SURE-PD3 Study Overview
Convergent laboratory, epidemiological and clinical observations have identified urate – the end product of purine metabolism in humans – as a neuroprotectant and the first molecular predictor of both reduced risk and slower progression of typical Parkinson’s disease (PD). Urate is also a potent antioxidant and confers protection in cellular and animal models of PD. Epidemiological studies of prospectively followed healthy populations have repeatedly demonstrated serum urate to be an inverse risk factor for PD. These findings led to the discovery that among people with early PD serum and CSF urate levels are predictors of slower progression, assessed clinically or by neuroimaging of dopamine transporter (DAT) loss over years. This led to the phase 2 SURE-PD trial, which demonstrated safety, tolerability and effectiveness of inosine as a CSF urate-elevating strategy in PD, supporting further clinical development.
SURE-PD3 (Study of URate Elevation in Parkinson’s Disease, phase 3) was a randomized, double-blind, placebo-controlled trial of urate-elevating inosine treatment to slow clinical decline in early PD. The primary aim of this study was to determine whether oral inosine dosed to moderately elevate serum urate (from ≤5.7 mg/dL to 7.1-8.0 mg/dL) over 2 years slows clinical decline in early PD, assessed as change in the primary outcome variable of the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Secondary aims include assessing long-term safety and effects on a) the development of disability warranting dopaminergic medication, b) short-term changes in parkinsonian symptoms, c) changes in functional disability and quality of life, d) non-motor measures of cognition, mood and autonomic function, and e) loss of striatal dopamine transporter signal.
The SURE-PD3 study terminated following preplanned futility analysis after 2/3 of subjects’ data were collected, and did not meet the threshold for non-futility.
SURE-PD3 Goals and Objectives
The main goal of the study is to determine whether inosine is suitable for phase III evaluation of its ability to modify the rate of disability progression in PD.
Specific primary aims entail the determination of the safety and tolerability of oral inosine, and its ability to elevate urate levels in serum or CSF; and the selection of an optimal dosing regimen.
Secondary aims entail the further optimization of a possible phase III study design.
Study Specific Data Contribution
SURE-PD3 Inclusion and Exclusion Criteria
The Parkinson Study Group (PSG) conducted a placebo-controlled, randomized, double-blind study to assess the disease-modifying potential of the drug inosine in people with early stage Parkinson’s disease (PD).
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor).