Functional Performance Evaluation of the Northwestern University Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons With Transfemoral Amputation
Phase: NA
Conditions: Amputation, Artificial Limbs
Sponsor: Northwestern University

 
 
 
 
 
Functional Performance Evaluation of NU-FlexSIV Socket 
NCT02678247 
March 14 2019 

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 1 of 28
Revised Template: November 10, 2014
PROTOCOL TITLE:
Functional Performance Evaluation of the Northwestern University Flexible Sub-
Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral Amputation 
PRINCIPAL INVESTIGATOR:
Stefania Fatone, PhD, BPO(Hons)
Department of Physical Medicine and Rehabilitation
312-503-5717
s-fatone@northwestern.edu
VERSION NUMBER:
Version 4.0
VERSION DATE:
March 14, 2019
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 2 of 28
Revised Template: November 10, 2014
Table of Contents
1.0
Objectives .................................................................................................................3
2.0
Background...............................................................................................................3
3.0
Inclusion and Exclusion Criteria ..............................................................................3
4.0
Study-Wide Number of Subjects..............................................................................3
5.0
Study-Wide Recruitment Methods ...........................................................................3
6.0
Multi-Site Research ..................................................................................................4
7.0
Study Timelines........................................................................................................4
8.0
Study Endpoints........................................................................................................4
9.0
Procedures Involved .................................................................................................4
10.0
Data and Specimen Banking.....................................................................................5
11.0
Data and Specimen Management .............................................................................5
12.0
Provisions to Monitor the Data to Ensure the Safety of Subjects.............................6
13.0
Withdrawal of Subjects*...........................................................................................6
14.0
Risks to Subjects*.....................................................................................................6
15.0
Potential Benefits to Subjects ...................................................................................7
16.0
Vulnerable Populations.............................................................................................7
17.0
Community-Based Participatory Research...............................................................7
18.0
Sharing of Results with Subjects ..............................................................................8
19.0
Setting.......................................................................................................................8
20.0
Resources Available .................................................................................................8
21.0
Prior Approvals.........................................................................................................9
22.0
Recruitment Methods................................................................................................9
23.0
Local Number of Subjects ........................................................................................9
24.0
Confidentiality ........................................................................................................10
25.0
Provisions to Protect the Privacy Interests of Subjects ..........................................10
26.0
Compensation for Research-Related Injury............................................................10
27.0
Economic Burden to Subjects.................................................................................10
28.0
Consent Process......................................................................................................10
29.0
Process to Document Consent in Writing...............................................................13
30.0
Drugs or Devices ....................................................................................................14
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 3 of 28
Revised Template: November 10, 2014
1.0
Objectives
1.1
Specific aims:
This proposal aims to provide evidence to support use of the NU-FlexSIV Socket 
for persons with transfemoral (above-the-knee) amputation. This will be 
accomplished by undertaking a prospective, assessor-blinded randomized cross-
over trial comparing comfort and functional performance with the NU-FlexSIV 
Socket to the standard-of-care ischial containment socket in persons with 
unilateral transfemoral amputation. 
The primary aims of the study are:
Aim 1: To demonstrate if the NU-FlexSIV Socket is more comfortable than the 
IC socket.
Aim 2: To demonstrate if the NU-FlexSIV Socket results in better functional 
performance than the IC socket.
Aim 3: To demonstrate the NU-FlexSIV Socket will result in better quality of life 
and “satisfaction with device” (i.e. prosthesis) than the IC socket.
1.2
Hypotheses to be tested:
Hypothesis 1: We hypothesize that the NU-FlexSIV Socket will provide increased 
comfort compared to the ischial containment socket.
Hypothesis 2a: We hypothesize that the NU-FlexSIV Socket will allow greater 
prosthetic side hip range of motion, in particular increased hip 
extension, leading to increased prosthetic side step length and 
hence walking speed compared to the ischial containment socket. 
Hypothesis 2b: We hypothesize that step width and lateral trunk flexion over the 
prosthetic limb will not differ between the NU-FlexSIV Socket and 
ischial containment socket.
Hypothesis 2c: We hypothesize that the NU-FlexSIV Socket will result in faster 
times to perform the 5-Times Rapid Sit-to-Stand Test, Four Square 
Step Test and T-Test of Agility compared to the ischial 
containment socket.
Hypothesis 3: We hypothesize that the NU-FlexSIV Socket will result in better 
health-related quality of life and satisfaction with device as 
assessed using the OPUS compared to the ischial containment 
socket.
2.0
Background
2.1
Relevant prior experience and gaps in current knowledge:
Current prosthetic sockets restrict function, lack comfort and cause secondary 
health problems. Although designed to support the body and enable effective 
biomechanical load transfer during walking and other activities, prosthetic sockets 
interface with residual limb tissues that are neither accustomed nor well-suited to 
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 4 of 28
Revised Template: November 10, 2014
the high pressure and shear loading that occurs during ambulation with a 
prosthesis. Despite high daily use (>12 hours), lack of socket comfort is the most 
common complaint of prosthesis users. Prosthetic sockets lead to many issues due 
to high pressure, shear stress, temperature and moisture, all of which are 
exacerbated in highly active persons with amputation and those with irregular 
residual limbs (e.g. due to traumatic amputation that have irregular shape, 
extensive scarring, invaginations, skin grafts, painful neuromas, etc.). Residual 
limb skin problems include cysts, calluses, verrucous hyperplasia, allergic 
reactions, and bacterial or fungal infections. Residual limb skin problems have 
been reported by 25% to 63% of persons with amputation in the general 
population and problems have a negative influence on ability to perform 
household tasks, prosthesis use, social functioning, and participation in sports.
Sub-ischial sockets challenge conventional understanding of the biomechanics of 
transfemoral sockets, especially regarding coronal plane stability. In able-bodied 
walking, the hip abductors, primarily the gluteus medius, maintain pelvic control 
during single limb stance. Contraction of the hip abductors counters the moment 
created about the hip by the body center of mass and helps to keep the pelvis level 
and trunk upright. When the abductors are compromised, lateral trunk lean over 
the stance limb may be observed (often referred to as a Trendelenberg gait). In the 
IC socket, skeletal contact over the medial aspect of the ischium and greater 
trochanter, create a medial-lateral ‘skeletal lock’ for coronal plane control. For 
sub-ischial sockets, these forces still remain but the socket geometry believed 
necessary to control them is gone.
The mechanism by which transfemoral prosthetic sockets provide coronal plane 
stability during gait has been recently debated. Dillon (2007) stated that in an IC 
socket coronal plane pelvic stability is derived almost entirely from containment 
of the ischium and ischial ramus and that when containment is not achieved, 
coronal plane stability is poor. Dillon (2007) has also argued that the ability of 
any socket to provide coronal plane stability relies in part on the soft tissue, 
especially the adductors, being compressed to increase stiffness. Compression of 
soft tissues may occur to a larger extent when vacuum-assisted suspension is used 
because both the liner and socket are considerably under-sized, potentially 
contributing to coronal plane stability.
In contrast to existing transfemoral sockets, the NU-FlexSIV Socket does not 
impinge on the pelvis because it has lower proximal trim lines; is highly flexible 
allowing muscles to move comfortably within the socket as they contract during 
activity and improving sitting comfort; and is held securely to the residual limb by 
suction from a vacuum pump as well as compression from the liner and socket 
being undersized, making for a firmer connection to the prosthesis.
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 5 of 28
Revised Template: November 10, 2014
2.2
Relevant preliminary data:
Our technique requires specific rectifications of the positive model which we have 
quantified using rectification mapping (Figure 1). 
Preliminary tests of individuals using sub-ischial sockets illustrate that they do not 
use significant trunk lean during walking (Figure 2). 
Figure 1 Modification pattern averaged across 30 pairs of rectified and 
unrectified casts of transfemoral residual limbs.
Figure 2 Midstance posture of subject wearing a sub-ischial socket (a). Lateral 
trunk flexion data comparing IC and sub-ischial sockets (b).
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 6 of 28
Revised Template: November 10, 2014
We recently described the relationship between IC, tissue loading and socket 
comfort (Fatone, Dillon et al. 2015). Using a small randomized cross-over trial, it 
was shown that with the ischium contained, tissue loading did not influence 
socket comfort. Sockets without IC required high tissue loading to be as 
comfortable as those with IC, while suboptimal tissue loading compromised 
comfort.
The objective of our FY09 PRORP Technology Development Award from DOD 
was to develop a highly flexible sub-ischial prosthetic socket with vacuum-
assisted suspension for highly active persons with transfemoral amputation. 
Hence, we used engineering analysis to characterize the socket, explored 
advanced manufacturing approaches for socket fabrication, characterized the 
function of commercially available vacuum pumps, designed and tested a hybrid 
mechanical/electrical pump, quantified the process of socket rectifications, and 
developed education materials to help teach this technique to other prosthetists. 
Additionally, preliminary evaluation of the NU-FlexSIV Socket with highly 
active persons with unilateral transfemoral amputation is underway at the Center 
for the Intrepid/Brooke Army Medical Center. To date, five of the six subjects we 
plan to test have been recruited for the study, with one subject having completed 
the entire protocol and four in process. At this point, subjects’ responses indicate 
that they prefer the NU-FlexSIV Socket to their usual IC socket. One common 
benefit reported was the ability to sit without the socket beneath the ischium. 
Objective outcome measures likewise support the superiority of the NU-FlexSIV 
Socket. Data from the first subject to complete the full testing protocol (Figure 3) 
showed that the NU-FlexSIV Socket resulted in 10° greater active peak hip 
flexion, 13° greater active peak hip extension and 9° more hip abduction; sit-to-
stand time improved by almost 2 seconds; hip range of motion increased 20.6°; T-
Test performance improved by 4 seconds (16%). Across 5 walking trials, hip 
range of motion increased 12.5° ± 1.2° with the NU-FlexSIV Socket and the hip 
was able to achieve extension during walking. Additional case data from two non-
military persons with transfemoral amputation is consistent with these findings. 
2.3
Scientific or scholarly background for rationale and significance of the 
research:
To our knowledge, only one other group has demonstrated the efficacy of 
brimless (i.e., subischial) sockets for persons with transfemoral amputation (Kahle 
Figure 3 Performance data from first subject to complete testing.
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 7 of 28
Revised Template: November 10, 2014
and Highsmith 2013, Kahle and Highsmith 2014). Using a small (n=10) 
randomized cross-over trial, gait and balance were found to be equivalent between 
sockets (IC and brimless) but subjects preferred the brimless socket. In this case, 
it appears that a rigid IC socket with a flexible brim was cut down to form the 
brimless socket. Similar improvements in comfort along with better functional 
outcomes may occur with sockets that are deliberately designed to be subischial, 
such as the NU-FlexSIV Socket.
3.0
Inclusion and Exclusion Criteria
3.1
Screening for eligibility:
Subjects interested in participating in this study will be screened for eligibility 
against the inclusion/exclusion criteria by one of the Certified Prosthetists through 
a clinical exam that assesses the status of the residual limb and walking ability.
3.2
Criteria that define who will be included or excluded in the study:
To participate in the study subjects must:

be older than 21 years,

have a unilateral transfemoral amputation,

have used a prosthesis for two or more years,

have a residual limb that is stable in volume and free from any 
wounds,

be physically fit enough to participate in the performance tests, 
effectively making them a Medicare Functional Classification Level 
of K3 (the ability or potential for ambulation with variable cadence - 
a typical community ambulator with the ability to traverse most 
environmental barriers and may have vocational, therapeutic, or 
exercise activity that demands prosthetic use beyond simple 
locomotion) or K4 (the ability or potential for prosthetic ambulation 
that exceeds basic ambulation skills, exhibiting high impact, stress, 
or energy levels - typical of the prosthetic demands of the child, 
active adult, or athlete),

have no previous experience of the sub-ischial socket, and

be expected to be able to complete all visits for the duration of the 
protocol.
Subjects will be excluded if:

they have a residual limb femur of less than 5 inches,

present with any other co-morbidities that affect function, 
including neurologic abnormalities, e.g. neuropathic pain that 
would interfere with the study, and/or

they do not speak and read English.
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 8 of 28
Revised Template: November 10, 2014
3.3
Individuals from the following populations will be excluded: 

Adults unable to consent

Individuals who are not yet adults (infants, children, teenagers)

Pregnant women

Prisoners
4.0
Study-Wide Number of Subjects
4.1
Total number of subjects to be accrued across all sites for multi-site 
trial:
N/A
5.0
Study-Wide Recruitment Methods
5.1
When, where, and how potential subjects will be recruited:
A convenience sample of participants will be recruited primarily by referral 
of prosthetists in the Chicago-land area. We will recruit both Veteran and 
non-Veteran subjects to participate in this study. With the assistance of Dr. 
Marc Applebaum, chief of Physical Medicine and Rehabilitation at the Jesse 
Brown VA Medical Center we will identify and recruit Veterans with 
unilateral transfemoral amputation. Non-Veteran participants will be 
recruited from the general community with the assistance of our clinical 
collaborators at Scheck & Siress Prosthetics, Orthotics and Pedorthics, the 
largest provider of orthotic and prosthetic clinical care in the Chicagoland 
area with over 40 certified and licensed orthotic and prosthetic practitioners 
and twelve accredited facilities.
As a secondary source of recruitment, information about the study will be 
circulated to other prosthetists in the midwest via the Midwest Chapter of 
the American Academy of Orthotists and Prosthetists, whose members 
include prosthetists practicing in Illinois, Indiana and Wisconsin; via 
amputee support groups and amputee sporting groups in the Chicago land 
area; as well as via the NUPOC and Scheck & Siress websites and facebook 
pages.
5.2
Methods to be used to identify potential subjects:
Subjects will be identified primarily by referral from local area prosthetists.
5.3
Materials used to recruit subjects:
Study flyer included in eIRB+ application.
6.0
Multi-Site Research
6.1
Processes to ensure communication among sites for multi-site study:
N/A
6.2
Method for communicating with participating sites:
N/A
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 9 of 28
Revised Template: November 10, 2014
7.0
Study Timelines
7.1
Duration of an individual subject’s participation in the study, duration 
anticipated to enroll all study subjects, estimated date for the 
investigators to complete primary analyses:

Subjects will participate in this study for approximately 14 weeks 
(Figure 4).

