Evidence map›Paper›PMID 30415890›Full record

Trial reportEBioMedicine2018

Dissociation between urate and blood pressure in mice and in people with early Parkinson's disease.

Xiqun Chen, Chizoba C Umeh, Robert E Tainsh, Danielle D Feng, Michael Maguire, Fuxing Zuo, Maryam Rahimian, Robert Logan, Xinliumei Wang, Alberto Ascherio and 4 more

Open access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Xiqun ChenDepartment of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: xchen17@mgh.harvard.edu.
Chizoba C UmehDepartment of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Robert E TainshDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Gray-Bigelow 444, 55 Fruit Street, Boston, MA 02114, USA.
Danielle D FengDepartment of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Michael MaguireDepartment of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Fuxing ZuoDepartment of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Maryam RahimianDepartment of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Robert LoganDepartment of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Xinliumei WangDepartment of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Alberto AscherioDepartment of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Eric A MacklinStatistics Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Emmanuel S BuysDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Gray-Bigelow 444, 55 Fruit Street, Boston, MA 02114, USA.
Michael A SchwarzschildDepartment of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Parkinson Study Group (PSG) The Safety of Urate Elevation in Parkinson's Disease (SURE-PD) investigators
Massachusetts General Hospital · USBrigham and Women's Hospital · USHarvard University · US

Funding

Phase 3 trial of inosine for Parkinson's disease CCCU01NS090259 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI SCHWARZSCHILD, MICHAEL A · 2015 to 2019
$16.9M
MC1R Basis of Melanoma-Parkinson's Link and Neuroprotective Potential of MC1RR01NS102735 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI CHEN, XIQUN · 2018 to 2022
$1.8M
Pursuing purinergic pathways to clinical trials for Parkinson's diseaseK24NS060991 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI SCHWARZSCHILD, MICHAEL A · 2008 to 2012
$954k
Neuroprotection by MC1R as the basis for the melanoma-Parkinson's disease linkR21NS090246 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI CHEN, XIQUN · 2015 to 2016
$450k
NINDS NIH HHS K24 NS060991NINDS NIH HHS R01 NS102735NINDS NIH HHS R21 NS090246NINDS NIH HHS U01 NS090259
6 · The paper itself

Abstract

backgroundEpidemiological, laboratory and clinical studies have established an association between elevated urate and high blood pressure (BP). However, the inference of causality remains controversial. A naturally occurring antioxidant, urate may also be neuroprotective, and urate-elevating treatment with its precursor inosine is currently under clinical development as a potential disease-modifying strategy for Parkinson's disease (PD).

methodsOur study takes advantage of a recently completed phase II trial evaluating oral inosine in de novo non-disabling early PD with no major cardiovascular and nephrological conditions, and of three lines of genetically engineered mice: urate oxidase (UOx) global knockout (gKO), conditional KO (cKO), and transgenic (Tg) mice with markedly elevated, mildly elevated, and substantially reduced serum urate, respectively, to systematically investigate effects of urate-modifying manipulation on BP.

findingsAmong clinical trial participants, change in serum urate but not changes in systolic, diastolic and orthostatic BP differed by treatment group. There was no positive correlation between urate elevations and changes in systolic, diastolic and orthostatic BP ((p = .05 (in inverse direction), 0.30 and 0.63, respectively)). Between UOx gKO, cKO, or Tg mice and their respective wildtype littermates there were no significant differences in systolic or diastolic BP or in their responses to BP-regulating interventions.

interpretationOur complementary preclinical and human studies of urate modulation in animal models and in generally healthy early PD do not support a hypertensive effect of urate elevation or an association between urate and BP. FUND: U.S. Department of Defense, RJG Foundation, Michael J. Fox Foundation LEAPS program, National Institutes of Health, American Federation for Aging Research, Parkinson's Disease Foundation Advancing Parkinson's Therapies initiative.

Indexed as

Blood PressureAnimalsDisease Models, AnimalFemaleHumansMaleMiceMice, KnockoutMiddle AgedParkinson DiseaseUric AcidUric AcidBlood pressureHypertensionHyperuricemiaUrateUrate oxidase

Identifiers

PMID30415890
PMCPMC6284456
OpenAlexW2900254225

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.