Split-belt Treadmill Training to Rehabilitate Freezing of Gait and Balance in Parkinson's Disease
Phase: NA
Conditions: Parkinson Disease, Freezing of Gait, Gait, Unsteady
Sponsor: University of Toronto

Split-belt treadmill training to rehabilitate freezing of gait and balance in 
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CLINICAL TRIAL PROTOCOL 
 
 
Split-belt treadmill training to rehabilitate freezing of gait and balance in 
Parkinson’s Disease 
 
 
Sanskriti Sasikumar, MD1 
Jean-Francois Nankoo, PhD2 
Julianne Baarbe, PhD2 
Robert Chen, MD1,2,3 
Antonio Strafella, MD, PhD1,2,3 
Alfonso Fasano, MD, PhD 1,2,3 
 
 
1Division of Neurology, University of Toronto, Toronto, Ontario, Canada 
2Krembil Research Institute, Toronto, Ontario, Canada 
3Movement Disorders Center, TWH, UHN, Division of Neurology, Toronto Western 
Hospital and University of Toronto, Toronto, Ontario, Canada 
 
 
 
 
 
 
 
 
 
 
Protocol Version # 1.8  
18th February 2020 
 

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Table of Contents  
 
I. Protocol Summary 
II. 1 General Information 
1.1 Protocol Title 
1.2 Lead Investigator 
   2 Background and Study Justification 
2.1 Introduction 
2.2 Rationale for the study 
2.3.1 Potential Risks 
2.3.2 Potential Benefits 
2.4 Study population 
3 Study Objectives and Hypothesis 
3.1 Objectives  
3.2 Study Hypotheses 
 
4 Study Design and Methodology 
4.1 Design Overview 
4.2 Expected Outcomes 
4.2.1 Primary Outcome Measure 
4.2.2 Secondary Outcome Measures 
5.0 Selection of Subjects 
 6.0 Study Intervention 
7.0 Statistics 
8.0 Data Handling and Record Keeping 
9.0 Consent and Ethics 
10.0 References 
 
 
List of Abbreviations/ Terminology (in alphabetical order) 
- 
ABC scale: Activities-specific Balance Confidence scale 
- 
FOG: Freezing of gait 
- 
HRQoL: Health-related quality of life 
- 
MOCA: Montreal cognitive assessment 
- 
MMSE: Mini Mental State Exam 
- 
NFOGQ: New Freezing of Gait questionnaire 
- 
PD: Parkinson’s Disease 
- 
PDQ: Parkinson’s Disease Questionnaire 
- 
SBTM: Split-belt treadmill 
- 
TM: Treadmill with belts tied to the same velocity 
 
 
 
 
 
 
 

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Protocol Summary 
 
Title:  
Split-belt treadmill training to rehabilitate freezing of gait and balance in Parkinson’s 
Disease  
 
Sample Size  
N= 28  
 
Study Population  
Individuals with Parkinson’s Disease without severe balance problems and with 
treatment-resistant freezing of gait 
 
Accrual Period 
6 months 
 
Study Design 
This is a prospective, single-blinded, parallel-group randomized control trial to assess 
the benefit of split-belt treadmill training in preventing falls and improving gait and 
balance. The intervention group will receive 18 sessions of SBTM training, and the 
control group will receive 18 sessions of TM training.  
 
Study Duration 
1. Enrolment 
2. 3 month falls monitoring 
3. Pre-training analysis 
4. Training (30 minutes to 1 hour, 3 times/week for 6 weeks) 
5. 3- month post-training follow-up 
 
Total time= 7.5 months 
 
Study Intervention  
Subjects will walk on a split-belt treadmill (Grail systems®, by Motek, Netherlands), with 
the two belts either moving at the same speed (‘tied’ configuration) or different speeds 
(‘split’ configuration). The ‘tied’ configuration is adjusted to the individual’s over 
ground speed. The Grail system also generates a virtual reality-based environment by 
generating a visual scenery. A motion capture system with 6 infrared cameras (Vicon 
Motion Systems Ltd, V5, UK; 420 Hz sampling frequency) will be used. This captures 
various variables of gait based on markers that are placed on the subject.  
 