It is anticipated that we will recruit 10 subjects per year for each of the 
first 3 years and 5 subjects in the 4th year of the clinical trial.

Data will be processed and analyzed for the final subject in month 33 
of the study.
8.0
Study Endpoints
8.1
Primary and secondary study endpoints:
Our primary end point, socket comfort, will be assessed using the Socket 
Comfort Score (Hanspal, Fisher et al. 2003) an ordinal scale where 0 = the 
most uncomfortable socket fit imaginable and 10 = the most comfortable 
socket fit. Poor socket comfort is one of the most common issues 
experienced by prosthesis users. Like pain, comfort is subjective and 
difficult to measure. Therefore, pain-measurement methods such as the 
numerical rating scale (NRS) were used as models for quantifying and 
communicating socket comfort. The Socket Comfort Score asks the standard 
question, “On a 0 to 10 scale, if 0 represents the most uncomfortable socket 
fit you can imagine, and 10 represents the most comfortable socket fit, how 
would you score the comfort of the socket fit of your artificial limb at the 
moment?”
Our secondary end point, functional performance, will be assessed using 
instrumented motion analysis to record biomechanics of walking at different 
speeds, a 5-time Rapid Sit-to-Stand Test (RSTS), Four-Square-Step Test 
(FSST), and T-test of Agility. The 5-time Rapid Sit-to-Stand Test, Four-
Figure 4 Study design and protocol.
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 10 of 28
Revised Template: November 10, 2014
Square-Step Test, and T-test of Agility are standardized clinical measures of 
performance. We will also assess patient reported functional performance, 
quality of life and satisfaction with device using the Orthotic and Prosthetic 
Users’ Survey (OPUS) (Heinemann, Bode et al. 2003).
8.2
Primary or secondary safety endpoints:
N/A
9.0
Procedures Involved
9.1
Study design:
The clinical trial will be an assessor-blinded prospective randomized cross-
over trial wherein participants with unilateral transfemoral amputation will 
be randomized to using one of two socket conditions (i.e., sub-ischial or 
ischial containment) before crossing over to the other socket condition. 
Random allocation (computer-generated) utilizing blocks of random size 
will be used to assign the initial treatment condition. The trial will be 
balanced such that all subjects will receive all treatments (i.e., both socket 
conditions) and that all subjects will participate for the same number of 
periods (i.e., two).
9.2
Research procedures:
The study is composed of two phases for each socket: socket preparation 
and then 6 weeks of socket wear during which 3 identical data collection 
sessions will be held (week 1, 3 weeks and 6 weeks). 
Socket Preparation Phase: 
All sockets will be made following standard clinical procedures that include 
taking an impression (i.e., cast) of the residual limb, converting the negative 
residual limb model to a positive mold made of plaster of Paris, rectifying 
the positive mold using the rectification procedures specific to each socket 
design, thermoforming a clear diagnostic check socket, and ultimately 
manually fabricating, fitting and aligning a definitive socket.
Data Collection:
At each visit we will collect the following data:
1. Socket Comfort Score (SCS) – The SCS is a simple rating of comfort on 
a scale of 0 to 10 where 0 is the most uncomfortable socket fit imaginable 
and 10 is the most comfortable socket fit. 
2. Orthotic and Prosthetic Users’ Survey (OPUS) – The OPUS is a set of 
surveys that evaluate the subject’s perception of function, quality of life, and 
satisfaction with the socket and prosthesis. The lower extremity function 
survey has 20 questions rated on a 5-point scale; the quality of life survey 
has 23 questions rated on a 5-point scale; and the satisfaction with device 
survey has 9 questions rated on a 5-point scale.
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 11 of 28
Revised Template: November 10, 2014
3. Biomechanics of Walking – How the subjects walks with each socket 
will be measured in a computerized motion analysis lab. Small reflective 
markers are taped to anatomical landmarks on the legs, pelvis and arms 
using hypoallergenic tape. The subject then walks back and forth at their 
own comfortable walking speed while cameras on the wall record where the 
reflective markers are in space and force plates mounted flush in the floor 
measure the force applied by each foot.
4. 5-Time Rapid Sit-to-Stand Test (RSTS) - The RSTS measures hip range 
of motion, lower limb muscle strength, and balance. The test involves 
measuring the time it takes for the subject to stand up and sit down five 
times with their arms folded across their chest as fast as they can. They will 
do this test twice with 3 minutes of rest in between each test.
5. Four-Square-Step Test (FSST) - The FSST evaluates dynamic standing 
stability and involves rapid stepping in different directions over an obstacle. 
The obstacle consists of a square cross made by resting four sticks flat on 
the floor. A stepping pattern is demonstrated to the subject and then one 
practice trial is allowed to ensure that they understand the pattern. They 
must try to complete the stepping pattern as fast as possible without 
touching the sticks. Both feet must make contact with the floor in each 
square. If possible, the subject must face forward during the entire test. They 
will do this test twice with 3 minutes of rest in between each test.
6. T-Test of Agility (T-Test) - The T-Test is typically used by athletes to test 
movement agility. Four markers are set out on the floor in the shape of a T. 
The subject starts at the marker located at the bottom of the T. When the 
investigator says “go” the subject moves forward as fast as they can to touch 
the second marker, they then shuffle sideways to the right to touch the third 
marker, and then they shuffle to the left, past the second marker, to touch the 
fourth marker. The subject then shuffles back to their right to touch the 
second marker and then moves backwards as fast as they can to touch the 
first marker. The test is timed and should be performed as fast as possible. 
The test is repeated three times and the best time is used. The subject will be 
allowed to rest for 3 minutes between tests.
9.3
(a) Procedures performed to lessen the probability or magnitude of 
risks:
All socket fabrication procedures used in this study are consistent with 
standard clinical care procedures. The standard clinical process of making a 
transfemoral prosthetic socket involves some loss of modesty and privacy 
given the intimate fit of the standard-of-care Ischial Containment socket 
with your groin and buttocks. Certified Prosthetists are trained to ensure 
