Effect of Urate-Elevating Inosine on Early Parkinson Disease Progression: The SURE-PD3 Randomized Clinical Trial

IMPORTANCE: Urate elevation, despite associations with crystallopathic, cardiovascular, and metabolic disorders, has been pursued as a potential disease-modifying strategy for Parkinson disease (PD) based on convergent biological, epidemiological, and clinical data. OBJECTIVE: To determine whether s...

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Veröffentlicht in:	JAMA : the journal of the American Medical Association 2021-09, Vol.326 (10), p.926-939
Hauptverfasser:	Schwarzschild, Michael A, Ascherio, Alberto, Casaceli, Cindy, Curhan, Gary C, Fitzgerald, Rebecca, Kamp, Cornelia, Lungu, Codrin, Macklin, Eric A, Marek, Kenneth, Oakes, David, Rudolph, Alice, Shoulson, Ira, Videnovic, Aleksandar, Scott, Burton, Gauger, Lisa, Aldred, Jason, Bixby, Melissa, Ciccarello, Jill, Gunzler, Steven A, Henchcliffe, Claire, Brodsky, Matthew, Keith, Kellie, Hauser, Robert A, Goetz, Christopher, LeDoux, Mark S, Hinson, Vanessa, Kumar, Rajeev, Espay, Alberto J, Jimenez-Shahed, Joohi, Hunter, Christine, Christine, Chadwick, Daley, Aaron, Leehey, Maureen, de Marcaida, J. Antonelle, Friedman, Joseph Harold, Hung, Albert, Bwala, Grace, Litvan, Irene, Simon, David K, Simuni, Tanya, Poon, Cynthia, Schiess, Mya C, Chou, Kelvin, Park, Ariane, Bhatti, Danish, Peterson, Carolyn, Criswell, Susan R, Rosenthal, Liana, Durphy, Jennifer, Shill, Holly A, Mehta, Shyamal H, Ahmed, Anwar, Deik, Andres F, Fang, John Y, Stover, Natividad, Zhang, Lin, Dewey, Richard B, Boyd, James T, Houston, Emily, Suski, Valerie, Mosovsky, Sherri, Cloud, Leslie, Shah, Binit B, Saint-Hilaire, Marie, James, Raymond, Zauber, Sarah Elizabeth, Reich, Stephen, Shprecher, David, Pahwa, Rajesh, Langhammer, April, LaFaver, Kathrin, LeWitt, Peter A, Kaminski, Patricia, Goudreau, John, Russell, Doozie, Houghton, David J, Laroche, Ashley, Thomas, Karen, McGraw, Martha, Mari, Zoltan, Serrano, Carmen, Blindauer, Karen, Rabin, Marcie, Kurlan, Roger, Morgan, John C, Ainslie, Melissa, Bodis-Wollner, Ivan, Schneider, Ruth B, Waters, Cheryl, Ratel, Amber Servi, Beck, Christopher A, Bolger, Patrick, Callahan, Katherine F, Crotty, Grace F, Klements, David, McMahon, Gearoid Michael, Pothier, Lindsay, Waikar, Sushrut S, Lang, Anthony, Mestre, Tiago
Format:	Artikel
Sprache:	eng
Schlagworte:	Adverse events Aged Autonomic nervous system Binding Biomarkers Biomarkers - blood Calculi Chemotherapy Clinical trials Cognition Disease Progression Dopamine Dopamine Plasma Membrane Transport Proteins - deficiency Dopamine receptors Dopamine transporter Double-Blind Method Double-blind studies Drug therapy Epidemiology Female Health services Humans Inosine - adverse effects Inosine - therapeutic use Kidney Calculi - chemically induced Male Metabolic disorders Middle Aged Movement disorders Neostriatum Nephrolithiasis Neurodegenerative diseases Original Investigation Parkinson Disease - blood Parkinson Disease - drug therapy Parkinson Disease - physiopathology Parkinson's disease Patients Placebos Quality of life Severity of Illness Index Titration Treatment Failure Uric acid Uric Acid - blood
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Zusammenfassung:	IMPORTANCE: Urate elevation, despite associations with crystallopathic, cardiovascular, and metabolic disorders, has been pursued as a potential disease-modifying strategy for Parkinson disease (PD) based on convergent biological, epidemiological, and clinical data. OBJECTIVE: To determine whether sustained urate-elevating treatment with the urate precursor inosine slows early PD progression. DESIGN, PARTICIPANTS, AND SETTING: Randomized, double-blind, placebo-controlled, phase 3 trial of oral inosine treatment in early PD. A total of 587 individuals consented, and 298 with PD not yet requiring dopaminergic medication, striatal dopamine transporter deficiency, and serum urate below the population median concentration (
ISSN:	0098-7484 1538-3598
DOI:	10.1001/jama.2021.10207