Exercise: SPARX and SPARX3

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Margaret Schenkman (University of Colorado) and Daniel Corcos (Northwestern) led SPARX with colleagues at several US centres, funded by the US National Institute of Neurological Disorders and Stroke (grant R01 NS074343). SPARX3 is sponsored by Northwestern University, with the University of Pittsburgh and the Parkinson Study Group as collaborators; Corcos is the principal investigator and the protocol's first author is Charity Patterson (Pittsburgh). Its registry record cites NIH grant U01NS113851.

What happened

SPARX (NCT01506479; enrolled May 2012 to November 2015). 128 people aged 40–80 with Parkinson's (Hoehn and Yahr stage 1–2) diagnosed within five years, and not expected to need Parkinson's medicine within six months, were randomised to three groups for six months: high-intensity treadmill walking (80–85% of maximum heart rate, four days a week; 43 people), moderate intensity (60–65%; 45 people), or a wait-list control with usual care (40 people). The high-intensity group managed 2.8 days a week (95% CI 2.4–3.2) at 80.2% of maximum heart rate. The change in the original UPDRS motor score (lower is better) was +0.3 (95% CI −1.7 to 2.3) in the high-intensity group, +2.0 (95% CI 0.38–3.7) in the moderate group and +3.2 (95% CI 1.4–5.1) in controls. The trial was a futility screen, not an efficacy test: the high-intensity group passed the pre-set non-futility threshold (P = .34 for the non-futility null hypothesis, so not rejected) and differed from controls at P = .03; the moderate group failed the threshold. The authors concluded that a larger efficacy trial was warranted (Schenkman et al., JAMA Neurol 2018;75(2):219–226, online December 2017).

SPARX3 (NCT04284436; Phase 3). A multicentre, randomised, evaluator-blinded trial of 370 people with Parkinson's diagnosed within three years and not on symptomatic medicine. Both arms exercise on a treadmill four days a week for 30 minutes over 18 months, at either moderate (60–65%) or high (80–85%) intensity. The primary outcome is the change in MDS-UPDRS motor score (part III) over 12 months, or until symptomatic treatment starts. Secondary outcomes include dopamine-transporter scan binding, six-minute walk distance, steps, cognition, fitness, quality of life, time to start medicine, and blood CRP and BDNF. The registry records an actual start of 30 August 2021, 370 enrolled, status "active, not recruiting" (verified April 2026), primary completion estimated July 2027 and study completion July 2028. No results are posted.

Why it moved us toward a cure

Exercise is one of the few things that reliably helps people with Parkinson's, and animal work suggests it may protect neurons. SPARX gave the first controlled sign that intensity matters. Because the drug field has repeatedly failed (dead ends), a non-drug approach with a clear biological question is a useful parallel route.

Outcome

Open. SPARX ran only six months, had a wait-list control and cannot separate symptom relief from true slowing. SPARX3's two arms both exercise, so it can show which dose is better but not exercise versus none. Enrolment is complete; the primary readout is not expected before mid-2027.

Sources

• Schenkman et al., JAMA Neurol 2018;75:219–226, DOI 10.1001/jamaneurol.2017.3517, PMID 29228079 · NCT01506479
• Northwestern release, Dec 2017
• SPARX3 protocol, Trials 2022;23:855, DOI 10.1186/s13063-022-06703-0, PMID 36203214 · ClinicalTrials.gov NCT04284436 (API, 19 Oct 2026)
• Not yet verified: the full list of SPARX3 sites (the earlier "US and Canadian" wording was removed as unsourced); any SPARX3 result.