privacy during this process. Risk is further minimized by recruiting subjects 
who have used a prosthesis for at least two years and are therefore familiar 
with the process.
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PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 12 of 28
Revised Template: November 10, 2014
It is possible that one or both sockets may not be comfortable or that one or 
both sockets may rub the residual limb and cause redness, blistering, or a 
sore, just as any new or ill-fitting socket may do. Inclusion/exclusion criteria 
will help minimize the risk of these problems by only allowing persons to 
participate who have used a prosthesis for at least two years, have a residual 
limb that is stable in volume and free from any wounds and no skin/residual 
limb issues that make fitting a socket problematic. Subjects will actively 
contribute to minimizing residual limb problems by checking their limb 
each day, informing investigators of problems as soon as they occur, and 
working with the study prosthetists to resolve any issues.
Transfemoral amputees are generally at greater risk for stumbling, tripping 
and falling than people who are not amputees. The risk of stumbling, 
tripping and falling may be increased while performing some of the mobility 
tests used in this study. All tests are standardized clinical outcome measures 
used with amputees and will be performed under controlled lab conditions to 
ensure that the subject is not distracted from the task and that all other 
conditions such as ambient lighting, floor surfaces, etc. are favorable, 
helping minimize risk. Subjects are asked to perform some of the tests “as 
fast as they can” rather than pushing them to exceed their own comfortable 
limits, further serving to minimize risk.
(b) Devices used in this research, the purpose of their use, and their 
regulatory approval status:
Two designs of custom made prosthetic 
sockets will be compared in this 
research: (1) the Ischial Containment 
(IC) Socket and (2) the NU-FlexSIV 
Socket (Figure 5).
The standard-of-care IC socket design 
will be determined on a per-subject 
basis by the Certified Prosthetist using 
standard clinical practice procedures. 
However, subject selection criteria will 
serve to decrease the variability in 
patient presentation such that it will 
minimize the choice of suspension 
options. Therefore, the IC socket will 
consist of a flexible inner socket with 
rigid frame using either skin fit suction 
suspension with a one way valve or silicon liner with locking mechanism. If 
a liner is used it will be sized according to manufacturer recommendations.
The NU-FlexSIV Socket will also be custom fit to each subject using 
standard clinical practice procedures. Subischial socket trim lines are 
typically 25mm distal to the ischial tuberosity and 50mm distal to the 
greater trochanter and while it also has a narrower medio-lateral than 
Figure 5 Ischial Containment 
Socket (left) and NU-FlexSIV 
Socket (right).
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 13 of 28
Revised Template: November 10, 2014
anterior-posterior dimension, it has a more rounded cross-sectional profile 
than the IC socket. All subjects will be fit with an undersized liner (i.e., liner 
one size smaller than the manufacture recommendation based on 
measurements) over which the sub-ischial socket will be fitted. Using the 
rectification procedures specific for this design, sockets are also 4-6% 
undersized. Suspension will be achieved using an Össur Unity mechanical 
vacuum pump.
With the exception of the prosthetic foot, prosthetic components distal to the 
socket (the knee and pylon) will be standardized within subjects. Subjects 
will use their current prosthetic knee so as to minimize the burden of 
learning to walk with a different knee. All subjects will be provided an 
Össur LP Variflex foot with Unity Pump to wear with both test sockets. This 
foot is suitable for K3 and K4 ambulators52 and can interface with any 
existing componentry while also providing a noiseless vacuum pump for use 
with the sub-ischial socket condition.
The purpose of both sockets is to restore the ability to walk for someone 
with a transfemoral amputation. Prosthetic sockets form the interface 
between the residual limb and prosthesis, allowing for support of body 
weight and transfer of forces between the amputee and the prosthesis.
The type of external limb prosthesis we propose to evaluate as part of this 
clinical trial is considered by the Food and Drug Administration (FDA) as a 
Class I device (low risk) and 510k exempt (although not necessarily IDE 
exempt). As part of our current IRB approval for a pilot study with the same 
device (STU00033446), a determination was made by the FDA that our 
device was not a custom device, necessitating that the Northwestern 
University Institutional Review Board (NU-IRB) make a significant risk 
determination. The NU-IRB made a determination that the use of the device 
constituted a non‐significant risk, which meant that we did not have to apply 
for an Investigational Device Exemption from the FDA.
According to FDA regulation 21CFR890 (External Limb Prosthetic 
Component) our device meets that requirement but does not have an 
automatic exemption. Hence, whether our device is subject to FDA 
regulation for this proposed work depends upon NU-IRB determination of 
whether the device as proposed for use in this study is a significant risk 
device. If the NU-IRB determines as it did previously for a similar smaller 
pilot study that our device constitutes a non-significant risk, then we will not 
be subject to FDA regulation and will not need to apply for an IDE. 
According to FDA requirements, as the manufacturer of the device, the 
Principal Investigator (PI) can make the determination that this is a non-
significant risk device. The subsequent IRB determination will either 
support the PI’s decision or override it and require that an IDE application 
be submitted to the FDA. Hence, based on previous experience regarding 
FDA and IRB determinations and recent correspondence with NU-IRB 
regarding this issue (see attached), the PI has determined that the device to 
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 14 of 28
Revised Template: November 10, 2014
be used in this study constitutes a non-significant risk and hence an IDE is 
not required and has not been applied for. We are aware that this 
determination is subject to change based on review by NU-IRB.
(c) Source records that will be used to collect data about subjects:
All data needed for this study will be collected directly from the subjects. 
Included in the eIRB+ application are the Subject Information Form, Socket 
Measurement Forms, OPUS and AMP data collection forms.
9.4
Data to be collected:

