Split-belt Treadmill Training to Rehabilitate Freezing of Gait and Balance in Parkinson's Disease

Study Overview
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Brief Summary
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Parkinson's disease (PD) related gait and balance disorders are challenging to treat because they cannot be optimized with pharmacological intervention alone. This treatment gap is important to address because gait asymmetry and incoordination are associated with increased falls in this population, which can be functionally debilitating and lead to increased morbidity and mortality. Freezing of gait (FOG) has also been associated with reduced quality of life independent of its association with impaired mobility. Gait disorders therefore represent an unmet need in the treatment of PD. A split-belt treadmill (SB-TM) can be used to adjust the speed of each leg separately and individuals can be prompted to 'adapt' to an asymmetric gait and 're-adapt' with return to symmetrical gait in a phenomenon known as 'after-effect'.

Detailed Description
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Parkinson's disease (PD) related gait and balance disorders are challenging to treat because they cannot be optimized with pharmacological intervention alone. This treatment gap is important to address because gait asymmetry and incoordination are associated with increased falls in this population, which can be functionally debilitating and lead to increased morbidity and mortality. Freezing of gait (FOG) has also been associated with reduced quality of life independent of its association with impaired mobility. Gait disorders therefore represent an unmet need in the treatment of PD. Physiotherapy with treadmill training is a means to address the limitations of pharmacotherapy in this population. Treadmill training increases stride length, lowers cadence and improves foot clearance; long-term treadmill training results in clinically improved gait velocity and postural stability. The advent of SB-TM training can further optimize the gait instability that arises from asymmetric pathology in this population. The SB-TM 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. The motor symptoms in PD develop asymmetrically, with the burden of symptoms often lateralizing to one side, so the SB-TM 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. 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. Adaptive learning occurs when there is an adjustment of leg-speed perception during locomotor movement. When using a split-belt treadmill (SB-TM) to adjust the speed of each leg, the step length and double support time during gait can be manipulated. 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. This method of rehabilitation can therefore be used to treat a range gait abnormalities and previous research has demonstrated the ability to restore symmetrical gait and reduced falls for up to 3 months in the stroke population. A preliminary study from our lab in individuals with PD and FOG demonstrated that velocity reduction by 25% on the least affected side resulted in a more symmetric and coordinated gait after 10 minutes of SB-TM training.

Official Title
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Split-belt Treadmill Training to Rehabilitate Freezing of Gait and Balance in Parkinson's Disease

Conditions
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Parkinson Disease, Freezing of Gait, Gait, Unsteady

Intervention / Treatment
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* Other: Split-belt treadmill training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Idiopathic PD Hoehn & Yahr Stage 2-3, on levodopa FOG, resistant to dopaminergic therapy Disease duration: 5-15 years Stable clinical response to medications or stimulation parameters (in case of DBS) for at least 3 months MMSE >24/30 Able to walk on a motor-driven treadmill Exclusion Criteria: Severe imbalance that limits ambulation (Hoehn &Yahr score above 3) Orthopedic conditions and other systemic disease affecting locomotion Cardiac conditions limiting the ability to walk uninterrupted for 1 hour Presence of other neurological disorder Inability to be fluent in English
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Split-belt treadmill (Grail systems®, by Motek, Netherlands)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>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). | Other: Split-belt treadmill training<br>* 18 sessions of SB-TM training, where 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%.<br>|
| Active Comparator: Control group<br>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). | Other: Split-belt treadmill training<br>* 18 sessions of SB-TM training, where 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%.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Falls | The incidence of falls for 3 months after completing treadmill training. Falls will also be assessed at multiple stages during the 7.5-month study period, to understand the duration of benefit of this intervention. This data will be obtained from the falls calendar that will be provided to subjects upon their recruitment to the study. | 3 months after completion of treadmill training | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gait parameters between intervention and control groups | Cadence (steps per minute) | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | Stride time (time elapsed between the first contact of two consecutive footsteps of the same foot in milliseconds) | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | Duration of stance (time during which the foot is in contact with the ground) o | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | Swing (swing phase of gait begins when the foot first leaves the ground and ends when the same foot touches the ground again) | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | Double limb support phase (he subperiod during which both feet are in contact with the ground) | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | Step length, calculated by multiplying the 'step time' and 'belt speed' | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | Step width height (the mediolateral space between the two feet) | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | Kinemetics of joint excursion (expression as degree of range of motion) | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | Foot angle (the angle made by the long axis of the foot from the heel to 2nd metatarsal and the line of progression of gait) | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | Ratio of single support time/ double support time, which reflects dynamic stability | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | Symmetry ratio (best leg step length/worst step) | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | 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 | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Gait parameters between intervention and control groups | Sequence effect (progressive reduction in step length), measured by a linear regression slope determined by plotting consecutive stride time intervals against stride number | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Health-related quality of life | Measured by the Parkinson's Disease Questionnaire-39 item self-report questionnaire (PDQ-39), scored out of 100 where a higher score reflects greater impact on quality of life | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Balance and postural stability | Measured by the Activities-specific Balance and Confidence (ABC) scale, possible range = 0 to 1600, Scores lower than 50 indicate a low level of functioning, scores above 50 but below 80 indicate a medium level, and those over 80 indicate a high level of functioning. | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Freezing of gait | Measured by the new freezing of gait questionnaire (NFOGQ).The total score ranges from 0 to 24, and higher scores denote more severe FOG. | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention | 
| Parkinson's disease signs and symptoms | Assessed by the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The maximum total UPDRS score is 199, indicating the worst possible disability from PD | Obtained at baseline evaluation, after 1.5 months of training, and 3-months post intervention |