Phase IIb Study of Intranasal Glutathione in Parkinson's Disease.

Autor: Mischley LK; Bastyr University Research Institute, Kenmore, WA, USA.; University of Washington (UW) Department of Radiology, Seattle, WA, USA., Lau RC; Oregon State University, Corvalis, OR, USA., Shankland EG; University of Washington (UW) Department of Radiology, Seattle, WA, USA., Wilbur TK; University of Washington (UW) Department of Radiology, Seattle, WA, USA., Padowski JM; Washington State University,Elson S. Floyd College of Medicine, College of Pharmacy, Spokane, WA, USA.
Jazyk: angličtina
Zdroj: Journal of Parkinson's disease [J Parkinsons Dis] 2017; Vol. 7 (2), pp. 289-299.
DOI: 10.3233/JPD-161040
Abstrakt: Background: Reduced glutathione (GSH) is an endogenously synthesized tripeptide depleted early in the course of Parkinson's disease (PD) and GSH augmentation has been proposed as a therapeutic strategy in PD.
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.
Methods: This was a double-blind, placebo-controlled trial of 45 individuals with Hoehn & Yahr Stage 1-3 PD. Participants were randomized to receive intranasal placebo (saline), 100 mg GSH, or 200 mg GSH thrice daily for three months, and were observed over a one-month washout period.
Results: All cohorts improved over the intervention period, including placebo. The high-dose group demonstrated improvement in total Unified PD Rating Scale (UPDRS) (-4.6 (4.7), P = 0.0025) and UPDRS motor subscore (-2.2 (3.8), P = 0.0485) over baseline, although neither treatment group was superior to placebo. One participant in the high-dose GSH cohort developed cardiomyopathy.
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.
Databáze: MEDLINE
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