A Randomized, Crossover Clinical Trial of Exoskeletal-assisted Walking to Improve Mobility, Bowel Function and Cardio-Metabolic Profiles in Persons With SCI
Phase: NA
Conditions: Spinal Cord Injury, Paraplegia, Tetraplegia
Sponsor: James J. Peters Veterans Affairs Medical Center

SPU-14-031 Protocol: 1 
Revised: April 2018 
Protocol: A Randomized, Crossover Clinical Trial of Exoskeletal-assisted Walking to Improve Mobility, 
Bowel Function and Cardio-Metabolic Profiles in Persons with SCI 
 
Background 
Rationale:  Paralysis from traumatic spinal cord injury (SCI) results in an abrupt reduction in the level of daily 
physical activity.  Those with more severe SCI lose the ability to stand and walk, becoming dependent on a 
wheelchair for mobility.  As a result of this sudden and near permanent immobilization, body composition1–3, 
cardiovascular function4,5, autonomic integrity6,7, and bowel function8–10 are but a few of the body systems that 
are adversely affected.  Paralysis from SCI also affects quality of life due to reduced ability to participate in the 
work force and reduced mobility for community integration 11–15.   
Powered exoskeletal systems provide a new mobility option and appear to have potential therapeutic 
value for persons with chronic SCI.  Phase I trials performed in subjects with non-ambulatory SCI resulted in 
Food and Drug Administration  (FDA) approval in 2011 for institutional use of the powered exoskeleton, 
ReWalk™ (Argo Medical Technologies, Inc., Marlborough, MA)16,17 and in 2012 for the Ekso™ (Ekso 
Bionics, Inc., Richmond, CA).  Investigators at the James J. Peters VA Medical Center (JJPVAMC), Bronx, 
NY, began a Phase II clinical trial in September 2011 (Clinicaltrials.gov Identifier: NC0145470) to study the 
effects of exoskeletal-assisted walking using the ReWalk.  Investigators at the Kessler Foundation Research 
Center (KFRC), Kessler Institute for Rehabilitation, West Orange, NJ began studying the effects of exoskeletal 
walking in the Ekso in 2012.  The investigators at the University of Maryland Rehabilitation and Orthopaedic 
Institute (UMROI), Baltimore, MD acquired the ReWalk system in 2013 and have begun studying the effects of 
this device on their participants.  Based on the experience of the investigative teams at each of these three 
centers, the following is a description of how these two systems are best used to accomplish exoskeletal-assisted 
walking in the SCI population and the physiological challenges placed upon the user to walk in these devices. 
 
Description of how these exoskeletal systems are used (in support of rational for physiological changes): The 
ReWalk™ and the Ekso™ powered exoskeletal systems are similar in that the external frame supports the 
paralyzed individual at the level of the feet, ankles, legs, pelvis, and lower trunk.  The operator is required to 
use Loftstrand crutches or a walker for balance and stability while standing, stepping and walking.  Over ground 
ambulation is accomplished with appropriate weight shifts by the user, as well as computer signals and powered 
motors at the hip and knee joints. In both systems, to ambulate over ground, the operator must actively place 
his/her body appropriately in space in preparation for each step. The process of walking is an action of leaning 
forward, losing and regaining balance.  The successful execution of this pattern in both the ReWalk, and to a 
lesser extent in the Ekso, places four important demands on the neuromuscular and sensory systems of the user.  
First, the user must learn to execute controlled movements of the trunk in order to provide the forward, 
backward, and lateral weight shifting needed to allow the system to initiate stepping and to maintain balance 
while upright.  These controlled movements are accomplished through activation of back extensor musculature 
(to attain an upright position and control forward flexion) and abdominal musculature (to provide trunk 
stability).  Second, the user must control the crutches, which requires activation of upper extremity and chest 
musculature to move the crutches and to provide stability to the shoulder complex as balance is stabilized 
through the upper extremities.  Third, the user must be aware of his/her body position in space, which is 
accomplished via proprioception, vestibular awareness, auditory recognition of the position of the legs from the 
sound of the motors and visual observation of body position.  Fourth, the user must coordinate his/her 
movements, shifting weight and crutch placement at the appropriate time and with the appropriate force to 
maintain balance while walking.  The two systems differ in that the ReWalk™ requires more active 
participation from the user’s muscles of the trunk, arms, shoulder, back, neck, and head in order to control the 
movements of the exoskeleton for walking and stopping, thus, making it more suitable for persons with lower 
SCI such as those with T3 and below who are more likely to have better trunk stability.  The Ekso™ system is 
more robotic and requires less trunk and upper body input from the user to weight shift in order to initiate 
walking, making it more suitable for persons with a higher cord SCI such as those with T2 and above.  These 
neuromuscular and sensory exoskeletal-assisted walking stimuli appear to be key attributes towards activating 

SPU-14-031 Protocol: 2 
Revised: April 2018 
trunk and upper body muscles that remain innervated above the level of injury and in those whose leg muscles 
below the level of injury have partial innervation as in those with zones of partial preservation. 
Preliminary Studies:  A Phase II, single group, pre and post intervention trial was conducted at the James J 
Peters VA Medical Center (JJPVAMC), Bronx, NY, to test the effect of exoskeletal-assisted walking on 
mobility and various secondary medical complications, as well as to continue to monitor for potential safety 
concerns (Clinical Trial #NCT01454570)18.   This preliminary study was funded by the VA Rehabilitation 
Research & Development Service and the JJPVAMC.  Exoskeletal-assisted walking in the ReWalk19 for 4 to 6 
hours per week (3x/week) was performed in ten participants with chronic (1½-14 years post injury) paraplegia 
(Table 1).  All participants were non ambulatory and wheelchair dependent for home and community mobility 
having ASIA (American Spinal Injury Association) impairment scale AIS A or B.  Three participants had lower 
extremity zones of partial preservation (Table 1). Walking tests [10 meter (10m WT) for time in seconds, 6 
minute (6min WT) for distance in m and timed-up-and-go (TUG) in seconds (s)] were performed for most 
sessions (at least weekly) throughout the study.  All participants improved their walking test scores by Session 
36 (Figure 1).  Data are reported as the mean ± SD of the group for each of their best achieved walking tests by 
Session 12 and Session 36 (Table 2).  By 12 sessions, the group achieved an average exoskeletal-assisted 10m 
walk time of 62 ±17 s (6 of 10 were <60 s) with mean ± SD 10m velocity of 0.18 ±0.05 m/s (range: 0.11to 0.29 
m/s), a 6min walk distance of 55 ±34 m (5 of 10 were >50 m) with a 6min velocity of 0.15 ±0.09 m/s (range: 
0.04 to 0.38 m/s), and a TUG time of 145 ±58 s (4 of 8 were <120 s) (Table 2 and Figure 2).  For the group, all 
participants improved in the three walking tests assessed by Session 36: 10m WT was 35 ±13 s (0.33 ±0.12 m/s; 
range: 0.16 to 0.56) with six of ten participants who achieved ≤60 seconds (≥0.17 m/s); the 6min WT was 98 
±41 m (0.27 ±0.11 m/s; range: 0.09 to 0.48) with five of ten having ≥50 m (≥0.14 m/s); and the TUG time was 
90 ±44 s (range: 54 to 204 s), with four of ten participants performing <120 seconds. The change from 12 to 36 
sessions for the 10m and 6min walking tests reflected an 89±60% (range: 17 to 239) and 105 ±87% (range: 25 
to 303) increase, respectively. At 36 Sessions, 8 of 10 The fastest attained 6min velocity by 36 sessions of all 
participants was #8 who had the greatest zone of partial preservation (albeit a non ambulator) with 0.48 m/s, 
about 1.1 mph.  In four subjects (1 cervical and 3 high thoracic level of SCI) studied at Kessler Institute for 
Rehabilitation/Kessler Foundation Research Center (KFRC) using the Ekso20; average walking velocity was 
0.17±0.08 m/s with a range of 0.10 to 0.29 m/s.  
 
 
Table 1.   Demographic and SCI characteristics of the study population 
SID 
Age 
(y) 
Ht 
(in) 
Wt 
(lb) 
BMI 
(kg/m2) 
DOI 
(y) 
Gender 
Ethnicity 
Level 
of 
Injury 
AIS 
(A/B) 
LEMS 
1 
34 
68 
147 
22.3 
9 
male 
Caucasian 
T4 
B 
0 
2 
49 
66 
150 
24.2 
4 
male 
Caucasian 
T10 
A 
0 
3 
44 
72 
175 
23.7 
4 
male 
Asian 
T4 
A 
4 
4 
58 
63 
144 
25.5 
1 
female 
Caucasian 
T8 
A 
0 
5 
61 
69 
160 
23.6 
14 
male 
Caucasian 
T11 
A 
3 
6 
24 
73 
165 
21.8 
5 
male 
Caucasian 
T5 
A 
0 
7 
40 
72 
190 
25.8 
2 
male 
Caucasian 
T1 
B 
0 
8 
50 
72 
220 
29.8 
6 
male 
Hispanic 
T9 
A 
0 
9 
56 
69 
185 
27.3 
4 
male 
Caucasian 
T7 
A 
30 
10 
37 
67 
140 
21.9 
7 
male 
Afric. Amer. 
T2 
A 
0 
SID-study identification number; y=years; in=inches; lb=pounds; BMI=body mass 
index; kg/m2=kilograms per meter squared; DOI=duration of injury; Afric. 
Amer.=African American; AIS=American Spinal Cord Injury Association Impairment 
Scale; LEMS=lower extremity motor score; and T=thoracic level lesion. 
 
 

SPU-14-031 Protocol: 3 
Revised: April 2018 
 
 
 
 
Table 2.  Walking Test Assessment Results 
(Mean±SD of Best Efforts by Session in 10 Participants) 
Sessions 
10 m WT 
6 min WT 
TUG 
(sec) 
(m/s) 
(m) 
(m/s) 
(sec) 
5 to 12 
62 ±17 
0.18 ±0.05 
55 ±34 
0.15 ±0.09 
145 ±58 
28 to 36 
35 ±13 
0.33 ±0.12 
98 ±41 
0.27 ±0.11 
90 ±44 
SD=standard deviation; m=meters; WT=walk test; min=minutes; TUG=timed 
up and go; sec=seconds; and m/s=meters per second. 
 
 
 
 
The effect of exoskeletal-assisted walking was investigated on 
bowel function by using three assessments: a Ten Question 
Bowel Function Survey (10Q BFS), the Bristol Stool Scale 
(BSS), and the short-form item bank for Bowel Management 
from the SCI QOL21,22 (all questionnaires and survey 
assessments may be found in the “Surveys” section).  The 10Q 
BFS captures information about the amount of time spent per day 
and the frequency per week for bowel evacuations, the amount of 
oral laxatives and stool softener use, frequency of digital 
stimulation, and frequency of unwanted bowel evacuation 
episodes.  The BSS is an indicator of how hard the stool is and 
the Bowel Management short form of the SCI QOL assesses the 
amount of burden.   All participants reported improvement for all 
three measures of bowel function (Figure 3).  By session 20, 
significant improvements in bowel function were reported in 6 participants:  reduced total time per bowel 
evacuation (BE) 78±34 to 33±7 minutes, p<0.05, power=0.98; Bristol Stool Scale (BSS) 2.6±1.1 to 4.2±0.4, 
p<0.05, power=0.98, indicating a hard to softer stool consistency; and improved weekly frequency of BE:  
2±0.5 to 4±0.5, p<0.05, power=0.99.  Improvement in bowel function continued for all of the training sessions 
but by one-month after cessation of the walking program the improved bowel function was no longer present23.   
Figure 1.  Results of Walking Tests at 12 and 36 Sessions by Participant 
 
 
Figure legend displays the each participant’s level of thoracic (T) spinal cord injury, AIS score and lower 
extremity motor score. 
m/s = meters per second;  legend: 5 to 12 and 
28 to 36 is the number of sessions. 

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Revised: April 2018 
Analysis of the 10Q BFS, BSS, and Bowel Management SCI-QOL was performed in 8 participants before and 
after 36 sessions (Figure 3).   
 
 
 
Figure 3.  Bowel Function results from the preliminary data, N=8. 
 
Pre=before exoskeletal-assisted walking training; Post=after 20 sessions; SCI=spinal cord injured participants; in Panel A, 
AB=able-bodied controls matched for age±5 years, gender, and ethnicity.  
 
Dual energy x-ray absorptiometry (DXA) was performed pre- and post-training (36 sessions) in nine of ten 
participants (one was lost to follow up due to an abrupt change in his school schedule). On average, the group 
lost total body mass (Figure 4).  In five participants most of this weight loss was attributed to fat and lean mass 
loss, but in four participants, the total mass loss was predominantly from fat tissue mass (Figure 4).  The nine 
participants demonstrated significant loss of regional and total body fat tissue mass [mean ±SD (95% 
confidence limits)]:  arms: -236 ±159 g (-114 to -358 g), P=0.0021;  legs: -641 ±493 g, (-262 to -1020 g), 
P=0.0045;  trunk:  -1030 ±566 g, (-595 to -1466 g), P=0.0006;  and total body: -1914 ±1150 g, (-595 to -2798), 
P=0.0011. Note, the body fat mass losses are strongly supported because the confidence limits were outside of 0 
and the power for the total and regional body fat losses was at 100%.  Regional and total body lean tissue mass 
improved in four of nine participants, albeit not statistically significant when analyzed for the total group. 
 
5
10
15
20
25
30
35
40
Scale:  10 best to 50 worst
Pre
Post
AB
SCI
*p=0.0031
†p<0.0001
A.  Ten-Question Bowel Survey
Mean = 50
40
45
50
55
60
65
70
75
Pre
Post
*p=0.0381
C.  Bowel Management
(SCI-QOL)
Pre
Post
p=0.0835
2
3
5 Desirable
6
1 Hard
4 Desirable
7 Liquid
Scale:  1 (hard)  to 7 (liquid)
B.  Bristol Stool Scale

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Revised: April 2018 
Figure 4.  Regional and Total Body Fat and Lean mass and Total Mass changes Pre and Post 
36 sessions of Exoskeletal-Assisted walking (N=9).
 
TB=total body; All nine participants lost fat mass.  Four gained lean and five lost lean along with fat mass, which is 
consistent with the total weight loss. Three of the four who gained lean had zones of partial preservation. 
To date, with over 1000 hours of exoskeletal-assisted walking, no study-related serious adverse events (SAEs) 
occurred during this Phase II clinical trial.  In the initial weeks of the clinical trial a few minor skin abrasions 
were noted that fully resolved with improved fitting and padding24.  
 
Relevance of the study and explain the applicability of the proposed findings:   
Mobility: While the USA is one of the best countries in the world for accessibility for the disabled, wheelchair-
dependent persons with SCI are at many distinct disadvantages, one of which is the daily loss of the ability to be 
at eye level with others who are standing.  Not all buildings have accessible ramps, and stairs continue present 
an obstacle for entrance. 
Medical complications of SCI:  Persons with SCI are plagued with poor bowel function which includes chronic 
constipation, fecal impaction, involuntary and untimely bowel evacuation accidents, and significant time 
consumption for bowel care8–10,25–28.  Difficulty with bowel evacuation is often listed as one of the top three 
concerns to people with SCI11.  Bowel function care for constipation and bowel incontinence for persons with 
SCI has been essentially unchanged for the past few decades10.   This care involves a regimented routine and the 
use of oral laxatives, stool softeners, suppositories, digital-rectal stimulation, and/or dietary fiber 
augmentation29.  In the able-bodied population, gastric emptying has been demonstrated to be increased with 
physical activity30.  The preliminary data, after exoskeletal-assisted walking, was highly supportive of improved 
bowel function in the participants studied to date.   Body composition is dramatically altered following SCI3,31–
34.  Fat mass is gained and lean is lost at an alarming rate during the first year after SCI1, and these changes 
continue throughout the course of the lives of those with SCI to a greater extent than in the able-bodied 
population3,35.   High density lipoprotein cholesterol (HDL-c) is reduced36–40.  Testosterone levels have been 
reported to be reduced  in men with SCI studied41–43.  In a few animal and human studies, testosterone has been 
shown to improve with exercise or be associated with higher values in those that exercise than in sedentary 
control subjects44–47.   One study by You, T., et al. demonstrated that aerobic exercise training could improve 
severe obesity-related hypogonadism in male rats48.  In a study performed in military personnel during basic 
training, it was demonstrated that training improved  strength, aerobic capacity, and testosterone47.  In older 
men, it has been shown that regular intensive exercise is associated with higher growth hormone and 
testosterone levels and that exercise may have a role in counteracting the normal decline in growth hormone 
with aging.44  As such, it may be reasonable to expect improvements in testosterone levels as a result of the 

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Revised: April 2018 
exoskeletal-assisted walking training. In a recent article, performed in able-bodied men, it was demonstrated 
that a strong relationship existed between reduction in estradiol and increased fat mass49.  Preliminary data 
supports a significant change in body fat in all participants studied to date. Four of nine participants 
demonstrated an improvement in leg and total body lean mass.  These four were those participants who also 
experienced an improved thoracic sensory level and/or had a zone of partial preservation.  It is reasonable to 
expect that the increased activity results in an improved body composition.  As such, the combination of the 
increased activity and loss of fat may would be expected to result in an improved HDL-c level and improved 
insulin sensitivity.  If this proposed study demonstrates that increased activity level results in subsequent 
improvement in body composition, insulin sensitivity, and HDL-c, then the risk for heart disease would be 
anticipated to be reduced.  Additionally, we believe that this study will demonstrate in a larger sample size that 
exoskeletal-assisted walking significantly, and relatively promptly improves bowel function. 
 
Objectives/Specific Aims/Hypotheses 
This clinical trial is designed to demonstrate that the walking skills achieved in the preliminary study at the 
JJPVAMC can be achieved in a larger sample of participants and at three study sites.   It is also designed to 
determine if the body composition and bowel function benefits that were observed with as few as four to six 
hours per week of walking over three months can be demonstrated in a larger sample.  The Phase II trial 
conducted at the JJPVAMC demonstrated that ten participants were able to use the device to successfully walk 
for four to six hours per week for three months.  It is unknown if a larger sample of persons with SCI can be 
taught to walk in these devices with a similar proficiency and competence as demonstrated in our pilot study.  
As such, the primary objectives of this proposal are to achieve successful walking skills in the exoskeletal-
assisted walking devices for an extended period of time and at specific velocities and distances over the course 
of 36 sessions in three months in people with chronic SCI who are wheelchair dependent for community 
mobility.   The secondary objectives are to determine if this amount of walking is effective in improving bowel 
function and body composition in the same patient population.  The exploratory objectives are to address 
additional questions concerning the retention or non-retention of the positive changes, the effects of the 
increased physical activity from exoskeletal-assisted walking (WALK) on vagal tone, orthostatic tolerance, lipid 
profile, total testosterone, estradiol levels, immune system factors, and quality of life (QOL). Other tertiary 
goals are to explore the relationships among these variables.  For example, if there is a change in HDL-c, total 
testosterone and estradiol levels, what is the relationship of this change with fat mass loss and/or is the 
magnitude of this change related to the achieved mobility and walking skills?  The Primary and Secondary 
specific aims are supported with the pilot data above and in the power calculations in the Statistical section. The 
exploratory aims are of interest and may be used to inform the investigators as to the feasibility and design of 
future work. 
 
