Phase IIb Study of Intranasal Glutathione in Parkinson's Disease

J Parkinsons Dis. 2017;7(2):289-299. doi: 10.3233/JPD-161040.


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.

Keywords: Nutrition; deficiency; neurodegeneration; neurodegenerative; neuroprotection; nutrient; nutritional; vitamin.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Adult
  • Aged
  • Double-Blind Method
  • Female
  • Glutathione / administration & dosage*
  • Glutathione / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy*
  • Treatment Outcome


  • Glutathione