Effects of Functional Electrical Stimulation Cycling Versus Cycling Only on Walking Performance and Quality of Life in Individuals With Multiple Sclerosis: A Pilot Study
Phase: NA
Conditions: Multiple Sclerosis
Sponsor: Stony Brook University

 
 
 
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TITLE:  Effects of Functional Electrical Stimulation Cycling versus Cycling Only on Walking Performance 
and Quality of Life in Individuals with Multiple Sclerosis:  A Pilot Study 
  
NCT02606604  
 
Date: June 20, 2016 
 
 

 
 
 
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Protocol Template Guidance 
For Submissions to CORIHS 
 
TITLE:  Effects of Functional Electrical Stimulation Cycling versus Cycling Only on Walking Performance and 
Quality of Life in Individuals with Multiple Sclerosis:  A Pilot Study 
 
INVESTIGATORS:  Lori Hochman, PT, MS, NCS, Lisa Muratori, PT, EdD 
      
A. SPECIFIC AIMS 
 
People with MS (PWMS) receive traditional rehabilitation during the course of their disease but there is a 
lack of consensus regarding intervention type and exercise dosage.1 Functional Electrical Stimulation Cycling 
of the lower extremities (FES-LE) is utilized clinically for PWMS; however, there is a lack of research, which 
supports its efficacy on gait, endurance, transfers and quality of life (QOL).  Previous studies regarding FES-LE 
cycling for PWMS were conducted on individuals with greater disability levels than those proposed in this study 
and did not measure the impact of this rehabilitation tool on quality of life.2,3 Previous studies have 
methodological weaknesses and lacked a sufficient number of subjects, a comparison group or a standardized 
progression protocol.  This study will seek to determine the benefits that FES-LE cycling has over cycling alone 
on walking performance and quality of life in PWMS. 
   
AIM 1: To determine if there is a difference between FES cycling and cycling only in PWMS on temporal 
and spatial components of gait.  
Walking speed is a commonly used measure in clinical practice and has been cited in the literature as 
the “sixth vital sign.”4 Gait speed will be measured using the Timed 25 meter walk test (T25FW) and 
participants will be instructed to walk at a “fast but safe speed” consistent with a protocol as suggested by 
Gijbels et al5 and Bethoux and Bennett.6   This measure was chosen since it is commonly used as part of the 
Multiple Sclerosis Functional Composite, its clinical utility, and ease of administration. 7   
Goldman et al examined changes in the T25FW in relation to changes in life roles.8 A T25FW of 6 to 
7.99 seconds is related to a change in occupation, unemployment, walking with a device and/or the need for 
some help with instrumental activities of daily living (IADL) while walking speeds greater than or equal to 8 
seconds are related to the need to use a walker and inability to perform IADLs.8  
In addition to the T25FW, a wireless inertial sensor (BTS G-Walk) will be used to collect gait and 
movement data during all physical outcome measures.  Evidence supports that body-worn motion sensors 
provide additional information about gait and balance that standard timed walking tests may not detect.9  
 

 
 
 
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AIM 2:  To determine if there a difference between FES cycling and cycling only in PWMS on quality of 
life measures.   
The MSQOL-54 is a multidimensional self-report quality of life questionnaire that takes 15-30 minutes 
to complete (permission to use MSQOL-54 received from Barbara Vickry, MD, MPD, via email communication, 
March 21, 2014).10 It measures health-related quality of life using both generic and disease specific measures 
and was constructed by experts in the field. 10 This measure was chosen since it is more comprehensive than 
other MS disease-specific quality of life scales and is recommended for use amongst international experts who 
participated in a multidisciplinary consensus meeting.11 
 
AIM 3:  To determine if there a difference between FES cycling and cycling only in PWMS in the 6 
Minute Walk Test. 
The 6MWT measures a person’s self-paced walking distance over a 6 minute period and is a valid and 
reliable measure of walking performance in PWMS.12–14 The 6MWT was found to have excellent test-retest 
reliability (ICC= .96, 95% CI .87- .99) over a one-week interval in PWMS (EDSS 2.0 – 6.5).15 Pilutti et al also 
found there to be a significant difference between the 6MWT performance in PWMS with mild vs. moderate to 
severe disability (mild= 530.7m, range 292.6 - 782.1m, moderate to severe= 349.8m, range 51.5 – 605.3m, p < 
.0001).16   It was also found that PWMS (EDSS 2 -6.4, median 4.0) classified as fallers demonstrated a 
significant difference in the their 6MWT distance compared to a group of non-fallers (fallers= 1288 feet, non-
fallers= 1533 feet, t= 2.2, p= .02).17 
Cadence and stride length have been found to explain difference in 6MWT performance in people with 
mild vs. moderate and severe MS when controlling for age (F[2,299}= 38.17, p<.001, partial –η2= .20; 
F[2,299}= 44.30, p<.001, partial – η 2= .23, respectively) but there was no significant difference in cadence 
between a control group and people with mild MS (p= .06).16 Using a regression analysis these researchers 
also found that cadence and stride length explained the difference in the 6MWT between PWMS and 
controls.16     
 
AIM 4:  To determine if there is difference between FES cycling and cycling only in PWMS in the 5 
Times Sit-to-Stand (5STS). 
The 5STS is a timed test that measures how long it takes for an individual to transition from standing to 
sitting for 5 repetitions.  Evidence supports that sit-to-stand tests may be appropriate, time efficient tests to use 
in the clinical setting to assess LE strength.18,19 A strong relationship between a 10 times sit-to-stand test and 
knee extensor and flexor strength was found in a 139 healthy individuals ages 20-62.18 Currently, there is no 
data available that demonstrates the reliability or validity of the 5STS in PWMS.   The 5STS has been found to 
be a valid and reliable measure of fall risk in people with PD20 and the older adult population.21,22  
 
B. BACKGROUND AND SIGNIFICANCE 
 

 
 
 
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MS is a disabling neurodegenerative disorders that can result in severe disability affecting every facet of an 
individuals life, creating a financial burden on the individual, family, health care system, and society.23 It is 
important for clinicians and people living with MS to have a variety of safe and effective tools to treat 
individuals with this long-term, progressive disease.  Due to the lack of research on the use FES-LE cycling in 
PWMS, this study will compare the effectiveness of FES-LE cycling to cycling alone, on variety of objective and 
subjective measures that span the ICF model and are easily applied in contemporary clinical practice. 
 
A common complaint amongst PWMS is gait and balance disturbances including falls.24 People with MS 
report a fall incidence of greater than 50% and this incidence increases as individual’s age and the disease 
progress.17,24When a large group of PWMS were surveyed the activities where they reported the most frequent 
falls included transfers, ambulation, standing activities, stairs/curbs, and during exercise/physical activity.24 
Individuals with greater disability in ambulation tend to achieve less than the recommended daily activity levels 
when compared than those individuals without ambulation limitations.25 
Exercise and living an active lifestyle are beneficial to PWMS.26,27 Individuals who exercise often report a 
decrease in the perception of fatigue.28 Improvements in fatigue outcome measures have been reported in a 
variety of exercise types including: high-intensity resistive exercises,29,30 yoga,31 and endurance/aerobic 
exercises.32 In addition, physically active PWMS monitored by accelerometers reported lower levels of 
disability, depression, fatigue, and pain.33  
In a time where healthcare dollars are being stretched and cost containment is on the forefront, therapists 
need to be efficient with their time, finding interventions that target multiple body structures while addressing 
activity limitations, participation and QOL.  The use of an intervention that combines resistance and aerobic 
training that provides a repetitive motion may be an effective tool for people with multiple sclerosis (PWMS). 
Functional Electrical Stimulation (FES) is a rehabilitation tool that stimulates intact peripheral motor nerves 
via electrical current evoking muscle contractions for the purpose of functional movement.34 It has been utilized 
in patients with paralysis or weakness due to upper motor neuron lesions.35 The use of FES in rehabilitation 
dates back to the early 1960’s with the use of a heel switch that triggered short bursts of electrical stimulation 
to the peroneal nerve resulting in ankle dorsiflexion.36 FES has evolved over the last 50 years and has been 
used to supplement or replace lost function due to neurological dysfunction.  It has been applied to assist 
individuals with activities such as reaching, grasping, walking, and cycling.37   
Functional Electrical Stimulation combined with lower extremity (FES-LE) cycling creates patterned 
movement of the legs and assists individuals with impaired voluntary control of their muscles in completing the 
cycling task.  It has be utilized in a wide variety of patient populations including, but not limited to, spinal cord 
injury, stroke, traumatic brain injury, parkinson’s disease, cerebral palsy and MS. Studies conducted in the 
stroke and SCI populations have demonstrated improvements in gait velocity, muscle mass, circulation, bone 
density, and range of motion, as well as a reduction of muscle spasms.38–42 For PWMS, several studies have 
documented the use of electrical stimulation (ES) for single muscle groups and few studies have applied it to 
multiple muscles using a FES-LE cycling training paradigm. 2,43–46  

 
 
 
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C. PRELIMINARY STUDIES 
Multiple studies report that PWMS benefit in a variety of ways from resistive and aerobic training.47–49 
Exercise equipment that can offer a safe, moderate intensity workout is readily available in the typical gym 
environment but this may not be the best option for PWMS that demonstrate gait or balance difficulties or need 
assistance transferring.  What makes FES-LE cycling different that other equipment is that once a person is 
familiar with FES-LE cycling it can be performed in the home environment, therefore offering options to those 
who do not have time or ability to travel outside the home or who have limited therapy through their insurance.   
There are a handful of small studies consisting of case reports and pilot studies that have examined the 
efficacy and effectiveness on FES cycling for PWMS.2,3,46,50 A review of the literature yields no randomized 
control trials or quasi-experimental studies in this specific area of research.  Krause, Szecsi, and Straube46 
report a single case study of a non-ambulatory, 46 year-old man with secondary progressive MS with an EDSS 
score of 7.5.  The investigators bilaterally stimulated three muscle groups during cycling: the gluteals, 
quadriceps, and biceps femoris.  This individual was able to tolerate 30 minutes of cycling with short 3-5 
minute breaks and did not experience difficulty tolerating the stimulation.  They reported he tolerated 
stimulation amplitudes up to 90mA but did not report the chosen frequency or pulse width for this patient.   This 
individual experienced a reduction in spasticity after each of the two training sessions as measured by the 
Modified Ashworth Scale (MAS) and the pendulum test.    The authors did not measure spasticity reduction 
hours or days later, therefore no conclusions can be made regarding the long-term effectiveness.  In addition, 
there were no outcomes or subjective descriptions reported that related this reduction of spasticity to gait, 
functional movement patterns, or quality of life. 
Szecsi et al examined the effect of FES-LE cycling on biomechanical and functional outcomes.3 Eight 
PWMS completed the FES-LE cycling training 3 times per week, each only 6 minutes long, for 2 weeks while 
also receiving conventional therapy.3 No adverse reactions were reported but four subjects dropped out, 
reasons provided were: change of schedule, change of medications, failure to comply, and difficulty with 
transfers due to a high degree of disability.3 Their quadriceps and hamstrings were stimulated in bilateral lower 
extremities during the stimulation trials.3 They utilized a fixed frequency of 20 Hz, a maximal amplitude of 127 
mA, and a fixed pulse width of 300 μsec.3 These settings may not be optimal to elicit strong contractions in all 
PWMS.  A frequency of 20 Hz is on the low end of what is recommended for FES-LE cycling and in a study by 
Eser et al, it was demonstrated in people with motor and sensory incomplete injuries that higher frequencies 
(50 and 60 Hz) demonstrate larger power outputs when pulse width and amplitude are held constant.51   
In another study by Szecsi et al the effects of cycling both with and without stimulation within each cycling 
session was studied.3 Symmetry of pedaling and power output was examined at various intervals during the 
study.3 Subjects with MS were able to achieve greater cycling power and symmetry of pedaling with FES than 
without FES.3 Functional outcomes were measured both before and after training and included the 10 MWT, 
MAS and Manual Muscle Testing (MMT).3 There were no significant changes in these measures except for a 

 
 
 
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short-term reduction in spasticity before and after each training session.3 Subjective feedback from participants 
revealed reports of increased functional abilities (e.g. transfers, stairs, activities of daily living) and quality of 
gait, such as improved leg lifting.3 It is unknown if more functional improvement would have been revealed if 
the training period were longer and more intense.  The training period is in this study was significantly below 
the exercise recommendations for PWMS.    
In a pilot study by Ratchford et al the research team examined the relationship between FES-LE cycling 
and function.2 Four individuals with primary or secondary progressive MS completed the study with EDSS 
ranging from 6.0 to 6.5 inclusive.  Individuals performed FES cycling in the home environment using an FES 
cycle (RT300) for 6 months.2 In addition to looking at impairments and functional measures at baseline, 3 
months, and after the 6 month period, they also examined the relationship between FES cycling and changes 
in cytokines and growth factors in cerebral spinal fluid (CSF).2 Participants were trained to use the FES cycle in 
their home and started with the same initial settings: a symmetric biphasic waveform, phase duration 250 
microseconds randomized ± 25%, and a frequency 33 to 45 pulses per seconds.2 Electrical stimulation was 
applied to the quadriceps, hamstrings, and gluteal muscles.2 There were no serious adverse advents but one 
participant reported an increase in spasticity, which was treated by an increase in their Baclofen dose.2 
Another participant with a history of irritable bowel syndrome reported increased bowel incontinence and this 
was remedied by adjustments in this individuals bowel program.2   
The outcomes of the Ratchford et al study were favorable but because of insufficient power, statistical 
interpretation was limited.  Participants were asked to cycle three times per week for one hour sessions.2 The 
mean number of sessions per week was 3.8, demonstrating that these individuals were able to tolerate training 
for the suggested time period.2 The average power output and mean distance per session over the first two 
weeks and the last two weeks were 3.2 watts and 9.9 miles and 4.6 watts 10.6 miles, respectively.2 The 
improvements in the main neurologic measures, the Two Minute Walk Test (2MWT), Timed 25-foot Walk Test, 
and the TUG, were 13%, 36%, and 22%, respectively.2 Investigators also observed improvements in self-
selected walking speed, double support time, and step length coefficient of variation, as measured on the 
instrumented GAITRite walkway.2 Results showed a decrease in pro-inflammatory cytokines and an increase 
in nerve-related growth factors in the PWMS who performed FES cycling when compared to healthy controls.2 
These preliminary findings suggest that FES cycling may reduce inflammation and promote neuronal repair 
along with improvements in clinical outcome measures.2   
In the largest retrospective study to date Hammond et al reported on 40 individuals who participated in a 
long-term FES-LE cycling program for 15 months.52 The sample of subjects had EDSS scores ranging form 2.5 
– 7.5 and were distributed across the three main types of MS (RRMS, SPMS, PPMS).52 Their main outcome 
measure was the EDSS and the International Standards for Neurological Classification of Spinal Cord Injury 
(ISNCSCI).  The ISNCSCI is an evaluation tool that examines sensory and motor function as well as anal and 
perianal function, but has yet to be validated in the MS population.52 Details regarding duration, intensity, 
stimulation parameters, and muscles stimulated were not published.  EDSS and ISNCSCI scores remained 
stable over the 15 month periods and in those with PPMS and RRMS, there was a slight decrease in EDSS 

 
 
 
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score, noting improvement in disability, although it was not statistically significant.52 Based on this study, long-
term FES cycling use may help to stabilize or prevent disease progression in PWMS. 
The results of the FES-LE cycling MS studies described above stimulated different muscles and utilized a 
variety of training protocols and stimulation parameters.2,3,46,50,52 In addition, it does not appear that any of the 
investigators chose to stimulate the tibialis anterior or gastrocnemius musculature, which are both integral 
muscles for efficient gait.  The anterior tibialis is the primary muscle utilized for clearing the foot during heel 
strike and swing and the gastrocnemius plays an integral role in the propulsion of gait during swing phase, both 
of these muscles can be effected in PWMS.53 
Based on review of research studies, the dosage of FES-LE cycling in this study will be 3 times per week 
for 8-week duration and will be applied to bilateral LEs and five muscle groups including the gluteals, 
quadriceps, hamstrings, tibialis anterior and gastrocnemius.  A progressive interval-training regime will be 
employed and each training session will last a total of 45 minutes and participants will be progressed 
accordingly using a systematic progression protocol.  
 
D. RESEARCH DESIGN AND METHODS 
  
1. Rationale/overview 
This study will be a prospective pretest-posttest comparison group design with repeated measures.  
The purpose of this study will be to assess the immediate and short-term effects of an 8-week LE cycling 
program on motor function, mobility and QOL for PWMS.  The goal of this study is to examine if FES-LE 
cycling is more effective than cycling alone.  Groups will be compared to determine changes in spatiotemporal 
gait characteristics, quality of life, endurance, and ability to transition from sit to stand following training. 
 
2. Research Site 
 
The study will be conducted at Stony Brook University’s (SBU) Rehabilitation Research and Movement 
Performance (RRAMP) laboratory in Stony Brook, NY.  An FES-LE ergometer (RT300, Restorative Therapies, 
Inc., Baltimore, MD) and a BTS G-Walk system along with BTS G-Studio software (BTG Bioengineering, viale 
Forlanini 40, 20024 Garbagnate Milanese MI, Italy and 147 Prince Street, Suite 11, Brooklyn, NY) will be 
utilized in this study.    
 
3. Study sample 
 
Twenty participants with a diagnosis of MS, at least 18 years of age who meet the inclusion/exclusion 
criteria (Table 1), will participate in this study.   
 
 

 
 
 
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Table 1 Inclusion and Exclusion Criteria 
Inclusion Criteria 
Exclusion Criteria 
Medical Diagnosis of MS 
Cognitive deficits (score < 22/30 on the 
Montreal Cognitive Assessment) that would 
interfere in their ability to sign consent and 
understand the procedures for the study. 
At least 18 years of age, inclusive 
History or presence of other neurological 
pathologies that interfere with movement 
Patient-determined Disease Steps (PDDS) 
score between 3.0 and 6.0 inclusive 
Received physical therapy within the last 4 
weeks prior to the study 
Ability to attend training sessions 3 times per 
week for an 8-10 week period 
History of an acute exacerbation of their MS 
symptoms within 4 weeks prior to the study 
Passing a submaximal exercise tolerance test 
Immunosuppressive or steroid therapy within 
the past 4 weeks 
Adequate hip range of motion (at least 110 
degrees) 
Significant spasticity (Modified Ashworth Score 
≥ 3 at the quadriceps and hamstring muscles) 
in the LE’s that interferes with the cycling 
motion 
Adequate knee range of motion (10-90 
degrees) 
History of congestive heart failure 
 
Coronary artery disease 
 
Uncontrolled hypertension 
 
History of epilepsy or history of seizures 
 
Cardiac demand pacemaker or implanted 
defibrillator 
 
Unhealed fractures in the lower extremities 
 
Pressure sores or open wounds on the LEs 
 
Pregnant or trying to conceive.     
 
4. Screening 
 
Potential participants will undergo a phone screening prior to their initial visit.  If the participant meets all 
the inclusion/exclusion criteria, they will be asked to set-up an appointment to meet with the primary 
investigator at the RRAMP lab.  At that time, consent will be obtained and the baseline measures will be 
gathered and participants will be randomized into either the FES cycle group or the cycling only group.  
Participants will undergo a subjective and objective evaluation to determine if they meet the inclusion and 
exclusion criteria that were not able to be determined via phone screening.  This evaluation will include an 

 
 
 
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assessment of cognition using the Montreal Cognitive Assessment (MoCA),54 joint range of motion using a 
goniometer, degree of spasticity, presence of spinal reflexes, sensory function, motor function, and functional 
mobility. Cognitive screening will be performed to screen for participants capacity to provide informed consent, 
understand basic instructions, and provide feedback during training sessions.  There does not appear to be a 
universally accepted screening measure to determine capacity to give informed consent in research studies 
but the screening should be related to the risks presented by the research.55 Although this study presents 
minimal risk to participants, it will be important for participants to have an understanding of the equipment and 
protocol being utilized.     
The assessment for exercise tolerance will follow the American College of Sports Medicine (ACSM) 
guidelines.56,57 ACSM recommends that before beginning an exercise regimen, professionals employ two or 
more techniques to measure relative intensity.56 ACSM suggests using submaximal testing56 as practical 
approach to testing since most physical therapists do not have the necessary equipment for metabolic testing.  
To monitor relative intensity, heart rate (HR), blood pressure (BP) and rating of perceived exertion (RPE) will 
be measured during a graded exercise test.56   A submaximal clinical exercise tolerance test (SXTT) will be 
measured on a LE ergometer since it is best to do testing on the piece of equipment that will be used for 
training.58   
The ACSM recommendations when performing exercise testing for persons with MS will be followed 
during this study.59 These recommendations include: 
 
testing in the morning if this is the optimal time for the participant 
 
beginning  with a warm-up of unloaded pedaling 
 
using of a fan for cooling 
 
using a continuous or discontinuous protocol of 3 to 5 minute stages with an increase of work rate 
of approximately 12 to 25 Watts (W) per stage 
 
monitoring heart rate and blood pressure 
 
using the RPE scale to estimate stress level (Appendix H– RPE Scale).56  
In this study, the SXTT will be conducted on the RT300 LE ergometer since it is the equipment being 
utilized during the study.  HR and pulse oxygen will be measured in sitting at baseline and then recorded in 
during the last 5 seconds of each interval during clinical testing.57 BP will be measured and recorded in sitting 
at baseline and during the last 45 seconds of each interval.57 The RPE scale will be explained to participants at 
rest and recorded during the last 15 seconds of each interval.  Data from the SXTT will be recorded on the 
participant data sheet.  Participants will be asked to cycle at a target speed between 35-45 rpm, while the PT 
systematically increases resistance. The participant will start with unloaded cycling and every 3 minutes the 
resistance will be increased by 3 Newton-meters (Nm) per stage which is approximately 14 Watts per 
stage.59,60   The SXTT will be discontinued when the participant reaches self-reported fatigue or if their vital 
signs fall outside a safe range.  Maximal workload will be defined at the last completed interval before 
termination. 

 
 
 
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ACSM’s guidelines for discontinuing testing include:57,60 
 
self-reported fatigue- participant expresses they can no longer pedal due to fatigue.  
 
reaching 70% heart rate reserve which is 85% of age-predicted HRmax, (HR max = 220 – age x .85).   
 
Failing to conform to exercise protocol, which for this study will be defined as falling 10 rpm below 
the target rpm speed of 35-45 for greater than 10 seconds. 
 
hypotensive responses-  systolic blood pressure drops ≥ 10 mm Hg from baseline.57 
 
hypertensive responses-  systolic blood pressure > 250 mm Hg  and/or a DBP of  > 115mm Hg.57 
 
symptom exacerbation58,59-  including headache, change in vision, numbness, sudden paralysis, 
dizziness, vertigo 
 
chest pain, shortness of breath, wheezing,  and leg cramps.57 
5. Procedures 
Outcome measures were selected based on the International Classification of Functioning, Disability, 
and Health (ICF) model, recommendations from the APTA Neurology Section’s Multiple Sclerosis Outcome 
Measures Taskforce,61 clinical expertise, and research goals of the current study (Table 3).  Members of the 
taskforce developed specific recommendations for practice environments (entry-level education, research, acute 
care, inpatient and outpatient) and also rated each outcome on a 4-point ordinal scale (4= highly recommended, 
the outcome measure has excellent psychometric properties and clinical utility;3= recommended, the outcome 
measure has good psychometric properties and good clinical utility; 2= unable to recommend at this time, there 
is insufficient information to support a recommendation of this outcome measure; 1= not recommended, the 
outcome measure has poor psychometric properties and/or poor clinical utility).  All measures that were 
recommended for research were considered if they were rated a 3 or 4.62 
The chosen battery of outcome measures for this study will be:  12 Item Multiple Sclerosis Walking 
Scale (MSWS-12), Modified Fatigue Impact Scale (MFIS), Multiple Sclerosis Quality of Life Inventory 
(MSQOL 54), Activities Specific Balance Scale (ABC), Godin Leisure-Time Exercise Questionnaire (GLT), 
Timed Up and Go, 5Times Sit-to-Stand , 6 Minute Walk Test, and Timed 25-Foot Walk. 
Selected outcome measures will be performed at the follow four intervals:  
 baseline- within one-week prior to the first training session;  
 mid-point of training- before training session #13; 
 post-training- between 1-3 days after the 24th training session, and  
 approximately one-month after the last training session. 
Physical tests will be administered in the following order for each participant: 6MWT, T25W, TUG, and 
5STS.  Participants will be provided at least a five-minute rest period between all physical tests.  Safety 
precautions during testing will include: a quiet area free of distractions, gait belt, guarding and assistance as 

 
 
 
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needed.  In order to measure both temporal and spatial gait parameters, the BTS G-Walk (BTG Bioengineering, 
viale Forlanini 40, 20024 Garbagnate Milanese MI, Italy and 147 Prince Street- Suite 11, Brooklyn, NY) will be 
utilized to collect gait data during the 6MWT, TUG, 5STS, and T25FW.   The G-Studio software will 
automatically generates spatio-temporal parameters including:  speed, cadence, stride length, step length, gait 
cycle duration, stance duration, swing duration, and single and double phase duration.   
 
Table 2. 
Outcome measures 
Outcome Measure 
Collection of Data 
Godin Leisure-Time Exercise Questionnaire (GLTEQ)a, p 
 
 
Baseline 
 
12 Item Multiple Sclerosis Walking Scale (MSWS-12)a 
 
Baseline 
 
Post-training 
 
1 month after training 
Modified Fatigue Impact Scale (MFIS)b, a, p 
 
Baseline 
 
Post-training 
 
1 month after training 
Multiple Sclerosis Quality of Life Inventory (MS-QOL 54)a, p 
 
Baseline 
 
Post-training 
 
1 month after training 
Activities Specific Balance Scale (ABC)p 
 
Baseline 
 
Post-training 
 
1 month after training 
Timed Up and Go (TUG)A 
 
Baseline 
 
Mid-point  
 
Post-training 
 
1 month after training 
Five Times Sit-to-Stand (5STS)A 
 
Baseline 
 
Mid-point 
 
Post-training 
 
1 month after training 
6 Minute Walk (6MWT)A 
 
Baseline 
 
Mid-point  
 
Post-training 
 
1 month after training 
Gait SpeedA 
Time 25-Foot Walk (T25FW)A 
Cadence, Gait symmetry, Stance duration, Swing duration, 
Single and double support phase duration, Step length, Stride 
length, Gait cycle durationA 
 
Baseline 
 
Mid-point  
 
Post-training 
 
1 month after training 
ICF Model Domain:  B, Body Structures & Function; A, Activity; P, Participation 
 
Video Recording 
This research project may include video recording during any outcome measure testing or cycling 
sessions for periods of minute or less.  Particapants will only be videotaped if they initial the video 
recording section on the consent form that indicates they give the PI permission to videotape.  This video 
recording will be available to be seen by the researcher, the Internal Review Board (IRB), any granting 
agencies, my dissertation committee, physical therapists and physical therapy students.  If this video is 
used in papers or talks, we will make sure your face is not visible.  We will keep this video in a locked 

 
 
 
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cabinet in RRAMP lab.  You can request not to be videotaped and this will not affect your eligibility or 
participation in the study. 
 
 
Training Protocols 
Participants will train for 45 minutes, three-days per week, for eight-weeks using an FES-LE cycle 
(Figure 3; Table 6) (RT300, Restorative Therapies Inc., Baltimore, Maryland, USA).  Basic demographic 
information (age, weight, and diagnosis) will be entered into Restorative Therapies Internet (RTI) Data Link and 
a random ID number will be generated and subjects will choose their own 4-digit pin number.  The participant 
number will be used as the participant ID number on all paperwork associated with the study.  
For FES-LE cycling, stimulated muscles will be standardized and will include the gluteals, hamstrings, 
quadriceps, anterior tibialis, and gastrocnemius.  At the beginning of every session, the skin will be cleaned 
with alcohol and dried prior to placing the electrodes on the skin.  Each participant will have their own set of 
electrodes that will be labeled with their participant number and will be stored at the research lab.  Electrodes 
will be placed according to the guidelines outlined and participant morphology (Table 5; Figure 7).   Before and 
after each training session, skin will be inspected for erythema, breakdown and/or irritation.    
Expirations dates on the electrodes will be checked prior to the commencement of training.  The 
manufacturer of the electrodes recommends that each electrode can be used for a maximum of 10-15 
sessions.  If an electrode no longer adheres appropriately to the skin, it will be discarded and a new electrode 
will be utilized.  In order to track usage, each participant’s package of electrodes will be labeled with the date 
and participant identification number. 
Table 7. 
Electrode sizing and placement 
Muscle 
Electrode 
Size 
Location of placement 
Quadriceps 
3” X 4” 
One will be placed one hand width above the knee 
centered on the belly of the quad and the second electrode 
will be placed at least a hand width above the first 
electrode. For participants with a longer thigh length, it will 
be placed higher in the middle of the quad belly. 
 
Hamstrings 
3” X 4” 
Electrodes will be placed directly underneath where the 
quad electrodes are centered in the middle of the 
hamstrings.   
Gluteals 
2” X 3.5” 
One electrode will be placed vertically with the top of the 
electrode parallel to the top gluteal cleft and the second 
electrode two-finger widths lateral to the first.   

 
 
 
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Anterior Tibialis 
1-2” x 4" and 
1- 2” X 3.5” 
One electrode will be placed proximally on the muscle 
belly and the second electrode will be placed distally about 
2/3 way down the shin. 
Gastrocnemius 
1-2” x 4" and 
1-2” X 3.5 
One electrode will run horizontal across the calf, just below 
the knee and the second electrode will be a minimum of 
two-finger widths below the first electrode just distal to the 
gastrocnemius belly. 
*The electrode sizes above are guidelines and will be adjusted for participant morphology.  If some is smaller 
than average, they may require smaller size electrodes in order to avoid overflow to other muscle groups. 
 
Participants will be positioned in a standard waiting room chair and their legs will be positioned on the 
pedals and secured with Velcro strapping according to the manufactures recommendations.  The bike and 
chair will be positioned to maintain 5-15 degrees of knee flexion when in the fully extended position of cycling.  
The height of the ergometer will be adjusted so that the rear of the participant’s thigh does not press into the 
seat cushion as they cycle.  A back support may be placed behind the participant as needed.  When 
necessary, adjustments to seat height and depth will be made utilizing cushions in order to optimize positioning 
and cycling angles.   
Setting Initial Stimulation 
After all initial measures are obtained, initial stimulation settings will be set during the baseline testing 
session prior to the training period.  Frequency for all participants will be at 43.5Hz for all muscle groups and 
will not be changed throughout the study.  During this baseline session all muscle groups will be turned on at 
the same time while the participant passively cycles (i.e. motor of the cycle is moving their legs) with the pulse 
width starting at 250 μsec for all muscle groups.  Amplitude will ramp up at 1% per second and the participant 
will be instructed to tell the investigator to limit the stimulation when the feel any of their muscles reach a point 
where the stimulation is starting to get uncomfortable.  The investigator will then adjust each muscle group 
individually to its maximal tolerable stimulation while the participant continues to passively cycle.   Adjustments 
in amplitude will be increased in increments of 1mA increments until a participant achieves a maximal but 
tolerable muscle contraction.  If a participant’s tolerance to stimulation is reached before a detectable 
contraction is palpated pulse width will be decreased by 10μsec increments and amplitude will be adjusted by 
1mA increments until a maximal muscle contraction to their tolerance is achieved.  The maximum level will be 
set at the value that has been determined to create a strongest tolerable motor response.   If a participant is 
still unable able to achieve a muscle contraction due to discomfort, the highest stimulation parameters they 
reached will be used and parameters will be adjusted during training sessions as they accommodate to the 
stimulation.  All initial settings will be automatically saved in RTI Data Link.  
FES Training Session Protocol 
The participant’s stimulation levels from their previous session will be used as starting parameters for 
each session.  If during training sessions the participant can tolerate more stimulation, amplitude will be 

 
 
 
14 
increased in 1 mA increments.  If they reach the maximum amplitude level of 140ma and can tolerate more 
stimulation, pulse width will be increased by 10μsec increments. 
Participants will experience a 2-minute warm-up period in which the ergometer’s motor provides 
passive cycling and moves the participants’ legs.  This will allow for the participant to work out any spasms or 
stiffness they may be experiencing.  The ergometer will then transition into “active mode” in which the electrical 
stimulation slowly ramps up to allow the individual to accommodate to the stimulation.  During this period, the 
participant will receive stimulation while also using their own muscle power against a set resistance while 
working to maintain a set target speed of 35-45 rpm.  In order to have participants working at a moderate 
intensity, starting resistance will be set at 60% of the maximal workload from the submaximal clinical exercise 
tolerance test (SXTT).58 Workload will then be progressively increased to a maximum of 80% of the workload.58  
Participants will be encouraged to cycle continuously for at least 45 minutes using an interval training 
protocol. They will cycle for 5 minutes with stimulation and then 1 minute passively cycle without stimulation.  
This 5:1 (5 minutes of active cycling with stimulation: 1 minute passive cycling without stimulation) cycle will 
repeat 7 times during the session.  Participants will then receive a 1-minute cool-down at the end where they 
receive no stimulation and the cycles motor passively moves the lower limbs.  
Since individuals in this study will have some degree of volitional control to cycle faster than their 
control speed, stimulation minimums/maximums will be set to the same level to ensure stimulation does not 
drop below the therapeutic level for each muscle group, therefore no matter how fast the participant cycles the 
stimulation will remain on during the 5 minute stimulation period.  The RT300 can provide ‘motor support” and 
the ergometer will be set for the participant to receive ‘motor support’ throughout the cycling period if they are 
not maintaining their target speed.    
If at any time during training a participant reports fatigue and needs to discontinue cycling, stimulation 
will be discontinued and the participant will continue the rest of their session in passive mode with the motor 
fully assisting their movement for the remainder of the therapy session (Figure 7). Once a participant can cycle 
the full 45 minutes using the 5:1 protocol, resistance will be increased by 5% increments every 3 sessions.   
The following instructions will be used prior to each training session: 
 “You will be cycling for 45 minutes.  The first 2 minutes are a warm-up period in which the cycle is taking 
you through the cycling motion, so just relax and let the bike do the work.  After the warm-up, start to 
actively cycle at a moderate effort level.  The stimulation will slowly ramp up over a 2-minute period to the 
stimulation levels we set during the previous session.  If at any time the stimulation gets uncomfortable, 
please let me know and we can adjust the stimulation for each muscle group.   You will cycle actively for 5 
minutes and then receive a 1-minute break where the cycle will do all the work.  This pattern of 5 minutes 
on, 1 minute off, will repeat 7 times during your training session.  If at any time you experience fatigue, 
please let me know and you can take a break for up to 5 minutes and then continue where you left off.  The 
cycle is set to go into a passive cycling mode if your speed falls 10 rpm below the set target speed of 35-45 
mph.  The stimulation will be turned off and you will finish the remainder of the session allowing the bike to 
do all the work.  If you feel that you cannot continue with passive cycling, please let me know and we can 
finish the session at anytime.” 
 
Cycling-only Protocol 

 
 
 
15 
Participants in this training groups the will be set-up on the RT300 in the same manner as those in the 
FES training group but they will not receive electrical stimulation nor wear stimulation pads; they will use the 
RT300 as an ergometer only.  During the cycling-only phase, participants will cycle continuously for 45 minutes 
using an interval training protocol (5 minutes of active cycling: 1 minute passive cycling) at a set target speed 
of 35-45 rpm.  This 5:1 cycle will repeat 7 times and then go into a 1-minute cool-down.  Total active cycling 
time will be 35 minutes.  If a participant needs a rest the cycle can go into passive mode and the motor of the 
cycle will provide full support.   Once the participant is able to tolerate 45 minutes of cycling without rests at or 
above the specified target speed, the resistance will be increased in 5% increments every 3 sessions.  
Participants in both groups will receive feedback from the screen on the bike (Figure 8) during and after 
their treatment sessions, including distance traveled, right to left cycling symmetry, heart rate and oxygen 
saturation.   
The following instructions will be used prior to each training session: 
 “You will be cycling for 45 minutes.  The first 2 minutes are a warm-up period in which the cycle is taking 
you through the cycling motion, so just relax and let the bike do the work.  After the warm-up, start to 
actively cycle at a moderate effort level.   You will cycle actively for 5 minutes and then receive a 1-minute 
break where the cycle will do all the work.  This pattern of 5 minutes on, 1 minute off, will repeat 7 times 
during your training session.  If at any time you experience fatigue, please let me know and you can take a 
break for up to 5 minutes and then continue where you left off.  The cycle is set to go into a passive cycling 
mode if your speed falls 10 rpm below the set target speed of 35-45 mph.  If that occurs, will finish the 
remainder of the session allowing the bike to do all the work.  If you feel that you cannot continue with 
passive cycling, please let me know and we can finish the session at anytime.” 
 
RT 300 Features 
The RT300 has several features that will be utilized during this study.  One feature is the “control speed 
offset.” If a participants cycling speed falls below the target speed by a pre-set revolutions per minute (rpm), 
the ergometer’s motor will take over for the remainder of the session and assist the participant.  The control 
speed offset will be set at – 10 rpm for all participants.  The target speed for all participants will be 35-45 rpm 
and if a participant’s speed falls below 35 rpm the ergometer’s motor will take over and the cycle will finish the 
session in passive mode.     
The SAGE stimulator also monitors electrode adherence and if an electrode falls off the system pauses 
and ceases stimulation and the motor turns off.   An error message will be displayed on the screen telling the 
user which electrode needs to be checked.  Once the electrode is secured, the session can continue.  
If at any time a participant feels light-headed, nauseous, or dizzy during the training session or if their 
parameters fall outside the ACSM exercise guidelines, training will be discontinued for the remainder of the 
session.   
All participants will be continuously monitored by a wireless heart rate and pulse oximeter with set 
parameters. Target HR goal for each participant will be set at 65% of their age-adjusted max HR (200 - age x 
.65). The maximum heart rate with set at 85% of age-adjusted max HR (220-age x .85).  Participants will be 
encouraged to keep their HR within a 65% to 85% range.  If a participant goes above their maximum heart for 
greater than 10 seconds, the ergometer and session will be paused and the participant will be given a 3-minute 

 
 
 
16 
rest until their HR comes down to their target heart rate.  If their HR does not come down into the appropriate 
range, they will continue the remainder of the session in the passive cycling mode.  The minimum heart rate 
will be set at 5 bpm below the participants resting baseline to allow for normal HR variability that can occur 
from day-to-day. 
If oxygen saturation (SPO2) falls below 88% the session will be paused and the participant will be 
instructed to perform deep breathing.   Once the participant is back to their baseline SPO2 saturation, they will 
be permitted to resume.  They will be allowed a maximum of 5 minutes to achieve baseline.  If they do not 
achieve their baseline within 5 minutes, they will continue the remainder of the session in the passive cycling 
mode.   
 
E.  STATISTICS 
 
Data Interpretation 
This study will follow an experimental pretest-posttest comparison group design with selected 
measures at baseline, 4 weeks (half-way through the intervention), 8 weeks (end of the intervention), and one-
month after training is completed (follow-up). 
Descriptive statistics, including frequency counts for categorical variables and measures of central 
tendency and dispersion for continuous variables will be calculated.  Baseline demographic data will be 
compared across treatment groups to assess the adequacy of randomization using the Mann-Whitney for 
continuous data and chi-square tests of independence for categorical data.  
The hypotheses of the research study will be examined using the Permutation Test for Paired 
Replicates with the treatment group (FES cycling vs. Cycling only) as the between participants independent 
variables and time (baseline and 4 weeks, 8 weeks, and 1 month) as the within subjects independent variable.  
This non-parametric statistical test was chosen due to the small sample size.   
All dropouts, and the reason for dropping out of the study, will be reported. A priori alpha level of 0.05 
will be used for all data analysis.   Interquartile ranges for all for all outcome measures will be reported. 
Data will also be analyzed using a Spearman’s rank correlation to see if there is a relationship between 
GLTEQ scores, which measures pre-training activity levels, and the participants post-training gait speed and 
6MW.  All data analysis will be performed using IBM SPSS statistics software. 
 
F. FUNDING STATUS, DETAILS 
 
No funding for this study has been secured at this time.   
 
 
G.  HUMAN SUBJECTS RESEARCH PROTECTION FROM RISK 
 
Risk to Subjects 

 
 
 
17 
 
This research protocol and risk to participants is minimal.   
 
 
Adequacy of Protection Against Risks 
Participants will be closely guarded by a trained investigator during all physical outcome measures and 
will be wearing gait belt, therefore the fall risk is this experiment is comparable to the risk individuals 
incur during everyday walking.  During training, participants will be seated and risk of injury is minimal.  
Participants may become tired or fatigued during training and rest breaks will be permitted.   
 
Potential Benefits of Proposed Research to the Subjects and Others 
The following benefits that occur from exercising regularly may occur as a result of being enrolled in 
this study.  This may include an improvement in: voluntary muscle control, fatigue, endurance and 
quality of life. 
 
Importance of the Knowledge to be Gained 
Previous studies have demonstrated FES-LE cycling is a safe, feasible, and effective exercise modality 
for non-progressive neurological disorders,2,42,63,64 but only a few studies have applied this modality to a 
neurodegenerative disorder, such as MS. These individuals have similar impairments and activity limitations 
to individuals with non-progressive disorders such as SCI and stroke, yet there is lack of strong evidence to 
support the use of this modality for PWMS.  FES-LE cycling may be an effective way for PWMS to safely 
exercise while having a positive effect on gait speed, aerobic capacity, function and quality of life (QOL).   In 
addition, the use of this technology may motivate an individual to engage in physical activity because the 
cycle provides real-time visual feedback. Once a patient is familiar with FES cycling they can perform it as 
part of a wellness program in the clinical setting or in the privacy of their own home.  The cycle being used 
in this study allows the therapist to monitor progress and change parameters remotely.65 In a study 
examining the perceived barriers to exercise, physical exertion and limited access to exercise locations 
were listed as the greatest barriers to exercise in PWMS.66 Since cycling is performed in a seated position, 
it is safe for individuals with balance deficits who are limited due to their inability to perform activities safely 
in a standing position without supervision.  Overtime this treatment paradigm could potentially save money 
and time not only for PWMS but also the healthcare system.  FES cycling is utilized in the home 
environment and is sometimes fully or partially covered by medical insurance.  In the past 10 years, FES 
home-based cycling has been successfully utilized in patient populations such as SCI2,67 and CP.68The 
purpose of this study will be to assess the immediate and short-term effects of an 8-week LE cycling 
program on motor function, mobility and QOL for PWMS.  The goal of this study is to examine if FES-LE 
cycling is more effective than cycling alone.   
 

 
 
 
18 
H.   DATA SAFETY MONITORING PLAN (for more than minimal risk studies) 
Not applicable 
 
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