Development of Adaptive Vacuum Suspension to Improve Prosthetic Fit and Residual Limb Health
Phase: NA
Conditions: Lower Limb Amputation
Sponsor: Indiana University

 
Development of Adaptive Vacuum Suspension to Improve 
Prosthetic Fit and Residual Limb Health 
 
NCT number: NCT03927404 
 
Document date: 04/20/2021 
PROTOCOL + STATITICAL 
ANALYSIS PLAN 
 
 
 
 
      
THE OHIO STATE UNIVERSITY 
      

1      version 4.20.2021 
 
Contents 
I .Background ................................................................................................................................................ 2 
II. Objective: .................................................................................................................................................. 2 
III. Inclusion Criteria: ..................................................................................................................................... 2 
IV. Exclusion Criteria: .................................................................................................................................... 3 
V. Study Design: ............................................................................................................................................ 3 
VI. Aim 1 (Completed): .................................................................................................................................. 4 
1. 
Study Visit 1....................................................................................................................................... 4 
VII. Aim 2 (partially completed if additional subjects are needed, they will be recruited at OWW with 
their approved IRB protocol): ....................................................................................................................... 4 
1. 
Study Visit 1 (Baseline) ...................................................................................................................... 4 
2. 
Study Visit 2, 3, 4 (month 1, 2, 3 ....................................................................................................... 5 
VIII. Aim 3 (n=30 will be performed at IU under current approved protocol): ............................................. 6 
IX. Study Procedures: .................................................................................................................................... 9 
X. Potential Risks: ........................................................................................................................................ 10 
XI.  Unanticipated Problems and Adverse Event Reporting........................................................................ 11 
XII. Discontinuation Criteria ........................................................................................................................ 12 
XIII. Procedures for Amendment of Protocol: ............................................................................................ 12 
XIV. Payment: .............................................................................................................................................. 12 
XV. Statistical Analysis:................................................................................................................................ 13 
XVI. References: .......................................................................................................................................... 13 
 
 
 
 
 
 
 
 
 
 

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I .Background:  
 
Achieving a comfortable and functional connection between an amputee and their prosthetic 
limb is critical to the success of the prosthesis. Therefore, the socket system is the most 
significant component for overall success of the prosthesis1,2. In an effort to maximize socket 
performance and comfort without adversely affecting residual limb health, a prosthetist custom 
fits a socket for every patient using plaster wraps or computer aided design. Currently, this 
process suffers from a lack of quantitative feedback to determine appropriate socket fit. 
Prosthetists aim to minimize suspension-dependent movement between the socket and 
residual limb, but current approaches are limited as they rely on anecdotal visual cues along 
with subjective verbal feedback from the patient. Prosthetists then use this   information to 
revise socket parameters such as volume, geometry, and type of suspension to provide current 
‘best’ fit for a patient. Regardless of prosthetist fitting, the volume of mature residual limb (>18 
months post-amputation3) are subject to daily4 and chronic5,6 changes in volume that 
compromise socket fit and performance. For the 1 million Americans that live with a lower-limb 
amputation, a growing number of which are service men and women7-9, these volume changes 
adversely affect fit, performance, and residual limb health6 – including skin breakdown and 
ulceration10 that can necessitate revision of the amputation. Indeed, for traumatic lower-limb 
amputations, the requirement for surgical revision is known to be as high as 30%11. 
 
II. Objective: 
Aim 1 will evaluate the relationship between vacuum pressure and limb movement inside the 
socket and how it changes with respect to vacuum pressure setting, gait speed and socket 
volume 
 
Aim 2 will evaluate the impact of socket movement on residual limb circulation and residual 
limb skin health 
 
Aim 3 will compare the effectiveness of an adaptive vacuum system to standard of care 
suspension prosthetics (pin-locking or suction).  
 
Study Population: Up to 170 amputees will be enrolled in the study overall. 
1. Aim 1:  10 trans-femoral amputees and 10 trans-tibial amputees will be enrolled.  
2. Aim 2: 15 trans-tibial and 15 trans-femoral amputees will be enrolled.  
3. Aim 3: n=120 (trans-tibial and trans-femoral amputees) will be enrolled.    
III. Inclusion Criteria: 
1. Ages of 18 and above 

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2. Unilateral trans-tibial or trans-femoral amputee 
3. Ambulate at a K2 level or higher 
4. At least 3 months post-amputation per physician discretion  
5. Residual limb length greater than 6.5 inches in length 
6. Able to follow directions and give informed consent on their own or through Legally 
Authorized Representative. 
7. Must be able to ambulate without assistance. An external assistance device such as cane 
or walker will be permitted.  
8. Adequate arterial blood flow of the index stump as evidenced by TcOM > 30 mmHG, 
measured within the past 12 months. 
IV. Exclusion Criteria: 
1. Conditions that prevent wearing a prosthetic socket; such as existing scab, ulcer, or 
keloid scar on amputation stump. 
2. Cognitive deficits or mental health problems that would limit ability to consent and 
participate fully in the study protocol  
3. Women who are pregnant or who plan to become pregnant in the near future  
 
V. Study Design: This study has 3 aims where trans-femoral and trans-tibial amputees will 
be enrolled.  
 
Subjects enrolled in Aim 1 (N=20) will have one study visit that will take place at The Ohio 
Willow Wood (OWW).  
 
Subjects enrolled in Aim 2 (N=30) will have a total of 4 visits at baseline, month 1, month 2, and 
month 3.  
 
Subjects in Aim 3 (120) will be enrolled at Indiana University (n=30 subjects), OWW (n=30), and 
at Walter Reed National Military Medical Center (WRNMMC) (n=60 subjects) with a total of 3 
visits at 0 week (baseline), 0-4 weeks (socket fitting visits), and 16 weeks (final visit)..  OWW and 
Walter Reed National Military Medical Center (WRNMMC) have  separate IRB protocol & 
approval to conduct their  part of subject recruitment and study visits.  Aims 2 and 3 will not be 
run concurrently. Subjects enrolled in Aim 2 can participate in Aim 3. Aim 2 studies performed 
at Ohio State and Indiana University.  Aim 2 has enrolled 15 subjects through Ohio State 
University & OWW (and these 20 subjects have completed their participation in the study) and 
the data is currently being analyzed to determine if additional subjects are required.  If analysis 
shows sufficient subjects have been enrolled to achieve the study aim, no additional subjects 
will be enrolled in Aim 2.  If there is insufficient data, the remainder of the Aim 2 subjects will 
be enrolled through OWW under their approved IRB with WIRB.  Aim 3 studies performed at IU, 
OWW and WRNMMC per their approved IRB protocols.  The vacuum suspension used for the 
study is new to all enrolled subjects  

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We are requesting the use of ResearchMatch.org for subject recruitment on this protocol. See 
attached General Description of ResearchMatch attached.  
 
Descriptions of prosthesis suspension platforms: 
 
Pin-locking prosthesis: A gel-liner with an attached pin, lanyard, KISS system that clicks 
into a locking mechanism (receiver) inside the socket. 
 
Suction prosthesis: A total contact weight bearing socket with a one-way expulsion 
valve to let air out. 
 
Adaptive vacuum test prosthesis (“test” system): The adaptive vacuum prosthesis is 
sold as a commercial device by the company Willow Wood with suggested U.S. L-Code 
L5781. The device is designated as a Class 1 Medical Device and 510(K) Exempt. This 
category is part of a low or moderate risk to patient safety and health. The Prosthetic 
socket system uses an active vacuum pump to push air out of the socket. The level of 
vacuum is controlled by hardware that automatically detects the socket fit based on in-
socket motion and adjusts vacuum as needed to eliminate this motion. 
 
VI. Aim 1 (Completed):  
1. Study Visit 1 This initial visit will take place at The Ohio Willow Wood and the following 
research activities will take place: 
• Informed Consent will be obtained 
• Baseline demographics, medical history, and medications will be recorded 
• Verify fit of the thermoplastic socket 
• Subject will perform multiple ambulation trials at controlled cadences while the 
vacuum pump is set turned off (0 inHg), 7 inHg, 10 inHg, 13 inHg, and 20 inHg. 
• Subject will repeat the ambulation task with different thickness liners to simulate 
global volume changes. 
• Subject will repeat the ambulation task with a gel pad insert to simulate local 
volume changes. 
 
VII. Aim 2 (partially completed if additional subjects are needed, they 
will be recruited at OWW with their approved IRB protocol):  
1. Study Visit 1 (Baseline) This initial visit will take place at OSUWMC & OWW where the 
following research activities will take place:  
• Informed Consent will be obtained 

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• Baseline demographics, medical history, and medications will be recorded 
• Subjects will perform seated tasks, standing tasks, and walking on a treadmill 
task. Skin health measurements will be taken before and after the activity 
period. 
• Hyperspectral Imaging – A non-invasive visible light imaging technology will 
measure tissue oxygenation 
• Hitachi Aloka Ultrasound – A hand held device will be moved gently across the 
skin and measure your blood flow of deeper skin tissues. 
• Skin Temperature-A small tab (small sticker) will be placed on the skin and tell us 
the temperature of your residual limb 
• Surface Electrical Capacitance – Small non-invasive probe place on skin to 
measure skin hydration 
• Trans epidermal water loss measurement (TEWL) – Small non-invasive probe 
compares relative humidity of skin surface to indicate epidermal barrier function 
• Transcutaneous Oxygen Measurement – Small non-invasive probe measures the 
amount of oxygen released through the skin layer 
• This data will be used to determine how socket movement affects the limb 
health measurements  
• The study prosthetist will set vacuum level set to first level 
• Digital Image 
 
2. Study Visit 2, 3, 4 (month 1, 2, 3) Subjects will return at 1, 2, and 3 months after study visit 
1 where the following research activities will take place:   
• Subject will perform seated tasks, standing tasks, and walking on a treadmill 
task. Skin health measurements will be taken before and after the activity 
period.  
• Hyperspectral Imaging  
• Hitachi Aloka Ultrasound  
• Skin Temperature 
• Surface Electrical Capacitance  
• TEWL measurement  
• Transcutaneous Oxygen Measurement  
• This data will be used to determine how socket movement affects the limb 
health measurements 
• The study prosthetist will set the vacuum level set to the next treatment level 
except at study visit 4.  
• At the end of visit 4, patients will be returned to their standard of care 
prosthesis. The study prosthetist will be available to review and adjust the fit of 
their existing prosthesis. 
• Digital Image 

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VIII. Aim 3 (n=30 will be performed at IU under current approved 
protocol):  
Rationale for the amendment: As per the approved DoD proposal, n=60 (n=30 each at IU and 
Willow wood for Limb Heath analysis, current approved IU IRB protocol) and n=60 subjects 
were supposed to be completed at Walter Reed (WR) for Functional analysis. We have received 
a request from WR to perform Functional analysis on the remaining subject that will be enrolled 
for limb health analysis (this is due to COVID-19 and availability of subjects at WR. The request 
from WR was also in view of short time line remaining (study end date 09/2021).    
After receiving consent, the first enrollment visit will be scheduled for the subjects to see the IU 
study prosthetist to initiate the “test” socket fitting visits.   
 
On this day, prior to socket fitting activities, the arterial blood flow will be measured on the 
index stump if not already completed per standard of care within the previous 12 months prior 
to enrollment for data analysis.  Those with an TcOM < 30 mmHG be excluded and no further 
study activities will be completed.  These subjects will be recorded as a screen fail and will not 
be enrolled. 
Others will move forward with socket fitting activities. 
 
A. 
Study Visit #1 - Socket Fitting visits (Week 0 - 4, +/- 2 weeks) – Note: this visit 
may consist of three (minimum) visits plus socket adjustment visits (as needed 
by the subject) on separate days (up to 4 weeks)  
i) 
limb shape capture, measurements or tracing  
ii) 
diagnostic static fitting and diagnostic dynamic fitting  
iii) 
delivery of definitive “research” socket 
 
Once delivery of the definitive research socket has been completed, the subject will be allowed 
to return for no greater than 4 adjustments (within 0-2 weeks from baseline) to obtain a 
comfortable fit in order to complete this study.  If subject requires more than 4 adjustment 
visits, the participation from the study will end.   
Once the subject is comfortable with the fitting, the date will be noted by the study team as 
“research socket use start date”. From this date, the subject will begin wearing the test socket 
for next 16 weeks.  
B.  Study Visit #2A - Baseline visit for residual limb health (Week 4, +/- 2 weeks)  Enrollment, 
after delivery of the definitive research socket and completion of the socket fitting visits, the 
following research activities will take place to obtain baseline measurements:  

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• Subjects will be asked to walk on a treadmill for 10 mins. The residual and sound 
(intact) limb health measurements will be taken before and after the activity 
period with the exception of conducting post-activity ultrasound and digital 
imaging. The purpose of acquiring ultrasound and digital imaging is to determine 
changes in skin structure on a long-term basis; thus, these measurements will 
only be collected during pre-activity procedures to observe changes in a resting 
state. The following health measurements will take place: 
o Surface Electrical Capacitance  
o TEWL measurement 
o Hyperspectral Imaging   
o Ultrasound (pre-activity only) 
o Perfusion/ Blood flow 
o Digital Image (pre-activity only) 
 
B.i. Study Visit #2B** - Baseline visit for gait assessment (Week 4, +/- 2 weeks)  
*Note* Study Visit #2A and #2B can be combined and performed in a single study visit upon 
the discretion of the subject.  
 Subjects will begin in their current standard of care prosthesis (the prosthesis worn at time of 
study enrollment), wherein the following research activities will take place in the following 
order:  
• Subjective questionnaires [Veterans RAND 36-Item Health Survey (VR 
• 36, PEQ, Socket Comfort Scores (SCS), and National Institute of Health 
(NIH) Patient-Reported 
• Outcomes Measurement Information System (PROMIS) 
• Functional evaluation [Comprehensive High-level Activity Mobility 
Predictor (CHAMP)] 
• Biomechanical evaluation of gait during 6min walking test 
a. Positioning markers will be placed on the subject while 
performing the walking assessment to track and describe the 
movement of the body in three dimensions.  
• Repeat SCS outcome 
** applicable to any new enrollments and/or any already enrolled subject completed their 
limb health part (16 weeks in test sockets followed by 4 weeks in SoC socket as wash off 
period) 
Following completion of these activities in study visit 2A & B, the subjects will be 
fitted with the adaptive vacuum suspension by a certified prosthetist that they 
will wear subsequently wear the device for 16 weeks 
 
The study team will follow up subjects with a weekly phone call to determine the 
compliance for the use of research socket.  

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C.         Study Visit #3A – Final Visit (Week 16, +/-2 weeks). After 16 weeks of wearing the 
“research” socket the following research activities will take place in the following 
order:  
• Subjects will be asked to walk on a treadmill for 10 mins. The following residual 
and sound limb health measurements will be taken before and after the activity 
period with the exception of conducting post-activity ultrasound and digital 
imaging, is as follows 
o Surface Electrical Capacitance  
o TEWL measurement 
o Hyperspectral Imaging   
o Ultrasound (pre-activity only) 
o Perfusion/ Blood flow 
o Digital Image (pre-activity only) 
 
C.i 
Study Visit #3B– the visit will take place either the same day of Visit 3A or 
another day within the Week 16, +/-2 weeks based on subject convenience, to 
repeat research activities previously performed in study visit # 2A  
• Subjective questionnaires [Veterans RAND 36-Item Health Survey 
(VR 36, PEQ, Socket Comfort Scores (SCS), and National Institute 
of Health (NIH) Patient-Reported Outcomes Measurement 
Information System (PROMIS) 
• Functional evaluation [Comprehensive High-level Activity Mobility 
Predictor (CHAMP)] 
• Biomechanical evaluation of gait during 6min walking test 
• Repeat SCS outcome 
 
• The subjects will be given a choice to keep the research socket or return to using 
their original prosthesis as normal. The study prosthetist will be available to 
review and adjust the fit of their standard of care prosthesis at this time. Note; 
Due to physical change and limb volume fluctuation over the study period, it is 
possible that at the end of the study the standard of care prosthesis will not fit 
your residual limb as it does at the beginning of the study. At the completion of 
the study it is recommended that the subject follow up with their primary care 
prosthetist for socket evaluation and fitting. 
• Any research-related tests or activities are performed at the expense of the 
research study and will not be billed to you or your insurance.   
• Any non-research related activities, tests, or necessary medical treatment will be 
provided to you and billed as part of your medical expenses.  Costs not covered 
by your health care insurer will be your responsibility.  Also, it is your 
responsibility to determine the extent of your health care coverage.   

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Walter Reed National Military Medical Center (WRNMMC) will recruit and enroll 60 subjects 
with a pin-locking prosthesis and has separate IRB approval to conduct the study.  The study 
visits will be per their approved IRB protocol (see attached). 
 
 
IX. Study Procedures: 
There may be risks that are not known about at this time. Side effects, risks, and discomforts may 
result from study participation.  
 
A. Demographic, medical, and subjective questionnaires: Subjects will be queried on self-
reported measures of user comfort and performance. Briefly, four subjective measures 
will be completed: VR-36, PEQ, SCS, and measures from the NIH PROMIS. The VR-36 was 
developed from the original RAND version of the Medical Outcomes Study 36-Item Health 
Survey as a short form functional assessment for veterans. The PEQ is composed of 9 
validated scales to measure various aspects of a prosthesis and the users feelings about 
it. The scales include: Ambulation, Appearance, Frustration, Perceived Response, Residual 
Limb Health, Social Burden, Sounds, Utility, and Well Being. The SCS is based on a 0-10 
numerical scale that assesses comfort rather than pain. The SCS will be administered by 
asking the participant: "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?". The NIH developed a system of 
reliable, precise measures to be used to capture patient-reported physical, mental, and 
social well-being. The PROMIS tools are aimed at helping clinical researchers most 
appropriately quantify how a patient is feeling or what they are able to do. 
 
B. Comprehensive High-level Activity Mobility Predictor (CHAMP) Test: The CHAMP test will 
be used to assess overall amputee performance and the effect of the socket suspension 
intervention over time. The conglomeration of clinical assessment tools into the CHAMP 
was specifically done to measure high-level mobility in service members with a lower limb 
amputation. CHAMP consists of the Single Leg Stance Test (SLS), the Edgren Side Step Test 
(ESST), Illinois Agility Test (IAT), and T Test. The SLS measures the time an amputee is able 
to stand in single support with their hands on their hips and is performed with eyes open 
and with eyes closed. The ESST measures the ability of the participant to side shuffle back 
and forth in the layout shown in Figure 20 for 10 seconds. A point is given for each cone 
passed which is totaled for the 10 seconds. The IAT and T-test requires additional agility 
and control to navigate the course. Participants will complete the tasks in the following 
order: SLS, ESST, T-Test, and IAT. To generate a composite CHAMP score, the best times 
or point for each task is converted to a 0-10 scale following the scoring system. The 

10      version 4.20.2021 
 
composite CHAMP score will range from 0-40, with 40 representing the highest level of 
performance. 
 
C. Biomechanical evaluation of gait: IU Neuroscience Gait lab will be used to collect 
kinematic data. The laboratory is equipped with an instrumented treadmill and infrared 
camera system. A harness system will be used to provide support and safety for the 
amputees while study participants walk on the treadmill for 6 minutes. A specially 
designed reflective marker set, will track movement between the socket and residual limb 
and allow analysis of motion not detected by the vacuum system, to quantify and 
characterize soft-tissue specific pistoning across suspension platforms. Reflective passive 
markers will be placed on the amputee and prosthesis, including the socket. A virtual 
marker position will be created for the residual limb from the physical markers. A series 
of segment definitions will be based off the reflective marker positions. The 3-
dimensional position and orientation of a segment will be tracked relative to the segment 
immediately proximal using transformation matrices. 
 
D. Transcutaneous Oxygen Measurement and skin temperature: 
The PeriFlux System 5000 uses non-invasive probes that will measure the skin 
temperature and transcutaneous Oxygen Measurement. The probe head is affixed to the 
residual limb by an adhesive sticker. 
 
E. Hyperspectral Imaging for tissue oxygenation and perfusion:  
Powered by spatial frequency domain imaging, this imaging system provides a more 
complete picture of tissue health by quantifying and mapping tissue oxygenation and 
perfusion. Data are displayed in the form of color-coded maps. 
 
 
X. Potential Risks: 
There may be risks that are not known about at this time. Side effects, risks, and discomforts may 
result from study participation.  
 
Prosthesis placement: While the goal of this project is to create a more comfortable prosthesis, 
it is possible that the subject could experience discomforts commonly associated with prosthesis 
use, such as perspiration, dry skin, rash, itching, blisters, high pressure in the socket, looseness 
in the socket, and mechanical rubbing that leads to ulceration which may lead to infection and 
additional surgery. Subjects with low levels of arterial blood flow have an additional risk of 
ulceration. 
 
Treadmill task:  

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There is a risk of falling during the research activities. This risk is mitigated by the ability of 
participants to self-select pace for the treadmill task and observation of treadmill activities by 
research staff. 
 
Transcutaneous Oxygen Measurement and skin temperature: 
The PeriFlux System 5000 poses minimal risk to the subject. Removal of the sticker after data 
acquisition may cause minor discomfort similar to removing a small band-aid. 
 
Hyperspectral Imaging for tissue oxygenation and perfusion:  
This non-invasive non-contact imaging technique poses minimal risk to the subject. 
 
Ultrasound:   
Ultrasound imaging is a noninvasive technique and is a minimal risk procedure. 
 
TEWL and Surface Electrical Capacitance Measurements:  
TEWL and Surface Electrical Capacitance measurements are noninvasive and propose less than 
minimal risk. 
 
Loss of Confidentiality 
Although efforts are made to protect your study records, there is always a risk that someone 
could get access to your private health records. 
 
XI.  Unanticipated Problems and Adverse Event Reporting 
Protocol deviations and Unanticipated Problems Involving Risks to Subjects or Others, Adverse 
Events, and Other Problems will be reported to the Indiana University per IU IRB reporting 
requirements.  
Unanticipated problems can occur in any type of research (medical or non-medical) and may 
include occurrences such as adverse events, subject complaints, protocol deviations, and other 
untoward events involving risk. Events requiring prompt reporting by investigators and research 
staff may involve physical, psychological, social, legal, or economic harms. 
Event reports and accompanying information will be screened for completeness by research 
staff members, additional clarifications will be requested from the investigator as necessary. 
Research staff members and the principal investigator will make an initial determination about 
whether the event represents a possible unanticipated problem involving risks to subjects or 
others and/or potential noncompliance. Reports of events determined during screening to 
represent possible unanticipated problems involving risks to subjects or others and/or 
serious/continuing noncompliance will be forwarded to the IRB for convened review. Reports of 
events that do not meet the requirements for prompt reporting may be reported at time of 
study renewal.  

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XII. Discontinuation Criteria  
 
Patients will be informed during the informed consent process (in writing and verbally) that they are 
free to withdraw from the trial at any time. The Investigator may exercise his medical judgment to 
terminate a patient’s participation in the trial due to clinically relevant changes in any clinical or 
laboratory parameter. The Sponsor-Investigator also reserves the right to discontinue/terminate the 
trial at any time. 
 
Discontinuation criteria for individual subjects include: (1) Non-compliance with the inclusion/exclusion 
criteria, (2) treatment non-compliance, such as use of another socket, (3) withdrawal from the study due 
to reasons not related to the treatment.   
XIII. Procedures for Amendment of Protocol: 
 
Protocol modifications will be approved by the IU IRB prior to implementation and WRNMMC 
site HQ will be notified if the change is significant or adversely impacts the risk/benefit 
assessment for the study. 
 
As per IU HRPP guidance on NSR devices reviews trial monitoring, an internal review of 
data/source verification will be performed and documented on a quarterly basis. The internal 
reviewer will will conduct the following activities: quarterly observation of research 
recruitment, informed consent process, research activities completed at research study visits, 
data collection and analysis. The internal review process may meet more frequently as deemed 
necessary and will be immediately notified of any serious and/or unanticipated event(s) related 
to procedures of the study. They will review all summary data, overall progress of the study and 
any individual serious and/or unanticipated event report(s). They do not have any conflicts of 
interest with the study team and/or protocol. In addition, a Data Safety Monitoring Board 
(DSMB) will provide independent oversight of the study, and will meet with the PI and research 
team at the following intervals: (1) prior to enrollment, after enrollment of the first 15 subjects 
for Aim 2, after enrollment of the first 30 subjects for Aim 3, and after all subjects have been 
enrolled and within 60 days of completion of the study for both Aims 2 and 3. The, DSMB will 
consist of a physician chairperson, a statistician, and a clinical trialist/ethicist. The Data Safely 
Monitoring Board will meet at the same intervals separate of the internal research reviewer. . 
 
XIV. Payment:  
All subjects will be compensated $100 for each of the completed visits.  Aim 1 subjects will be 
compensated $100 for the completed study visit 1. Aim 2 subjects will have 4 total visits and 
will be eligible for a maximum of $400 for completion of all study visits. Aim 3 subjects will have 
3 total visits and will be eligible for a maximum of $450 for the completion of all visits per 
following schedule: Visit #1 ($50), Visit #2A &B ($150, for completing all socket fitting activities 

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& baseline) and Visit #3A&B ($250). Subjects will not be paid if any of study visits are not 
completed.  
 
XV. Statistical Analysis: 
Patient demographics and clinical characteristics will be described using frequencies and 
percentages for categorical data and median and the interquartile range (IQR) for continuous 
data.  In Aim 1, random-effects linear regression will be used to assess the relationship between 
wave amplitude and distal movement (or lateral shift) controlling for vacuum pressure.  Patient 
ID will be the random-term in the model.  In Aim 2, random-effects linear regression will also be 
used to compare percent change in limb perfusion across adaptive EVS and suction at 12 weeks 
controlling vacuum pressure and controlling for the baseline EVS and suction values.  In Aim 3, a 
random-effects linear regression model will be used to establish the relationship in amputee 
performance (as measured by the CHAMP tasks) and residual limb health across EVS and 
suction and across EVS and pin-locking/lanyard in a cross-over design. The model includes 
terms for group (EVS vs. suction or EVS vs. pin-locking/lanyard), sequence (EVS to suction vs. 
suction to EVS or EVS to pin-locking/lanyard vs. pin-locking/lanyard to EVS), and visit (second vs. 
first). All statistical models will account for the effect of age, diabetes status and smoking 
history by including them as the covariates in the models. As per need, subjects may be 
stratified based upon diabetes status and arterial blood flow status.  The p-values produced in 
the study will be adjusted using the Holms procedure to control the overall type I error at 0.05 
due to the multiple comparisons.  All analyses will be run using Stata 13.1, Stata Corporation, 
College Station, Texas. 
 
 
 
 
 
XVI. References:  
 
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2. Schultz, A.E., Baade, S.P. & Kuiken, T.A. Expert opinions on success factors for upper-
limb prostheses. J Rehabil Res Dev 44, 483-489 (2007). 
3. Berke, G. Post-operative management of the lower extremity amputee: Standards of 
care. Official findings of the state-of-the-science conferences #2. J Prosthet Orthot. 16, 
6-12 (2004). 

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4. Zachariah, S.G., Saxena, R., Fergason, J.R. & Sanders, J.E. Shape and volume change in 
the transtibial residuum over the short term: preliminary investigation of six subjects. J 
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5. Fernie, G.R. & Holliday, P.J. Volume fluctuations in the residual limbs of lower limb 
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6. Sanders, J.E. & Fatone, S. Residual limb volume change: systematic review of 
measurement and management. J Rehabil Res Dev 48, 949-986 (2011). 
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servicemembers with major traumatic limb loss from Vietnam and OIF/OEF conflicts. J 
Rehabil Res Dev 47, 373-385 (2010). 
8. Krueger, C.A., Wenke, J.C. & Ficke, J.R. Ten years at war: comprehensive analysis of 
amputation trends. The journal of trauma and acute care surgery 73, S438-444 (2012). 
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10. Bui, K.M., Raugi, G.J., Nguyen, V.Q. & Reiber, G.E. Skin problems in individuals with 
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