Amped-PD: Amplifying Physical Activity Through Music in Parkinson Disease

Study Overview
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Brief Summary
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Regular, habitual exercise is a critical component of the long-term management of Parkinson disease (PD). However, PD-specific motor (e.g. slow and diminished movements, variable step timing) and non-motor (e.g. depression, apathy) problems collectively hinder physical activity. Rhythmic auditory stimulation (RAS) is a rehabilitation technique that employs coupling of auditory cues with movement. Walking with RAS has been shown to benefit walking rhythmicity, quality, and speed. These walking benefits make RAS advantageous in promoting moderate intensity walking activity -- an important health-objective in the management of PD. However, the therapeutic potential of RAS in self-directed walking programs has not been examined. In this pilot, we will utilize a breakthrough digital therapeutic that delivers music-adaptive RAS to alleviate PD-specific problems by regulating stepping patterns. Using music as a substrate for cue delivery, this digital therapeutic leverages gait benefits from RAS along with enjoyment of music listening, thus making it a viable and engaging modality that will yield habits of regular walking. Habits are automatically recurring psychological dispositions that emerge from repeated behaviors. The investigators posit that music cues provide recurring contextual cues that automatically evoke habitual response of exercise, thus has the potential to prompt regular physical activity. This study will enroll 61individuals with mild-to-moderate PD (Run-in: 17; Main Trial: 44). The experimental intervention, Amped-PD, is a 6-week, user-managed community-based walking program that utilizes music-adaptive RAS that progressively increases walking intensities. This study will examine if Amped-PD (Experimental Intervention) is more effective than a standard-of-care walking program (Active-Control Intervention) in improving physical activity based on moderate intensity walking, and in improving motor deficits related to quality of walking in individuals with mild-to-moderate PD. This study will also examine whether the resultant habits formed from each intervention matter in relation to training-related changes in physical activity.

Detailed Description
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Parkinson disease (PD) is the fastest growing source of disability among neurological disorders. Diminished physical activity is highly prevalent in PD and often lead to the onset of disability. Regular, habitual exercise is a critical component of the long-term PD management. However, PD-specific motor (e.g. slow and diminished movements, variable step timing) and non-motor (e.g. depression, apathy) problems collectively hinder physical activity. Rhythmic auditory stimulation (RAS) is a rehabilitation technique that employs the coupling of auditory cues with movement. When used during walking, RAS has been shown to benefit walking rhythmicity, quality, and speed. Therefore this rehabilitation technique can be advantageous in promoting moderate intensity walking activity. While clinical studies support RAS-based intervention, its translation to real-world, community-based environments and for long-term exercise for the promotion of physical activity is limited. The difference that determines viability of RAS for out-of-lab applications lie in the distinction between external entrainment (open-loop) versus autonomous entrainment (closed-loop). Open-loop RAS requires high levels of vigilance and is prone to error accumulation, which is problematic with gait dysfunction in PD. On the other hand, closed-loop RAS allows for natural and stable entrainment. A closed-loop approach in this case is a necessity of the task and a technological challenge to translate RAS to community-based settings. In this pilot, the investigators will utilize a breakthrough digital therapeutic that employs closed-loop RAS to alleviate PD-specific problems by regulating stepping patterns. Using music as a substrate for cue delivery, this digital therapeutic leverages gait benefits from RAS along with enjoyment of music listening, thus making it a viable and engaging modality that will yield habits of regular walking. The investigators posit that music that is linked to enjoyment serves as context cues that define the pre-condition to engaging in habitual walking exercise and increased physical activity. With repetition, these recurring contextual triggers (i.e. music) automatically evoke a habitual response of exercise, and thus has the potential to amplify physical activity. The main aims of the study seek to examine if Amped-PD (Experimental Intervention) is more effective than a standard-of-care walking program (Active-Control Intervention) in improving physical activity based on moderate intensity walking (Aim 1), and in improving motor deficits related to quality of walking (Aim 2) in individuals with mild-to-moderate PD. Additionally, this study will examine whether habit formation mediates the relationship between the intervention (Amped-PD or Active-Control) and physical activity (Aim 3). The investigators hypothesize that Amped-PD will have greater improvements in amounts of moderate intensity walking and stride-to-stride variability based on stride length and swing time. Further, habit formation will be one mechanism that will explain the link between the intervention and physical activity. Secondary research aims will examine whether Amped-PD is more effective than Active-Control in improving motor and non-motor features based on short- and long-distance walking function, spatiotemporal measures of walking, step activity based on daily step counts, disease severity scores, quality of life, self-efficacy on walking, and depression. This study will utilize the breakthrough digital music therapeutic developed and manufactured by MedRhythms (Portland, ME). To examine the effects of the intervention, the investigators will use clinical measures of motor and gait function, participant self-reports on habit formation, and quantified movement data on walking and physical activity using wearable sensors. This study will be implemented by carrying out the following study visits: (1) Primary screen over the phone, (2) Clinical Screening and Baseline Assessment, (3) Community-based, self-directed walking program (6 weeks), (3) Post-training Assessment; (4) Follow-up training (2 weeks), and (5) Final Follow-Up Assessment. Altogether, these procedures may take up to 10 weeks.

