Despite advances in pharmaceutical and surgical approaches to the treatment of Parkinson?s disease (PD), an effective disease modifying treatment remains elusive. Exercise is accepted as an adjunctive treatment to the disease; however, its disease altering properties are unclear. Data indicate that high intensity exercise has neuroprotective properties and improves motor functioning in animal models of PD. Our promising translational work in humans indicated aerobic exercise improves global motor function, upper extremity performance, and altered patterns of central nervous system activation. We recently completed a 100 person randomized clinical trial, CYClical Lower Extremity exercise for Parkinson?s trial (CYCLE Trial) (NIH R01NS673717), and results indicated an 8-week high intensity aerobic exercise program significantly improved MDS-UPDRS III scores, turning and gait speed, and information processing. The positive results persisted up to eight weeks after exercise cessation. These positive results provide strong rationale to evaluate the effectiveness of a long-term CYCLE protocol in a home-based setting in an effort to impact a greater number of individuals with PD. The primary aim of this project is to determine if long-term, high intensity aerobic exercise alters disease progression in individuals with PD. A pragmatic randomized clinical trial is proposed in which blinded clinical assessments will be coupled with biomechanical measures of motor and non-motor performance to determine the impact of high-intensity exercise on PD progression. In sum, 250 PD patients recruited from the Cleveland Clinic and University of Utah will be randomized to a high-intensity home exercise or usual and customary care (UCC) group. The CYCLE Trial protocol will be delivered to the home of the exercise group through the consumer-based Peloton Indoor Cycle, and participants will be instructed to exercise 3x/week for 12 months; the UCC group will be instructed to engage in their normal activities. The exercise and control groups will undergo identical motor and non-motor evaluation protocols at enrollment, 3, 6, 9, and 12 months. In addition to clinical measures such as the MDS-UPDRS III, systematic quantification of motor and non-motor outcomes will be collected using the PD-Performance Test (PD-PT), a validated set of biomechanical-based iPad applications created in Dr. Alberts? lab. Overall activity levels will be monitored for both groups via a wearable sensor. Combining clinical and biomechanical measures of motor and cognitive performance will accelerate the investigation and understanding of potential mechanisms underlying the positive effects of exercise on disease progression. Finally, exercise performance data including heart rate, cadence and power from each session will be gathered to monitor exercise compliance and build an exercise response predictive model. The model will facilitate a transition from general recommendation to a patient-specific exercise prescription in which potential outcomes can be estimated.

Public Health Relevance

This project will determine the disease altering properties of high intensity exercise by randomizing 250 individuals with PD across two study sites (Cleveland Clinic and University of Utah) into a high-intensity home- based cycling program or a usual and customary care control group. Both groups will be monitored over a 12- month period; motor and non-motor outcomes will be measured via standardized clinical assessments and biomechanical-based iPad applications to determine disease altering characteristics of aerobic exercise. The development of a model to predict the effectiveness of high intensity aerobic exercise based on patient-specific factors (demographic information, demographics, and disease variables) will facilitate widespread patient- specific exercise prescription.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Musculoskeletal Rehabilitation Sciences Study Section (MRS)
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Lungu, Codrin Ion
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Cleveland Clinic Lerner
Other Basic Sciences
Schools of Medicine
United States
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Ozinga, Sarah J; Linder, Susan M; Alberts, Jay L (2017) Use of Mobile Device Accelerometry to Enhance Evaluation of Postural Instability in Parkinson Disease. Arch Phys Med Rehabil 98:649-658
Penko, Amanda L; Barkley, Jacob E; Koop, Mandy Miller et al. (2017) Borg scale is valid for ratings of perceived exertion for individuals with Parkinson's disease. Int J Exerc Sci 10:76-86
Ozinga, Sarah J; Koop, Mandy Miller; Linder, Susan M et al. (2017) Three-dimensional evaluation of postural stability in Parkinson's disease with mobile technology. NeuroRehabilitation 41:211-218
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Rosenfeldt, Anson B; Rasanow, Matthew; Penko, Amanda L et al. (2015) The cyclical lower extremity exercise for Parkinson's trial (CYCLE): methodology for a randomized controlled trial. BMC Neurol 15:63
Penko, Amanda L; Hirsch, Joshua R; Voelcker-Rehage, Claudia et al. (2014) Asymmetrical pedaling patterns in Parkinson's disease patients. Clin Biomech (Bristol, Avon) 29:1089-94
Ozinga, Sarah J; Alberts, Jay L (2014) Quantification of postural stability in older adults using mobile technology. Exp Brain Res 232:3861-72

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