use of an investigational medical device and COUHES determines the device 
poses significant risk to human subjects, the investigator (or sponsor) must obtain an Investigational 
Device Exemption (IDE) number from the FDA.  
Will drugs or biological agents requiring an IND be used? YES 
 
NO 
 
If yes, please provide details:       
 
Will an investigational medical device be used? YES 
 NO 
 
If yes, please provide details:  The FDA considers an investigation of a Non-Significant Risk device 
to have an approved IDE when an IRB concurs with the Non-Significant Risk determination and 
approves the study. MIT COUHES considers the 2-DoF prosthesis to be used in the current 
application to be a Non-Significant risk device here, as well as in another of our protocols 
#1609692618 (Herr). 
The battery-powered 2-DoF ankle-foot prosthesis comprises a pair of on-board motors that are used in 
parallel to actuate both the ankle and subtalar joints, and embedded sensors. The high-torque 
brushless motors reduce the required transmission ratio, resulting in a quiet, efficient, robust design. 
The 2-DoF ankle-foot prosthesis is attached to the subject's customary prosthetic socket.  
4. Radiation If the study uses radiation or radioactive materials it may also have to be approved by 
the Committee on Radiation Exposure to Human Subjects (COREHS). COUHES will determine if you 
need COREHS approval. 
Will radiation or radioactive materials be used? YES 
 
NO 
 
If yes, please provide details:       
Will any type of lasers be used 
YES 
 
NO 
 
If yes, please provide details:       
 
5. Diets 

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III. PERSONNEL  
 
IV. HUMAN SUBJECTS 
1.  Subjects (that will be consented for this study) 
A. Maximum number of subjects: 32 
Adults: 32                  Minors: 0 
B. Age(s): Minimum Age: 18 years   
Maximum Age:  65 years 
 
C.  Inclusion/exclusion criteria 
 
i.   What are the criteria for inclusion or exclusion? This NIH study calls for eleven 
participants in each of two groups - intervention and control. The intervention group includes 
AMI subjects who have previously undergone a BKA during which two AMIs are surgically 
reconstructed within the residual limb at the time of an experimental “AMI amputation”. 
Currently, AMI amputations are only being done under IRB approval at the Brigham and 
Women’s Hospital (BWH) by Dr. Matthew Carty. Carty is an MIT Visiting Scientist on our 
team and a Staff Surgeon at BWH. The control group includes Non-AMI subjects who have 
previously undergone standard BKA surgery, and are prospectively matched to an AMI subject 
based on the time since amputation, body habitus, and age. Additional study inclusion criteria 
include: (i) generally good health without any significant respiratory or other health problems 
that significantly impair normal ambulatory function, (ii) demonstration of full healing at the 
amputation site, which is generally achieved approximately three months following amputation, 
(iii) proficient use of a standard lower extremity prosthesis, and (iv) capability to ambulate with 
variable cadence at a “K” level of at least K3 to K4). Tobacco users, pregnant women, and 
children are excluded. 
 
ii.   Are any inclusion or exclusion criteria based on age, gender, or race/ethnic origin?  
If so, please explain and justify. Our subject criteria are non-exclusive in that we consider 
participants of any sex/gender, race, and/or ethnic orientation.  
 
iii.   Please explain the inclusion of any vulnerable population (e.g. children, cognitively 
impaired persons, non-English speakers, MIT students), and why that population is being 
studied.  
Children are excluded from the AMI subject cohort in this study due to the fact that pediatric patients 
are not eligible to undergo the required precursor surgical procedure. The AMI surgery is an 
 
Will special diets be used? YES 
 
NO 
 
If yes, please provide details      
Fill out the personnel list at the end of this form. If the personnel list is not included, the 
application will be returned to you. 

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experimental operation that currently is only being done with IRB approval at the BWH, and the 
BWH is an adult-only facility; pediatric patients are therefore not approved to undergo the AMI 
surgery. Due to the matching criteria that have been established for the identification of Non-AMI 
control subjects in this study, which include patient age, children are also excluded from the Non-
AMI subject cohort. 
 
