Schenkman · JAMA neurology 2018 · Phase 2 randomized controlled trial · n=128

Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease: A Phase 2 Randomized Clinical Trial.

Cited 517 times in the scientific literature.

Level 2 - randomized trial

Phase 2 multicenter randomized controlled trial with masked outcome assessors

PubMed 29228079 · doi:10.1001/jamaneurol.2017.3517 · record verified 2026-08-30

What was done

A phase 2, multicenter randomized clinical trial (SPARX) evaluated 128 unmedicated patients with de novo idiopathic Parkinson disease (Hoehn and Yahr stage 1–2, aged 40–80 years, diagnosed within 5 years). Participants were randomly assigned to 6 months of high-intensity treadmill exercise (4 days/week, 80%–85% maximum heart rate [HRmax], n=43), moderate-intensity treadmill exercise (4 days/week, 60%–65% HRmax, n=45), or a wait-list control group (n=40). Primary outcomes included feasibility/safety and the 6-month change in Unified Parkinson's Disease Rating Scale (UPDRS) motor score assessed by masked examiners.

What was found

Participants in the high-intensity group achieved a mean exercise frequency of 2.8 days/week (95% CI, 2.4 to 3.2) at 80.2% HRmax (95% CI, 78.8% to 81.7%). The moderate-intensity group achieved 3.2 days/week (95% CI, 2.8 to 3.6) at 65.9% HRmax (95% CI, 64.2% to 67.7%). The mean 6-month change in UPDRS motor score was 0.3 (95% CI, -1.7 to 2.3) in the high-intensity group versus 3.2 (95% CI, 1.4 to 5.1) in the control group (P = .03). The high-intensity group met the predefined nonfutility threshold compared to control, whereas the moderate-intensity group did not. Musculoskeletal adverse events occurred as anticipated but were not severe.

Why it matters

This study shows that high-intensity endurance exercise is safe and feasible for patients with early-stage, untreated Parkinson disease and may stabilize motor symptoms compared to standard care, supporting progression to a phase 3 trial.

Limits

The study was a phase 2 futility trial with a modest sample size and short duration (6 months), not powered as a definitive efficacy trial. Enrollment was restricted to sedentary, unmedicated patients with early-stage disease (Hoehn and Yahr 1–2), limiting generalizability to patients with advanced disease or those taking dopaminergic medications. The cohort was predominantly non-Hispanic white (84.4%), and the abstract does not report the specific UPDRS motor score change for the moderate-intensity group.

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