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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT04000360.

Keywords: Aerobic Exercise; Cycling; Exercise Prescription; Parkinson Disease.

Figure 1

Study flow diagram for participants assigned to the aerobic exercise and usual and customary care groups. Both groups undergo baseline testing on 2 occasions (on and off anti-parkinsonian medication) and 6 and 12 months (off anti-parkinsonian medication) following enrollment. Those in the aerobic exercise group are asked to exercise 3 times per week for 12 months; details regarding exercise intervention and progression are provided in the text.

Figure 2

Exercise progression rubric. The physical therapist utilizes the objective metrics characterizing each exercise session (ie, heart rate, cadence, and resistance) from the stationary cycle, the subjective exercise effort from the participant, and clinical expertise for ongoing exercise progression.