Effectiveness of a Long-Term, Home-Based Aerobic Exercise Intervention on Slowing the Progression of Parkinson Disease: Design of the Cyclical Lower Extremity Exercise for Parkinson Disease II (CYCLE-II) Study

OBJECTIVE: Previous short duration studies have demonstrated that high-intensity aerobic exercise improves aspects of motor and non-motor function in people with Parkinson disease (PwPD); however, the effectiveness of a long-term exercise intervention on slowing disease progression is unknown. The primary aim of this study is to determine the disease-altering effects of high-intensity aerobic exercise, administered on an upright stationary cycle, on the progression of PD. A secondary aim is to develop a prognostic model for 12-month changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) of PwPD undergoing an aerobic exercise intervention. METHODS: This pragmatic, multisite, single-rater blinded, randomized controlled trial will recruit PwPD from 2 large, urban, academic medical centers. Participants (N = 250 PwPD) will be randomized to (1) home-based aerobic exercise or (2) usual and customary care. Those in the aerobic exercise arm will be asked to complete in-home aerobic exercise sessions at 60% to 80% of heart rate reserve 3 times per week for 12 months utilizing a commercially available upright exercise cycle. The usual and customary care group will continue normal activity levels. Daily activity will be monitored for both groups throughout the 12-month study period. The primary outcome, both to assess disease-modifying response to aerobic exercise and for prognostic modeling in the aerobic exercise arm, is 12-month rate of change in the MDS-UPDRS III. Clinical and biomechanical measures will also be used to assess upper and lower extremity motor function as well as non-motor functions. IMPACT: Should long-term aerobic exercise demonstrate disease-modifying capability, this study will provide evidence that "Exercise is Medicine" for PwPD. Further, the derived prognostic model will inform a patient-specific exercise prescription for PwPD and expected effects on PD progression.