Due to the matching criteria with AMI and non-AMI cohorts, children are also excluded from the 
intact subject cohort. 
 
 
2.  Subject recruitment Identification and recruitment of subjects must be ethically and legally 
acceptable and free of coercion. Describe below what methods will be used to identify and recruit 
subjects. Attach any and all recruitment documents associated with the protocol (i.e. flyers, e-mails, 
advertisements, etc.) 
The subjects in the intervention group will be drawn from the pool of patients who have undergone an 
experimental “AMI Amputation” at the BWH, as described above, in the Inclusion Criteria section. 
The BWH IRB-approved protocol covering the AMI Amputation includes as an enrollment criterion 
the willingness to undergo testing at MIT under a separate protocol approved by MIT’s IRB  
(COUHES) because some of the data needed to help validate the surgery is being collected at MIT. 
The subjects in the control group will be drawn from patients who have undergone a standard BKA 
procedure at either the BWH or another hospital. Recruitment will be done via flyers, word of mouth, 
referrals, and external inquiries that our research group receives from the general public. We shall 
directly contact individuals who have already worked on our studies, certified prosthetists, and 
rehabilitation centers.  We will leverage the professional networks of the PI, Herr (an academic 
researcher with expertise in prosthetic devices and neural interfaces, and who has undergone BKA 
bilaterally), and MIT team member/BWH staff surgeon Carty (a physician-scientist and expert in 
plastic & reconstructive surgery). 
 
Potential participants in the MIT study will receive our materials (a Letter and Information Sheet). Dr. 
Lisa Freed or another member of our MIT study team will meet with each potential participant 
individually to review the study protocol, and to have any questions answered.  If the individuals 
decide to participate in the study, they will be asked to sign our Informed Consent Form.  
3.  Informed consent. Documented informed consent must be obtained from all participants in 
studies that involve human subjects. You must use the templates available on the COUHES website to 
prepare these forms. Draft informed consent forms must be returned with this application. Under 
certain very limited circumstances, COUHES may waive the requirement for informed consent. If you 
are requesting a waiver or alteration of consent, please attach the Waiver or Alteration of Informed 
Consent Request form.  
 [Attach informed consent form(s) with this application.] 
4. Subject compensation. Payment must be reasonable in relation to the time and trouble associated 
with participating in the study. It cannot constitute an undue inducement to participate. 
Describe all plans to pay subjects in cash or other form of payment (i.e. gift certificate)  
Subjects will be paid $20 per hour for their involvement in the experiment. This may change if 

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necessary for recruitment. Should a subject withdraw from the study for any reason, they will be 
compensated for the time they did participate. 
Will subjects be reimbursed for travel and expenses? 
In-town travel expenses will not be reimbursed. 
 
5.  Potential risks. A risk is a potential harm that a reasonable person would consider important in 
deciding whether to participate in research. Risks can be categorized as physical, psychological, 
sociological, economic and legal, and include pain, stress, invasion of privacy, embarrassment or 
exposure of sensitive or confidential data. All potential risks and discomforts must be minimized to the 
greatest extent possible by using e.g., appropriate monitoring, safety devices and withdrawal of a 
subject if there is evidence of a specific adverse event. 
What are the risks / discomforts associated with each intervention or procedure in the study? 
(1) 
Risk of prosthetic device malfunction. Since the powered 2-DoF prosthesis is an active device, 
there is a risk of malfunction. 
(2) 
Risk of skin discomfort. Since surface EMG electrodes and other wearable sensors are applied 
using adhesive, there is a chance of discomfort upon sensor application or removal, and a chance of 
leaving adhesive residue behind on the subject’s skin or clothing. 
(3) 
Risk of fall. As is the case when any person uses a prosthetic device for walking or terrain 
traversal, there is a risk of falling.  
(4) 
Risk of fatigue. There is a risk of becoming fatigued during the study. 
(5) 
Risk of muscle discomfort. There is a risk of muscle discomfort when the clinician places the 
fine-wire electrodes, and during the muscle stimulation study which involves the use of small, 
controlled bursts of electricity. Sensations associated with muscle stimulation are typically described 
as “tingly” and we expect you to feel your muscle contracting. 
(6) 
Risk of infection. There is a risk of infection if fine-wire electrodes are left in place overnight. 
(7) 
Risk of confidentiality breach. There is a risk that data confidentiality may be compromised.  
What procedures will be in place to prevent / minimize potential risks or discomfort? 
(1) The individuals developing the prosthesis make every effort to reduce the risk of prosthetic device 
malfunction. In the case that a malfunction occurs, then the prosthesis defaults from an active state to 
an inactive state and becomes nearly rigid and much like a standard passive ankle-foot prosthesis. Bob 
Emerson, a certified prosthetist who directs A Step Ahead Prosthetics in Burlington, MA, is a long-
time professional colleague of the PI and will provide expert advice and assistance as needed.    
(2) Subjects are given an option to wear clothing provided by the lab. Alcohol wipes are offered 
to help remove adhesive residue from subjects’ skin or clothing. 
(3) To protect against risk of falling, our lab is equipped with handrails, parallel bars and a 
safety harness. There will be a "spotter" standing next to the subject at all times during standing 
or ambulatory trials. 
(4) To protect against risk of fatigue, subjects are given breaks between trials, and may ask to 
take a break or ask to stop at any time. 
(5) To minimize muscle discomfort, an experienced clinician will place the fine-wire electrodes to 
mitigate the discomfort associated with this procedure. During muscle stimulation, all stimulation 
settings are within historically safe limits and tuned for each subject. We begin at low intensity, and 
slowly increase intensity until the subject tell us we have reached a limit of comfortable stimulation or 
until we reach the limit of what is historically safe (whichever comes first). Once we determine this 
limit, we set up the stimulation system to ensure that this limit is never surpassed. Participants are 

                                                         COUHES - STANDARD APPLICATION – ver. 3/31/2017 - 
 
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instructed to let us know if they need to take a break or if they want us to remove the electrodes or 
stop the stimulation. Participants are instructed to let us know immediately if the muscle stimulation 
becomes at all painful, in which case we will stop the study. 
(6) To protect against risk of infection, sterile fine-wire electrodes are placed by an experienced 
clinician. In the event that sessions are scheduled over two consecutive days, the fine-wire electrodes 
may remain in place overnight. In this scenario, the clinician applies local antibiotic ointment to the 
insertion points and bandages the limb. The subject is instructed not to remove the bandage, not try to 
use the socket or bear weight on the limb, and, in the event she/he has any problems or concerns with 
the electrodes overnight, that the clinician will be available by telephone. To date, there were no 
adverse effects of fine-wire electrode studies during COUHES protocol (1609692618-Herr), under 
which the experiments performed were identical to those proposed herein. 
(7) To further prevent / minimize potential risks or discomfort related to the fine-wire electrode 
studies we will involve an independent safety monitor. Dr. Rickard Braanemark M.D., Ph.D. has 
agreed to being included. Dr. Braanemark is chosen for his significant clinical contribution to and 
expertise in the safe implementation of human-device interfaces for amputee populations. He will 
receive and review our progress and safety data for these studies involving fine-wire electrodes and 
provide the Principal Investigator, Dr. Herr, with recommendations for preventing/mitigating risks. 
(8) Although efforts are made to ensure that the human subject data being collected are stored in a 
secure manner, and labeled using a numerical code rather than a subject’s name, there is a risk that 
data confidentiality could be compromised. However, it is not anticipated that release of these data 
poses a significant risk to the subjects. 
6.  Potential benefits 
What potential benefits may subjects receive from participating in the study? 
There are no immediate benefits from participating in this study. The prosthetic device and system 
components we are using are prototypes and are not immediately available. 
What potential benefits can society expect from the study? 
The plan outlined in this study uniquely combines leading-edge technologies in surgery, wearable 
robotic devices, prosthetic control strategies, and device-based afferent feedback. Recent clinical 
developments in the fields of reconstructive surgery (e.g., targeted muscle reinnervation; regenerative 
peripheral nerve interfaces) and implantable devices for neuro-stimulation and recording provide 
evidence in support of the importance of knowledge to be gained. The technologies proposed herein 
are next steps toward affording prosthesis wearers new motor and sensory capabilities that can 
improve the health, productivity, independence, and quality of life of individuals living with limb loss. 
The potential benefits of this study to society outweigh the minimal risks that are involved. 
7.  Data collection, storage, and confidentiality 
How will data be collected? 
The data from the 2-DoF prosthesis, the motion-capture system, EMG electrodes, and ultrasound 
transducers are collected either wirelessly or non-wirelessly and securely stored on local computers in 
the MIT Media Lab Biomechatronics Group.  
Is there audio or videotaping? YES 
 
NO 
 Explain the procedures you plan to follow. 
We record photographs, videotapes, and audiotapes in digital format for analysis and development 
purposes. These data will be stored on password-protected computers in the MIT Media Lab 

                                                         COUHES - STANDARD APPLICATION – ver. 3/31/2017 - 
 
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Biomechatronics Group and in the MIT Media Lab network hub folder, which is managed by the 
Media Lab IT department and individually password-protected. Access to these materials is limited to 
IRB-trained investigators associated with this study. If photos, video, audio or video data are 
published, reported, or used for educational purposes, subject identity will be protected or disguised 
by blurring or blocking the face. If any other uses of these data are contemplated, subjects will be 
contacted by phone, mail or Email requesting specific their consent from to do so.  
Will data be associated with personal identifiers or will it be coded? 
Personal identifiers 
 
Coded  
 Explain the procedures you plan to follow. 
All data and files particular to a subject will be anonymized (each subject will be assigned a numerical 
code for naming files e.g. subject1_month_day_year). Only the Principal Investigator (Dr. Herr) and 
Key Personnel (Dr. Freed and Dr. Carty) will have access to the coded data linking the subjects’ 
names with their numbers. These individuals will store the code, separately from the data itself, on 
password-protected computers in the MIT Media Lab Biomechatronics Group. 
Where will the data be stored and how will it be secured? 
Study data will be stored on password-protected computers in the MIT Media Lab Biomechatronics 
Group (MIT E14-274 and E15-463). Study data will also be stored in the MIT Media Lab network 
hub folder, which is managed by the Media Lab IT department and individually password-protected. 
Only Biomechatronics group MIT personnel with valid IRB training certificates will have access to 
this folder. Individuals who no longer have valid IRB certificates, or who leave the group, will no 
longer be granted access this folder.  
What will happen to the data when the study is completed? 
The data will remain in the MIT Media Laboratory network secure server for processing and reference. 
Upon subject request, digital photos and videos can deleted from the data server once study is 
completed. The code linking subjects’ names with their numbers will remain accessible only to the 
Principal Investigator. If results of the research are published or reported, no information will be 
included that can reveal the subject’s identity. If used in reports, publications, or for other educational 
purposes, the data will not include any information that could reveal a subject's identity. If videos 
photos are used in reports, publications, or for other educational purposes, subject identity will be 
protected. If any other uses of these data are contemplated, subjects will be contacted by phone, mail or 
Email requesting their specific consent to do so.  
 
Can data acquired in the study affect a subject’s relationship with other individuals (e.g. 
employee-supervisor, patient — physician, student-teacher, family relationships)? 
No 
8.  Deception Investigators must not exclude information from a subject that a reasonable person 
would want to know in deciding whether to participate in a study. 
Will information about the research purpose and design be withheld from subjects? 
YES 
 
NO 
  
 
If YES, explain and justify. Not Applicable 

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9.  Adverse effects. Serious or unexpected adverse reactions or injuries, and/or unanticipated 
problems involving risks to subjects or others must be reported to COUHES within 48 hours. Other 
adverse events should be reported within 10 working days. 
What follow-up efforts will be made to detect any harm to subjects, and how will COUHES be 
kept informed? 
Contact information for the Principal Investigator and Key Personnel will be provided to the subjects 
for the purpose of reporting any adverse effect or injury. These study personnel will report any 
adverse events to COUHES within the required time frames. 
 
