Sex differences by design and outcome in the Safety of Urate Elevation in PD (SURE-PD) trial

Michael A Schwarzschild; Eric A Macklin; Rachit Bakshi; Shamik Battacharyya; Robert Logan; Alberto J Espay; Albert Y Hung; Grace Bwala; Christopher G Goetz; David S Russell; John L Goudreau; Sotirios A Parashos; Marie H Saint-Hilaire; Alice Rudolph; Joshua M Hare; Gary C Curhan; Alberto Ascherio

doi:10.1212/WNL.0000000000008194

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Sex differences by design and outcome in the Safety of Urate Elevation in PD (SURE-PD) trial

Journal article

Peer reviewed

Sex differences by design and outcome in the Safety of Urate Elevation in PD (SURE-PD) trial

Michael A Schwarzschild, Eric A Macklin, Rachit Bakshi, Shamik Battacharyya, Robert Logan, Alberto J Espay, Albert Y Hung, Grace Bwala, Christopher G Goetz, David S Russell, …

Neurology, Vol.93(14), pp.e1328-e1338

2019-10-01

DOI: https://doi.org/10.1212/WNL.0000000000008194

PMID: 31484712

Abstract

Follow-Up Studies

Humans

Male

Treatment Outcome

Mental Status and Dementia Tests

Parkinson Disease - drug therapy

Biomarkers - blood

Sex Characteristics

Inosine - therapeutic use

Parkinson Disease - diagnosis

Female

Uric Acid - blood

Parkinson Disease - blood

To investigate whether women and men with Parkinson disease (PD) differ in their biochemical and clinical responses to long-term treatment with inosine. The Safety of Urate Elevation in Parkinson's Disease (SURE-PD) trial enrolled 75 people with early PD and baseline serum urate below 6 mg/dL and randomized them to 3 double-blinded treatment arms: oral placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation for up to 2 years. Parkinsonism, serum urate, and plasma antioxidant capacity were measured at baseline and repeatedly on treatment; CSF urate was assessed once, at 3 months. Here in secondary analyses results are stratified by sex. Inosine produced an absolute increase in average serum urate from baseline that was 50% greater in women (3.0 mg/dL) than in men (2.0 mg/dL), consistent with expected lower baseline levels in women. Similarly, only among women was CSF urate significantly greater on mild or moderate inosine (+87% [ < 0.001] and +98% [ < 0.001], respectively) than on placebo (in contrast to men: +10% [ = 0.6] and +14% [ = 0.4], respectively). Women in the higher inosine dosing group showed a 7.0 Unified Parkinson's Disease Rating Scale (UPDRS) points/year lower rate of decline vs placebo ( = 0.01). In women, slower rates of UPDRS change were associated with greater increases in serum urate ( = -0.52; = 0.001), and with greater increases in plasma antioxidant capacity ( = -0.44; = 0.006). No significant associations were observed in men. Inosine produced greater increases in serum and CSF urate in women compared to men in the SURE-PD trial, consistent with the study's design and with preliminary evidence for slower clinical decline in early PD among women treated with urate-elevating doses of inosine. NCT00833690. This study provides Class II evidence that inosine produced greater urate elevation in women than men and may slow PD progression in women.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.67 Parkinson's Disease
Web Of Science research areas: Clinical Neurology
ESI research areas: Neuroscience & Behavior

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Title: Sex differences by design and outcome in the Safety of Urate Elevation in PD (SURE-PD) trial
Creators: Michael A Schwarzschild - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA. michaels@helix.mgh.harvard.edu
Eric A Macklin - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Rachit Bakshi - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Shamik Battacharyya - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Robert Logan - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Alberto J Espay - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Albert Y Hung - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Grace Bwala - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Christopher G Goetz - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
David S Russell - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
John L Goudreau - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Sotirios A Parashos - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Marie H Saint-Hilaire - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Alice Rudolph - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Joshua M Hare - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Gary C Curhan - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Alberto Ascherio - From the Departments of Neurology (M.A.S., R.B., S.B., R.L., A.Y.H., G.B.) and Medicine (E.A.M.), Massachusetts General Hospital, Boston; University of Cincinnati (A.J.E.), OH; Rush University (C.G.G.), Chicago, IL; Michigan State University (J.L.G.), East Lansing; Struthers Parkinson's Center (S.A.P.), Minneapolis, MN; Boston University (M.H.S.-H.), MA; University of Rochester (A.R.), NY; University of Miami (J.M.H.), FL; Brigham and Women's Hospital (G.C.C.), Boston, MA; Yale University School of Medicine (D.S.R.), New Haven, CT; and Department of Nutrition (A.A.), Harvard School of Public Health, Boston, MA
Publication Details: Neurology, Vol.93(14), pp.e1328-e1338
Publisher: United States
Grant note: U01 NS090259 / NINDS NIH HHS
Academic Unit: Leadership Department; Miller School of Medicine; Interdisciplinary Stem Cell Institute
Language: English
Resource Type: Journal article
PMID: 31484712
Record Identifier: 991031578492302976