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Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease: A Phase 2 Randomized Clinical Trial
Open accessAbstract
Importance: Parkinson disease is a progressive neurologic disorder. Limited evidence suggests endurance exercise modifies disease severity, particularly high-intensity exercise. Objectives: To examine the feasibility and safety of high-intensity treadmill exercise in patients with de novo Parkinson disease who are not taking medication and whether the effect on motor symptoms warrants a phase 3 trial. Design, Setting, and Participants: The Study in Parkinson Disease of Exercise (SPARX) was a phase 2, multicenter randomized clinical trial with 3 groups and masked assessors. Individuals from outpatient and community-based clinics were enrolled from May 1, 2012, through November 30, 2015, with the primary end point at 6 months. Individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1 or 2) aged 40 to 80 years within 5 years of diagnosis who were not exercising at moderate intensity greater than 3 times per week and not expected to need dopaminergic medication within 6 months participated in this study. A total of 384 volunteers were screened by telephone; 128 were randomly assigned to 1 of 3 groups (high-intensity exercise, moderate-intensity exercise, or control). Interventions: High-intensity treadmill exercise (4 days per week, 80%-85% maximum heart rate [n = 43]), moderate-intensity treadmill exercise (4 days per week, 60%-65% maximum heart rate [n = 45]), or wait-list control (n = 40) for 6 months. Main Outcomes and Measures: Feasibility measures were adherence to prescribed heart rate and exercise frequency of 3 days per week and safety. The clinical outcome was 6-month change in Unified Parkinson's Disease Rating Scale motor score. Results: A total of 128 patients were included in the study (mean [SD] age, 64 [9] years; age range, 40-80 years; 73 [57.0%] male; and 108 [84.4%] non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the moderate-intensity group (P < .001). The mean change in Unified Parkinson's Disease Rating Scale motor score in the high-intensity group was 0.3 (95% CI, -1.7 to 2.3) compared with 3.2 (95% CI, 1.4 to 5.1) in the usual care group (P = .03). The high-intensity group, but not the moderate-intensity group, reached the predefined nonfutility threshold compared with the control group. Anticipated adverse musculoskeletal events were not severe. Conclusions and Relevance: High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson disease. An efficacy trial is warranted to determine whether high-intensity treadmill exercise produces meaningful clinical benefits in de novo Parkinson disease. Trial Registration: clinicaltrials.gov Identifier: NCT01506479.
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“aerobic exercise has been extensively researched for its role in improving cognition in AD patients and motor function in PD patients.542–545”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [544]
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Metadata
- Authors
- Schenkman, M., Moore, C. G., Kohrt, W. M., Hall, D. A., Delitto, A., Comella, C. L., Josbeno, D. A., Christiansen, C. L., Berman, B. D., Kluger, B. M., Melanson, E. L., Jain, S., Robichaud, J. A., Poon, C., & Corcos, D. M.
- Affiliations
- University of Colorado Anschutz (US)
- University of Pittsburgh (US)
- VA Eastern Colorado Health Care System (US)
- Rush University Medical Center (US)
- University of Illinois Hospital & Health Sciences System (US)
- Northwestern University (US)
- Corresponding author
- Schenkman, Margaret
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2018-02-01
- Volume
- 75
- Issue
- 2
- Pages
- 219
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC5838616
- OpenAlex
- W2773186181
- Cited by
- 515
- References
- 45
- Citations by year
- 2026: 59 · 2025: 72 · 2024: 82 · 2023: 71 · 2022: 66 · 2021: 70 · 2020: 38 · 2019: 33 · 2018: 24
- FWCI
- 18.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Parkinson's Disease Foundation
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK048520)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Balance, Gait, and Falls Prevention
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Physical Activity and Health
- Keywords
- Parkinson's disease, high-intensity exercise, treadmill exercise, motor symptoms, exercise adherence, exercise safety, moderate-intensity exercise, early-stage Parkinson's disease
- MeSH terms
- High-Intensity Interval Training, Adult, Aged, Aged, 80 and over, Exercise Test, Exercise Therapy, Female, Humans, Longitudinal Studies, Male, Middle Aged, Parkinson Disease, Retrospective Studies, Treatment Outcome
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