CNS Uptake of Intranasal Glutathione

Parkinson's Disease Clinical Trial

Official title: Central Nervous System Uptake of Intranasal Glutathione in Parkinson's Disease

Status Completed

Clinical Trial Summary

Excessive free radical formation and depletion of the brain's primary antioxidant, glutathione, are established components of Parkinson's disease (PD) pathophysiology. While there is rationale for the therapeutic use of reduced glutathione (GSH) in PD, and even some preliminary evidence to suggest the use of GSH can lead to symptomatic improvement, obstacles surrounding currently employed delivery methods have hindered the clinical utility of this therapy. Intranasal GSH, (in)GSH, is a novel method of glutathione augmentation. The aim of this study is to evaluate whether 200 mg of (in)GSH results in measurable changes in brain glutathione concentrations, as measured by magnetic resonance spectroscopy (MRS) in 15 individuals with PD.

Clinical Trial Description

Objectives

Primary Aim: To determine whether intranasal reduced glutathione, (in)GSH, is capable of augmenting CNS glutathione levels.

Hypothesis: Mean MRS glutathione concentration will rise from baseline following administration of 1 cc 200 mg/ml (in)GSH.

Design and Outcomes:

This pilot study seeks to obtain baseline data regarding the feasibility of MRS to detect a change in CNS glutathione concentration following administration of 200 mg (in)GSH. CNS glutathione levels will be measured using magnetic resonance spectroscopy (MRS), with the putamen as the region of interest. Baseline brain GSH concentrations will be measured by MRS at approximately the same time each day in all individuals before and after administration of study medication.

Outcome Measure: Describe the change in mean GSH concentration following administration of (in)GSH. The data analysis will be ipsative- results will be reported as percent change from the individual's own baseline GSH concentration.

Interventions and Duration:

If a participant communicates he/she understands the study, meets inclusion criteria, and provides informed consent, individuals will be scheduled for a single visit at the University of Washington for MR imaging (MRI), clinical evaluation, and blood draw. (~ 3 hours). Participants will be asked to be optimally medicated at the time of study visit, to the best of their ability.

Sample Size and Population:

This is a proof-of-concept pilot trial. Based on the data from the single test subject, a sample size of 15 would provide 80% power to detect an increase in CNS glutathione concentrations between pre- and post- administration values, if we are willing to accept an alpha value of 0.2.

1.1 Primary Aims

Primary Aim: To determine whether intranasal reduced glutathione, (in)GSH, is capable of augmenting CNS glutathione concentration. (Region of Interest: putamen)

Hypothesis: Mean MRS glutathione concentration will rise from baseline approximately 15 minutes following administration of 200 mg/ml (in)GSH in 1 cc saline.

1.2 Secondary Objectives

Hypothesis: Baseline CNS glutathione concentrations and RBC glutathione concentrations will be correlated.

1. To determine whether brain MRS [glutathione] and red blood cell (RBC) glutathione levels are correlated.

Outcome: A ROC curve will be drawn between mean brain [glutathione] and RBC total glutathione. ;

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

• NCT number: NCT02324426
• Study type: Interventional
• Source: University of Washington
• Status: Completed
• Phase: Phase 1
• Start date: December 2014
• Completion date: March 2015