Patient Characteristics: age, height/weight, time since 
amputation, etiology of amputation, residual limb length, 
residual limb tissue type (soft, medium, firm), hip flexion 
contracture magnitude, current prosthesis description, Socket 
Comfort Score in existing socket, and Medicare Functional 
Classification Level assessed using the Amputee Mobility 
Predictor (AMP). 

Socket Measurements: See Socket Measurement Forms in eIRB+ 
application.

Patient-Reported Outcomes: Socket Comfort Score and OPUS.

Functional Performance Measures: biomechanics of gait, 5-times 
Rapid Sit-to-Stand Test, Four Square Step Test, T-Test of Agility.
9.5
For HUD uses provide a description of the device, a summary of how 
you propose to use the device, including a description of any screening 
procedures, the HUD procedure, and any patient follow-up visits, tests 
or procedures:
N/A
10.0
Data and Specimen Banking
10.1 Data or specimens banking for future use:
Specimens are not applicable.
The investigators will retain all data recorded during the study. Any 
electronic data maintained at NUPOC is on encrypted and password 
protected computers in locked rooms and paper files are stored in locked 
cabinets in locked rooms. Both computers and paper files are accessible 
only to NUPOC personnel. Data will not be destroyed.
De-identified data will be entered into RedCap for analysis by the 
statistician.
10.2 Data to be stored or associated with each specimen:
N/A
10.3 Procedures to release data or specimens:
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
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Revised Template: November 10, 2014
N/A
11.0
Data and Specimen Management
11.1 Data analysis:
Before analyses begin, all variables will be plotted using histograms to 
inspect the shape of distributions and to check for outliers. We will not drop 
cases nor transform variables but if we identify any possibility that 
assumptions have been violated, we will employ alternative analysis 
approaches. As part of data screening, we will describe the amount of data 
that are missing, and we will compare participants with and without missing 
data. 
Hypothesis 1: We hypothesize that the NU-FlexSIV Socket will provide 
increased comfort compared to the ischial containment socket.
Our primary end point is Socket Comfort Score at 6 weeks, which has been 
reported to have a sensitivity to socket change of 1 to 3 points (Hanspal, 
Fisher et al. 2003). Additionally, it has been argued that the Socket Comfort 
Score may be considered a continuous variable, and therefore suitable for 
parametric analysis, given the large number of ordered categories and the 
linear nature of changes in socket comfort with different configurations of 
socket conditions (Fatone, Dillon et al. 2015). Hence, a matched pairs t-test 
(alpha=0.05) will be used to assess the primary outcome, Socket Comfort 
Score.
Hypothesis 2a: We hypothesize that the NU-FlexSIV Socket will allow 
greater prosthetic side hip range of motion, in particular increased hip 
extension, leading to increased prosthetic side step length and hence walking 
speed compared to the ischial containment socket.
Hypothesis 2b: We hypothesize that step width and lateral trunk flexion over 
the prosthetic limb will not differ between the NU-FlexSIV Socket and 
ischial containment socket.
For these secondary hypotheses, data analysis will include the following gait 
variables: walking speed (m/s), step width (m), step length (m), sagittal 
plane hip range of motion (degrees), maximum hip extension (degrees), and 
lateral trunk lean over the prosthetic limb during stance (degrees). A 
multiple analysis of variance (MANOVA, alpha=0.05) will be used to 
compare gait variables across socket conditions as it is the most rigorous 
approach given the relationship that exists between these dependent 
variables (e.g., walking velocity and step length are correlated). The 
challenge of this approach is being convinced that underlying assumptions 
are met.
Hypothesis 2c: We hypothesize that the NU-FlexSIV Socket will result in 
faster times to perform the 5-Times Rapid Sit-to-Stand Test, Four Square 
Step Test and T-Test of Agility compared to the ischial containment socket.
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 16 of 28
Revised Template: November 10, 2014
The difference in these timed performance tests across socket conditions 
will be tested using repeated measures t-tests with alpha=0.05 which will be 
adjusted using the Bonferroni correction to account for Type 1 error.
Hypothesis 3: We hypothesize that the NU-FlexSIV Socket will result in 
better health-related quality of life and satisfaction with device as assessed 
using the OPUS compared to the ischial containment socket.
The OPUS uses Likert scale responses for each item of each module. 
However, these responses can be converted into a single score for each 
module. If assumptions of normality are met, analysis with parametric 
procedures can be used to assess differences in module scores between 
sockets. Hence, we will use repeated measures t-tests with alpha=0.05 which 
will be adjusted using the Bonferroni correction to account for Type 1 error.
11.2 Power analysis:
To determine a sample size estimate, we have utilized data obtained from a 
previous pilot study.44 In that study, we collected Socket Comfort Scores 
from six persons with unilateral transfemoral amputation wearing an ischial 
ramal containment socket and the same socket with a wider medio-lateral 
dimension (effect size, d = 0.754). Using the G*Power computer program, 
this effect size was used to estimate sample size. This data was used because 
we do not have pilot data for this particular study design. For a 2-tailed 
matched pairs t-test we would need a total sample size of 25 to detect an 
effect size of 0.754 with a critical alpha of 0.05 and power of 0.95. In order 
to account for possible attrition in subject numbers we will recruit 35 
persons with unilateral transfemoral amputation.
11.3 Steps to be taken to secure the data to maintain confidentiality during 
storage, use, and transmission:
All personnel involved with the study have or will complete IRB required 
training. 
Subjects will be assigned a study code at enrollment and all study related 
forms to be completed by our clinical collaborators will be labelled only 
with the study code. Forms that require the subject’s identity and cannot be 
coded (e.g. payment paperwork) will only be completed at NUPOC and not 
at the clinical sites. The master list of study codes will be maintained at 
NUPOC by the PI. This master list will only be maintained in hard copy 
format, in a locked cabinet in the PI’s office which is also locked.
The collaborating prosthetists will only create and use the forms required for 
recording the fitting and fabrication of their particular socket and these can 
be de-identified. Once the subject has completed that phase of the study, 
forms are given in person or by mail to the PI to collate with the main 
subject file to be held at NUPOC.
All electronic data maintained at NUPOC is on encrypted and password 
protected computers located in locked rooms and all paper files are stored in 
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
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Revised Template: November 10, 2014
locked cabinets in locked rooms. Both computers and paper files are 
accessible only to NUPOC personnel. 
All data entered into RedCap will be de-identified summary data needed for 
statistical analysis.
11.4 Procedures to be used for quality control of collected data:
A cross-over study has two advantages over both parallel and non-crossover 
longitudinal study designs. First, the influence of confounding covariates is 
reduced because each cross-over patient serves as their own control. This is 
particularly important given the custom nature of prosthetic interventions. 
Second, cross-over designs can be statistically efficient, requiring fewer 
subjects than non-cross-over designs. This is of particular benefit for 
prosthetic studies given the cost, time and effort involved in providing 
custom prosthetic devices for use every day during the study. Cross-over 
studies are typically subject to order effects, which in this case the most 
likely is shrinking of the residual limb during the first intervention phase. 
This shrinkage is typical of what happens any time a new, more tightly 
fitting socket is provided to a person with amputation. However, the effect 
of shrinkage is accounted for by having casting and fabrication of the 
second test sockets occur after data collection in the first socket is 
completed. While a washout period is not strictly necessary, it is effectively 
included as subjects will need to transition back to their usual, pre-study 
socket/prosthesis while the second test socket is fabricated.
Socket allocation will be concealed from the investigators until after a 
subject is enrolled. The starting socket design will be enclosed in 
sequentially numbered, opaque, sealed envelopes. Envelopes will be opened 
sequentially and only after the participant’s name and other details are 
written on the appropriate envelope.
Blinding of prosthetic interventions is challenging given that they are 
devices that must be custom-fabricated and donned each day by the subject. 
Hence, for this study only the assessor, our research engineer, Ms Lilly 
Tran, will be blinded. To maintain blinding the assessor will remain 
uninvolved in any aspect of the study except administration of performance 
and patient-reported measures and 
processing motion analysis data. 

The assessor will not be present 
for motion analysis data 
collection given that this 
requires exposure of the 
prosthesis and socket for 
appropriate marker placement. 
Since all that is recorded is the 
location of retro-reflective 
markers on the subject, it is not 
Figure 6 Motion analysis data 
processing window.
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 18 of 28
Revised Template: November 10, 2014
possible to tell while processing the motion analysis data what 
socket the subject was wearing because the data is viewed only as a 
stick figure (Figure 6). 

Performance and patient-reported measures can be administered 
fully clothed, which will disguise the socket being tested. During 
these assessments, subjects will be instructed not to reveal to the 
assessor which socket they are wearing.
Given the customized, manually-fabricated nature of prosthetic sockets, 
each test socket will be provided to study subjects by a separate Certified 
Prosthetist known for their skill with the particular socket design. This will 
ensure that each socket is the best and most consistent example of each 
particular socket design.
Since accommodation to sockets is unknown, data will be collected at 
baseline (within one week of definitive socket fitting) and after 3 and 6 
weeks of every day socket use. These time points were chosen to enhance 
subject retention. Since we anticipate that one socket will be more 
comfortable than the other, it is possible that some subjects will find it 
challenging to use the less comfortable socket for a long period of time. By 
keeping each testing phase reasonably short (i.e., 6 weeks) we hope to retain 
as many subjects as possible. Additionally, by collecting data at 3 time 
points, we hope that if subjects are unable to continue to wear the socket for 
the entire six weeks, we will have initial and intermediate times points for 
comparison.
Step activity monitors attached to the test prostheses will allow monitoring 
of every day socket use. This will provide information regarding compliance 
with use of each prosthesis. As a secondary consideration, it will allow us to 
check whether there is a relationship between comfort and step activity. 
When assessing the biomechanics of walking data consistency will be 
assured by (1) collecting all data in the same laboratory using the same 
instrumentation; (2) having marker placement conducted by the same 
experienced person who has been shown previously to have high reliability 
in this task; and (3) having a single person post-process all the data.
Since we hypothesize that the sub-ischial socket will be more comfortable 
than the standard-of-care ischial containment socket, it may be difficult to 
convince current wearers of the sub-ischial socket to revert to wearing an 
ischial containment socket every day for the time required by the study. It is 
also likely that those who have already adopted the sub-ischial socket will 
be particularly biased against the ischial containment socket, leading to 
larger differences in our primary endpoint. To account for this issue, we 
plan to recruit only those patients with no previous experience of the sub-
ischial socket.
11.5 Handling of data study-wide:
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
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Revised Template: November 10, 2014
Any electronic data maintained at NUPOC is on encrypted and password 
protected computers located in locked rooms and all paper files are stored in 
locked cabinets in locked rooms. Both computers and paper files are 
accessible only to NUPOC personnel.
The collaborating prosthetists will only create and use the forms required for 
recording the fitting and fabrication of their particular socket and these can 
be de-identified. Once the subject has completed that phase of the study, 
forms are given in person or by mail to the PI to collate with the main 
subject file to be held at NUPOC.
Data will be retained indefinitely. There are no plans to destroy the data.
12.0
Provisions to Monitor the Data to Ensure the Safety of Subjects
N/A
13.0
Withdrawal of Subjects*
13.1 Anticipated circumstances under which subjects will be withdrawn 
from the research without their consent:
The PI can remove subjects from the research study without their approval if 
they fail to regularly attend study visits, fail to communicate about socket 
and residual limb problems, and fail to work with the prosthetists to resolve 
socket fitting or residual limb issues.
13.2 Procedures for orderly termination:
If the above circumstances occur, the PI will contact the subject to advise 
them that their participation in the research is being terminated. Depending 
on what phase of the study the subject is in, the PI will need to organize for 
the subject to receive their regular prosthesis back intact. This is required 
because the study prosthetist must place the subject’s prosthetic knee back 
into their regular prosthesis. 
13.3 Procedures to be followed when subjects withdraw from the research:
If subjects decide to leave the research, they must contact the investigator so 
that the investigator can arrange for their regular prosthesis to be returned to 
them intact. This requires that the study prosthetist place their prosthetic 
knee back into their regular prosthesis. 
14.0
Risks to Subjects*
14.1 Foreseeable risks, discomforts, hazards, or inconveniences to the 
subjects related the subjects’ participation in the research:
Participating in this study will expose subjects to many of the same 
risks as you are regularly exposed to as an above-the-knee prosthesis 
user. 
(1) The standard clinical process of making a transfemoral prosthetic 
socket involves some loss of modesty and privacy given the intimate 
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
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fit of the standard-of-care Ischial Containment socket with the groin 
and buttocks. This is a temporary situation that occurs primarily 
during the socket preparation phase of the study.
(2) It is possible that one or both sockets may not be comfortable or 
that one or both sockets may rub the residual limb and cause redness, 
blistering, or even a sore, just as any new or ill-fitting socket may do. 
Regular inspection of the residual limb by the subject at the end of 
each day will help identify red spots and blisters before they become 
sores. Immediate communication of these issues to the study 
investigators and prompt action by the study prosthetist can help 
minimize the likelihood that red spots become sores.
(3) As transfemoral amputees, all subjects are at greater risk for 
stumbling, tripping and falling than people who are not amputees. 
Additionally, the risk of stumbling, tripping and falling may be 
increased while performing some of the mobility tests used in this 
study.
14.2 Procedures that may have risks to the subjects that are currently 
unforeseeable:
N/A
14.3 Procedures that may have risks to an embryo or fetus should the 
subject be or become pregnant:
N/A
14.4 Risks to others who are not subjects:
N/A
15.0
Potential Benefits to Subjects
15.1 Potential benefits that individual subjects may experience from 
taking part in the research. Include as may be useful for the 
IRB’s consideration, the probability, magnitude, and duration of 
the potential benefits:
Possible benefits that invidivual subject’s may experience from 
participating in this research include (1) contributing to the 
development of evidence to support whether or not the new socket 
design is more comfortable and functional than the current standard-
of-care transfemoral socket; and (2) receipt of one or two new 
sockets. 
Since the sockets made for this study are made to uniquely fit 
individual subjects, they will be allowed to keep either or both 
sockets assuming they fit well. Sockets will be provided to the 
subject at the end of the study to take to their regular prosthetist who 
can work with them if they want to continue wearing one of the 
sockets.
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
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Revised Template: November 10, 2014
15.2 Indicate if there is no direct benefit:
N/A
16.0
Vulnerable Populations
16.1 If the research involves individuals who are vulnerable to 
coercion or undue influence, describe additional safeguards 
included to protect their rights and welfare:
N/A
17.0
Community-Based Participatory Research
17.1 Involvement of the community in the design and conduct of the 
research:
N/A
18.0
Sharing of Results with Subjects
18.1 Sharing of results with subjects or others:
Results will not be shared with subjects or others.
19.0
Setting
19.1 Sites where the research team will conduct the research:
The research team will identify and recruit potential subjects: A 
convenience sample of participants will be recruited primarily by 
referral of prosthetists in the Chicago-land area. We will recruit both 
Veteran and non-Veteran subjects to participate in this study. With 
the assistance of Dr. Marc Applebaum, chief of Physical Medicine 
and Rehabilitation at the Jesse Brown VA Medical Center we will 
identify and recruit Veterans with unilateral transfemoral 
amputation. Non-Veteran participants will be recruited from the 
general community with the assistance of our clinical collaborators 
at Scheck & Siress Prosthetics, Orthotics and Pedorthics, the largest 
provider of orthotic and prosthetic clinical care in the Chicagoland 
area with over 40 certified and licensed orthotic and prosthetic 
practitioners and twelve accredited facilities.
As a secondary source of recruitment, information about the study will be 
circulated to other prosthetists in the midwest via the Midwest Chapter of 
the American Academy of Orthotists and Prosthetists, whose members 
include prosthetists practicing in Illinois, Indiana and Wisconsin.
Research procedures will be performed at NUPOC and at Scheck and Siress 
Prosthetics, Orthotics and Pedorthics. NUPOC includes the Jesse Brown VA 
Medical Center Motion Analysis Research Laboratory.
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
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VA regulations will apply for Veterans who may participate in the study, 
however there are no site-specific regulations or customs at Scheck & 
Siress. 
Approval for recruitment of Veteran subjects will be sought from the Jesse 
Brown VA Medical Center IRB. Scheck & Siress do not have an IRB of 
their own, so NU IRB will be the presiding authority.
20.0
Resources Available
20.1 Qualifications of study team:
The clinical team is headed by Principal Investigator, Stefania Fatone, PhD, 
BPO(Hons). Dr. Fatone is a prosthetist/orthotist with nearly 20 years of 
experience conducting biomechanical research, including small clinical 
studies based on gait analyses of persons who use prostheses and orthoses. 
Dr. Fatone has completed all NU and VA IRB required training for human 
subject research.
Dr. Thomas Schnitzer, MD/PhD, has extensive experience in design and 
implementation of clinical trials and will work closely with the PI to provide 
guidance and advice on the conduct and management of the current clinical 
trial. Dr. Schnitzer has completed all IRB required training for human 
subject research.
Ryan Caldwell, CP, and John Angelico, CP, both Certified Prosthetists, will 
be responsible for each of the prosthetic sockets to be tested in this study. 
Mr. Caldwell is the originator of the NU-FlexSIV Socket and has extensive 
experience providing this socket technology successfully as part of his 
prosthetic clinical practice at Scheck & Siress Prosthetics, Orthotics and 
Pedorthics. Mr. Angelico has over 30 years of experience as an American 
Board Certified and Illinois Licensed Prosthetist and is an examiner for the 
American Board for Certification in Prosthetics, Orthotics and Pedorthics. 
Mr. Caldwell has completed all IRB required training for human subject 
research and Mr. Angelico is currently undertaking training.
Dr. Steven Gard, PhD, is both faculty at Northwestern and a VA Research 
Health Scientist. He will be responsible for managing allocation of 
interventions and ensuring that other investigators are unaware of allocation 
until after a subject is enrolled in the study. He will also assist with 
recruitment of Veteran subjects and manage VA IRB requirements. Dr. 
Gard has completed all NU and VA IRB required training for human subject 
research.
Dr. Marc Applebaum, MD, chief of Physical Medicine and Rehabilitation at 
the Jesse Brown VA Medical Center, will identify and recruit Veterans with 
unilateral transfemoral amputation at the Jesse Brown VA Medical Center.
Rebecca Stine, MS, is the Manager of the Jesse Brown VA Medical Center 
Motion Analysis Research Laboratory located at NUPOC. Ms. Stine has 
nearly 30 years of experience in the use of instrumented motion analysis. 
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
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Ms. Stine will collect all gait data and contribute to the interpretation of the 
data. As manager, Ms. Stine is responsible for maintenance and operation of 
the JBVAMC-MARL facility and equipment. Ms. Stine has completed all 
NU and VA IRB required training for human subject research and serves on 
the new Jesse Brown VA Medical Center IRB.
Lilly Tran, MS, is a research engineer at the NUPOC who will assume the 
role of blinded assessor for this study. Ms. Tran has completed all IRB 
required training for human subject research.
Michael Oros, CPO, is President and CEO of Scheck & Siress and will help 
support implementation of the project at Scheck & Siress. Mr. Oros is 
currently undertaking training.
A statistician will be engaged to provide statistical support throughout the 
project.
20.2 Other resources available to conduct the research:

Currently, about 1.9 million people are living with limb loss in the 
United States. A total of 19,864 lower limb amputation procedures 
were performed in the state of Illinois from 2009 to 2012. A total of 
760 transfemoral amputation procedures were performed in 2012. 

We plan to recruit 10 subjects per year for the first 3 years of the 
clinical trial and 5 in the 4th year for a total of 35. These subjects will 
be a mix of civilians and Veterans. Given the size of the amputee 
population in Illinois and the scope of the clinical practice of our 
collaborators, we believe that this recruitment goal is feasible.

The key personnel involved in this study will devote the equivalent of 
a day a week to this research project for the next three years.

NUPOC is located on the Chicago campus of Northwestern University 
at 680 N. Lake Shore Drive, Suite 1100, Chicago, IL. NUPOC has a 
total of 20,000 sq. ft. of purpose designed space that is fully accessible 
to individuals with disabilities (i.e., no physical barriers are present 
which require any more than minimal effort to overcome). NUPOC 
includes a VA-sponsored research program under the auspices of the 
Jesse Brown VA Medical Center (JBVAMC). Hence, our research 
facilities include the Jesse Brown VA Medical Center Motion 
Analysis Research Laboratory (JBVAMC-MARL). JBVAMC-MARL 
is a 1200 sq. ft. state-of-the-art human movement research laboratory 
designed especially for making measurements necessary for 
characterizing human movements. Dr. Steven Gard is the director of 
the JBVAMC-MARL. JBVAMC-MARL is fully accessible to 
individuals with disabilities (i.e., no physical barriers are present 
which require any more than minimal effort to overcome).

The Jesse Brown VA Medical Center (JBVAMC) provides care to 
approximately 58,000 enrolled veterans who reside in the City of 
Chicago and Cook County, Illinois, and in four counties in 
northwestern Indiana. JBVAMC is affiliated with the Feinberg School 
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
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of Medicine of Northwestern University. The main hospital is located 
on the west side of Chicago at 820 S Damen Ave, Chicago, IL. A 
shuttle bus runs at regular intervals between the downtown medical 
campus of Northwestern University and JBVAMC, to facilitate 
interaction of patients, staff and research subjects between institutions. 
At JBVAMC, Dr. Marc Applebaum provides rehabilitation services 
and clinics for persons with amputation.

Scheck & Siress is one of the most respected and well-stablished 
orthotic and prosthetic practices in the greater Chicagoland area. 
Founded in Oak Park, IL in 1953, Scheck & Siress is the largest 
provider of orthotic and prosthetic clinical care in the region, 
comprised of over 40 ABC Certified and Illinois Licensed orthotic and 
prosthetic practitioners and 12 ABC accredited facilities, including 
locations affiliated with Marianjoy Rehabilitation Center, University 
of Illinois (Chicago) Hospital, Rush University Medical Center, 
Northwestern Memorial Hospital, Ingalls Hospital, and Loyola 
University Medical Center.

The study team will meet four times a year to discuss the project and 
ensure that all persons assisting with the research are adequately 
informed about the protocol, the research procedures, and their duties 
and functions.
21.0
Prior Approvals
21.1 Approvals to be obtained prior to commencing the research:
Prior to participation of any human subjects, the approval of all required 
Institutional Review Boards (IRB) will be sought. This includes, umbrella 
study approval from the Northwestern University IRB, approval from the 
Jesse Brown VA Medical Center (JBVAMC) IRB, and administrative 
review and approval from the U.S. Army Medical Research and Materiel 
Command Office of Research Protections Human Research Protection 
Office (HRPO). Northwestern University will be the IRB of record for study 
related activity that takes place at Scheck & Siress. Additionally, prior to 
enrollment of the first subject, this clinical trial will be registered at 
clinicaltrials.gov.
22.0
Recruitment Methods
22.1 Recruitment of potential subjects:
A convenience sample of participants will be recruited primarily by referral 
of prosthetists in the Chicago-land area. We will recruit both Veteran and 
non-Veteran subjects to participate in this study. With the assistance of Dr. 
Marc Applebaum, chief of Physical Medicine and Rehabilitation at the Jesse 
Brown VA Medical Center we will identify and recruit Veterans with 
unilateral transfemoral amputation. Non-Veteran participants will be 
recruited from the general community with the assistance of our clinical 
collaborators at Scheck & Siress Prosthetics, Orthotics and Pedorthics, the 
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
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Revised Template: November 10, 2014
largest provider of orthotic and prosthetic clinical care in the Chicagoland 
area with over 40 certified and licensed orthotic and prosthetic practitioners 
and 12 accredited facilities.
As a secondary source of recruitment, information about the study will be 
circulated to other prosthetists in the midwest via the Midwest Chapter of 
the American Academy of Orthotists and Prosthetists, whose members 
include prosthetists practicing in Illinois, Indiana and Wisconsin.
22.2 Source of subjects:
See 22.1.
22.3 Methods used to identify potential subjects:
See 22.1.
22.4 Materials that will be used to recruit subjects:
Study flyer included in eIRB+ application.
22.5 Amount, timing, and method of any payments to subjects:
Subjects will be paid $100 per study visit up to a maximum $1400. 
We will only pay for the study visits completed. Payment will be by 
check at the completion of the study. We will also provide 
discounted parking passes for the 222 Huron Street Parking Garage 
for the data collection visits that take place at NUPOC.  
23.0
Local Number of Subjects
23.1 Total number of subjects to be accrued locally:
30
23.2 Break-down of subjects by study location or procedure group:
N/A
23.3 Number of subjects who are expected to be enrolled and screened, and 
the number of subjects needed to complete the research procedures:
We plan to enroll and screen 35 subjects and need 25 to complete the 
research.
24.0
Confidentiality
24.1 If this is a multicenter study, describe the local procedures for 
maintenance of confidentiality:
N/A
25.0
Provisions to Protect the Privacy Interests of Subjects
25.1 Steps to be taken to protect subjects’ privacy interests:
Efforts will be made to limit the use and disclosure of subject’s personal 
information, including research study and medical records, to people who 
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 26 of 28
Revised Template: November 10, 2014
have a need to review this information. However, we cannot promise 
complete secrecy. Organizations that may inspect and copy the subject’s 
information include the IRB and other representatives of Northwestern 
University required to process various paperwork related to research (e.g. 
subject payment), the US Department of Defense (DOD), the DOD Human 
Research Protections Office, the Veterans Administration, and collaborators 
at Scheck and Siress Prosthetics, Orthotics and Pedorthics. 
Subjects are required to interact with both study prosthetists, the motion 
analysis lab manager, the research engineer and the PI. This is the minimum 
interaction required to conduct the study. However, not all investigators 
need to have access to all the personal information collected as part of this 
project. The PI will work to compartmentalize the data collection forms 
such that only the information necessary for each study personnel to execute 
their study related tasks will be available.
25.2 Steps we will take to make the subjects feel at ease with the research 
situation:
The standard clinical process of making a transfemoral prosthetic socket 
involves some loss of modesty and privacy given the intimate fit of the 
standard-of-care Ischial Containment socket with your groin and buttocks. 
Certified Prosthetists are trained to ensure these activities take place in a 
private space. We are also recruiting subjects who have used a prosthesis for 
at least two years and are therefore familiar with the process as this will ease 
their experience of the study procedures. 
25.3 Permission to access any sources of information about the subjects:
N/A
26.0
Compensation for Research-Related Injury
26.1 Describe the available compensation in the event of research-
related injury.
N/A
26.2 Contract language relevant to compensation for research-related 
injury:
N/A
27.0
Economic Burden to Subjects
27.1 Costs that subjects may be responsible for because of participation in 
the research:
N/A
28.0
Consent Process
28.1 Process for obtaining consent:
We will follow “SOP: Written Documentation of Consent (HRP-091).” 
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 27 of 28
Revised Template: November 10, 2014
The consent process will take place at the end of screening or at the first 
study visit prior to beginning any study related procedures. The first study 
visit takes place at one of the Scheck & Siress clinical offices.
Subjects may have as much time as they like between being informed of the 
study and obtaining consent. Consent forms can be taken home for the 
subject for further perusal.
Non-English Speaking Subjects
N/A
Waiver or Alteration of Consent Process (consent will not be obtained, 
required information will not be disclosed, or the research involves 
deception)
N/A
Subjects who are not yet adults (infants, children, teenagers)
N/A
Cognitively Impaired Adults
N/A
Adults Unable to Consent
N/A
29.0
Process to Document Consent in Writing
29.1 How consent of the subject will be documented in writing:
We will follow “SOP: Written Documentation of Consent (HRP-091).”
29.2 Waiver of requirement to obtain written documentation of consent:
N/A
29.3 Consent document:
Consent document included in the eIRB+ application.
30.0
Drugs or Devices
30.1 Plans to store, handle, and administer devices:
Both prosthetic sockets are custom-made to fit the individual and as 
such no storage is needed and they cannot be used with other 
subjects as they won’t fit.
30.2 Information about claim of an abbreviated IDE (non-significant 
risk device):
The PI of this study is the holder of the current abbreviated IDE. The 
type of external limb prosthesis we propose to evaluate as part of this 
clinical trial is considered by the Food and Drug Administration 
(FDA) as a Class I device (low risk). As part of our current IRB 
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

PROTOCOL TITLE: Functional Performance Evaluation of the Northwestern University 
Flexible Sub-Ischial Vacuum (NU-FlexSIV) Socket for Persons with Transfemoral 
Amputation
Page 28 of 28
Revised Template: November 10, 2014
approval for a pilot study with the same device, a determination was 
made by the FDA that our device was not a custom device, 
necessitating that the Northwestern University Institutional Review 
Board (NU-IRB) make a significant risk determination. The NU-IRB 
made a determination that the use of the device constituted a 
non‐significant risk, which meant that we did not have to apply for 
an Investigational Device Exemption from the FDA.
Our device can be classified as an external limb prosthetic 
component according to 21 CFR 890.3420. We believe that the NU-
FlexSIV Socket like the standard-of-care Ischial Containment Socket 
meets the custom device definition as it is hand fabricated by the 
prosthetist for each subject using current clinical techniques. Given 
overwhelming similarities in structure between the NU-FlexSIV 
Socket and the standard-of-care Ischial Containment Socket we 
contend that the NU-FlexSIV Socket is a design variant of the type 
of sockets used safely every day by transfemoral amputees. Hence, 
we believe that our socket can be considered minimal risk. 
References
Dillon, M. (2007). Insights into socket geometry and coronal plane alignment. 12th 
World Congress of the International Society for Prosthetics and Orthotics, 
Vancouver, Canada.
Fatone, S., M. Dillon, R. Stine and R. Tillges (2015). "Coronal plane socket stability 
during gait in persons with unilateral transfemoral amputation: pilot study." Journal 
of Rehabilitation Research and Development 51(8): 1217-1228.
Hanspal, R. S., K. Fisher and R. Nieveen (2003). "Prosthetic socket fit comfort score." 
Disability and Rehabilitation 25(22): 1278-1280.
Heinemann, A. W., R. Bode and C. O’Reilly (2003). "Development and measurement 
properties of the orthotics and prosthetics users’ survey (OPUS): A comprehensive 
set of clinical outcome instruments." Prosthetics and Orthotics International 27(3): 
191-206.
Kahle, J. T. and M. J. Highsmith (2013). "Transfemoral sockets with vacuum-assisted 
suspension comparison of hip kinematics, socket position, contact pressure, and 
preference: ischial containment versus brimless." J Rehabil Res Dev 50(9): 1241-
1252.
Kahle, J. T. and M. J. Highsmith (2014). "Transfemoral interfaces with vacuum assisted 
suspension comparison of gait, balance, and subjective analysis: Ischial containment 
versus brimless." Gait & Posture 40(2): 315-320.
IRB #: STU00201300 Approved by NU IRB for use on or after 4/16/2020 through 4/15/2021.

 
 
 
 
 
Functional Performance Evaluation of NU-FlexSIV Socket 
NCT02678247 
March 14 2019