Official Title
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Amped-PD: Amplifying Physical Activity Through a Novel Digital Music Therapeutic in Parkinson Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: Digital music therapeutic
* Behavioral: Active-Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of idiopathic, typical Parkinson disease (based on the UK PD Society Brain Bank Criteria7) by a physician Modified Hoehn and Yahr stages 1-3 per physical exam by a licensed physical therapist 40 - 85 years of age Community-dwelling Able to walk independently without physical assistance or an assistive device for at least 10 minutes. Have stable PD medications for at least two weeks prior to enrollment. Willing and able to provide informed consent. Provide HIPAA Authorization to allow communication with the primary healthcare provider for communication (as needed) during the study period. Exclusion Criteria: < 40 years of age Diagnosis of atypical Parkinsonism Modified Hoehn and Yahr stages 4-5 Moderately or significantly disturbing freezing episodes during daily walking based on the New Freezing of Gait Questionnaire History of >1 fall over the past 3 months Cognitive impairment (i.e., Mini-Mental State Exam Score (MMSE) < 24) Unable to walk independently (i.e. without physical assistance or assistive device) at a comfortable speed of 0.4m/s or greater (i.e., 10-meter Walk Test (10mWT)) Unable to independently use the music-based digital therapeutic during training Significant hearing impairment Currently participating in physical therapy Currently performing regular walking exercise > 3x/week for 30 minutes per session. Cardiac conditions that may limit safe participation in exercise Orthopedic conditions that may limit safe participation in exercise Any other medical conditions that would preclude successful participation as determined by a physical therapist

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

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: Participants are randomly assigned to either intervention of (1) Amped-PD, or (2) Active-Control.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amped-PD<br>6-week community-based, self-directed walking program that uses a novel digital therapeutic that delivers music-adaptive rhythmic auditory stimulation. | Device: Digital music therapeutic<br>* The digital music therapeutic is comprised of foot sensors, a smart phone with pre-installed proprietary software application, and headphones. The device obtains real-time walking data through movement sensors that communicate wirelessly with the smartphone application software. Music cues are tailored to the person's walking pattern, and are transmitted wirelessly to the headphones. Music cues are time-shifted to the user's baseline cadence and adjusted in real-time based on the user's walking performance metrics.<br>* Other names: MedRhythms device;|
| Active Comparator: Active-Control<br>6-week community-based, self-directed walking program without using a novel digital therapeutic or any form of rhythmic auditory stimulation. | Behavioral: Active-Control<br>* The Active-Control intervention will implement a similarly structured community-based walking program as Amped-PD, with the only exception the digital music therapeutic.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical activity based on the amount of moderate intensity walking | The amount of moderate intensity walking, defined as mean number of minutes per day with >100 steps/min. This will be measured using research-grade activity monitors (StepWatch Activity Monitor, Modus Health, Edmonds, WA) validated for use in PD. | Baseline | 
| Physical activity based on the amount of moderate intensity walking | The amount of moderate intensity walking, defined as mean number of minutes per day with >100 steps/min. This will be measured using research-grade activity monitors (StepWatch Activity Monitor, Modus Health, Edmonds, WA) validated for use in PD. | During training up to 4 days from start of training | 
| Physical activity based on the amount of moderate intensity walking | The amount of moderate intensity walking, defined as mean number of minutes per day with >100 steps/min. This will be measured using research-grade activity monitors (StepWatch Activity Monitor, Modus Health, Edmonds, WA) validated for use in PD. | Immediately after the intervention (up to 6 weeks) | 
