{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T03:05:01Z","timestamp":1785380701549,"version":"3.55.0"},"reference-count":42,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2017,3,20]],"date-time":"2017-03-20T00:00:00Z","timestamp":1489968000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2017,3,20]]},"abstract":"<jats:p>Background: Reduced glutathione (GSH) is an endogenously synthesized tripeptide depleted early in the course of Parkinson\u2019s disease (PD) and GSH augmentation has been proposed as a therapeutic strategy in PD.<\/jats:p>\n                  <jats:p>Objective: This Phase IIb study was designed to evaluate whether a Phase III study of intranasal GSH, (in)GSH, for symptomatic relief is warranted and to determine the most appropriate trial design for a disease-modification study.<\/jats:p>\n                  <jats:p>Methods: This was a double-blind, placebo-controlled trial of 45 individuals with Hoehn &amp; Yahr Stage 1\u20133 PD. Participants were randomized to receive intranasal placebo (saline), 100\u200amg GSH, or 200\u200amg GSH thrice daily for three months, and were observed over a one-month washout period.<\/jats:p>\n                  <jats:p>Results: All cohorts improved over the intervention period, including placebo. The high-dose group demonstrated improvement in total Unified PD Rating Scale (UPDRS) (\u20134.6 (4.7), P\u200a=\u200a0.0025) and UPDRS motor subscore (\u20132.2 (3.8), P\u200a=\u200a0.0485) over baseline, although neither treatment group was superior to placebo. One participant in the high-dose GSH cohort developed cardiomyopathy.<\/jats:p>\n                  <jats:p>Conclusions: Although predicted improvements in PD total and motor scores were observed, these data do not suggest (in)GSH is superior to placebo after a three month intervention. The symptomatic effects are sufficient to warrant a delayed-start or wash-out design study for disease-modification trials. Whether long-term use of (in)GSH leads to clinical improvements that are sustained and significantly different than placebo will require appropriately-powered longer-duration studies in larger cohorts. The improvement in the placebo arm was more robust than has been observed in previous PD studies and warrants further investigation.<\/jats:p>","DOI":"10.3233\/jpd-161040","type":"journal-article","created":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T10:40:58Z","timestamp":1492771258000},"page":"289-299","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":77,"title":["Phase IIb Study of Intranasal Glutathione in Parkinson\u2019s Disease"],"prefix":"10.1177","volume":"7","author":[{"given":"Laurie K.","family":"Mischley","sequence":"first","affiliation":[{"name":"Bastyr University Research Institute, Kenmore, WA, USA"},{"name":"University of Washington (UW) Department of Radiology, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Lau","sequence":"additional","affiliation":[{"name":"Oregon State University, Corvalis, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric G.","family":"Shankland","sequence":"additional","affiliation":[{"name":"University of Washington (UW) Department of Radiology, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy K.","family":"Wilbur","sequence":"additional","affiliation":[{"name":"University of Washington (UW) Department of Radiology, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannie M.","family":"Padowski","sequence":"additional","affiliation":[{"name":"Washington State University,Elson S. Floyd College of Medicine, College of Pharmacy, Spokane, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,4,20]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(82)90390-1"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410360305"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90355-B"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9409363"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1007\/BF01271295"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199603220-00018"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00229.x"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-132483"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1089\/acm.2010.0716"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1007\/BF02284971"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(96)00103-0"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22401"},{"key":"ref013","first-page":"32","volume":"26","author":"Mischley LK","year":"2011","journal-title":"J Orthomol Med"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1089\/acm.2011.0673"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26351"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1038\/npjparkd.2016.2"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90461-S"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23383"},{"issue":"15","key":"ref019","first-page":"S579","volume":"21","author":"Sechi G","year":"2006","journal-title":"Mov Disord"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157602"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-016-0606-3"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.3758\/BF03193146"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22218"},{"key":"ref024","unstructured":"SmithC (2010) Levodopa dose equivalency: A systematic review [PowerPoint slides]. 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