Landmark 66 · Trial in people
SURE-PD3: inosine
Urate rose as planned, but Parkinson's did not slow in 298 people. Kidney stones were more common on inosine.
In short
A Phase 3 trial that deliberately raised blood urate, an antioxidant linked to slower Parkinson's in observational studies, found no slowing and more kidney stones.
- What it is
- Trial in people
- Outcome
- Did not work
- When
- 2021
- Size
- 298 people · Phase 3
- Approach
- Help cells clean up
- Research lane
- Oxidative stress
- Trial registry
- NCT02642393
- Last checked
- 19 Oct 2026
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
Michael Schwarzschild (Massachusetts General Hospital) and the Parkinson Study Group SURE-PD3 investigators, at 58 US sites. JAMA 2021;326:926-939.
What happened
People who naturally have higher blood urate tend to have slower Parkinson's, so the team tested inosine, a compound the body turns into urate. SURE-PD3 enrolled 587 consented people and randomised 298 with early Parkinson's who were not yet on dopamine drugs, had a dopamine-transporter deficit on scan and low urate (below 5.8 mg/dL). Between August 2016 and December 2017, 149 received inosine, dose-adjusted to push urate to 7.1-8.0 mg/dL, and 149 got placebo, for up to two years (follow-up to June 2019). A prespecified interim futility analysis closed the trial early; 273 (92%) of those randomised had completed it. The MDS-UPDRS parts I-III score rose 11.1 points a year on inosine against 9.9 on placebo (difference 1.26, 95% CI -0.59 to 3.11; P = .18). Urate rose by 2.03 mg/dL from a baseline of 4.6, as intended. Dopamine-transporter loss and other secondary measures did not differ. Serious adverse events were fewer on inosine (7.4 vs 13.1 per 100 patient-years), but kidney stones were more common (7.0 vs 1.4).
Why it moved us toward a cure
The idea came from the population finding that people with higher urate get Parkinson's less often and progress more slowly (landmark 131). It was a rigorous test of a hypothesis built from population data, and it shows the drug did what it was meant to (urate rose) without effect on the disease. It followed a 75-person safety trial (SURE-PD, JAMA Neurol 2014), which showed inosine was tolerated and raised urate by 2.3 and 3.0 mg/dL. It is a caution for "natural protective factor" ideas, as with coenzyme Q10.
Outcome
Dead end. The authors wrote that the findings "do not support the use of inosine as a treatment for early PD."
Sources
- Schwarzschild et al., JAMA 2021;326(10):926–939, PMID 34519802 · PubMed
- ClinicalTrials.gov NCT02642393 (298 enrolled; completed June 2019; results posted)
- SURE-PD, JAMA Neurol 2014;71:141-150, PMID 24366103
- Not yet verified: the original epidemiology on urate and Parkinson's (see landmark 131); the full text beyond the abstract.
How it connects
Built on
- tests Urate epidemiology · 2007
Led to
None recorded.