| Physical activity based on the amount of moderate intensity walking | The amount of moderate intensity walking, defined as mean number of minutes per day with >100 steps/min. This will be measured using research-grade activity monitors (StepWatch Activity Monitor, Modus Health, Edmonds, WA) validated for use in PD. | Follow-up (up to 2 weeks post-intervention) | 
| Gait quality based on variability of stride length | Stride-to-stride variability of stride lengthof the gait cycle will be measured using wearable sensors. | Baseline | 
| Gait quality based on variability of stride length | Stride-to-stride variability of stride length of the gait cycle will be measured using wearable sensors. | Immediately after the intervention (up to 6 weeks) | 
| Gait quality based on variability of stride length | Stride-to-stride variability of stride length of the gait cycle will be measured using wearable sensors. | Follow-up (up to 2 weeks post-intervention) | 
| Gait quality based on variability of swing time | Stride-to-stride variability of swing time subphase of the gait cycle will be measured using wearable sensors. | Baseline | 
| Gait quality based on variability of swing time | Stride-to-stride variability of swing time subphase of the gait cycle will be measured using wearable sensors. | Immediately after the intervention (up to 6 weeks) | 
| Gait quality based on variability of swing time | Stride-to-stride variability of swing time subphase of the gait cycle will be measured using wearable sensors. | Follow-up (up to 2 weeks post-intervention) | 
| Self-Report Behavioral Automaticity Index (SRBAI) | The Self-Report Behavioral Automaticity Index (SRBAI) will be used to assess habit formation. This index is a patient-reported outcome that examines habit automaticity. This self-report index comprises of 12 statements with constructs spanning behavior repetition, automaticity, and identity, with responses made on 11-point Likert scales (0 = strongly disagree; 10 = strongly agree). Higher scores indicate stronger habit formation (min = 0, max = 100). Select items from this test make up the Self-Report Habit Index, which examines strength and automaticity of habits. | Baseline | 
| Self-Report Behavioral Automaticity Index (SRBAI) | The Self-Report Behavioral Automaticity Index (SRBAI) will be used to assess habit formation. This index is a patient-reported outcome that examines habit automaticity. This self-report index comprises of 12 statements with constructs spanning behavior repetition, automaticity, and identity, with responses made on 11-point Likert scales (0 = strongly disagree; 10 = strongly agree). Higher scores indicate stronger habit formation (min = 0, max = 100). Select items from this test make up the Self-Report Habit Index, which examines strength and automaticity of habits. | Immediately after the intervention (up to 6 weeks) | 
| Self-Report Behavioral Automaticity Index (SRBAI) | The Self-Report Behavioral Automaticity Index (SRBAI) will be used to assess habit formation. This index is a patient-reported outcome that examines habit automaticity. This self-report index comprises of 12 statements with constructs spanning behavior repetition, automaticity, and identity, with responses made on 11-point Likert scales (0 = strongly disagree; 10 = strongly agree). Higher scores indicate stronger habit formation (min = 0, max = 100). Select items from this test make up the Self-Report Habit Index, which examines strength and automaticity of habits. | Follow-up (up to 2 weeks post-intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 10-Meter Walk Test (10MWT) | This is a test of short-distance walking function. The participant will be asked to walk at comfortable walking speed (CWS) and maximum walking speed (MWS) on a ten-meter straight walkway. | Baseline | 
| 10-Meter Walk Test (10MWT) | This is a test of short-distance walking function. The participant will be asked to walk at comfortable walking speed (CWS) and maximum walking speed (MWS) on a ten-meter straight walkway. | Immediately after the intervention (up to 6 weeks) | 
| 10-Meter Walk Test (10MWT) | This is a test of short-distance walking function. The participant will be asked to walk at comfortable walking speed (CWS) and maximum walking speed (MWS) on a ten-meter straight walkway. | Follow-up (up to 2 weeks post-intervention) | 
| 6-Minute Walk Test (6MWT) | This is test of long-distance walking function. The participant will be asked to cover as much distance as they safely can for 6 minutes, and total distance is the main metric from this test. | Baseline | 
| 6-Minute Walk Test (6MWT) | This is test of long-distance walking function. The participant will be asked to cover as much distance as they safely can for 6 minutes, and total distance is the main metric from this test. | Immediately after the intervention (up to 6 weeks) | 
| 6-Minute Walk Test (6MWT) | This is test of long-distance walking function. The participant will be asked to cover as much distance as they safely can for 6 minutes, and total distance is the main metric from this test. | Follow-up (up to 2 weeks post-intervention) | 
| Walking cadence during in-clinic walking | Quantified metrics of walking cadence (steps/min) will be collected using wearable sensors. | Baseline | 
| Walking cadence during in-clinic walking | Quantified metrics of walking cadence (steps/min) will be collected using wearable sensors. | Immediately after the intervention (up to 6 weeks) | 
| Walking cadence during in-clinic walking | Quantified metrics of walking cadence (steps/min) will be collected using wearable sensors. | Follow-up (up to 2 weeks post-intervention) | 
| Gait velocity during in-clinic walking | Quantified metrics of walking velocity (m/s) will be collected using wearable sensors. | Baseline | 
| Gait velocity during in-clinic walking | Quantified metrics of walking velocity (m/s) will be collected using wearable sensors. | Immediately after the intervention (up to 6 weeks) | 
| Gait velocity during in-clinic walking | Quantified metrics of walking velocity (m/s) will be collected using wearable sensors. | Follow-up (up to 2 weeks post-intervention) | 
| Stride length during in-clinic walking | Quantified metrics of stride length (m) will be collected using wearable sensors. | Baseline | 
| Stride length during in-clinic walking | Quantified metrics of stride length (m) will be collected using wearable sensors. | Immediately after the intervention (up to 6 weeks) | 
| Stride length during in-clinic walking | Quantified metrics of stride length (m) will be collected using wearable sensors. | Follow-up (up to 2 weeks post-intervention) | 
| Step activity based on daily step counts | Daily step counts refer to the total number of steps taken on the leg with the monitor. This will be measured using research-grade activity monitors (StepWatch Activity Monitor, Modus Health, Edmonds, WA) validated for use in PD. | Baseline | 
| Step activity based on daily step counts | Daily step counts refer to the total number of steps taken on the leg with the monitor. This will be measured using research-grade activity monitors (StepWatch Activity Monitor, Modus Health, Edmonds, WA) validated for use in PD. | During training up to 4 days from start of training | 
| Step activity based on daily step counts | Daily step counts refer to the total number of steps taken on the leg with the monitor. This will be measured using research-grade activity monitors (StepWatch Activity Monitor, Modus Health, Edmonds, WA) validated for use in PD. | Immediately after the intervention (up to 6 weeks) | 
| Step activity based on daily step counts | Daily step counts refer to the total number of steps taken on the leg with the monitor. This will be measured using research-grade activity monitors (StepWatch Activity Monitor, Modus Health, Edmonds, WA) validated for use in PD. | Follow-up (up to 2 weeks post-intervention) | 
| Movement Disorder Society Unified Parkinson Disease Rating Scale motor subsection (MDS-UPDRS III) | The MDS UPDRS is the most widely used clinical rating scale for Parkinson disease. Part III is a motor examination (33 scores summed from 18 questions) conducted by the rater. Total scores can range from 0 to 141, with higher scores indicating worse disease severity. | Baseline | 
| Movement Disorder Society Unified Parkinson Disease Rating Scale motor subsection (MDS-UPDRS III) | The MDS UPDRS is the most widely used clinical rating scale for Parkinson disease. Part III is a motor examination (33 scores summed from 18 questions) conducted by the rater. Total scores can range from 0 to 141, with higher scores indicating worse disease severity. | Immediately after the intervention (up to 6 weeks) | 
| Movement Disorder Society Unified Parkinson Disease Rating Scale motor subsection (MDS-UPDRS III) | The MDS UPDRS is the most widely used clinical rating scale for Parkinson disease. Part III is a motor examination (33 scores summed from 18 questions) conducted by the rater. Total scores can range from 0 to 141, with higher scores indicating worse disease severity. | Follow-up (up to 2 weeks post-intervention) | 
| Self-Efficacy of Walking - Duration (SEW-D) | The SEW-D is a 10-item self-report that will be administered to determine participants' beliefs of their physical capabilities to successfully complete incremental 5-minute intervals (5 to 40 minutes) of walking at a moderately fast pace, with responses made on 11-point Likert scale (0% = not at all confident; 100% = highly confident). | Baseline | 
| Self-Efficacy of Walking - Duration (SEW-D) | The SEW-D is a 10-item self-report that will be administered to determine participants' beliefs of their physical capabilities to successfully complete incremental 5-minute intervals (5 to 40 minutes) of walking at a moderately fast pace, with responses made on 11-point Likert scale (0% = not at all confident; 100% = highly confident). | Immediately after the intervention (up to 6 weeks) | 
| Self-Efficacy of Walking - Duration (SEW-D) | The SEW-D is a 10-item self-report that will be administered to determine participants' beliefs of their physical capabilities to successfully complete incremental 5-minute intervals (5 to 40 minutes) of walking at a moderately fast pace, with responses made on 11-point Likert scale (0% = not at all confident; 100% = highly confident). | Follow-up (up to 2 weeks post-intervention) | 
| Geriatric Depression Scale (GDS) | The GDS is a brief, self-report involving yes/no questions instrument on psychological aspects and social consequences of depression in the elderly. The short form of GDS of 15-items will be used in this study. Higher scores indicate greater depression (min = 0, max = 15). | Baseline | 
| Geriatric Depression Scale (GDS) | The GDS is a brief, self-report involving yes/no questions instrument on psychological aspects and social consequences of depression in the elderly. The short form of GDS of 15-items will be used in this study. Higher scores indicate greater depression (min = 0, max = 15). | Immediately after the intervention (up to 6 weeks) | 
| Geriatric Depression Scale (GDS) | The GDS is a brief, self-report involving yes/no questions instrument on psychological aspects and social consequences of depression in the elderly. The short form of GDS of 15-items will be used in this study. Higher scores indicate greater depression (min = 0, max = 15). | Follow-up (up to 2 weeks post-intervention) | 
| Parkinson's Disease Questionnaire - 39 (PDQ-39) | The PDQ- 39 is a self-report questionnaire that assesses quality of life over the past month across 8 different dimensions. Items are scored based on a 5-point ordinal system with lower scores reflecting better quality of life. Lower scores reflect better quality of life (min = 0, max = 100). | Baseline | 
| Parkinson's Disease Questionnaire - 39 (PDQ-39) | The PDQ- 39 is a self-report questionnaire that assesses quality of life over the past month across 8 different dimensions. Items are scored based on a 5-point ordinal system with lower scores reflecting better quality of life. Lower scores reflect better quality of life (min = 0, max = 100). | Immediately after the intervention (up to 6 weeks) | 
| Parkinson's Disease Questionnaire - 39 (PDQ-39) | The PDQ- 39 is a self-report questionnaire that assesses quality of life over the past month across 8 different dimensions. Items are scored based on a 5-point ordinal system with lower scores reflecting better quality of life. Lower scores reflect better quality of life (min = 0, max = 100). | Follow-up (up to 2 weeks post-intervention) | 
| Mini Balance Evaluation Systems Test (Mini BESTest) | This test comprises of 14 items that span anticipatory postural adjustments, reactive postural control, sensory orientation, and dynamic gait. The test has a maximum score of 28, with each item is scored from 0-2 (0 = lowest level of function, 2 = highest level of function). | Baseline | 
| Mini Balance Evaluation Systems Test (Mini BESTest) | This test comprises of 14 items that span anticipatory postural adjustments, reactive postural control, sensory orientation, and dynamic gait. The test has a maximum score of 28, with each item is scored from 0-2 (0 = lowest level of function, 2 = highest level of function). | Immediately after the intervention (up to 6 weeks) | 
| Mini Balance Evaluation Systems Test (Mini BESTest) | This test comprises of 14 items that span anticipatory postural adjustments, reactive postural control, sensory orientation, and dynamic gait. The test has a maximum score of 28, with each item is scored from 0-2 (0 = lowest level of function, 2 = highest level of function). | Follow-up (up to 2 weeks post-intervention) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson disease, rhythmic auditory stimulation, digital therapeutics, behavior change, habits, physical activity