 
10.   Health Insurance Portability and Accountability Act (“HIPAA”). If your study (i) involves 
individually identifiable health information and (ii) is sponsored by MIT Medical, an MIT Health Plan 
or another healthcare provider, then you must complete the questions below because HIPAA likely 
applies to your study.  For more information regarding the applicability of HIPAA to human subjects 
research, please click here.  
Do you plan to obtain, use or disclose identifiable health information in connection with your 
research study? 
YES 
 
NO 
 
If YES, then all participants must complete an Authorization for Release of Protected Health 
Information Form. Please attach a copy of this draft form. You must use the template available on the 
COUHES website. 
 
Alternatively, COUHES may grant a Waiver of Authorization in certain very limited circumstances 
when use of individually identifiable health information would pose only minimal risk to study 
participants (among other requirements).  For additional information regarding whether your study 
might qualify for a waiver, please click here. 
Are you requesting a Waiver of Authorization? 
YES 
 
NO 
 
If YES, explain your rationale for concluding that: (i) use of participant health information poses no 
more than minimal risk; (ii) the research could not be conducted without the waiver and (iii) the 
research could not be conducted without the information.  In addition, please explain your plan for (i) 
ensuring the participant health information is not improperly used or disclosed either within MIT or 
to any outside third parties and (ii) destroying identifiers at the earliest possible opportunity. 
      
Will the health information you will receive for use in this study be de-identified? 
YES 
 
NO 
 
If YES, you do not need to obtain a signed Authorization for Release of Protected Health Information 
Form from study participants.  Note, however, that if you receive identifiable participant health 
information that you plan to convert into de-identified information for use by other researchers, then 
you must obtain a signed Authorization for Release of Protected Health Information Form from each 
participant before receiving their identifiable health information for use in your study.   
      

                                                         COUHES - STANDARD APPLICATION – ver. 3/31/2017 - 
 
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V.  INVESTIGATOR’S ASSURANCE 
Will you be using or disclosing a limited data set? 
YES 
 
NO 
 
If YES, and you will only receive participant health information in limited data set form, then you do 
not need to obtain a signed Authorization for Release of Protected Health Information Form from 
study participants. You must complete a formal data use agreement with the party from whom you will 
receive the limited data set information in order for your application to be approved. 
 
 If YES, and you will receive identifiable participant health information that you plan to convert into 
limited data set form for use by other researchers, then you must obtain a signed Authorization for 
Release of Protected Health Information Form from each participant before receiving their 
identifiable health information for use in your study. You must complete a formal data use agreement 
in order for your application to be approved. 
I certify the information provided in this application is complete and correct. 
I understand that I have ultimate responsibility for the conduct of the study, the ethical 
performance of the project, the protection of the rights and welfare of human subjects, and 
strict adherence to any stipulations imposed by COUHES 
I agree to comply with all MIT policies, as well all federal, state and local laws on the protection 
of human subjects in research, including: 
• ensuring all study personnel satisfactorily complete human subjects training; 
• performing the study according to the approved protocol; 
• implementing no changes in the approved study without COUHES approval; 
• obtaining informed consent from subjects using only the currently approved consent 
form; 
• protecting identifiable health information, to the extent required by law, in accordance 
with HIPAA requirements; and 
• promptly reporting significant or untoward adverse effects. 
 
Signature of Principal Investigator  
 
Date  
 
 
Print Full Name and Title  
  
 
Signature of Department Head  
 
Date  
 
 
Print Full Name and Title  
  
By signing this form you confirm a scientific review of the proposed research has been conducted, 
and that the proposed research is of scientific and scholarly validity. 

                                                         COUHES - STANDARD APPLICATION – ver. 3/31/2017 - 
 
- 17 - 
 
The electronic file should be sent as an attachment to an e-mail: couhes@mit.edu. In addition, two 
single sided hard copies (one with original signatures) should be sent to the COUHES office: 
Building E25-Room 143B. 

