CNS Uptake of Intranasal Glutathione

April 29, 2015 updated by: Laurie Mischley, University of Washington

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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 Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age > 18 years.
  • Ability to attend a 3 hour study visit in Seattle, WA.
  • Ability to read and speak English.
  • Have three or more of the required positive criteria for PD from Step 3 of the UK Brain Bank Diagnostic Criteria for Parkinson's Disease.
  • A modified Hoehn & Yahr Stage 2-3. (bilateral disease, not severely disabled.)

Exclusion Criteria:

  • Any contra-indication to magnetic resonance imaging, including pacemaker, pacemaker wires, aneurysm clip, or any electronic implant, weight over 136 kg (300 lb), metal embedded in soft tissue or in the eye, prosthetic eye, claustrophobia, substance abuse, use of recreational drugs, pregnancy, or other medical contraindications.
  • A history of epilepsy, stroke, brain surgery, or structural brain disease.
  • The presence of other serious illnesses (discretion of study clinician, e.g. concurrent cancer treatment.)
  • Pregnant.
  • A history of sulfur sensitivity, e.g. reaction N-acetylcysteine, MSM, SAMe.
  • A recent history of asthma.
  • Supplementation with glutathione (oral, intravenous, intranasal, or nebulized) or the glutathione precursor, N-acetylcysteine, for six months prior to baseline study visit.
  • History of sensitivity to sulfur containing medications/ supplements, i.e. NAC, MSM.
  • Current drug or alcohol use or dependence.
  • Inability/unwillingness to provide informed consent. (e.g. diagnosis of dementia, confusion about study goals or participation.)
  • Acute infection (e.g. upper respiratory, dermal) in the previous 30 days.
  • Diagnosis of any mental illness, ever. (Mental illness has been associated with glutathione depletion.)
  • Diagnosis of any chronic disease, ever. (e.g. Hep C, autoimmune disease, etc.)
  • Head tremor or head dyskinesia that cannot be comfortably controlled for 90 minutes.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Reduced Glutathione
The study medication is packaged in sterile 1 ml pre-filled syringes, each containing 200 mg/ ml of reduced glutathione (GSH), which will be delivered intranasally.
Drug: Reduced Glutathione
200 mg GSH delivered in 1 cc sterile saline using a syringe with a Mucosal Atomization Device (MAD) tip.
Other Names:
  • (in)GSH

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The concentration of metabolites before and after (in)GSH will be compared (change in mean GSH concentration)
Time Frame: 15 minutes after administration
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.
15 minutes after administration

Secondary Outcome Measures

Outcome Measure
Time Frame
A ROC curve will be generated to compare MRS [glutathione] to peripheral measures of RBC glutathione.
Time Frame: 15 minutes after administration
15 minutes after administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

Michael J. Fox Foundation for Parkinson's Research

Investigators

  • Principal Investigator: Kevin Conley, PhD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

March 1, 2015

Study Registration Dates

First Submitted

December 4, 2014

First Submitted That Met QC Criteria

December 23, 2014

First Posted (Estimate)

December 24, 2014

Study Record Updates

Last Update Posted (Estimate)

April 30, 2015

Last Update Submitted That Met QC Criteria

April 29, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 48273-A

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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