The over-ground walking speed before and after each training session will be determined 
by calculating the time it takes the subject to walk 10m.   
 
At the pre-training assessment and post-training follow-up, subjects will walk on a 6-
metre walkway and dedicated movement analysis software (Zeno walkway® by 

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Protokinetics, USA) to measure individual gait speed, assess additional gait parameters 
of over-ground walking and capture turns, which is otherwise not possible using the 
treadmill. 
 
Video assessment of gait will be captured during both 6m walkway and treadmill 
analyses.  
 
Primary Objective 
Cumulative incidence of falls 3 months after treadmill training. 
 
Secondary Objectives 
To determine:  
-Balance and postural stability, measured by the ABC scale 
-Freezing of gait, measured by the NFOGQ 
-Gait parameters between the TM and SBTM groups 
-Factors that determine strong after-effect after SBTM training 
-Health-related quality of life (PDQ39) 
-UPDRS I-IV 
 
Exploratory Objectives 
-Gait parameters on treadmill versus over-ground walking  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.0 General Information 
 

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1.1 Protocol Title 
Split-belt treadmill training to rehabilitate freezing of gait and balance in Parkinson’s 
Disease  
 
1.2 Lead Investigator 
Dr. Alfonso Fasano, MD, PhD 
Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra 
Program in Parkinson’s Disease, Toronto Western Hospital–UHN, 
Division of Neurology, University of Toronto 
Toronto, Ontario, Canada 
Phone: 416 603 6422 
Fax: 416 603 5004 
 
2.0 Background and Study Justification  
 
2.1 Introduction 
 
Gait disorders in Parkinson’s Disease (PD) are characterized by bradykinesia, gait 
asymmetry and an increased risk of falls during gait transition.1 Patients with freezing of 
gait (FOG) are particularly disabled, because they experience progressive decrease in step 
length2 and increase in gait asymmetry,3 thus increasing their risk of falls during tasks 
like gait initiation,4 turning5 and avoiding obstacles.6  
 
Treadmill training is an existing rehabilitation strategy for physiotherapy in PD, as it 
increases stride length, lowers cadence and improves foot clearance; long-term treadmill 
training results in clinically improved gait velocity and postural stability.7, 8 The advent of 
SBTM training can further optimize the gait instability that arises from asymmetric 
pathology in this population.9 The SBTM has 2 belts, which can either move in unison 
(tied) or at different speeds (split), and it has been effective in restoring symmetrical gait 
in the stroke population, with gait adaptations retained for up to 3 months.10 The motor 
symptoms in PD develop asymmetrically, with the burden of symptoms often lateralizing 
to one side,11 so the SBTM offers a unique opportunity to modulate spatial and temporal 
gait parameters to study gait adaptation in the PD population.  
 
Split-belt treadmill training uses the concept of adaptive learning, which is error-driven 
motor leaning in response to changes in the external environment.12-17 It can be used to 
target specific gait deviations, and preliminary research has indicated that it can improve 
gait disorders in PD by decreasing limb asymmetry.18 Adaptive learning occurs when 
there is an adjustment of leg-speed perception during locomotor movement. When using 
a split-belt treadmill (SBTM) to adjust the speed of each leg, the step length and double 
support time during gait can be manipulated.18, 19 Individuals can therefore be prompted 
to ‘adapt’ to the asymmetric gait (e.g., the leg walking on a slow belt will take longer 
steps to accommodate to the leg walking on the faster belt) and ‘re-adapt’ with return to 
symmetrical gait.18, 20 
 
 

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2.2. Rationale for the study  
 
Parkinson’s disease-related gait and balance disorders are challenging to treat, and the 
motor symptoms of PD cannot be optimized with pharmacological intervention alone. 
This treatment gap is important to address because gait asymmetry and impairments in 
bilateral coordination of gait having been associated with falls and can be functionally 
debilitating for individuals with PD.3, 21-24 Research on individuals with deep brain 
stimulation (DBS) has shown that decreasing the subthalamic nucleus voltage stimulation 
by 50% on the least affected limb decreases the asymmetry in FOG, and can therefore 
reduce the duration and frequency of FOG.22 However, DBS is an invasive procedure and 
not all patients qualify for it, so it’s important to determine alternate strategies to improve 
freezing of gait in PD. 
 
There is also currently no standard of care for the physiotherapy that individuals with PD 
receive, and there are a wide range of approaches that therapists employ that extend 
beyond treadmill training. Even those who undergo treadmill training do not follow a 
fixed protocol, pre-determined treadmill speed or duration spent on the treadmill. 
Moreover, although physicians encourage patients to have physiotherapy, not everyone 
ca afford it they have to pay out of pocket to cover the cost of the services they receive. 
There is a lacking consensus on the rehabilitation that this population needs.  
 
Our aim is to assess the benefit of SBTM training to rehabilitate gait imbalance and 
freezing of gait in PD. In doing so, we can contribute towards a protocol to identify and 
treat certain gait discrepancies in PD. A study by Fasano et al demonstrated that velocity 
reduction by 25% on the least affected side results in a more symmetric and coordinated 
gait with reduced sequence effect, after 10 minutes of SBTM training.2, 25  
 
The study will assess the:  
• Feasibility of using SBTM training (3 days/week for 6 weeks) to improve gait 
parameters in PD, specifically FOG and balance 
• Identify factors that prolong the benefit of the after-effect 
 
Innovative aspects of our proposal include:  
• Whereas preliminary reports have suggested the benefit of SBTM walking in PD, 
there has not previously been a trial to assess the impact of prolonged training on 
adaptation and aftereffects. 
• Previous studies have used fixed velocities on the SBTM, but we will adjust 
velocities to the subject’s over-ground walking speed  
• We will employ virtual reality technology with treadmill training to mimic natural 
gait as closely as possible in a simulated setting.  
 
2.3 A summary of the known and potential risks and benefits, if any, to human 
subjects. 
 
2.3.1 Potential Risks  
 

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Split belt treadmill training carries little to no risk. The potential risk of falls on a 
treadmill are addressed by a harness that subjects will be strapped into during the training 
period. The duration of the training can last up to 1 hour, which could cause patients to 
feel fatigued, and further increase the risk of falls. However, we have implemented a 
progressive increase of training duration, included rest breaks in to the training protocol, 
and the inclusion criteria selects subjects based on their stamina to tolerate this 
intervention (e.g. patients with shortness of breath, obesity, cardiac conditions, severe 
dysautonomia, etc. will be excluded).  
 
2.3.2 Potential Benefits 
 
This trial offers a means to rehabilitate gait in a non-invasive and cost-effective manner. 
Additionally, based on reports from pilot studies, SBTM reduces the sequence effect 
which is hallmark feature of FOG that is not otherwise treatable with levodopa. The 
overall benefit of reducing the risk of falls alleviates the anxiety that these individuals 
have around walking. 
 
2.4 Description of the population to be studied. 
 
The study population includes individuals with idiopathic PD who experience FOG 
without severe imbalance (defined as Hoehn & Yahr stage of 3 or more). These patients 
will be selected from the Movement Disorders Clinic at Toronto Western Hospital, and 
will have to be stabilized on their treatment (drugs and/or stimulation settings in case of 
DBS) management for at least 3 months. Based on the inclusion criteria, these subjects 
will be selected recognizing that they will need to ambulate on a motor-driven treadmill.  
 
The study will be conducted in compliance with the protocol, ICH, GCP and the 
applicable regulatory requirements.  
 
3.0 Study Objectives and Hypothesis  
 
3.1 Objectives  
Our aim is to study the feasibility and safety of SBTM training on the rehabilitation of 
FOG and gait imbalance in PD, as well as its efficacy compared to TM training. 
Individuals with PD and FOG will be randomized to 2 groups, where they will receive 18 
sessions of TM training or 18 sessions of SBTM training. The primary outcome measure 
will be the incidence of falls for 3 months after completing treadmill training. Falls will 
be assessed at multiple stages during the 7.5-month study period (using a falls calendar; 
refer to Appendix I, Figure 1), to understand the duration and benefit of the SBTM 
intervention. Additional objectives include:  
 
• Balance and postural stability, measured by the Activities-specific Balance 
Confidence (ABC) scale (Appendix I, Figure 4) 
• Freezing of gait, measured by the New Freezing of Gait Questionnaire (NFOGQ) 
(Appendix I, Figure 3) 
• Gait parameters as a means of gait analysis between the TM and SBTM groups 

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• Factors that determine strong after-effect after SBTM training 
• Health-related quality of life (PDQ39) 
• Unified PD Rating Scale I-IV 
• Gait parameters on treadmill versus over-ground walking  
 
3.2 Study hypotheses. 
 
• SBTM is superior to conventional TM training in improving response time and 
ability to adapt to gait asymmetry, and therefore improves FOG and reduces risk 
of falls in patients with PD.  
• The after-effect from SBTM training is reproducible to over-ground walking 
• Younger PD patients, with shorter disease duration and no cognitive impairment 
are more likely to adapt to gait manipulations from the SBTM, and demonstrate 
prolonged after-effects 
• SBTM results in HRQoL improvement in PD with FOG 
 
 
4 Study Design and Methodology 
 
4. 1 Design overview  
 
This is a prospective, single-blind, parallel-group randomized control trial to assess the 
feasibility and safety of SBTM in preventing falls and improving gait and balance, as 
well as its efficacy compared to TM training. The assessor will be blinded to their 
randomization. Patients will not be blinded to the intervention, and will be informed 
about the rationale of the study. The subject population will include 28 people with PD 
and FOG, who will be randomized into one of 2 groups. The intervention group will 
receive 18 sessions of SBTM training, whereas the control will receive 18 sessions of TM 
training (refer to Figure 1). After to being recruited to the trial, subjects and/or their 
caregivers will document the frequency and details of falls 3 months leading up to the 
training period using a Falls calendar (refer to Appendix I, Figure I). During this time, 
they will continue their routine activities without restriction, including any physiotherapy 
they might be receiving. The study is divided into 3 phases:  
 
1. Pre-training analysis:  
Prior to randomization, subjects will undergo a 6-meter walk test to determine their 
baseline gait parameters. We will use the Zeno walkway® gait mat (® by Protokinetics, 
USA) to obtain quantitative gait and posturographic analysis. The analysis is standardized 
to a 5-step protocol: 1) stand for 25 seconds at the starting edge of the walkway, 2) walk 
at regular pace towards the other end, 3) turn around towards the right, 4) walk back 
towards the starting point and 5) stand for 10 seconds. These 5 steps will be repeated 
twice (to assess the left turn and posturography with closed eyes) and data of straight 
walk will be averaged. Subjects will have a clinical assessment of gait and UPDRS (I-IV) 
scoring, and will fill out the HRQoL (PDQ39) and standardized falls questionnaire (refer 
to Appendix I, Figure II).  
 

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2. Training: 
The training sessions (intervention and control) will take place 3 times a week for 6 
weeks (refer to Figure 2). The first training session will take place in the same week as 
the pre-training analysis. The duration of training will vary each week, as described 
below, but will be no longer than 1 hour. The sessions will take place as follows:  
 
i) The patient’s over-ground walking speed will be determined based on Zeno 
walkway® (by Protokinetics, USA)  gait mat analysis. The 5-step protocol, to 
obtain more sophisticated gait parameters will be performed after the last training 
session. Gait parameters will not be repeated for the first training session because 
they will be obtained at the pre-training analysis which takes place in the same 
week (refer to Table 1).   
ii) Acclimatization on treadmill (2 minutes). The belts of the treadmill are tied to the 
same velocity, and will be increased to the subject’s over-ground walking velocity 
at their comfort.  
 
iii) a) Intervention group: The velocity of the belt will be adjusted to the over-ground 
speed of the subject, and will be reduced on the least affected side by 25%. While 
the speed of the treadmill will not change throughout the study, the duration of the 
training will increase each week. In the first week, the SBTM training will take 
place for 10 minutes. There will be a 5-minute rest period, and the split-belt 
conditions will continue for another 10 minutes of training (total training time= 
20 minutes). 
 
b) Control group: The subject will continue to walk under tied-belt conditions 
adjusted to the over-ground walking speed. In the first week, the treadmill training 
will be for 10 minutes. They will get a 5-minute break, similar to the intervention 
group, and continue for another 10 minutes under tied-belt conditions. 
 
The duration of each session will increase by 8 minutes every week. For example, 
in week 1, the treadmill training will be for a total of 20 minutes; in week 2, for 
28 minutes; in week 3, for 36 minutes, and so forth, until it gets to 60 minutes by 
week 6. The rest period will remain at 5 minutes each session, and will always 
take place at the halfway mark. All 3 sessions in the week will have the same 
duration of training.  
 
If the subject cannot tolerate the velocity or duration of the session, the protocol 
will be adjusted to most recently tolerated session (and will be recorded for 
further interpretation and analysis).  
 
iv) Tied adaptation: The treadmill belts will be tied to the over-ground velocity in the 
intervention group (5 minutes). The control group will continue to ambulate for 
an additional 5 minutes.  
 
Gait analysis: In the intervention group, the treadmill gait analysis will be captured 
(Vicon Motion Systems Lts, V5, UK; 420 Hz sampling frequency) twice a week, at the 

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beginning and end of the training session (40 sec for each recording). Prior to the first 
and last training sessions, gait analysis will be carried out towards the end of the 
acclimatization period (‘baseline’), at the beginning of the SBTM (‘early adaptation’), 
after 10 minutes of SBTM (‘late adaptation’, to capture the modifications induced by this 
condition), and at the beginning of the tied adaption (‘after effect’), in keeping with 
Fasano et al , 2016.26 Each recording will be captured for 30 seconds. 
 
In the control group, the TM gait analysis will be captured once a week, at the beginning 
the training session (40 sec for each recording). Additionally, gait analysis will be carried 
out towards the end of the first training session (‘baseline’) and at the beginning of the 
last epoch of training (beginning of last 5 minutes). 
  
3. Post-training follow-up: 
This will take place 3 months after treadmill training. The subject will ambulate on the 
Zeno walkway® gait mat (® by Protokinetics, USA) as per the standard 5-step protocol, 
have a clinical assessment and UPDRS (I-IV) scoring, and complete the HRQoL 
(PDQ39) and a standardized falls questionnaire (refer to Appendix I, Figure 2). They will 
also provide their falls calendar (provided to the patient at recruitment; refer to Appendix 
I, Figure 1) that documents their adverse events.  
 
Duration of the trial and other considerations:  
The duration of the study is 7.5 months. During this time, the subject’s PD medications 
will not be adjusted by the study team, and they will be advised to take their medications 
per their usual schedule and as recommended by their neurologist. However, in case of 
decline of motor conditions or occurrence of other bothersome symptoms, medications 
changes will be allowed and the change will be recorded along with the reason that 
prompted it 
 
  
Figure 1: Schedule of assessments  
 

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Figure 2: Overview of training schedule. The velocity of the treadmill is matched to the 
patient’s over-ground walking speed, captured at the gait mat analysis before the first 
training session. The velocity on the least affected side is reduced by 25% on the SBTM. 
The velocity otherwise remains the same throughout the training period. However, the 
duration of training increases by 8 minutes every week. The timing of the gait analyses 
from Weeks 2-5 are identical. GM=gait mat analysis using Zeno walkway® (by 
Protokinetics, USA);GA=40 second gait analysis on treadmill; GAi=detailed gait 
analysis of the interventional group at beginning and end of training period; this includes 
a 30 second analysis of the end of the acclimatization period (‘baseline’), beginning of 
the SBTM (‘early adaptation’), after 10 minutes of SBTM (‘late adaptation’ and at the 
beginning of the tied adaption (‘after effect’); GAC= detailed gait analysis of the control 
group at the beginning and end of the training period; this takes place at the end of the 
training period of the first session, and before the last 5 minutes of the last session for 40 
seconds each;  SBTM=split-belt treadmill; TM=Treadmill with belts tied to same velocity  
 
4.2 Expected Outcomes 
 
4.2.1 Primary outcome measure: 
The incidence of falls for 3months after completing treadmill training. This will be 
assessed at multiple stages during the 7.5-month study period (as detailed in the Study 
Design), to understand the duration of benefit of this intervention. This data will be 
obtained from the falls calendar (Appendix I, Figure I) that will be provided to subjects 
upon their recruitment to the study.  
 
4.2.2 Secondary outcome measures: 
 
• Gait analysis between intervention and control groups will be measured using the 
following parameters:  

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o Cadence 
o Stride time 
o Duration of stance 
o Swing 
o Double limb support phase 
o Step length, calculated by multiplying the ‘step time’ and ‘belt speed’ 
o Step width height 
o Kinemetics of joint excursion (expression as degree of range of 
motion) 
o Foot angle 
o Ratio of single support time/ double support time, which reflects 
dynamic stability 
o Symmetry ratio (best leg step length/worst step) 
o Coefficients of variation (which measures the variability of the 
temporal parameters of the swing phase duration and gait cycle time, 
and is represented by the (SD/mean) x100 
o Sequence effect (progressive reduction in step length), measured by a 
linear regression slope determined by plotting consecutive stride time 
intervals against stride number 
• Health-related quality of life (PDQ39) 
• Balance and postural stability, measured by the ABC scale (Appendix I, Figure 4) 
• Freezing of gait, measured by the NFOGQ (Appendix I, Figure 3) 
• PD signs and symptoms assessed by the MDS-UPDRS scale 
 
All secondary outcome measures will be obtained at baseline evaluation, at the end of the 
training of period, and 3-months post intervention (refer to Table 1).  
Adverse events will be collected with a standardized list of problems plus patient’s 
interview for unsolicited issues. 
To minimize bias, all outcome measures will be collected in a single-blinded fashion. 
Statistical analysis will be conducted by a researcher blinded to group allocation. 
 
 

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Table 1: Timeline of assessments.  
 
5.0 Selection of Subjects 
 
Twenty-eight PD patients with FOG will be recruited at the Movement Disorders Clinic 
by the primary investigator. If interested, the potential study participant will be screened, 
informed and consented according to the following criteria. Participants will be recruited 
regardless of whether they are receiving concurrent physiotherapy. 
 
Inclusion criteria include:  
1. Idiopathic PD 
2. Hoehn & Yahr Stage 2-3, on levodopa 
3. FOG, resistant to dopaminergic therapy 
4. Disease duration: 5-15 years  
5. Stable clinical response to medications or stimulation parameters (in case of DBS) 
for at least 3 months 
6. MMSE >24/30 
7. Able to walk on a motor-driven treadmill 
Exclusion criteria:  
1. Severe imbalance that limits ambulation (Hoehn &Yahr score above 3) 
2. Orthopedic conditions and other systemic disease affecting locomotion 
3. Cardiac conditions limiting the ability to walk uninterrupted for 1 hour 
4. Presence of other neurological disorder 
5. Inability to be fluent in English 
 
6.0 Study Intervention  
 
Subjects will walk on a split-belt treadmill (Grail systems, by Motek, Netherlands), with 
the two belts either moving at the same speed (‘tied’ configuration) or different speeds 

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(‘split’ configuration). The ‘tied’ configuration is adjusted to the individual’s over ground 
speed, which alters on a weekly basis (refer to ‘Study Design’ for details).  
 
The Grail system also generates a virtual reality-based environment by generating a 
visual scenery. The scenery will be standardized to South Manhattan and the belts will be 
synchronized to the visual input. A motion capture system with 6 infrared cameras (Vicon 
Motion Systems Ltd, V5, UK; 420 Hz sampling frequency) will be used (refer to Figure 
3). This system captures and calculates various temporal variables of gait, based on 
vertical coordinates and foot markers that are placed on the subject. Video assessment of 
gait will be captured with 3 video cameras synchronized to the motion system.  
 
The over-ground walking speed will be analyzed using a 6-metre walkway and dedicated 
movement analysis software (Zeno walkway® by Protokinetics, USA). Video assessment 
of gait will be captured with 2 video cameras.  
 
 
Figure 3: Treadmill training with the virtual reality system. A) The gait lab, featuring the 
SBTM (Grail systems®, by Motek, Netherlands), virtual reality screen, and desk where 
the study coordinator will monitor the experiment. The arrow points to one 6 infrared 
cameras (Vicon Motion Systems Ltd, V5, UK; 420 Hz sampling frequency) which 
constitute the motion capture system B) Simulation of a subject walking on the SBTM, 
while attached to a harness to prevent falls, adapted from the MOTEK website. 
 
 
7.0 Statistics 
 
This will be conducted on an intention-to-treat principle using all participants who 
complete randomization. Demographic characteristics and baseline data will be 
summarized by ‘conventional’ descriptive statistics (i.e., means, standard deviations and 
95% confidence intervals for continuous variables, median and inter‐quartile ranges for 
non‐normal continuous ordinal data and percentages for categorical data), and will be 
evaluated for normalcy and homogeneity. Fall rate will be analyzed by calculating 
relative risk using negative binomial regression models that adjust for any potential 
confounders. The secondary outcome measures will be analyzed using repeated measures 

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analysis of variance (ANOVA) to assess differences between the intervention and the 
active control groups, and across the endpoints of the assessments. All analyses will be 
adjusted for multiple comparisons.  
 
Statistical analysis will be conducted by a researcher blinded to group allocation. 
 
Power analysis was performed for this trial. The primary outcome measure is falls rate 
during the 3-month follow-up period after treadmill training. To demonstrate superiority 
of the SBTM to conventional TM training, we set an a priori threshold of 20% reduction 
in falls rate. The sample size was calculated based on a trial by Mirelman and 
colleagues,20 who studied the impact of conventional treadmill training with non-
immersive virtual reality on falls rate. As this reflects the control group in this trial, we 
used their reported incidence of falls post-training, and estimated the standard deviation 
using the range rule (s=range/4). Because the duration of follow-up in our study is 3 
months, we halved the mean and standard deviation. To obtain a power of 80% and alpha 
of 0.05, we need to recruit 14 subjects per group.  
 
8.0 Data Handling and Record Keeping 
 
Case report forms (CRFs) will be used to collect study data. The CRFs will be 
electronically viewed and signed by the principal investigator. All CRFs will be 
completed within two weeks of the visit date. Only the clinical investigators will have 
access to the participants’ data. The information that is collected for the study will be 
kept in a locked and secure area at Toronto Western Hospital by the study team for 10 
years.   
 
9.0 Consent and Ethics 
 
Voluntary written informed consent will be required for participation in this study and 
will be obtained from participants with PD and FOG.  
 
No study procedures will be undertaken until such consent is obtained. Even after a 
patient has provided initial consent to participate, baseline and subsequent visits and the 
implementation of study procedures will be used as opportunities to again explain what is 
being done, why it is being done, to assure continuing informed consent on the part of the 
proxy, to maintain assent by the patients, and to assess capacity.  
 
Capacity to give consent will be assessed in clinical interviews of participants by 
clinicians experienced in clinical research who will also be trained in this for the study. 
During these interviews, these clinicians will assess the ability of participants to: 
- 
Comprehend the study and its consent form, by asking them to repeat the key 
elements of the research 
- 
Understand the study and its consent form, by answering questions about the key 
elements of the research 
- 
Appreciate of the personal nature and consequences of what will or could happen 
to them if they participate. 

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If in this process a potential participant is found not capable of fully providing consent 
for participation, then they will not be recruited to the study. The process of obtaining 
consent  will be documented in every case. Should the patient be illiterate, an impartial 
witness (i.e. individual who is not part of the study team or family) will sign as a 
surrogate.  
 
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