                                                         COUHES - STANDARD APPLICATION – ver. 3/31/2017 - 
 
- 18 - 
 
 
Massachusetts Institute of Technology 
Committee on the Use of 
Humans as Experimental Subjects 
Protocol # 
(assigned by 
COUHES) 
      
 
PERSONNEL LIST 
 
This form must be attached to both standard and exempt form applications. Any application submitted 
without a completed personnel list will be returned to you.  
Personnel is defined as anyone who plays a role in research involving human subjects, including direct 
contact, indirect involvement, analysis of data, blood or tissue samples. This extends to principal 
investigators, associate investigators, student investigators, study coordinators, visiting scientists, 
consultants, laboratory technicians and assistants. 
All study personnel must be listed below. This listing must include contact information, a brief statement 
of qualifications and their study role.  
 
Important note: all study personnel are required to complete Human Subject Training before work 
begins on the project. Proof of training must be attached for non-affiliates. (Documentation from 
collaborating institutions may be submitted in lieu of training certificates.)  
 
A. MIT AFFILIATES 
Personnel name, and e-mail 
address 
Qualifications: 
Describe briefly 
Study role(s): 
Check if 
obtaining 
consent 
Contact* 
Name: Dr. Maria Ramos 
Gonzalez 
Email: mariarg@media.mit.edu 
PhD in Mechanical 
Engineering, 
Distinguished 
Postdoctoral Fellow 
Key personnel, serves as 
contact person, prepares NIH 
reports, assists in overall 
research 
 
Name: Professor Hugh Herr 
Email: hherr@media.mit.edu 
PhD, Professor, 
MIT Media Lab 
Biomechatronics 
Group Director      
Principal Investigator. 
Oversees all research activities 
and ensures that all research is 
properly conducted 
 
 
Name: Dr. Matthew J. Carty 
Email: mcarty@partners.org 
MD, MIT Visiting 
Scientist, Staff 
Surgeon, BWH and 
Faulkner Hospitals; 
& HMS Associate 
Professor of 
Surgery 
Key Personnel. Places the fine-
wire electrodes and takes part 
in all research activities    
 
Name: Seong Ho Yeon 
Email: syeon@mit.edu 
PhD Candidate,  
MIT-MAS  
Assists in conducting research 
 

                                                         COUHES - STANDARD APPLICATION – ver. 3/31/2017 - 
 
- 19 - 
Name: Tsung-Han (Robin) 
Hsieh 
Email: thhsieh@mit.edu 
PhD Candidate,  
MIT-MAS  
Assists in conducting research 
 
Name: Tony Shu 
Email: tonyshu@mit.edu 
PhD Candidate,  
MIT-MAS 
Assists in conducting research 
 
Name: Dr. Gabriel N. Friedman 
Email: 
gfriedman1@mgh.harvard.edu 
 
or  GNF1@mit.edu 
MD, a Surgeon at 
the Massachusetts 
General Hospital 
Places fine-wire electrodes and 
takes part in all research 
activities. 
 
Name: Hyungeun Song 
Email: hngnsong@mit.edu 
Postdoctoral 
Associate 
Assists in conducting research 
 
Name: Samantha Gutierrez-
Arango 
Email: samga@media.mit.edu 
SM Student, MIT-
MAS 
Assists in conducting research  
 
Name: Junqing Qiao 
Email: Qiaoj@media.mit.edu 
SM Candidate  
Assists in conducting research 
 
Name: Dr. Dun-Wei Huang 
Email: dhuang11@mit.edu 
MD Clinician at 
MGH 
Clinician and research affiliate, 
place the fine-wire electrodes, 
and take part in all research 
activities 
 
Name: Dr. Wen Chih Liu 
Email: liuandy@mit.edu 
MD Clinician at 
MGH 
Clinician and research affiliate, 
place the fine-wire electrodes, 
and take part in all research 
activities 
 
*NOTE: Please designate a person with whom COUHES should communicate regarding issues or 
questions about the protocol.   
 
 
B. NON-MIT AFFILIATES 
Name, affiliation, and e-
mail address 
Qualifications: 
Describe briefly 
Study role(s): 
Check if 
obtaining 
consent 
Check if 
human 
subject 
training 
has been 
completed 
Name:       
Email:       
      
      
 
 
Name:       
Email:       
      
      
 
 
Name:       
Email:       
      
      
 
 
Name:       
Email: