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SURE-PD3
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.
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.
Total Participants (Cohort records that met the AMP PD minimum clinical data criteria):
259
AMP PD Designation:
Data from the SURE-PD3 cohort is designated with the prefix “SU” in the AMP PD Portal. SURE-PD3 data in the AMP PD portal includes: Demographics, family history, medication history, MDS-UPDRS, MoCA, Hoehn & Yahr, PDQ-39, Modified Schwab and England, and WGS.
Additional Study Information:
SURE-PD3 Goals and Objectives
The goal of this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial is 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.
The goal of this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial is 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.
Secondary outcome measures include:
- Safety and tolerability of Inosine treatment
- Number of subjects requiring initiation of dopaminergic treatment.
- Rate of change of other clinical measures (e.g., PDQ-39, MoCA, Schwab & England, etc.)
Source:
https://clinicaltrials.gov/ct2/show/NCT02642393?term=SURE+PD+3&cond=Parkinson+Disease&draw=2&rank=1
SURE-PD3 Study Specific Data Contribution
In Release 2.5 from May 2021, participants from the SURE-PD3 cohort are represented in AMP PD clinical and WGS data. Of 261 SURE-PD3 cohort participants whose clinical records met AMP PD minimum clinical data criteria, 259 have corresponding WGS sample data (2 are represented by a linked WGS duplicate sample) and 261 are represented in the AMP PD joint genotyping dataset.
SURE-PD3 Inclusion and Exclusion Criteria
Inclusion and Exclusion criteria for SURE-PD 3 included:
Inclusion Criteria
- Willingness and ability to give written informed consent and to comply with trial procedures.
- Fulfillment of diagnostic criteria for idiopathic PD with at least two of the cardinal signs of PD (resting tremor, bradykinesia, rigidity) present at 2nd screening and baseline evaluations, as assessed by the Site Investigator.
- Absence of current or imminent (within 90 days of enrollment) PD disability requiring dopaminergic therapy, as assessed by the Site Investigator. Modified Hoehn and Yahr Scale Stage 1 to 2.5 inclusive.
- Age 30 or older at the time of PD diagnosis.
- Diagnosis of PD made within 3 years prior to 1st Screening Visit.
- Non-fasting serum urate ≤ 5.7 mg/dL at 1st Screening Visit (SC1).
- If the subject is female, then:
- Being surgically sterile (hysterectomy or tubal ligation), or
- Being postmenopausal (last menstruation was two years or more prior to 2nd Screening Visit), or
- For those of childbearing potential:
- Using a reliable form of contraception (e.g., IUD, birth control pills, etc.) for 60 days or more prior to Baseline Visit and agreeing to continue such use for 30 days post last dose of study drug.
- And having a negative pregnancy test at screening.
Exclusion Criteria
- Atypical parkinsonism, including that due to drugs, metabolic disorders, encephalitis, cerebrovascular disease, normal pressure hydrocephalus, or other neurodegenerative disease.
- Dopamine transporter (DAT) brain scan without evidence of dopamine deficit.
- History of gout.
- History of uric acid or urate urolithiasis, or recurrent urolithiasis all of unknown type.
- A screening test positive for uric acid crystalluria, urine pH ≤ 5.0, or an estimated glomerular filtration rate < 60 ml/min/1.73 m2.
- History of myocardial infarction or stroke.
- Symptomatic congestive heart failure with a documented ejection fraction below 45%.
- History of severe chronic obstructive pulmonary disease.
- Mini Mental State Exam score < 25; i.e., a score of 0 to 24.
- Use of any anti-parkinsonian medication (including levodopa, dopamine agonists, amantadine, entacapone and the anticholinergic agents trihexyphenidyl and benztropine) other than monoamine oxidase-B inhibitors within 60 days of Baseline, or in excess of 90 days.
- Change in the dosage of (or initiation of) a monoamine oxidase-B (MAO-B) inhibitor within 90 days prior to Baseline, i.e., entry on a MAO-B inhibitor requires a stable dosage for the 90 days prior to Baseline.
- Use of the following within 30 days prior to the Baseline Visit: inosine, allopurinol, febuxostat, probenecid, more than 50 IU of vitamin E daily, or more than 300 mg of vitamin C daily (though a daily standard multivitamin such as Bayer One-A-Day® or Centrum® is permissible), reserpine, methylphenidate, amphetamines, cinnarizine, monoamine oxidase-A inhibitors, tetrabenazine, neuroleptics or other dopamine blocking drugs.
- Use of the following within 90 days prior to the DAT neuroimaging screening evaluation: modafinil, armodafinil, metoclopramide, alpha-methyldopa, methylphenidate, reserpine, or amphetamine derivative.
- Unstable dosing of a thiazide -- such as hydrochlorothiazide (e.g., Esidrex), chlorothiazide (e.g., Diuril), chlorthalidone (e.g., Hygroton), indapamide (e.g., Lozol), metolazone (e.g., Zaroxolyn), which are permissible as long as the subject is on a stable dose from 1 week prior to the 1st Screening Visit through the Baseline Visit.
- Known unstable medical or psychiatric condition that may compromise participation in the study. (Note that difficulty swallowing large capsules might preclude participation due to the size of the study drug capsules.)
- Clinically serious abnormality in the screening visit laboratory studies or ECG, as determined by the Site Investigator.
- Participation in another investigational treatment study within 30 days prior to the Baseline Visit.
- Known hypersensitivity or intolerability to inosine.
- Known hypersensitivity to DaTscan (either the active substance of ioflupane I-123 or to any of the excipients).
SURE-PD3 Study Protocol
A link to the full protocol (.pdf) can be found in “Study Documents” at: https://clinicaltrials.gov/ct2/show/NCT02642393?term=SURE+PD+3&cond=Parkinson+Disease&draw=2&rank=1