Specific Aims 
Primary Aims:   
1. By session 12 (first month of WALK training), the participants will be able to perform the following 
exoskeletal-assisted walking tests with or without minimal assistance:  
a. 10m WT  
i. 90% in ≤60 seconds (≥0.17 m/s) 
ii. 10% in ≤40 seconds (≥0.25 m/s) 
b. 6min WT  
i. 80% at a distance of ≥50 m (≥0.14 m/s) 
ii. 20% at a distance ≥80 m (≥0.22 m/s);  
c. TUG  
i. 80% in ≤120 seconds 
ii. 20% in ≤90 seconds 
 

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Revised: April 2018 
2. By session 36 (three months of WALK training), participants will have improved their ability to walk 
faster and longer distances and will be able to perform exoskeletal-assisted walking tests with or without 
minimal assistance as follows: 
a. 10m WT - 70% in ≤40 seconds (≥0.25 m/s) 
b. 6min WT - 70% at a distance ≥80 m (≥0.22 m/s)  
c. TUG - 60% in ≤90 seconds. 
 
Secondary Aims are to affect the following by three months of exoskeletal-assisted walking (WALK): 
1. To improve bowel function as measured by established survey instruments; and 
2. To reduce total body fat mass and percent as measured by DXA. 
 
Exploratory Aims: 
1. To improve autonomic/cardiovascular function (vagal tone) measured by high frequency component of 
the 24-hour holter monitor; 
2. In persons with T6 and above, to improve orthostatic hypotension (OH) tolerance measured by a 
standard OH challenge test from supine to seated; 
3. To improve HDL-c, Homeostatic Model of Assessment – Insulin Resistance (HOMA-IR), serum total 
testosterone and estradiol levels measured by serum and plasma assay kits; and 
4. To improve quality of life (QOL) measured by item banks from the SCI-QOL and Patient Reported 
Outcomes Measurement Information System (PROMIS). 
 
Hypotheses 
Primary Hypothesis (are tested pre and post the WALK arm only):   
1. By session 36, 70% of the participants compared with 10% at session 12 will be able to perform the 10m 
WT ≤40 seconds (≥0.25 m/s); 
2. By session 36, 70% of the participants compared with 10% at session 12 will be able to perform the 
6min WT distance ≥80 m (≥0.22 m/s); and 
3. By session 36, 60% of the participants compared with 20% at session 12 will be able to perform the 
TUG in ≤90 seconds. 
 
Secondary Hypotheses (are tested between the WALK arm and the UA arm, within-subject) 
4. Bowel function will improve by 25% using the Ten-Question bowel survey.  (Note, the components of 
this survey represent a 50% reduction in bowel evacuation (BE) time, a 25% increase in BE weekly 
frequency per week, a 50% reduction in BE medication use, and/or a 25% improvement in stool 
consistency from harder to softer.) 
5. Total body fat mass is hypothesized to be reduced on average by 9±7 percent (an average of 1.9±1.2 kg 
decrease from baseline). 
 
Exploratory Hypotheses: 
1. In Group 1 (WALK first), the bowel improvement changes will return to baseline values by one month 
of the UA arm. 
2. In Group 1 (WALK first), the body fat mass and percent changes will return to baseline values by 3 
months of the UA arm. 
3. Associated with increased activity, there will be improved autonomic/cardiovascular function (vagal 
tone) as measured by the high frequency component of the holter monitor recordings and the tolerance 
to orthostatic challenge. 
4. Associated with increased activity and fat mass loss, there will be statistically significant improvement 
in HDL-c, HOMA-IR, serum total testosterone and estradiol levels  
5. Quality of life (using select SCI-QOL item banks) will be reported to be improve after in the WALK 
arm, but not for the UA arm 

SPU-14-031 Protocol: 8 
Revised: April 2018 
 
Safety concerns with the use of the exoskeletal devices will continue to be evaluated.  Any serious (SAEs) or 
adverse events (AEs) will be recorded and reported the appropriate oversight bodies. 
 
Study Design 
Research design:  A Phase III randomized clinical trial (RCT) will be performed using a crossover design and 
employing an exoskeletal-assisted walking intervention.  The experimental arm will be compared to a usual 
activities (UA) arm, as the control, in 132 persons with chronic SCI (>6 month post injury) who are wheelchair-
dependent for outdoor mobility in the community.  Eligible participants will be randomized (within site) to one 
of two groups for 12 weeks (three months): Group 1 (n=32) will receive exoskeletal-assisted walking (WALK) 
first for 12 weeks then crossover UA for a second 12 weeks; Group 2 (n=32) will receive UA first for 12 weeks 
then cross-over to the WALK arm for 12 weeks of training.  The WALK arm will consist of supervised 
exoskeletal-assisted walking training, three sessions per week (4-6 h/week) for 36 sessions for their second 12-
week period.  The UA arm will consist of identification of usual activities for each participant, encouragement 
to continue with these activities and attention by study team members throughout the 12-week UA arm.  These 
activities will be recorded in a weekly log.  A fixed answer format will be used to capture this information. 
 
Rationale for intervention to be studied:  This research design has several advantages. Group 1 will serve as the 
intervention follow-up to assess retention or non-retention of change due to the intervention on the outcome 
variables. Group 2 will serve as a lead-in to assess stability of the outcome variables prior to the intervention.  
Additionally, because of tremendous variability in the SCI population and difficulty with case-control matching, 
the cross-over design will help to control for variability between participants because each participant will serve 
as their own control.  Veterans and nonveterans with SCI generally do not receive further structured 
rehabilitation once they have completed the acute and sub-acute phases of their rehabilitation.  As such, the 
usual lifestyle activities have been chosen as the control for this study. Dr. Spungen has discussed the optimal 
control for an exoskeletal-assisted walking program.  She has consulted with the Chiefs of several SCI Services 
in both the VA and non-VA rehabilitation hospitals.  A case-controlled, matched RCT study would be strongest 
with two interventions:  exoskeletal-assisted walking compared with any other form of physical activity such as 
robotically assisted body weight supported treadmill training (Lokomat), body weight supported treadmill 
training, arm ergometry etc.  However, there are two considerations that make this type of study not feasible.  
One is that it would be extremely difficult to case-control match for independent variables within site, and the 
second is that most participants would likely not agree to participate if there was a 50% chance they would not 
get the exoskeletal-assisted walking arm.  In order to control for an attention effect, participants in the UA arm 
will keep weekly activity logs and be contacted by phone calls from the study team to receive attention and 
encouragement to continue participation in the UA of their choice.  In order to control for attention aspects of 
this type of study, participants will also make in person twice monthly visits to their sites during the UA arm.  
During these visits, study team staff will review their UA logs and administers the 10Q BFS and BSS.  
 
Because the achievement of improved secondary medical outcomes is likely dependent on the ability to walk in 
the exoskeletons, the primary outcome will be achievement of mobility skills in the exoskeletal devices.  It has 
not been demonstrated in a large sample that people with SCI can use the device as described by the pilot data.  
Secondary outcomes will be change in fat mass and bowel function.  Exploratory outcomes will be change in 
cardiovascular and autonomic measures and quality of life surveys [using the newly validated SCI quality of life 
(SCI-QOL) tool for bowel, bladder and five emotional domains]21,50.   
 
Description of walking in the ReWalk:  The ReWalk exoskeletal system requires the user to actively shift their 
body appropriately over their legs in order to maintain balance on the stance leg allowing the swing leg to clear 
the floor. This is accomplished with coordinated movements involving the upper extremity muscles in the trunk, 
arms, shoulder, back, neck, and head for the body to maintain balance dynamically as the system assists the legs 
to move in a normal walking pattern. Balance is maintained with the use of Loftstrand crutches. At all times 

SPU-14-031 Protocol: 9 
Revised: April 2018 
during exoskeleton walking, participants must use both crutches. A mode selector, which is worn on the wrist, 
is used to select “walk mode” once the person is stable during standing. Following walk mode selection, the 
user shifts onto the left leg and slightly forward so that the right leg is offloaded. The tilting/leaning action 
triggers the device to swing the right leg forward and the user weight shifts so that their trunk is over the right 
leg as they step onto the right foot. This will then initiate the left leg to swing forward; the use weight shifts 
onto it and continuous walking is achieved if this coordinated weight shifting and stepping onto each leg is 
continued. The unit will stop walking in two ways. If the user does not shift their weight onto the front foot, 
then the ReWalk will time out after two seconds and return to the standing position. The second way is if the 
person does not shift their weight appropriately to have the swing leg clear the floor. This will cause the leg to 
have some additional external force that the ReWalk will sense and cause the system to return to standing mode.  
The stepping and walking gait pattern of the ReWalk is very similar to normal walking51.   The gait pattern 
settings in the ReWalk can be preset in order to increase or decrease the step length, speed of the step and/or the 
amount of foot clearance the person will have during walking, permitting a velocity of 0.10 to 0.80 m/s. 
  
In order to successfully accomplish walking with the ReWalk, considerable coordination between the upper 
extremity muscles in the trunk, arms, shoulder, back, neck, and head is needed in conjunction with dynamic 
standing balance.  A specific pattern of trunk positioning, crutch placement and weight shifting is needed.  To 
prepare for walking, the user must attain a stable standing position with the crutches placed slightly in front of 
him/her.  To begin walking, the user must shift their weight onto the left foot to unweight the right foot. The 
right foot steps forward first, and this is initiated when the user slightly leans forward, by bringing the crutches 
forward, away from the stepping leg to allow it to swing forward and clear the floor.  As the stepping leg moves 
forward and extends toward the ground, the user shifts weight forward, stepping onto that leg and then 
sequentially brings the crutches forward for the next step.  Immediately after the weight is shifted, the user must 
straighten his/her posture with their body perpendicular to the ground before leaning forward to initiate the next 
step.  This is similar to a normal walking pattern.  As the leg contralateral to the initial step leg swings forward, 
the participant must shift the crutches away from that leg to allow it to step forward.  This process is repeated 
for continued walking.   
 
Description of walking in the Ekso:  The users are progressed through a series of steps to participate in over 
ground ambulation. The first method, called FirstStep.  This is when the trainer triggers the step by using a 
controller while verbally cueing the participant that the device is taking a step. The second method, called 
ActiveStep is when the user to initiates the stepping action by pressing a button on a pair of instrumented 
crutches for each step. The last method, called ProStep, is when the user shifts their weight lateral and forward 
onto the front foot, until sensors indicate when an appropriate shift has been performed. The stepping pattern 
can be adjusted to change the step time and step length. The trajectory of the foot allows for foot clearance 
similar to a marching pattern. The device has the ability for provide some abduction and plantar/dorsi flexion 
positioning.  This device has the ability to alter the stepping, which would allow the user to take faster or slower 
steps with a longer or shorter stride length, thus permitting a walking velocity of 0.10 to 0.45 m/s. Stopping is 
achieved by holding a stationary position and by not activating sensors. The Ekso allows for varying robot-
assist levels that can be decrease or increased bilaterally. The robot assistance can operate will full or variable 
assist, dependent on the level of function of the individual. At all times during exoskeleton walking, participants 
must use both crutches 
 
Rationale for both devices:  The ReWalk and Ekso devices have functional similarities, both requiring the use 
of crutches for balance.  The maximum velocity of the ReWalk is 0.80 m/s and of the Ekso, 0.45 m/s19,20.  The 
rationale for using both systems comes from previous clinical experience of the investigators at the JJPVAMC 
and KFRC.  The Ekso, because it provides more robot-assistance (i.e., the leg is lifted in a marching style gait to 
assure foot clearance, is better able to accommodate those participants with a low cervical (C) or high thoracic 
(T) level who have less trunk stability and are not able to weight shift to clear the stepping leg. The ReWalk 
offers a more natural walking pattern, more extensive walking and requires more user input than the Ekso; thus, 

SPU-14-031 Protocol: 10 
Revised: April 2018 
this device is better suited for those with lower thoracic SCI (T3 and below) who can perform weight shifting 
and clear the foot for stepping.  By including both the Ekso (for T2 and above in those who have some spared 
hand function to hold the crutches or can have them securely attached) and the ReWalk (for T3 and below), the 
effect of exoskeletal-assisted walking can be investigated across all levels of cervical, thoracic and lumbar SCI.   
 
Study variables to be measured:  Baseline screening evaluations for eligibility will include a history and 
physical examination with a complete International Standards for Neurological Classification of SCI (ISNCSCI) 
examination [the ISNCSCI includes a full American Spinal Cord Injury Impairment Scale (AIS)], range of 
motion, Ashworth spasticity examination at selected lower extremity joints, standard orthostatic tolerance test, 
and bone mineral density (BMD).  The primary outcome assessments will consist of the 10m, 6min and TUG 
walking tests.  The walking tests will be performed and recorded for each session of the WALK arm. The 
secondary outcomes include body composition and bowel function.  A full battery of outcome assessments will 
be performed at baseline and after completion of the intervention of WALK arm (after 36 sessions) and the UA 
(after 12 weeks) periods.  Interim assessments for the SCI QOL will be performed at midpoint, after 18 
sessions.  Bowel function will be measured bi-weekly throughout both arms of the study (Table 3). 
 
 
 

SPU-14-031 Protocol: 11 
Revised: April 2018 
 
Table 3.  Schedule of Testing for each Intervention Arm 
 
Group 1 
Pre 1 
Exoskeletal-Assisted Walking Intervention (WALK) 
Post 1 
Usual Activities (UA) 
Post 2 
Month 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
Week 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
18 
20 
21 
22 
23 
24 
25 
26 
WALK Sessions1 
  
  
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
Cross-
over 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
WALK Skills2 
  
  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
  
  
  
  
  
  
  
  
Log record 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
  
  
DXA Scan 
x 
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
x 
  
ISNCSCI Exam 
x 
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
x 
  
Holter monitor 
  
x 
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
x 
OH BP test 
  
x 
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
x 
Blood Draw 
x 
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
x 
  
SCI-QOL 
  
x 
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
x 
Bowel Function 
x 
x 
  
x 
  
x 
  
x 
  
x 
  
x 
  
x 
x 
  
  
x 
  
x 
  
x 
  
x 
  
x 
  
x 
x 
  
Group 2 
Pre 2 
Usual Activities (UA) 
Post 3 
Exoskeletal-Assisted Walking Intervention (WALK) 
Post 4 
Month 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
Week 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
18 
20 
21 
22 
23 
24 
25 
26 
WALK Sessions1 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Cross-
over 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
  
  
WALK Skills2 
  
  
  
  
  
  
  
  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
  
  
Log record 
  
  
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
1 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
DXA Scan 
x 
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
x 
  
ISNCSCI Exam 
x 
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
x 
  
Holter monitor 
  
x 
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
x 
OH BP test 
  
x 
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
x 
Blood Draw 
x 
  
  
  
  
  
  
  
x 
  
  
  
  
  
  
  
x 
  
SCI-QOL 
  
x 
  
  
  
x 
  
  
  
  
x 
  
  
  
x 
  
  
  
  
x 
Bowel Function 
x 
x 
  
x 
x 
  
x 
x 
  
x 
x 
x 
  
  
x 
x 
  
x 
x 
  
x 
x 
x 
  
1WALK Sessions include heart rate (HR), blood pressure (BP) and Rating of Perceived Exertion (RPE) recordings before, during and after walking and/or more often as 
clinically indicated. 
2WALK Skills include 10m WT, 6min WT, TUG, and assorted mobility skills for turning, stopping, reaching, and navigating doors. 
DXA=dual energy x-ray absorptiometry scan; ISNCSCI=International Standards for Neurological Classification of Spinal Cord Injury (SCI); OH BP=postural orthostatic 
hypotension blood pressure tolerance test; and SCI-QOL=spinal cord injury quality of life surveys. 

SPU-14-031 Protocol: 12 
Revised: April 2018 
Description of Assessments 
Mobility Skills: Exoskeletal-assisted walking tests for the 10m WT, 6min WT, and TUG will be performed at 
least one time per week during the WALK arm intervention.  It was observed during the Phase II trial that 
weekly assessment of the walking tests provided structured feedback to the participants regarding their progress 
in mastering the use of the powered exoskeleton and was useful in motivating the participants.   Additional 
mobility skills (turning, wall rest, stopping, and navigating doors) will be assessed throughout the WALK arm; 
but not to be considered as part of the primary outcomes.  The walking tests will be performed as per the 
standardized descriptions52,53 with modifications for the exoskeletons.  The PI and lead biomedical engineer 
from the JJPVAMC (Mr. Pierre Asselin) have significant experience and expertise in performing these walking 
and mobility tests and will travel to the other two sites to train the staff for standardization purposes across the 
sites during the designated start-up time of the study. 
 
Body Composition:  A dual energy x-ray absorptiometry (DXA) scan for regional and total body fat, lean and 
bone tissue masses will be performed three times: at baseline, at crossover, and after the second arm of the 
study for both the WALK and UA arm interventions.  Standardized DXA scans will be performed as previously 
described at all three study sites2,3,54. 
 
ISNCSCI:  A neurological evaluation for sensory and motor function, level of injury and lower extremity motor 
scores will be performed according to the ISNSCI standards55.  This exam will be performed three times: at 
baseline, at crossover, and after the second leg of the study for both the WALK and UA arm interventions. 
 
Bowel function surveys:  The 10Q Bowel Function Survey (BFS) and the Bristol Stool Scale will be 
administered before both interventions and then bi-weekly (two times/month) for a total of 16 times during the 
two arms of the study.  This information will be used to determine key components to a participant’s weekly 
bowel regime23.  The Bowel Management item bank short form from the SCI-QOL will be performed three 
times: at baseline, at crossover, and after the second arm for both the WALK and UA arm interventions.  The PI 
will instruct the three sites on the standardized method for administering these assessments. 
 
SCI-QOL:  The Spinal Cord Injury Quality of Life measurement tool is the first validated SCI-specific QOL 
measurement tool for the field22,50,56.  The specific short form item banks to be use are:  Ability to Participate, 
Independence, Positive Affect, and Resilience.  These will be performed three times: at baseline, at crossover, 
and after the second arm for both the WALK and UA arm interventions.  The PI will instruct the three sites on 
the standardized method for administering these assessments. 
 
Blood draw:  Over the whole study, a total of three phlebotomy samples (Approximately 13 ml/draw; 3 
teaspoons) will be drawn from the participants after an overnight fast.  Blood samples will be separated for the 
lipid profile (assays performed by Quest diagnostics), and the kit assays for fasting plasma insulin and glucose 
(FPI, FPG), total testosterone (TotT), and estradiol (E2/E3).  All kit assays will be performed at the SCDRC at 
the JJPVAMC; the three samples from each participant will be in the same assay kit to avoid inter-assay 
variability.  The SCDRC core laboratory has been performing kit assays for over 20 years and has published 
dozens of papers from the results of these assays.  The draws will consist of the following:  fasting plasma 
insulin (FPI, 2 ml, green top tube), fasting plasma glucose (FPG, 1 ml, grey top tube), total testosterone (TotT,1 
ml, red top tube), and estradiol (E2/E3, 1 ml, red top tube). An additional blood draw (Approximately 8 ml) will 
be drawn for the lipid profile and immune system factors. Three ml will be required for the lipid profile and sent 
to Quest Diagnostics and 5 ml for the immune system factors sent to Dr. Ona Bloom, at The Feinstein Institute 
for Medical Research, Manhasset, NY. The Quest Diagnostics and immune system transfer tubes will labeled 
only with your participant ID number and study time point. Quest diagnostics will pick up samples as regularly 
scheduled at each of the sites. A representative from Dr. Bloom’s lab will come to pick up the samples directly 
upon each draw. The total amount of blood to be drawn for each data point collection is approximately 13 ml.  

SPU-14-031 Protocol: 13 
Revised: April 2018 
The blood draw will occur 3 times over the course of the whole study before intervention, at crossover WALK 
or UA) and after intervention (WALK or UA). 
 
Lipid Profile:  Total cholesterol (TC), low density lipoprotein cholesterol (LDL-c), triglyceride (TG) and high 
density lipoprotein cholesterol (HDL-c) values will be measure by Quest Diagnostics Laboratory and samples 
will be collected at baseline, crossover and at the end of the second arm of the study. 
Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) The standard equation for the HOMA-IR 
will be used to calculate insulin resistance [HOMA-IR = FPG (mg/dl) x FPI(µU/mL) / 405] as first described by 
Matthews et.al57.  The HOMA-IR has been demonstrated to be a good indicator of insulin resistance in inactive 
populations, including the SCI population and to be sensitive to weight loss changes58–60. 
 
Total Testosterone (TT): Serum total testosterone will be determined by a radioimmunoassay (RIA; MP 
Biomedicals, Costa Mesa, CA) kit with an intra-assay CV of 10.0, 9.6, and 13% at 1.4, 4.6, and 8.0 
nmol/L41,61,62. 
 
Estradiol (E2/E3):  Serum estradiol values will be determined by a commercial kit assay using RIA (MP 
Biomedicals, Costa Mesa, CA) with an intra-assay CV of 15.7, 5.5, and 3.5% at 25.4, 152, and 657 pg/mL63. 
 
Immune System Factors: Markers of systemic inflammation are elevated and immune system function is altered 
in persons with chronic SCI, as demonstrated by articles published by Dr. Ona Bloom, Co-Investigator, 
Associate Investigator, The Feinstein Institute for Medical Research; WOC employee JJPVAMC. In an 
exploratory analysis, inflammatory mediators will be measured by Dr. Bloom in sera using commercially 
available single- and multi-plex suspension immunoassays, and then measured on the Bio-Rad Luminex 
Magpix platform with Bio-plex Manager software or other standard ELISA platform, as indicated by the 
manufacturer. Immune mediators to be measured include: C reactive protein (CRP), HMGb1, IL-1, IL-1Ra, 
IL-6, IL-8, IL-10, IL-15, MIF, MIP1-/CCL3, TNF- leptin, and adipokine, using standard methods and 
manufacturer’s protocols. Due to its clinical utility and widespread use as a biomarker of systemic inflammation 
in studies related to exercise and risks for coronary heart disease, the primary outcome assessment of systemic 
inflammation will be levels of CRP.  All other biological mediators measured described above will be 
considered as secondary biological outcome measures.  
 
Cardiovascular Autonomic Tone:  A 24-hour Holter Monitor will be used to collect heart rate and blood 
pressure data for analysis of heart rate and blood pressure variability as non-invasive assessments of cardiac 
vagal tone and peripheral sympathetic vasomotor tone.  The 24-hour Holter monitor provides accurate beat-to-
beat measurement of heart rate and blood pressure and calculates variations in the inter-beat-interval of R-
waves and systolic peaks to estimate cardiovascular autonomic regulation.  The high resolution and sample rate 
enables quality amplification of cardiac and arterial pulse waveforms for more accurate estimates.  The Holter 
monitor will be placed around the chest for heart rate assessment and a blood pressure cuff will be placed 
around the upper arm to monitor blood pressure which will self-inflate approximately every 20 minutes over the 
24 hours of monitoring.  
 
Postural orthostatic hypotension blood pressure tolerance test (OH BP): The non-invasive autonomic test of 
postural changes is described as the heart rate response to standing64,65 has been modified to be performed  in 
persons with SCI due to skeletal muscle paralysis and limitations in assuming the standing position.  Therefore, 
the HR response to postural change will be assessed during re-positioning from the supine to the seated 
position, as previously described66.  Participants will be in the supine position on a bed or elevated gym mat and 
beat-to-beat HR will be recorded for 60 seconds, followed by passive re-positioning to the seated position on a 
bed or elevated gym mat with the hip and knee at a 90° angle and the lower leg hanging off the side.  Passive 
repositioning will be accomplished by one staff member lifting the participant’s torso by the shoulders, while 
supporting the head and neck, and a second staff member shifting the subject perpendicular to the bed and 

SPU-14-031 Protocol: 14 
Revised: April 2018 
allowing the participant’s legs to hang off the side.  Participants will be instructed not to assist in the passive 
movement during this transition, and will be supported by staff. 
 
Methods for recruiting subjects:  Three sites will participate in this study: 1) JJPVAMC will be the Lead Site 
and has four ReWalk units; 2) UMROI will be a sub award site and has two ReWalk units with the potential to 
acquire two additional units through collateral funding and 3) KFRC will be a sub site of the JJPVAMC through 
the satellite Center of the Spinal Cord Damage Research Center which is located at Kessler Institute of 
Rehabilitation.  KFRC has one Ekso unit.  The JJPVAMC and KFRC study sites each have close to 3 years of 
experience conducting studies using the exoskeletal systems for persons with SCI. UMROI has recently 
acquired two ReWalk units and has experience conducting a DOD CDMRP Clinical Trial in persons with SCI. 
UMROI has begun to study the ReWalk in their patients.  Potential participants will be recruited from the 
research databases at each institution and from the clinical outpatient services.   At the UMROI site, the 
principal investigator also is the Director of the SCI support team clinic at the Baltimore VA Medical Center, so 
he will be able to recruit from both a civilian and a veteran population.  Currently, both the JJPVAMC and 
KFRC have a waiting list of participants who have contacted either Center to become involved an exoskeletal-
assisted walking program.   All three study sites have a positive and significant history of recruiting and 
conducting ethically appropriate clinical trials in persons with SCI. 
 
Expected withdrawal rates:  In 13 participants enrolled to date at the JJPVAMC, three withdrew (one due to job 
relocation, one due to an unrelated medical illness, and one due to difficulty with travel).  It is expected that 
these and/or similar reasons will affect the compliance and attendance of this study to some degree.  As such a 
total of 132 participants will be enrolled as follows:  JJPVAMC (n=28, T3 and below), KFRC (n=16, T2 and 
above) and UMROI (n=20, T3 and below).   An enrollment schedule by site is provided (Table 4). 
 
 
Group assignment process:  Participants will be block randomized within site. 
 
Statistical Plan and Data Analysis:  
The best value achieved for each walking test during sessions 5 to 12 (T1) and from 13 to 36 (T2) will be 
recorded separately to be used for comparative analysis.  These best T1 and T2 scores will be used to determine 
Table 4.  Original Enrollment Schedule by Site 
Study Sites and 
Groups 
Y1 
Y2 
Y3 
Y4 
Sub 
Total 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
JJPVAMC 
(T3 and 
below, 
ReWalk) 
Group 1 
2 
4 
4 
4 
14 
Group 2 
2 
4 
4 
4 
14 
subtotals 
 
 
4 
 
 
8 
 
 
8 
 
 
8 
 
 
 
 
28 
JJPVAMC 
at KFRC 
(C5 to T2, 
Ekso) 
Group 1 
2 
2 
2 
2 
8 
Group 2 
2 
2 
2 
2 
8 
subtotals 
 
 
4 
 
 
4 
 
 
4 
 
 
4 
 
 
 
 
16 
UMROI 
(T3 and 
below, 
ReWalk) 
Group 1 
2 
3 
3 
2 
10 
Group 2 
2 
3 
3 
2 
10 
subtotals 
 
 
4 
 
 
6 
 
 
6 
 
 
4 
 
 
 
 
20 
Total Participants by Year 
12 
18 
18 
16 
64 

SPU-14-031 Protocol: 15 
Revised: April 2018 
percent of occurrence with the hypothesized goals.  Achievement of the hypothesized goals in the WALK 
intervention group for the primary outcomes (10mWT, 6minWT and TUG at the 12- and 36-session time 
points) will be reported as categorical data and presented as a percent of occurrence with the 95% upper and 
lower confidence intervals (CI).  Continuous variables for the Secondary outcomes of the body composition and 
bowel function variables will be presented as mean ±SD.  For the continuous variables, a difference score or 
percent change from pre to post will be calculated for the WALK and UA arms of the study.  Comparisons 
between WALK (Pre-Post) vs. UA (Pre-Post) difference scores will be performed using paired t-tests.   Pre to 
post comparisons for variables that are not normally distributed will be performed by non-parametric tests such 
as the Wilcox signed rank test or the paired sign test. 
 
Walking outcomes (10mWT, 6minWT, and TUG): Achievement of the hypothesized goals in the WALK 
intervention group will be reported as categorical data and presented as percent occurrence with 95% 
confidence intervals (CI). For each of these outcomes, the best value achieved during the T1 period (sessions 5-
12) and the T2 period (sessions 13-36) will be recorded separately and compared to the hypothesized goals, as 
listed below: 
 
Primary Hypothesis (are tested pre and post the WALK arm only):   
1. By session 36, 70% of the participants compared with 10% at session 12 will be able to perform the 10m 
WT ≤40 seconds (≥0.25 m/s); 
2. By session 36, 70% of the participants compared with 10% at session 12 will be able to perform the 
6min WT distance ≥80 m (≥0.22 m/s); and 
3. By session 36, 60% of the participants compared with 20% at session 12 will be able to perform the 
TUG in ≤90 seconds. 
 
Power Calculation:  A one-sample method was chosen to test the observed proportion against the expected 
proportion determined from the preliminary data of the percent of those who achieved these goals.  Using the 
most stringent criteria above of 20% (session 12) versus 60% (session 36) who achieve the TUG goal, there is 
100% power (alpha=5%, double sided Z-power=5.6) with 13 of 63 (20%) versus 38 of 64 (60%) achieving the 
goal.  If the attrition rate is as high as 25%, then the power is still 100%, (alpha=5%, double sided Z-
power=4.53), with 10 of 48 (20%) at session 12 versus 29 of 48 (60%) of the participants achieving the goal at 
session 36. 
 
Secondary Hypotheses 
1. Bowel function will improve as demonstrated by 25% improvement on the Ten-question bowel survey. 
2. Total body fat mass is hypothesized to be reduced by 2.0±1.2 kg 
Power Calculation:  The preliminary data demonstrated a total score change of 31.5±7.1 to 22.5±5.3, N=8 and a 
total body fat mass change from 24.14±8.45 to 22.22±8.19, N=9, alpha=0.05, using a pairwise method, the 
power for both was 100%.  Allowing for 25% dropout, the power is still 100% for 48 participants at an 
alpha=0.05. 
 
Please note, that both the primary and secondary hypotheses are well powered due to the huge effect observed 
in the preliminary data.  However, performing this study in fewer participants will not permit us to ask many of 
the exploratory questions.  There is no empirical data to support an appropriate power calculation for the 
exploratory hypotheses. 
 
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